Lysine salt and method of manufacturing a lysine derivative

Abstract

The invention relates to a Bsmoc-protected lysine salt of formula (1X), e.g., a hydrochloric acid salt (n = 1, HY = hydrochloric acid). It further relates to a method of manufacturing Bsmoc-protected lysine derivatives, which employs the Bsmoc-protected lysine salt of formula (1X) and comprises the step of reacting the epsilon amino group of lysine with an 10 activated carboxylic acid derivative. Some of the obtainable Bsmoc-protected lysine derivatives with their side chain modification are useful as starting materials in solid phase peptide synthesis.

Description

[0001] Bachem Holding AG BAC75079PC April 10, 2024 Lysine salt and method of manufacturing a lysine derivative Description The present invention relates to a Bsmoc-protected lysine salt, which is protected at its alpha nitrogen with 1,1-dioxobenzo[b]thiophen-2-ylmethyloxycarbonyl (Bsmoc). It relates further to a method of manufacturing a Bsmoc-protected lysine derivative, which employs the Bsmoc- protected lysine salt as a starting material and comprises a reaction of its epsilon nitrogen atom with an activated carboxylic acid derivative under formation of an amide group. It relates also to the use of the Bsmoc-protected lysine salt in the synthesis of a peptide. Semaglutide (CAS-No.910463-68-2) is an active pharmaceutical ingredient and is known as a glucagon-like peptide-1 receptor agonist. Semaglutide, when it is written in the three-letter-code of peptides, has the following formula: H-His1-Aib-Glu-Gly-Thr5-Phe-Thr-Ser-Asp-Val10-Ser-Ser-Tyr-Leu-Glu15-Gly-Gln-Ala-Ala- Lys20(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2- aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp25-Leu-Val-Arg-Gly-Arg30-Gly-OH (SEQ ID NO:5) Accordingly, Semaglutide has a linear 31-mer peptide backbone and carries at the epsilon nitrogen atom of its lysine20 a fatty acid side chain, the epsilon nitrogen atom of lysine20 is substituted with HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl]-2-[2-(2- aminoethoxy)ethoxy]acetyl. WO 2006-097537 A2 discloses in its example 4 the peptide Semaglutide. Semaglutide is synthesized by an acylation of the eplison-nitrogen atom of lysine20 at an already complete linear peptide backbone. Accordingly, the fatty acid side chain at lysine20 is introduced after the complete linear peptide backbone of Semaglutide has been synthesized. CN 104356224 A discloses a synthesis of Semaglutide, which employs as a building block a Fmoc-protected lysine derivative, which carries already the fatty acid side chain. Accordingly, lysine20carrying already a fatty acid side chain is introduced during the synthesis of the linear peptide backbone of Semaglutide. The employed Fmoc-protected lysine derivative (CAS-No. 1662688-20-1) is depicted below . CN 113461801 A discloses at its example 1 a solid phase peptide synthesis of the aforementioned Fmoc-protected lysine derivative (CAS-No.1662688-20-1) via a solid-phase conjugated Alloc-protected lysine derivative (CAS-No.2721349-46-6), which is depicted below . CN 115677827 A discloses at its example 4 a synthesis of Boc-Lys(tert-BuO-CO-(CH2)16-CO- gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Ala-OAll (CAS-No.2921565-74-2) via a Boc-protected lysine derivative (CAS-No.2921565-73-1), which is depicted below . WO 96-25394 discloses 2-(4-nitrophenylsulfonyl)ethoxycarbonyl respectively Nsc-group as an amino-protecting group in solid phase peptide chemistry and states on its page 18 that Nsc- group is perfectly resistant to the action of acidic reagents usually used for the cleavage of protective groups of tert-butyl type. Protein and Peptide Letters (1997), vol.4, No.5, p.307-312 discloses a comparative study of Fmoc- and Nsc-groups in automated solid phase peptide synthesis. It is concluded that comparative synthesis of three test peptides result in similarly looking HPLC-UV chromatograms. On page 312, a retention time of Nsc-Phe-OH with 16 minutes versus a retention of Fmoc-Phe-OH with 24 minutes is stated for an analytical HPLC with a C18 column and 0.1 % trifluoroacetic acid in a water / acetonitrile gradient. A decomposition seems not to occur at Nsc-Phe-OH in view of the statement of one retention time. Tetrahedron Letters (1994), vol.35, no.42, p.7821-7824 discloses on its page 7822 the preparation of Nsc-Lys(Boc)-OH via its trimethylsilyl derivative. A yield of 83% is reported for a homogeneous product after recrystallization. During the work-up, an exposure to an aqueous 5% sodium hydrogencarbonate solution at an extraction has taken place. Organic Letters (2001), vol.3, no.5, p.781-783 discloses solid phase peptide synthesis with alpha-azide-protected amino acids and states at its table 2 that alpha-azido acids outperform comparative Fmoc-amino acid at several tested peptide sequences. Journal American Chemical Society (1997), vol.119, p.9915-9916 discloses Bsmoc group, which is an abbreviation for 1,1-dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl, as an amino- protecting group in peptide synthesis. Bulletin of Korean Chemical Society (1998), vol.19, no.6, p.696-698 discloses 2-(phenyl- sulfonyl)ethoxycarbonyl respectively Psc group for the orthogonal protection of the epsilon amino group of lysine in conjunction with the Boc group, i.e. Boc-Lys(Psc)-OH, and its usage in liquid phase peptide synthesis. RU 2196144 C1 discloses at its example 11 a peptide Psc-D-Phe-Cys(Bzm)-Phe-D-Trp(For)- Lys(Psc)-Thr-Cys(Bzm)-Thr-ol(Psc)2 (SEQ ID NO:12) with Psc meaning 2-(phenylsulfonyl)- ethoxycarbonyl. EP 3819308 A1 discloses a process for the manufacture of protected amino acids substituted at their sidechains. At step 1f of its example 1, Fmoc-Lys-OH is persilylated with N-methyl-N- trimethylsilylacetamide and afterwards reacted with an activated tBuOOC-(CH2)16-CO- Glu(AEEA-AEEA)-OtBu to obtain Fmoc-Lys([tBuOOC-(CH2)16-CO-gamma-Glu-OtBu)-AEEA- AEEA]-OH. At step 3b of its example 3, Fmoc-Lys-OH is persilylated with N-methyl-N- trimethylsilylacetamide and afterwards reacted with Pal-Glu(Osu)-OtBu to obtain Fmoc-Lys(Pal- Glu-OtBu)-OH. International application No. PCT / EP2023 / 077884 discloses a method of manufacturing a peptide P, which comprises a step of condensing of an alpha amino acid derivative S-am, which has one unprotected alpha amino group or one unprotected alpha imino group, with a protected alpha amino acid derivative of formula Pr-L

[0002] , wherein the amino protecting group RL-N-1is 1,1-dioxobenzo[b]thiophen-2-ylmethyloxycarbonyl (Bsmoc). A method of manufacturing the alpha amino acid derivative of formula Pr-L is also disclosed. In general, an increase of the yield of a condensing reaction is desirable. Especially, if the condensing reaction is a part of a multi-step reaction scheme for a larger molecule, for example a molecule with a molecular weight above 1000 g / mol - which is often the case for a (poly-) peptide. A reason is that a removal of those one or more by-products, which are generated due to an ineffective condensing reaction and are comparatively large molecules, from the targeted molecule turns often out to be difficult. This is often due to an overall still similar physical behavior and necessitates in the case of a (poly-) peptide often a purification by a preparative high performance liquid chromatography. Thus, an initial purity of the crude material containing the targeted larger molecule is of relevance and contributes to an effectiveness of the condensing reaction. Furthermore, it is beneficial, if an applied starting material has a sufficient, at least temporary stability against degradation at a contact with a base or an acid, for example at a contact with trifluoroacetic acid in the technical area of peptide synthesis. The meaning of ‘at least temporary’ refers to a sufficient stability under common conditions like room temperature, exposure times of for example up to an hour and for example a presence of water. On the one hand, this allows for example typically a benign synthetic accessibility of the applied starting material, for example during an aqueous work-up. Here again, an initial purity of a crude material containing the starting material and thus an avoidance of a preparative liquid chromatography is of relevance. On the other hand, a possibility for an analytical monitoring of the starting material with a typically acidic analytical reverse phase high performance liquid chromatography in case of a (poly-) peptide allows a better insight into and thus steering of the condensing reaction. Another desirable aspect in case of a (poly-) peptide is that a condensing reaction allows to remain in the scheme of a base-catalyzed deprotection of an amino-protecting group for a further condensing reaction. Thus, a new reactive amino group respectively a new reactive imino group for the further condensing reaction to form an amide bond can be generated without endangering an acid-sensitive linking group to a resin or endangering an acid-sensitive protection group at a side chain of a respective, already condensed amino acid in the pre-existing peptide. Furthermore, a condensing reaction, which does not lead to a presence of a heavy metal during a following deprotection reaction of an amino-protecting group, is sometimes desirable. For a benign synthetic accessibility of the applied starting material, it is also of interest that synthetic precursors of the applied starting material have a sufficient, at least temporary stability against degradation. The meaning of ‘at least temporary’ refers in case of a synthetic precursor to a stability against degradation adapted to the position of the synthetic precursor in a synthesis pathway to the finally applied starting material. A synthetic precursor has a hold position if the synthetic precursor is stored in isolated form until the beginning of a chemical reaction or is worked-up to a storable isolated form at the end of a chemical reaction. In contrast, a synthetic precursor has a transient position in the synthesis pathway to the finally applied starting material if the synthetic precursor is not isolated from the reaction mixture of the chemical reaction. A synthetic precursor with a hold position has preferably a storage stability, which allows a storage in isolated form at room temperature over a prolonged period. This allows a transport with less temperature control and a stockpiling at the production facility, where the chemical reaction will take place. An additional advantage is also a stability of the synthetic precursor with a hold position once it is dissolved in a solvent or suspended in a suspension medium. For example, this allows a preparation of a larger amount of a solution of the synthetic precursor with a hold position. The larger amount can be stored in a tank and used in portions for several different chemical reactions, which are conducted at different times during a production campaign. The synthetic precursor with a hold position should preferably be usable in a chemical reaction of the synthesis pathway without a need for a previous chemical transformation or in case of a need, only a simple chemical transformation immediately before the desired chemical reaction. A lysine derivative, whose alpha nitrogen atom is protected by an Fmoc group and carries no other base-sensitive protecting groups, often allows an exchange of the protecting group at the alpha nitrogen atom by a base-induced Fmoc-deprotection and a subsequent introduction of a different protecting group. However, a synthesis pathway, which avoids a deprotection and reprotection circle by using already initially the finally desired protecting group for the alpha nitrogen atom of the lysine, is more desirable. It has now surprisingly been discovered that Bsmoc-Lys-OH is significantly less stable than Fmoc-Lys-OH. This applies inter alia for Bsmoc-Lys-OH in an isolated solid form and for Bsmoc- Lys-OH dissolved as a solution. It has now been found a compound of formula 1X wherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid. A toluenesulfonic acid is for example para-toluenesulfonic acid (CAS-No.104-15-4), meta- toluenesulfonic acid (CAS-No.617-97-0), ortho-toluenesulfonic acid (CAS-No.88-20-0) or a mixture thereof. Preferably, toluenesulfonic acid is para-toluenesulfonic acid. Propanesulfonic acid is for example 1-propanesulfonic acid (CAS-No.5284-66-2), 2-propanesulfonic acid (CAS- No.14159-48-9) or a mixture thereof. Preferably, propanesulfonic acid is 1-propanesulfonic acid. Butanesulfonic acid is for example 1-butanesulfonic acid (CAS-No.2386-47-2), 2- butanesulfonic acid (CAS-No.16794-12-0), 2-methyl-2-propanesulfonic acid (CAS-No.16794- 13-1), or a mixture thereof. Preferably, butanesulfonic acid is 1-butanesulfonic acid. Camphorsulfonic acid is for example (-)-camphorsulfonic acid (also named (1R,4S)-7,7- dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonic acid, CAS-No.35963-20-3), (+)- camphorsulfonic acid (also named (1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1- methanesulfonic acid, CAS-No.3144-16-9) or a mixture thereof (also named 7,7-dimethyl-2- oxobicyclo[2.2.1]heptane-1-methanesulfonic acid, (+ / -)-camphorsulfonic acid, CAS-No.5872- 08-2). Preferably, camphorsulfonic acid is (+)-camphorsulfonic acid. Hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid, phosphoric acid and sulfuric acid have in common a pKavalue below 2.3. In case of phosphoric acid, its first pKa value of 2.15 is meant, whereas the first pKa value and the second pKa value of sulfuric acid are below 2.3. An advantage of this low pkavalue of HY is that its related anion Y- is rather inert in a chemical reaction, where a carboxylic acid derivative reacts with a molecule, which possesses an unprotected amino group or an unprotected imino group under formation of an amide group. Preferably, the compound is of formula 1X, wherein when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid or difluoroacetic acid, when n is 0.5 HY is sulfuric acid. A molar excess of HY, which is added at a preparation of a compound of formula 1X, can be more easily removed by evaporation, if the boiling point of HY is comparatively low. Preferably, HY has a boiling point below 200 °C at 101,325 Pa. Preferably, HY is hydrochloric acid (- 85 °C), trifluoroacetic acid (72.4 °C), hydrobromic acid (- 67 °C), hydroiodic acid (-35 °C), nitric acid (83 °C), trichloroacetic acid (198 °C), dichloroacetic acid (194 °C) or difluoroacetic acid (133 °C). More preferably, HY has a boiling point below 140 °C at 101,325 Pa. More preferably, HY is hydrochloric acid (- 85 °C), trifluoroacetic acid (72.4 °C), hydrobromic acid (- 67 °C), hydroiodic acid (-35 °C), nitric acid (83 °C) or difluoroacetic acid (133 °C). Very preferably, HY has a boiling point below 90 °C at 101,325 Pa. Very preferably, HY is hydrochloric acid (- 85 °C), trifluoroacetic acid (72.4 °C), hydrobromic acid (- 67 °C), hydroiodic acid (-35 °C) or nitric acid. Preferred is a compound of formula 1X, wherein when n is 1 HY is hydrochloric acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, 2-propane-sulfonic acid, 1-butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid or nitric acid, when n is 0.5 HY is sulfuric acid. Preferred is a compound of formula 1X, wherein when n is 1 HY is hydrochloric acid, trifluoroacetic acid, para-toluenesulfonic acid or methanesulfonic acid, when n is 0.5 HY is sulfuric acid. Preferably, the compound of formula 1Xhas been stored for at least 12 hours. More preferably, the compound of formula 1Xhas been stored for a period between 12 hours and 1 month, very preferably for a period between 18 hours and 3 weeks, particularly for a period between 24 hours and 2 weeks, more particularly for a period of 36 hours and 7 days and very particularly for a period of 48 hours and 120 hours. Preferred is a compound of formula 1X, wherein the compound has been stored for at least 12 hours. Preferably, the compound of formula 1Xhas been stored at a temperature between 4 °C and 40 °C, more preferably at a temperature between 7°C and 38 °C, very preferably at a temperature between 9 °C and 36 °C, particularly at a temperature between 14 °C and 34 °C, more particularly at a temperature between 17 °C and 32 °C, very particularly at a temperature between 19 °C and 30 °C, especially at a temperature between 21 °C and 28 °C. Preferably, the compound of formula 1X is in a solid state. More preferably, the compound of formula 1Xis in the solid state at a temperature between 4 °C and 40 °C, very preferably at a temperature between 21 °C and 28 °C, very preferably at a temperature of 23 °C. Solid state herein means that the compound of formula 1Xaccounts for 50 to 100 weight-percent of a composition comprising the compound of formula 1X. Accordingly, a frozen solution of a compound of formula 1X, which has a weight percentage of a compound of formula 1X from for example 10 weight-percent, is not considered herein as a compound of formula 1X in the solid state. Preferred is a compound of formula 1X, which is in a solid state. Preferably, the compound of formula 1Xis dissolved or suspended. More preferably, the compound of formula 1Xis dissolved or suspended in a solvent composition SolvI-1, which comprises N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2- pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane, water, or a mixture thereof. Propyl acetate is n-propyl acetate, isopropyl acetate or a mixture thereof, preferably isopropyl acetate. Butyl acetate is n-butyl acetate, sec-butyl acetate, iso-butyl acetate, tert-butyl acetate or a mixture thereof, preferably sec-butyl acetate. Propanol is n-propanol, iso-propanol or a mixture thereof, preferably iso-propanol. Butanol is n-butanol, sec-butanol, iso-butanol, tert- butanol or a mixture thereof, preferably tert-butanol. Xylene is ortho-xylene, meta-xylene, para- xylene or a mixture thereof, preferably meta-xylene. Hexane is n-hexane, 2-methylpentane, 3- methylpentane, 2,3-dimethylbutane, 2,2-dimethylbutane or a mixture thereof, preferably n- hexane. Heptane is n-heptane, 2-methylhexane, 3-methylhexane, 2,2-dimethylpentane, 2,3- dimethylpentane, 2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethlypentane, 2,2,3- trimethylbutane or a mixture thereof, preferably n-heptane. Octane is for example n-octane, 2- methylheptane, 3-methylheptane, 4-methylheptane, 3-ethylhexane, 2,2-dimethylhexane, 2,2,4- trimethylpentane or a mixture thereof, preferably n-octane. Preferably, the solvent composition SolvI-1 comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, water or a mixture thereof. More preferably, the solvent composition SolvI-1 comprises N,N- dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, methanol, ethanol, propanol, butanol, water or a mixture thereof. Very preferably, the solvent composition SolvI-1 comprises N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2- pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, nitromethane, acetonitrile, gamma-butyrolactone, methanol, ethanol, propanol, butanol, water or a mixture thereof. Particularly, the solvent composition SolvI-1 comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, acetonitrile, methanol, ethanol, propanol, butanol, water or a mixture thereof. More particularly, the solvent composition SolvI-1 comprises N,N-dimethylformamide, water or a mixture of water with N,N- dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, acetonitrile, methanol, ethanol, propanol or butanol. Very particularly, the solvent composition SolvI-1 comprises N,N-dimethylformamide or a mixture of water and 1,4-dioxane. Especially, the solvent composition consists of N,N-dimethylformamide or a mixture of water and 1,4-dioxane in a relation between 1 to 2 and 1 to 4 (volume water to volume 1,4-dioxane). Preferably, the concentration of a compound of formula 1X in the solvent composition SolvI-1 is between 5 mg / mL and 150 mg / mL, more preferably between 10 mg / mL and 120 mg / mL, very preferably between 20 mg / mL and 100 mg / mL, particularly between 30 mg / mL and 80 mg / mL, more particularly between 35 mg / mL and 70 mg / mL, very particularly between 40 mg / mL and 60 mg / mL and especially 50 mg / mL. Preferred is a compound of formula 1X, which is dissolved or suspended in a solvent composition SolvI-1, which comprises N,N-dimethylformamide, N,N-dimethylacetamide, N- methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2- methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3- dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane, water, or a mixture thereof. The explanations and preferences described above for a compound of formula I and a solvent composition SolvI-1 apply similarly to further embodiments of the invention. A further embodiment of the invention is a method of manufacturing a lysine derivative LYSX, which method comprises the steps (aI-1), (cI-1) and (dI-1) or comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2), (aI-1) providing a compound of formula 1X wherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid; (cI-1) combining the provided compound of formula 1X and an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-1) reacting the epsilon nitrogen atom of the provided compound of formula 1X with the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-1) might partly also take place already during step (cI-1); or (aI-2) providing a compound of formula 1Xas defined at (aI-1); (bI-2) silylating the provided compound of formula 1Xwith a silylation agent to obtain a silylated compound; (cI-2) combining the silylated compound and an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-2) reacting the epsilon nitrogen atom of the silylated compound with the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-2) might partly also take place already during step (cI-2). The method variant 1, which comprises the steps (aI-1), (cI-1) and (dI-1), does not comprise a step of silylating the provided compound of formula 1Xafter step (aI-1) and prior to or during steps (cI-1) and (dI-1). The method variant 2, which comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2), includes at its step (bI-2) a silylation of the compound of formula 1X. A silylation occurs at least at the alpha-carboxylic acid group of the compound of formula 1X. Whether a silylation occurs also at the epsilon amino group of the compound of formula 1X is not clarified. In case of an excess of an added molar amount of the silylation agent, the silylation of the epsilon amino group is stoichiometrically possible. There might also be an equilibrium between solely protonated epsilon amino groups, unprotonated silylated epsilon amino groups and protonated silylated epsion amino groups. The addressed options are depicted below for a silylation with . An actual equilibrium, if so, will then depend likely on the amount and type of silylation agent, a temperature, reaction medium etc. A silylation agent at step (bI-2) is for example trimethylsilyl chloride, N-methyl-N-trimethylsilyl acetamide, N,O-bis(trimethylsilyl)acetamide, N,O-bis(trimethylsilyl)trifluoroacetamide, trimethylsilyl methanesulfonate or trimethylsilyl triflate. Preferably, the silylation agent is trimethylsilyl chloride or N-methyl-N-trimethylsilyl acetamide. The silylation at step (bI-2) is preferably a trimethylsilylation and the silylation agent is a trimethylsilylation agent. The molar amount of the silylation agent at step (bI-2) is preferably in excess to the molar amount of the provided compound of formula 1X. The molar ratio between the provided compound of formula 1Xand the silylation agent at step (bI-2) is more preferably between 1 to 1.1 and 1 to 6, very preferably between 1 to 1.3 and 1 to 5, particularly between 1.5 and 1 to 4, more particularly between 2 and 3.5 and very particularly 1 to 3. A reaction temperature at step (bI-2) is preferably between 0 °C and 55 °C, more preferably between 10 °C and 50 °C, very preferably between 15 °C and 48 °C, particularly between 20 °C and 45 °C and more particularly between 22 °C and 40 °C. The silylation at step (bI-2) is preferably a trimethylsilylation and the silylation agent is a trimethylsilylation agent. Preferred is a method of manufacturing a lysine derivative LYSX, wherein the method comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2) and at step (bI-2), the silylation agent is trimethylsilyl chloride, N-methyl-N-trimethylsilyl acetamide, N,O-bis(trimethylsilyl)acetamide, N,O- bis(trimethylsilyl)trifluoroacetamide, trimethylsilyl methanesulfonate or trimethylsilyl triflate. Preferred is a method of manufacturing a lysine derivative LYSX, wherein the method comprises the steps (aI-1), (cI-1) and (dI-1) and is free of a step of silylating the provided compound of formula 1Xafter step (aI-1) and prior to or during steps (cI-1) and (dI-1). Preferred is a method of manufacturing a lysine derivative LYSX, wherein the method comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2). At step (aI-1), providing of the compound of formula 1X is for example by providing of the compound of formula 1Xin a solid state, for example comminuted to a powder. Another example is a solution or a suspension of the compound of formula 1Xin a solvent composition SolvI-1. The suspension is preferably fine and homogenous enough to allow a meaningful dosing for step (cI-1). The steps (cI-1) and (dI-1) of method variant 1, which comprises the steps (aI-1), (cI-1) and (dI- 1), are not necessarily sensitive to the presence of water or a protic solvent. This is since some amide coupling reactions can occur in water, in a water-containing solvent composition, in an alcohol or in an alcohol-containing solvent composition. The steps (bI-2), (cI-2) and (dI-2) of method variant 2, which comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2), is sensitive to the presence of water or a protic solvent in general. This is because the silylation agent reacts typically with water and alcohols. Furthermore, the silylated compound at step (cI-2) and step (dI-2) reacts also with water and perhaps to some extent also with alcohols. At step (aI-2), providing of the compound of formula 1Xis for example by providing of the compound of formula 1X in a solid state, for example comminuted to a powder. Another example is a solution or a suspension of the compound of formula 1X in an anhydrous solvent composition SolvI-2. The suspension is preferably fine and homogenous enough to allow a meaningful dosing for step (bI-2). Solvent composition SolvI-2 is anhydrous, i.e., free of water, and is free of alcohols. Solvent composition SolvI-1 differs from solvent composition SolvI-2 by comprising also methanol, ethanol, propanol, butanol or water. Solvent composition SolvI-2 comprises N,N-dimethylformamide, N,N-dimethylacetamide, N- methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2- methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3- dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane or a mixture thereof. Propyl acetate is n-propyl acetate, isopropyl acetate or a mixture thereof, preferably isopropyl acetate. Butyl acetate is n-butyl acetate, sec-butyl acetate, iso-butyl acetate, tert-butyl acetate or a mixture thereof, preferably sec-butyl acetate. Xylene is ortho-xylene, meta-xylene, para- xylene or a mixture thereof, preferably meta-xylene. Hexane is n-hexane, 2-methylpentane, 3- methylpentane, 2,3-dimethylbutane, 2,2-dimethylbutane or a mixture thereof, preferably n- hexane. Heptane is n-heptane, 2-methylhexane, 3-methylhexane, 2,2-dimethylpentane, 2,3- dimethylpentane, 2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethlypentane, 2,2,3- trimethylbutane or a mixture thereof, preferably n-heptane. Octane is for example n-octane, 2- methylheptane, 3-methylheptane, 4-methylheptane, 3-ethylhexane, 2,2-dimethylhexane, 2,2,4- trimethylpentane or a mixture thereof, preferably n-octane. Preferably, the solvent composition SolvI-2 comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, diethyl ether, methyl tert-butyl ether, diisopropyl ether or a mixture thereof. More preferably, the solvent composition SolvI-2 comprises N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2- pyrrolidone, N-butyl-2-pyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone or a mixture thereof. Very preferably, the solvent composition SolvI-2 comprises tetrahydrofuran, 2-methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, acetonitrile, gamma-butyrolactone or a mixture thereof. Particularly, the solvent composition SolvI-2 comprises tetrahydrofuran, 2-methyltetra- hydrofuran, 1,3-dioxolane, 1,4-dioxane, acetonitrile or a mixture thereof. More particularly, the solvent composition SolvI-2 comprises tetrahydrofuran or a mixture of tetrahydrofuran and acetonitrile. Very particularly, the solvent composition SolvI-2 consists of tetrahydrofuran or a mixture of tetrahydrofuran and acetonitrile in a relation between 1 to 1 and 1 to 5 (volume tetrahydrofuran to volume acetonitrile). Preferred is a method of manufacturing a lysine derivative LYSX, wherein at step (aI-1), the compound of formula 1X is provided as a solution or a suspension in a solvent composition SolvI-1, which comprises N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)- 2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3- dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane, water, or a mixture thereof; and wherein at step (aI-2), the compound of formula 1X is provided as a solution or a suspension in an anhydrous solvent composition SolvI-2, which comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2- methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane or a mixture thereof. The temperature at step (cI-1) or (cI-2) is for example in a range of 0 °C to 40 °C, preferably in a range of 4 °C to 35 °C, more preferably in a range of 10 °C to 30 °C, very preferably in a range of 20 °C to 28 °C and particularly in a range of 22 °C to 25 °C, which is considered for at step (cI-1) and step (cI-2) as room temperature. The temperature at step (dI-1) or (dI-2) is for example in a range of 0 °C to 50 °C, preferably in a range of 4 °C to 40 °C, more preferably in a range of 10 °C to 30 °C, very preferably in a range of 20 °C to 28 °C and particularly in a range of 22 °C to 25 °C, which is considered for at step (dI-1) and step (dI-2) as room temperature. An addition of a base, which itself does not react with the activated carboxylic acid derivative under formation of a covalent bond, liberates the epsilon nitrogen atom from its protonation by the acid HY. Thus, the nucleophilicity of the epsilon nitrogen atom is significantly increased and a reaction with the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group, is accelerated. If so, the addition of the base, which itself does not react with the activated carboxylic acid derivative under formation of a covalent bond, is conducted at step (cI-1) or step (dI-1) of method variant 1 and at step (cI-2) or step (dI-2) of method variant 2. The base, which itself does not react with the activated carboxylic acid derivative under formation of a covalent bond, is preferably a base, which is free of an unprotected amino group or an unprotected imino group. In case a very strong base is chosen, a racemization at the alpha carbon atom at the lysine core can occur in case of an only minor molar excess versus the molar amount of the compound of formula 1X. However, a D-lysine type of impurity is typically not desired at a (L-) lysine derivative LYSX. The molar amount of base, which is added, is for example at least the molar amount of the provided compound of formula 1X, preferably the base is added in an excess of 1.05 to 1.5 molar equivalents. A base, which is free of an unprotected amino group or an unprotected imino group, is for example diisopropylethylamine, triethylamine, N-methylmorpholine, 1,8- diazabicyclo(5.4.0)undec-7-ene or 1,5-diazabicyclo(4.3.0)non-5-ene. Preferably, the base is diisopropylethylamine. Preferred is a method of manufacturing a lysine derivative LYSX, wherein at step (cI-1) or at step (dI-1), a base, which is free of an unprotected amino group or an unprotected imino group, is added, and at step (cI-2) or step (dI-2), a base, which is free of an unprotected amino group or an unprotected imino group, is added. The activated carboxylic acid derivative is for example obtained by a pre-activation reaction. At the pre-activation reaction, a carboxylic acid derivative is reacted with a protonated form of the leaving group. The protonated form of the leaving group is for some leaving groups also called a coupling additive. A condensing agent of the pre-activation reaction, which is added to the pre- activation reaction, is driving the pre-activation reaction. A condensing agent of the pre- activation reaction is for example diisopropylcarbodiimide, dicyclohexylcarbodiimide or 1-tert- butyl-3-ethylcarbodiimide. At some instances, the condensing agent and the leaving group are already combined in one molecule, which directly reacts with the carboxylic acid derivative. An example for this is (benzotriazolyl)tetramethyluronium tetrafluoroborate. A carboxylic acid derivative, which is already activated, avoids the presence of an additional carboxylic acid group, i.e., in addition to the carboxylic acid group at the alpha carbon atom of lysine, which is sililyated in case of method variant 2, during steps (cI-1) and (dI-1) or during steps (cI-2) and (dI- 2). An activated carboxylic acid derivative is for 201 , compound 203 , compound act-carb-01 or compound act-carb-02 . A leaving group (LG) of the activated carboxylic acid derivative is for example (named as protonated leaving group) N-hydroxysuccinimide, N-hydroxyphthalimide, 1-hydroxybenzo- triazole, 1-hydroxy-7-azabenzotriazole or pentafluorophenol. Preferably, the leaving group of the activated carboxylic acid derivative is N-hydroxysuccinimide, N-hydroxyphthalimide, 1- hydroxybenzotriazole or 1-hydroxy-7-azabenzotriazole, more preferably N-hydroxysuccinimide, or 1-hydroxybenzotriazole, very preferably N-hydroxysuccinimide. A carboxylic acid derivative prior to its activation is for example compound carb-1 , compound carb-2 (carb-2) , palmitic acid, compound 202 , compound carb-3 , compound 306 , . The lysine derivative LYSXcontains a structural element of formula 2X wherein * indicates a covalent connection to a carbon atom, and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formula 3X wherein * indicates a covalent connection to a carbon atom, LG is a leaving group. It is understood that the carbon atom, which is covalently connected at formula 2Xis the same carbon atom, which is covalently connected at formula 3X. Preferably, the carbon atom has itself overall 4 covalent connections, i.e., the carbon atom is a sp3 hybridized carbon atom, or 3 covalent connections, i.e., the carbon atom is a sp2 hybridized carbon atom. At the sp3 hybridized carbon atom, one of the 4 covalent connections is the covalent connection to formula 2Xrespectively formula 3X, the other three covalent connections are to three different atoms. At the sp2hybridized carbon atom, one of the 3 covalent connections is the covalent connection to formula 2Xrespectively formula 3X, the other two covalent connections are to two different atoms. These two preferences are expressed in the following formulae 2X-sp3 and 3X-sp3 or 2X-sp2 and 3X-sp2. Preferably, the lysine derivative LYSX contains a structural element of formulae 2X-sp3 or 2X-sp2 wherein * indicates a covalent connection, and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formulae wherein * indicates a covalent connection to a carbon atom, LG is a leaving group. More preferably, the carbon atom has itself preferably 3 covalent connections, i.e., the carbon atom is a sp3hybridized carbon atom. More preferably, the lysine derivative LYSXcontains a structural element of formula 2X-sp3and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formulae 3X-sp3. Preferred is a method of manufacturing a lysine derivative LYSX, wherein the lysine derivative LYSX contains a structural element of formulae 4X-A or 4X-B wherein * indicates a covalent connection, R4X-B-N-1is an amino-protecting group; and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formulae wherein * indicates a covalent connection, LG is a leaving group, R5X-B-N-1is an amino protecting group. Preferred is a method of manufacturing a lysine derivative LYSX, wherein the lysine derivative LYSX contains a structural element of formulae 6X-A-a, 6X-A-b or 6X-A-c wherein * indicates a covalent connection, R6X-A-b-O-1 is a carboxylic acid proctecting group; and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formulae 7X-A-a, 7X-A-b or 7X-A-c wherein * indicates a covalent connection, LG is a leaving group, R7X-A-b-O-1 is a carboxylic acid protecting group. The lysine derivative LYSX is for example a compound of formula Pr-L , wherein RL-O-1 and RL-O-2 are independently of each other a carboxylic acid protecting group, an example of a compound of formula Pr-L is compound 508 compound 309 compound 310

[0003] compound 511 compound 514 or compound 517 . An example for further steps at a method of manufacturing a lysine derivative LYSX, which is a compound of formula Pr-L, are (prl-b) and (prl-c) (prl-b) removing an amino protecting group RA-N-1at a lysine derivative LYSX, which is a compound of formula Pr-A , wherein RA-N-1is an amino protecting group different to Bsmoc, to obtain a compound of formula Pr-A-am , (prl-c) condensing the compound of formula Pr-A-am with a compound of formula B , are defined as for formula Pr-L, to obtain the compound of formula Pr-L. Preferably at step (prl-c), the compound of formula Pr-A-am, is persilylated to obtain a persilylated intermediate compound, the compound of formula B is activated with a condensing agent of step (prl-c) to obtain an activated compound of formula B, the persilylated compound and the activated compound are combined, and react with each other. Alternatively, the compound of formula Pr-A-am can be used as a hydrochloric acid salt, i.e., compound 310. Compound 309 is a compound of formula Pr-A with RA-N-1 being a tert-butyloxycarbonyl group. Preferably, the lysine derivate LYSXis a compound of formula Pr-L, compound 309, compound 310, compound 511, compound 514 or compound 517. More preferably, the lysine derivative LYSXis compound 508, compound 309, compound 310, compound 511, compound 514 or compound 517. Very preferably, the lysine derivative is compound 508, compound 511, compound 514 or compound 517. Preferred is a method of manufacturing a lysine derivative LYSX, wherein the lysine derivative LYSX is a compound of formula Pr-L, compound 309, compound 310, compound 511, compound 514 or compound 517. The explanations and preferences described above for a compound of formula I and a solvent composition SolvI-1, and a method of manufacturing a lysine derivative LYSX apply similarly to further embodiments of the invention. A further embodiment of the invention is a method of manufacturing a peptide PX, wherein the method comprises a step (cX) (cX) condensing an alpha amino acid derivative S-am, which has one unprotected alpha amino group or one unprotected alpha imino group, with a lysine derivative LYSX, which is obtained from a method of manufacturing the lysine derivative LYSX, which method of manufacturing the lysine derivative LYSXcomprises the steps (aI- 1), (cI-1) and (dI-1) or comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2), (aI-1) providing a compound of formula 1X wherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid; (cI-1) combining the provided compound of formula 1Xand an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-1) reacting the epsilon nitrogen atom of the provided compound of formula 1Xwith the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-1) might partly also take place already during step (cI-1); or (aI-2) providing a compound of formula 1Xas defined at (aI-1); (bI-2) silylating the provided compound of formula 1Xwith a silylation agent to obtain a silylated compound; (cI-2) combining the silylated compound and an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-2) reacting the epsilon nitrogen atom of the silylated compound with the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-2) might partly also take place already during step (cI-2); to obtain an intermediate peptide Int-PX. The peptide PX differs from the lysine derivative LYSX by not having an alpha carboxylic acid group at the lysine. The carboxylic acid group of the lysine derivative LYSXhas condensed with the one unprotected alpha amino group or one unprotected alpha imino group of the alpha amino acid derivative S-am. The carbonyl group of the previous alpha carboxylic acid group of the lysine derivative LYSXis part of an amide bond at the intermediate peptide Int-PXand, if the intermediate peptide Int-PX is different to the final peptide PX, at the peptide PX. The intermediate peptide Int-PX can be the peptide PX, if no further chemical modification of the intermediate peptide Int-PX takes place, or can be different to the peptide PX, if a further chemical modification of the intermediate peptide Int-PX takes place. An example for a method of manufacturing a peptide PX, which is a peptide P, is a method of manufacturing a peptide P, the method comprises a step (c) (c) condensing an alpha amino acid derivative S-am, which has one unprotected alpha amino group or one unprotected alpha imino group, with a compound of formula Pr-L , wherein RL-O-1and RL-O-2are independently of each other a carboxylic acid protecting group, to obtain a peptide Pr-L-S. The peptide P is preferably a compound of formula Pr-L-S (as depicted below). It will be understood that the term “peptide P” is a designation of the peptide that is synthesized. The designation “P” may also be omitted or set in parentheses without altering the meaning of the peptide which is defined by structural characteristics. The term “Pr-L-S” describes the structure as defined in the depicted structures. It is intended to show the structural elements as laid out below. This designation “Pr-L-S” may also be omitted or set in parentheses without altering the meaning of the peptide which is defined in the depicted structures. For condensing the one unprotected alpha amino group or the one unprotected alpha imino group of the alpha amino acid derivative S-am with the lysine derivative LYSX, preferably the compound of formula Pr-L, the carboxylic acid group of the lysine of the lysine derivative LYSX , preferably of the compound of formula Pr-L, is typically activated with a condensing agent of step (cX), preferably step (c). The condensing agent of step (cX), preferably of step (c), leads to an activated lysine derivative LYSX, preferably an activated compound of formula Pr-L, which contains instead of the hydroxy group at the carboxylic acid group a leaving group of step (cX), preferably step (c), which makes the activated lysine derivative LYSX, preferably an activated compound of formula Pr-L, more reactive towards the unprotected alpha amino group or the unprotected alpha imino group of the alpha amino acid derivative S-am. Dependent on the specific condensing agent of step (cX), preferably of step (c), the activated lysine derivative LYSX, preferably an activated compound of formula Pr-L, is an intermediate suitable for an isolation at room temperature or an intermediate unsuitable for an isolation at room temperature. The condensing agent of step (cX), preferably of step (c), is for example a carbodiimide derivative. The carbodiimide derivative is for example diisopropylcarbodiimide, dicyclohexylcarbodiimide, 1-tert-butyl-3-ethylcarobdiimide or 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide. Preferably, the carbodiimide derivative is diisopropylcarbodiimide, dicyclohexyl- carbodiimide or 1-tert-butyl-3-ethylcarbodiimide. More preferably, the carbodiimide derivative is diisopropylcarbodiimide or 1-tert-butyl-3-ethylcarbodiimide. Very preferably, the carbodiimide derivative is diisopropylcarbodiimide. Preferably, the carbodiimide is applied together with a coupling additive of step (cX), preferably of step (c). The coupling additive of step (cX), preferably of step (c), is for example cyano-hydroxyimino-acetic acid ethyl ester, 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, 5-hydroxyimino-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, ethyl 1-hydroxy-1,2,3-triazole-4-carboxylate, 2-hydroxypryridine N-oxide or a mixture thereof. Preferably, the coupling additive of step (cX), preferably of step (c), is cyano-hydroxyimino-acetic acid ethyl ester, 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole or 2-hydroxypryridine N- oxide. More preferably, the coupling additive of step (cX), preferably of step (c), is cyano- hydroxyimino-acetic acid ethyl ester or 1-hydroxybenzotriazole. Very preferably, the coupling additive of step (cX), preferably of step (c), is cyano-hydroxyimino-acetic acid ethyl ester. In case that the alpha amino acid derivative S-am contains an unprotected carboxylic acid group, the activation of the lysine derivative LYSX, preferably a compound of formula Pr-L, must occur prior to a contact with the alpha amino acid derivative S-am. In case the alpha amino acid derivative S-am possesses a functional group, which would interfere with the condensing of step (cX), preferably of step (c), and which is different to the one unprotected alpha amino group or the one unprotected alpha imino group, then the functional group is protected by a suitable protecting group. The alpha amino acid derivative S-am is preferably free of an unprotected guanidino group or an unprotected mercapto group. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein at step (cX), preferably at step (c), the lysine derivative LYSX, preferably the compound of formula Pr-L, is activated with a condensing agent of step (cX), preferably of step (c). Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein at step (cX), preferably at step (c), a coupling additive of step (cX), preferably of step (c), is present. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein at step (cX), preferably at step (c), the lysine derivative LYSX, preferably the compound of formula Pr-L, is activated with a condensing agent of step (cX), preferably step of (c), which is a carbodiimide derivative, and a coupling additive of step (cX), preferably of step (c), which is cyano- hydroxyimino-acetic acid ethyl ester, is present. Step (cX), preferably step (c), takes preferably place in the presence of a solvent of step (cX), preferably of step (c). The solvent of step (cX), preferably of step (c), dissolves the lysine derivative LYSX, preferably the compound of formula Pr-L. In case the alpha amino acid derivative S-am is covalently linked to a resin, the solvent of step (cX), preferably of step (c), preferably swells the resin. A solvent of step (cX), preferably of step (c), is for example N,N- dimethylformamide, N-methyl-2-pyrrolidone, N-butyl-pyrrolidone, dimethyl isosorbide, gamma- valerolactone, dihydrolevo-glucosenone (e.g. commercially available Cyrene (TM)), dimethyl sulfoxide, tetrahydropyran, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, 1,3- dioxolane, ethyl acetate, dichloromethane, acetonitrile, toluene, water and mixtures thereof. Preferably, the solvent of step (cX), preferably of step (c), comprises N,N-dimethylformamide. More preferably, the solvent of step (cX), preferably of step (c), comprises at least 20 vol.% N,N- dimethylformamide, very preferably 40 vol.%, especially 70 vol.%, more especially 90 vol.% and very especially more than 95 vol.%. Preferably, the solvent of step (cX), preferably of step (c), is N,N-dimethylformamide. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein the step (c) is conducted in a solvent of step (c) and the solvent of step (c) comprises N,N- dimethylformamide. Preferably, the step (cX), preferably the step (c), is conducted at a temperature between 5 °C and 50 °C, more preferably between 10 °C and 40 °C, very preferably between 15 °C and 35 °C, particularly between 18°C and 30 °C, more particularly between 19 °C and 28 °C, very particularly between 20 °C and 27°C and especially between 22 °C and 25 °C. Between 22 °C and 25 °C is defined for step (cX), preferably step (c), as at room temperature. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein the step (cX), preferably the step (c), is conducted at a temperature between 15 °C and 35 °C. Preferably, the lysine derivative LYSX, preferably the compound of formula Pr-L, is applied in a molar excess versus the alpha amino acid derivative S-am at step (cX), preferably at step (c). The molar excess is for example a molar amount of the lysine derivative LYSX, preferably a compound of formula Pr-L, which is between 1.05 to 3.5 times the molar amount of the alpha amino acid derivative S-am. Preferably, the molar amount is between 1.3 to 3.0 times, more preferably between 1.5 to 2.5 times, very preferably between 1.7 to 2.3 times, particularly between 1.8 to 2.2 times and more particularly between 1.9 to 2.1 times. Preferably, the condensation agent of step (cX), of step (c), is applied in a molar excess versus the lysine derivative LYSX, preferably the compound of formula Pr-L, at step (cX), preferably step (c). The molar excess is for example a molar amount of the condensation agent of step (cX), preferably of step (c), which is between 1.05 and 3 times the molar amount of the lysine derivative LYSX, preferably of the compound of formula Pr-L. Preferably, the molar amount is between 1.3 to 2.5 times, more preferably between 1.5 to 2.3 times, very preferably between 1.7 to 2.2 times, particularly between 1.8 to 2.2 times and more particularly between 1.9 to 2.0 times. The overall amount of the condensation agent of step (cX), preferably of step (c), is for example added to the lysine derivative LYSX, preferably to the compound of formula Pr-L, at once or in two or more portions. A portion of the condensation agent of step (cX), preferably of step (c), for example between 50 to 70 wt.% of the overall amount of the condensation agent of step (cX), preferably of step (c), is for example added to the lysine derivative LYSX, preferably to the compound of formula Pr-L, which is dissolved in the solvent of step (cX), preferably of step (c). The resulting solution is stirred for example between 5 and 30 minutes and then added to the alpha amino acid derivative S-am. Preferably, the coupling additive of step (cX), preferably of step (c), is applied in a molar amount versus the lysine derivative LYSX, preferably the compound of formula Pr-L, which molar amount is between 0.5 and 3 times the molar amount of the lysine derivative LYSX, preferably the compound of formula Pr-L. The molar amount is for example between 0.8 to 2.5 times the molar amount of the lysine derivative LYSX, preferably of the compound of formula Pr-L. Preferably, the molar amount is between 0.9 to 2.2 times the molar amount of the lysine derivative LYSX, preferably of the compound of formula Pr-L, more preferably between 1.1 to 2.0, very preferably between 1.3 to 1.7 and particularly between 1.4 to 1.6 times. A peptidic bond is herein understood as a covalent bond between an alpha amino group or an alpha imino group of a first alpha amino acid residue and an alpha carboxylic acid group of a second alpha amino acid residue. The alpha amino acid derivative S is herein understood as either a compound, which is free of a peptidic bond, or a compound, which has at least one peptidic bond. In the latter case, the alpha amino acid derivative S is for example a dipeptide derivative, a tripeptide derivate or a tetrapeptide derivative. At both compounds, there is a N- terminal alpha amino group, which can also be an alpha imino group, of the N-terminal amino acid residue and a C-terminal carboxylic acid group or a carboxamide group of the C-terminal amino acid residue. At the compound, which is free of a peptidic bond, the N-terminal alpha amino group, which can also be an alpha imino group, and the C-terminal carboxylic acid group or carboxamide group are substituents of the same alpha carbon atom respectively belong to the same alpha amino acid residue. The alpha amino acid derivative S-am is for example linked to a resin. The resin comprises a linking group and a polymeric support. The linking group is covalently attached to the polymeric support. The linking group serves to attach covalently an alpha amino acid residue, wherein the covalent attachment of the alpha amino acid residue is cleavable. Typically, the C-terminal alpha amino acid residue is covalently attached to the resin. The resin is for example resin-1 or resin-2. Resin-1 possesses a linking group, which is especially suited for a covalent attachment of an oxygen atom of a carboxylic acid group. The linking group of resin-1 - written as a di-yl-substituent - is for example 2-chlorotrityl-p- amidomethyl, 2-chlorotrityl-yl or 4-(methyleneoxy)benzyl. Resin-2 possesses a linking group, which is especially suited for a covalent attachment of a nitrogen atom of a carboxylic acid amide group. The linking group of resin-2 - written as a di-yl-substituent - is for example xanthen-3-(oxymethylene)-9-yl or alpha-(2,4-dimethoxyphenyl)-alpha-(4-(N-methyleneamido- methyleneoxy)phenyl)methyl. The polymeric support of resin-1 or resin-2 is for example polystyrene, a copolymer containing polymerized styrene units and polymerized ethylene oxide units or polyethylene oxide. The alpha amino acid derivative S-am is for example a single molecule. Preferably, the alpha amino acid derivative S-Am is covalently linked to a resin. Preferably, the alpha amino acid derivative S-Am is a single molecule. Preferably, the alpha amino acid derivative S-Am is free of an unprotected carboxylic acid group. The peptide P contains a structural element of formula L with # and ## indicating covalent connections (L), wherein RL-O-1and RL-O-2are independently of each other H or a carboxylic acid protecting group. The covalent connection of formula L, which is indicated by #, is towards the alpha nitrogen atom of the alpha amino acid residue, which is the N-terminal alpha amino acid residue of the alpha amino acid derivative S-am. The covalent connection of formula L, which is indicated by ##, is towards for example a hydrogen atom, an amino protecting group or the alpha carbonyl group of the alpha amino acid residue, which is the C-terminal alpha amino acid residue of a further alpha amino acid derivative. The alpha amino acid derivative S-am, which has one unprotected alpha amino group or one unprotected alpha imino group, is preferably an alpha amino acid derivative of formula S-I-am or S-II-am I-am) II-am) , wherein RSI-1 is -(AAnx) -O-[resin- nx m 1], -(AA )m-N-[resin-2], -O-[resin-1], -N-[resin- 2], -(AAnx)m-ORSI-1-1, ORSI-1-1or NH2, RSI-2is H, C1-6 alkyl or C1-6 alkyl mono-substituted with ORSI-2-1, SRSI-2-2, SCH3, NRSI-2-3RSI-2-4, CO-ORSI-2-5, CO-NRSI-2-6RSI-2-7, N’-RSI-2-8-N’’-RSI-2-9-guanidino, phenyl, para-(RSI-2-10O)-phenyl, 1-RSI-2-11-imidazol-4-yl or 1-RSI-2-12-indol-3-yl, -(AAnx)m- is a substituent consisting of m condensed alpha amino acid residues AAnx with each x being an integer and x running from 1 to m, each condensed alpha amino acid residue AAnx is independently chosen and in case it possesses a side chain with a functional group, the functional group is unprotected or protected by a protecting group provided that an interfering functional group is protected, m is an integer from 1 to 30, RSI-1-1is H or a carboxylic acid protecting group, RSI-2-1is H or a hydroxy protecting group, RSI-2-2 is a thiol protecting group, RSI-2-3 and RSI-2-4 are H, an amino protecting group or form together an amino protecting group provided that not both are H, RSI-2-5 is H or a carboxylic acid protecting group, RSI-2-6 and RSI-2-7 are H or an amide protecting group, RSI-2-8and RSI-2-9are H or a guanidino protecting group provided that not both are H, RSI-2-10is a protecting group for an aromatic hydroxy group, RSI-2-11 is H or a protecting group for an imidazole nitrogen atom, RSI-2-12 is H or a protecting group for an indole nitrogen atom, RSII-1 is as defined for RSI-1. A carboxylic acid protecting group is for example tert-butyl, benzyl, phenacyl, 2-phenyl-isoprop- 2-yl or methyl, preferably tert-butyl. Preferably, the carboxylic acid protecting group is tert-butyl or 3-methlyl-pent-3-yl. More preferably, the carboxylic acid protecting group is tert-butyl. Preferably, RL-O-1and RL-O-2are a carboxylic acid protecting group, which is removed under acidic conditions, more preferably under exposure to trifluoracetic acid. Preferably, RL-O-1and RL-O-2 are independently of each other tert-butyl or 3-methyl-pent-3-yl. More preferably, RL-O-1 and RL-O-2 are the same and tert-butyl or 3-methyl-pent-3-yl. Very preferably, RL-O-1 and RL-O-2 are tert-butyl. A hydroxy protecting group is for example tert-butyl, benzyl, 2-bromobenzyl- oxycarbonyl, trityl or 2-chlorotrityl, preferably tert-butyl. In case of an alpha amino acid residue, which comprises a hydroxy group in beta-position, the hydroxy protecting group is also for example a group 1,1-dimethyldiyl, which forms an oxazolidine ring together with the nitrogen atom in alpha-position, the carbon atom in alpha position and the oxygen atom of the hydroxy group in beta-position (so-called pseudoproline). A thiol protecting group is for example tert- butyl, 4-methylbenzyl, acetamidomethyl, trityl, tert-butylsulfanyl, tetrahydropyran-2-yl, diphenylmethyl or 2,4,6-trimethoxybenzyl. An amino protecting group is for example tert-butyl- oxycarbonyl, 9-fluorenyl-methoxycarbonyl, benzyloxycarbonyl or allyloxycarbonyl. An amide protecting group is for example 9-H-xanthen-9-yl, 2,4,6-trimethoxybenzyl, dimethylcyclo- propylmethyl, trityl or 3-methylpent-3-yl. A guanidino protecting group is for example 2,2,4,6,7- pentamethyldihydrobenzofuran-5-ylsulfonyl (= Pbf), 2,2,5,7,8-pentamethylchroman-6-ylsulfonyl, mesitylsulfonyl, tosyl, trityl or methoxytrityl, preferably 2,2,4,6,7-pentamethyldihydrobenzofuran- 5-ylsulfonyl. A protecting group for an aromatic hydroxy group is for example tert-butyl, benzyl, 2-chlorotrityl or 2-bromogenzyloxycarbonyl. A protecting group for an imidazole nitrogen is for example tert-butyloxycarbonyl, 2,4-dinitrophenyl, benzyloxymethyl, trityl or methoxytrityl, preferably tert-butyloxycarbonyl. A protecting group for an indole nitrogen is for example tert- butyloxycarbonyl or formyl, preferably tert-butyloxycarbonyl. AAn1 connects covalently with the nitrogen atom of its alpha amino group to the carbon atom of the carbonyl group depicted at formula S-I-am or S-II-am. AAnm connects covalently with the carbon atom of a carbonyl group to an oxygen or a nitrogen atom. The carbonyl group is preferably the alpha carbonyl group of AAnm. An example of a functional group of a side chain, which interferes with condensing at step (cX), preferably at step (c), is for example an amino group. Accordingly, the amino group is protected by a protecting group. AAnxis for example, in the respective condensed form as an alpha amino acid residue, glycine, alanine, serine, serine with its side chain protected by tert-butyl, threonine, threonine with a side chain protected by trityl, cysteine with its side chain protected by tert-butyl, valine, leucine, isoleucine, methionine, proline, phenylalanine, tyrosine with its side chain protected by tert- butyl, tryptophane with its side chain protected by tert-butyloxycarbonyl, aspartic acid with its side chain protected by tert-butyl, glutamic acid with its side chain protected by tert-butyl, asparagine, asparagine with its side chain protected by trityl, glutamine, glutamine with its side chain protected by dimethylcyclopropylmethyl, histidine with its side chain protected by trityl, lysine with its side chain protected by allyloxycarbonyl or arginine with its side chain protected by 2,2,4,6,7-pentamethyldihydrobenzofuran-5-ylsulfonyl. An example for the substituent -(AAnx)m- with m = 3, AAn1 = Gly, AAn2 = Arg(Pbf) and AAn3 = Gly is -(Gly-Arg(Pbf)-Gly)- as depicted below with * and ** indicating the covalent connections. C1-6 alkyl is for example methyl, 1-methylethyl, 1-methylpropyl or 2-methylpropyl. C1-6 alkyl mono-substituted with ORSI-2-1 is for example hydroxymethyl, hydroxymethyl protected by RSI-2-1, 1-hydroxyethyl or 1-hydroxyethyl protected by RSI-2-1. C alkyl mono-su SI-2-2 1-6 bstituted with SR is for example mercaptomethyl protected with RSI-2-2. C1-6alkyl mono-substituted with SCH3is for example 2-(methylthio)ethyl. C1-6 alkyl mono-substituted with NRSI-2-3RSI-2-4is for example 4- aminobutyl protected by RSI-2-3, RSI-2-4or RSI-2-3and RSI-2-4. C1-6alkyl mono-substituted with CO- ORSI-2-5is for example carboxymethyl protected with RSI-2-5or 2-carboxyethyl protected by RSI-2-5. C1-6alkyl mono-substituted with CO-NRSI-2-6RSI-2-7is for example 2-amino-2-oxoethyl or 2-amino- 2-oxoethyl protected by RSI-2-6, RSI-2-7 or RSI-2-6 and RSI-2-7. C1-6 alkyl mono-substituted with CO- NRSI-2-6RSI-2-7 is for example also 3-amino-3-oxopropyl or 3-amino-3-oxopropyl protected by RSI-2- 6, RSI-2-7 or RSI-2-6 and RSI-2-7. C1-6alkyl mono-substituted with N’-RSI-2-8-N’’-RSI-2-9-guanidino is for example 3-guanidino-propyl protected by RSI-2-8, RSI-2-9 or RSI-2-8 and RSI-2-9. C1-6 alkyl mono- substituted with phenyl is for example benzyl. C1-6alkyl mono-substituted with para-(RSI-2-10O)- phenyl is for example 4-hydroxybenzyl protected by RSI-2-10. C1-6 alkyl mono-substituted with 1- RSI-2-11-imidazol-4-yl is for example imidazol-4-ylmethyl or imidazol-4-ylmethyl protected by RSI-2-11at the 1-position of the imidazole ring. C1-6alkyl mono-substituted with 1-RSI-2-12-indol-3-yl is for example indol-3-ylmethyl or indol-3-ylmethyl protected by RSI-2-12 at the 1-position of the indole ring. Preferably, RSI-1 is -(AAnx)m-O-[resin-1], -(AAnx)m-N-[resin-2], -O-[resin-1], -N-[resin-2] or NH2. More preferably, RSI-1 is -(AAnx)m-O-[resin-1], -(AAnx)m-N-[resin-2], -O-[resin-1] or -N-[resin-2]. Preferably, RSI-1-1is a carboxylic acid protecting group. Preferably, RSI-2-5is a carboxylic acid protecting group. Preferably, all AAnxare free of an unprotected carboxylic acid. More preferably, RSI-1-1and RSI-2-5are independently from each other a carboxylic acid protecting group and all AAnx are free of an unprotected carboxylic acid group. More preferably, the alpha amino acid derivative of formula S-I-am or S-II-am is free of an unprotected carboxylic acid group. Preferably, RSI-2 is different to H. More preferably, RSI-2 is C1-6 alkyl or C1-6 alkyl mono-substituted with ORSI-2-1, SRSI-2-2, SCH3, NRSI-2-3RSI-2-4, CO-ORSI-2-5, CO-NRSI-2-6RSI-2-7, N’-RSI-2-8-N’’-RSI-2-9- guanidino, phenyl, para-(RSI-2-10O)-phenyl, 1-RSI-2-11-imidazol-4-yl or 1-RSI-2-12-indol-3-yl. Very preferably, RSI-2is C1-6alkyl mono-substituted with ORSI-2-1, SRSI-2-2, SCH3, NRSI-2-3RSI-2-4, CO- ORSI-2-5, CO-NRSI-2-6RSI-2-7, N’-RSI-2-8-N’’-RSI-2-9-guanidino, phenyl, para-(RSI-2-10O)-phenyl, 1- RSI-2-11-imidazol-4-yl or 1-RSI-2-12-indol-3-yl. Particularly, RSI-2 is C1-6 alkyl mono-substituted with CO-ORSI-2-5 or CO-NRSI-2-6RSI-2-7. Preferably, m is an integer from 1 to 25, more preferably from 1 to 20, very preferably from 1 to 15, particularly from 2 to 12, more particularly from 3 to 11 and very particularly from 4 to 10. Preferably, the alpha carbon atom of the compound of formula S-I-am, which is substituted by RSI-2, is in the S-configuration provided that RSI-2is different to H. Preferably, the alpha carbon atom of the compound of formula S-II-am, which is substituted by the carbonyl group covalently linked to RSII-1, is in the S-configuration. When the alpha amino acid derivative S-am at step (c) is a compound of formula S-I-am or S-II- am, then the peptide Pr-L-S obtained at step (c) is a compound of formula Pr-L-S-I or Pr-L-S-II , wherein RL-O-1and RL-O-2are defined as for formula Pr-L, RSI-1, RSI-2and RSII-1are defined as for formula S-I-am or S-II-am. Preferred is a method of manufacturing a peptide PX, wherein the alpha amino acid derivative S- am is a compound of formula S-I-am or S-II-am. Preferred is a method of manufacturing a peptide P, wherein the alpha amino acid derivative S- am is a compound of formula S-I-am or S-II-am and the peptide Pr-L-S obtained at step (c) is a compound of formula Pr-L-S-I or Pr-L-S-II. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein the alpha amino acid derivative S-am of step (cX), preferably of step (c), is of formula S-I-am with RSI-1 is a -(AAnx)10-O-[resin-1], AAn1 is Phe, AAn2 is Ile, AAn3 is Ala, AAn4 is a Trp with a protected side chain, AAn5 is Leu, AAn6 is Val, AAn7 is an Arg with a protected side chain, AAn8 is Gly, AAn9 is an Arg with a protected side chain and AAn10 is Gly, resin-1 is a 2-chlorotritylamidomethyl resin and RSI-2is 2-(tert-butyloxycarbonyl)ethyl. Preferred is a method of manufacturing a peptide PX, preferably a peptide P, wherein the alpha amino acid derivative S-am of step (c) is of formula S-I-am with RSI-1is a -(AAnx)10-O-[resin-1], AAn1 is Phe, AAn2 is Ile, AAn3 is Ala, AAn4 is a Trp with a protected side chain, AAn5 is Leu, AAn6 is Val, AAn7 is an Arg with a protected side chain, AAn8 is Gly, AAn9 is an Arg with a protected side chain and AAn10 is Gly, resin-1 is a 2-chlorotrityl resin and RSI-2 is 2-(tert-butyloxycarbonyl)- ethyl. Preferred is a method of manufacturing a peptide P, wherein RL-O-1and RL-O-2are independently of each other tert-butyl or 3-methyl-pent-3-yl. Preferred is a method of manufacturing a peptide PX, wherein the lysine derivative LYSXis a compound of formula Pr-L, particularly compound 508, compound 309, compound 511, compound 514 or compound 517. Preferred is a method of manufacturing a peptide P, wherein the compound of formula Pr-L is compound 508. A chemical name for the molecular structure of formula Bsmoc is 1,1-dioxobenzo[b]thiophene-2- ylmethyloxycarbonyl, which is commonly also named benzo[b]thiophenesulfone-2-methyloxy- carbonyl. Preferably, the method of manufacturing a peptide PX comprises a step (dX) of removing the Bsmoc-protecting group from the alpha nitrogen atom of the intermediate peptide Int-PX. Preferably, the method of manufacturing a peptide P comprises a step (d) of removing the amino protecting group RL-N-1at the compound of formula Pr-L-S-I or Pr-L-S-II to obtain a compound of formula L-S-I-am or L-S-II-am , wherein RL-O-1, RL-O-2, RSI-1, RSI-2and RSII-2are defined as for formula Pr-L-S-I or Pr-L-S-II. The removal of the Bsmoc protecting group at step (dX), respectively the amino protecting group RL-N-1 at step (d), is conducted with a deprotection composition of step (dX), respectively of step (d). A deprotection composition of step (dX), resepectively of step (d), is for example 20 vol.% piperidine in N,N-dimethylformamide. At the method of manufacturing a peptide P, a suitable selection of the other protecting groups of the compound of formula Pr-L-S-I or Pr-L-S-II leads to a compound of formula L-S-I-am or L-S-II-am, which contains the deprotected alpha amino group and is free of another unprotected amino group or an unprotected imino group, preferably also free of an unprotected carboxylic acid group. Preferred is a method of manufacturing a peptide PX, which comprises the step (dX) (dX) removing the Bsmoc-protecting group at the intermediate peptide Int-PX. Preferred is a method of manufacturing a peptide P, which comprises the step (d) (d) removing the amino protecting group RL-N-1 at the compound of formula Pr-L-S-I or Pr-L-S-II to obtain a compound of formula L-S-I-am or L-S-II-am. Preferably, the method of manufacturing a peptide PXcomprises a step (eX) of condensing the Bsmoc-deprotected intermediate Int-PXfrom step (dX) with an alpha-amino acid derivative of formula T RT-N-1-(AApy)q-OH (T) wherein RT-N-1 is an amino protecting group, -(AApy)q- is a substituent consisting of q condensed alpha amino acid residues AApywith each y being an integer and y running from 1 to q, each condensed alpha amino acid residue AApyis independently chosen and in case it possesses a side chain with a functional group, the functional group is unprotected or protected by a protecting group provided that an interfering functional group is protected, AApq connects covalently with the carbon atom of its alpha carbonyl group to the hydroxy group, q is an integer from 1 to 30. Preferably, the method of manufacturing a peptide P comprises a step (e) of condensing the compound of formula L-S-I-am or L-S-II-am with an alpha-amino acid derivative of formula T RT-N-1-(AApy)q-OH (T) wherein RT-N-1 is an amino protecting group, -(AApy)q- is a substituent consisting of q condensed alpha amino acid residues AApy with each y being an integer and y running from 1 to q, each condensed alpha amino acid residue AApy is independently chosen and in case it possesses a side chain with a functional group, the functional group is unprotected or protected by a protecting group provided that an interfering functional group is protected, AApqconnects covalently with the carbon atom of its alpha carbonyl group to the hydroxy group, q is an integer from 1 to 30, RL-O-1, RL-O-2, RSI-1, RSI-2and RSII-2are defined as for formula L-S-I-am or L-S-II- am, RT-N-1 and -(AApy)q- are defined as for formula T. The alpha amino group of AAp1 is protected by RT-N-1. At step (eX), AApq connects covalently with the carbon atom of its alpha carbonyl group to the depicted hydroxy group of formula T at formula T. AApq connects covalently with the carbon atom of its alpha carbonyl group to the alpha nitrogen atom of the deprotected intermediate Int-PXfrom step (dX). At step (e), AApqconnects covalently with the carbon atom of its alpha carbonyl group to the depicted nitrogen atom of the formula T-L-S-I or T-L-S-II at formula T-L-S-I or T-L-S-II at formula T-L-S-I or T-L-S-II. The compound of formula T contains one unprotected carboxylic acid group. The one unprotected carboxylic acid group is formed by the alpha carbonyl group of the amino acid residue AApq and the hydroxy group depicted at formula T. An example of a functional group of a side chain, which interferes with condensing at step (eX), respectively step (e), is for example an amino group. Accordingly, the amino group is protected by a protecting group. Examples for AApyare those listed for AAnxat step (c). An example of a compound of formula T with q = 1, RT-N-1= 9-fluorenylmethyloxycarbonyl and AAp1 = alanine residue is for Fmoc-Ala-OH as below . Preferably, q is an integer from 1 to 25, more preferably from 1 to 20, very preferably from 1 to 15, particularly from 1 to 10, more particularly from 1 to 8, very particularly from 1 to 5, especially from 1 to 3, more especially from 1 to 2 and very especially q is 1. For condensing the one unprotected alpha amino group of the compound of formula L-S-I-am or L-S-II-am, the carboxylic acid group of the compound of formula T is typically activated with a condensing agent of step (e). The condensing agent of step (e) leads to an activated compound of formula T, which contains instead of the hydroxy group at the carboxylic acid group a leaving group, which makes the activated compound of formula T more reactive towards the unprotected alpha amino group of the compound of formula L-S-I-am or L-S-II-am. Dependent on the specific condensing agent of step (e), the activated compound of formula T is an intermediate suitable for an isolation at room temperature or an intermediate unsuitable for an isolation at room temperature. In case that the compound of formula L-S-I-am or L-S-II-am contains an unprotected carboxylic acid group, the activation of the compound of formula T has to occur prior to a contact with the compound of formula L-S-I-am or L-S-II-am. The condensing agent of step (e) is for example a carbodiimide. The carbodiimide is for example diisopropyl- carbodiimide. Preferably, the carbodiimide is applied together with a coupling additive of step (e). The coupling additive of step (e) is for example cyano-hydroxyimino-acetic acid ethyl ester. Preferred is a method, which comprises the step (e) (e) condensing the compound of formula L-S-I-am or L-S-II-am with an alpha-amino acid derivative of formula T to obtain a compound of formula T-L-S-I or T-L-S-II. Preferably, the method comprises after the condensing at step (c) one or more further condensing cycles to elongate the peptide Pr-L-S obtained at step (c) by one or more further alpha amino acid residues. A condensing cycle comprises a first step of removing the amino protecting group of the alpha amino group of the N-terminal alpha amino acid residue of the peptide to be elongated to obtain one unprotected amino group at the peptide to be elongated. The amino group the alpha amino group of the N-terminal alpha amino acid residue means also an imino group, for example in case of proline being the N-terminal alpha amino acid residue of the peptide to be elongated. The condensing cycle comprises also a second step of condensing the one unprotected amino acid group from the first step with an alpha amino acid derivative, which has an alpha amino group at its N-terminal amino acid residue, which is protected by an amino protecting group and which has one unprotected alpha carboxylic acid group, which is located at its C-terminal amino acid residue, to obtain a peptide resulting from the condensing cycle. An example of the first step is the step (d). An example of the second step is the step (e). Optionally, a condensing step is followed by a capping step, i.e. treating of a reaction mixture, which contains the obtained peptide of the condensing step, by acetic acid anhydride. The capping step is prior to removing an amino protecting group, e.g. a first step of removing an amino protecting group as part of a condensing cycle. Potential residual amino groups or imino groups, which have not reacted in the condensing step, are thus acetylated and not amenable in the next condensing step. Preferred is a method, which comprises one or more further condensing cycles applied to the compound of formula T-L-S-I or T-L-S-II, each of the one or more further condensing cycles comprises a first step of removing the amino protecting group RT-N-1of the compound of formula T-L- S-I or T-L-S-II respectively the amino protecting group of the alpha amino group of the N- terminal amino acid residue of the peptide resulting from the previous condensing cycle to obtain the related peptide with one unprotected amino group, and a second step of condensing the unprotected amino group of the related peptide obtained at the first step with an alpha amino acid derivative, which has an alpha amino group at its N-terminal amino acid residue, which is protected by an amino protecting group and which has one unprotected alpha carboxylic acid group, which is located at its C-terminal amino acid residue, to obtain a peptide resulting from the condensing cycle. In case the alpha amino acid derivative S-am is covalently linked to a resin, the intermediate peptide Int-PX obtained at step (cX), preferably the peptide Pr-L-S obtained at step (c), is also covalently linked to the resin. This applies also to an elongated peptide obtained in one or more further condensing cycles. The peptide obtained at the last conducted condensing step can be cleaved from the resin by a cleavage composition to obtain a cleaved peptide. Whether protecting groups of the elongated peptide are retained, partly removed, or completely removed at the cleaved peptide depends inter alia on the cleavage composition, the reaction conditions and the specific protecting groups. Preferably, the alpha amino acid derivative S-am at step (cX) is covalently linked to a resin and the method of manufacturing a peptide PX, comprises a step (xX) of (xX) cleaving the peptide obtained from the last conducted condensing step from the resin by a cleaving composition to obtain a cleaved peptide. Preferably, the alpha amino acid derivative S-am at step (c) is covalently linked to a resin and the method of manufacturing a peptide P, comprises a step (x) of (x) cleaving the peptide obtained from the last conducted condensing step from the resin by a cleaving composition to obtain a cleaved peptide. In case the alpha amino acid derivative S-am at step (cX), respectively at step (c), is covalently linked to a resin via a carbonyl group of its C-terminal alpha amino acid residue, the cleaved peptide contains a carboxylic acid group at its C-terminal alpha amino acid residue, which has an unprotected alpha carboxylic acid group or an unprotected alpha carboxamide group. Preferred is a method of manufacturing a peptide PX, wherein the alpha amino acid derivative S- am at step (cX) is covalently linked to a resin and the method comprises the step (xX) (xX) cleaving the peptide obtained from the last conducted condensing step from the resin by a cleaving composition to obtain a cleaved peptide. Preferred is a method of manufacturing a peptide P, wherein the alpha amino acid derivative S- am at step (c) is covalently linked to a resin and the method comprises the step (x) (x) cleaving the peptide obtained from the last conducted condensing step from the resin by a cleaving composition to obtain a cleaved peptide. Preferably, the method of manufacturing a peptide PXcomprises a step (yX) of (yX) removing all remaining protecting groups from the peptide obtained from the last conducted condensing step to obtain a peptide free of protecting groups. Preferably, the method of manufacturing a peptide P comprises a step (y) of (y) removing all remaining protecting groups from the peptide obtained from the last conducted condensing step to obtain a peptide free of protecting groups. Removing of a protecting group occurs by a deprotection composition. If the protecting groups of the peptide obtained from the last conducted condensing step are all removable by the same deprotection composition, e.g. all protecting groups are labile towards trifluoroacetic acid, then the removal requires only one deprotection composition of step (yX), respectively of step (y). In case the peptide obtained from the last conducted condensing step is covalently linked to a resin, the step (yX), respectively the step (y), and the step (xX), respectively the step (x), can occur at the same time, if the cleavage composition of step (xX), respectively of step (x), acts also as a deprotection composition of step (yX), respectively of step (y), for all protecting groups of the peptide obtained from the last conducted condensing step, e.g. all protecting groups are labile towards trifluoroacetic acid and the covalent bond to the linking group of the resin is also labile towards trifluoroacetic acid. Preferred is a method of manufacturing a peptide PX, wherein the method comprises the step (yX) (yX) removing all remaining protecting groups from the peptide obtained from the last conducted condensing step to obtain a peptide free of protecting groups. Preferred is a method of manufacturing a peptide P, wherein the method comprises the step (y) (y) removing all remaining protecting groups from the peptide obtained from the last conducted condensing step to obtain a peptide free of protecting groups. An example of a peptide P, which is free of protecting groups, is semaglutide (CAS-No.910463- 68-2) as depicted in the three letter code of alpha amino acid residues (except for the condensed L-lysine residue with its fatty acid conjugation motif covalently linked to its epsilon nitrogen atom, which is depicted as a structural element of formula L) with the numbering of the alpha amino acid residues starting with 1 for N-terminal condensed L-histidine residue and ending with 31 for C-terminal condensed glycine residue (corresponding to SEQ ID NO:5): . The explanations and preferences described above for the method of manufacturing a peptide PX and for its steps apply similarly to other embodiments of the invention. A further embodiment of the invention is a lysine derivative LYSX, which is a compound of formula Pr-L , wherein RL-O-1 and RL-O-2 are independently of each other a carboxylic acid protecting group; a compound of formula , wherein RA-N-1 is an amino protecting group different to RL-N-1, 1-(4,4-dimethyl-2,6- dioxocyclohexylidene)ethyl and 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl, RL-N-1 is an amino protecting group of formula Bsmoc with * indicating the bond to the nitrogen atom (Bsmoc); compound 310 (as depicted above); compound 511 (as depicted above); compound 514 (as depicted above) or compound 517 (as depicted above). Preferably, RA-N-1 is tert-butyloxycarbonyl at formula (Pr-A), i.e., compound 309 (as depicted above). The lysine derivate LYSXis preferably compound 508, compound 309, compound 310, compound 511, compound 514 or compound 517. More preferably, the lysine derivative LYSXis compound 508, compound 511, compound 514 or compound 517. Preferred is a lysine derivative LYSX, which is a compound of formula Pr-L, wherein RL-O-1 and RL-O-2 are independently of each other tert-butyl or 3-methyl-pent-3-yl. Preferred is a lysine derivative LYSX, which is a compound of formula Pr-L, wherein RL-O-1 and RL-O-2 are tert-butyl. Preferred is a lysine derivative LYSX, which is a compound of formula Pr-L, which is compound 508. A further embodiment of the invention is a use of a lysine derivative LYSX, which is a compound of formula Pr-L , wherein RL-O-1 and RL-O-2 are independently of each other a carboxylic acid protecting group; a compound of formula , wherein RA-N-1is an amino protecting group different to Bsmoc, 1-(4,4-dimethyl-2,6-dioxocyclo- hexylidene)ethyl and 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl; compound 310 (as depicted above); compound 511 (as depicted above); compound 514 (as depicted above) or compound 517 (as depicted above) in the synthesis of a peptide PX. Preferably, the lysine derivative LYSX is a compound of formula Pr-L RA-N-1 in the synthesis of a peptide P. A further embodiment is the invention is a method of manufacturing a compound of formula 1X wherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid, which comprises the step (aa) step (aaX) providing 118 step (abX) adding HY to the provided compound 118 to obtain the compound of formula 1X. A further embodiment is the use of a compound of formula 1X wherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid, in the synthesis of a peptide. The peptide is for example a lysine derivative LYSXor a peptide PX. Brief description of the Figures Fig.1 depicts a complete HPLC-UV chromatogram from D-02-1. One of the two peaks represents compound 701 and the other one is a decomposition product. Both peaks are marked and their area percentages are stated. Fig.2 depicts an extract of the HPLC-UV chromatogram from D-02-1 of Fig.1 between around 14 and 20 minutes. The two peaks, one of which represents compound 701, are marked and their area percentages are stated. Fig.3 depicts a complete HPLC-UV chromatogram from D-02-2. A peak representing compound 702 is marked and its area percentage is stated. Fig.4 depicts an extract of the HPLC-UV chromatogram from D-02-2 of Fig.3 between around 10 and 22 minutes. The peak representing compound 702 is marked and its area percentage is stated. Fig.5 depicts a complete HPLC-UV chromatogram from D-02-3. A peak representing compound 702 is marked and its area percentage is stated. Fig.6 depicts an extract of the HPLC-UV chromatogram from D-02-3 of Fig.5 between around 14 and 24 minutes. The peak representing compound 702 is marked and its area percentage is stated. Fig.7 depicts a complete HPLC-UV chromatogram from D-02-4. A peak representing compound 702 is marked and its area percentage is stated. Fig.8 depicts an extract of the HPLC-UV chromatogram from D-02-4 of Fig.7 between around 11 and 22 minutes. The peak representing compound 702 is marked and its area percentage is stated. Fig.9 depicts a complete HPLC-UV chromatogram from D-02-5. A peak representing compound 702 is marked and its area percentage is stated. Fig.10 depicts an extract of the HPLC-UV chromatogram from D-02-5 of Fig.9 between around 14 and 20 minutes. The peak representing compound 702 is marked and its area percentage is stated. Fig.11 depicts a complete HPLC-UV chromatogram from D-02-6. A peak representing compound 702 is marked and its area percentage is stated. Fig.12 depicts an extract of the HPLC-UV chromatogram from D-02-6 of Fig.11 between around 14 and 20 minutes. The peak representing compound 702 is marked and its area percentage is stated. Fig.13 depicts a complete HPLC-UV chromatogram from D-04-2. A peak representing compound 704 is marked and its area percentage is stated. Fig.14 depicts an extract of the HPLC-UV chromatogram from D-04-2 of Fig.13 between around 10 and 22 minutes. The peak representing compound 704 is marked and its area percentage is stated. Fig.15 depicts a complete HPLC-UV chromatogram from D-04-3. A peak representing compound 704 is marked and its area percentage is stated. Fig.16 depicts an extract of the HPLC-UV chromatogram from D-04-3 of Fig.15 between around 14 and 24 minutes. The peak representing compound 704 is marked and its area percentage is stated. Fig.17 depicts a complete HPLC-UV chromatogram from D-04-4. A peak representing compound 704 is marked and its area percentage is stated. Fig.18 depicts an extract of the HPLC-UV chromatogram from D-04-4 of Fig.17 between around 11 and 22 minutes. The peak representing compound 704 is marked and its area percentage is stated. Fig.19 depicts a complete HPLC-UV chromatogram from D-04-5. A peak representing compound 704 is marked and its area percentage is stated. Fig.20 depicts an extract of the HPLC-UV chromatogram from D-04-5 of Fig.19 between around 14 and 20 minutes. The peak representing compound 704 is marked and its area percentage is stated. Fig.21 depicts a complete HPLC-UV chromatogram from D-04-6. A peak representing compound 704 is marked and its area percentage is stated. Fig.22 depicts an extract of the HPLC-UV chromatogram from D-04-6 of Fig.21 between around 14 and 22 minutes. The peak representing compound 704 is marked and its area percentage is stated. Fig.23 depicts a complete HPLC-UV chromatogram from D-06-1. A peak representing compound 706 is marked and its area percentage is stated. Fig.24 depicts an extract of the HPLC-UV chromatogram from D-06-1 of Fig.23 between around 9 and 14 minutes. The peak representing compound 706 is marked and its area percentage is stated. Fig.25 depicts a complete HPLC-UV chromatogram from D-07-1. A peak representing compound 707 is marked and its area percentage is stated. Fig.26 depicts an extract of the HPLC-UV chromatogram from D-07-1 of Fig.25 between around 10 and 14 minutes. The peak representing compound 707 is marked and its area percentage is stated. Fig.27 depicts a complete HPLC-UV chromatogram from D-08-1. A peak representing compound 708 is marked and its area percentage is stated. Fig.28 depicts an extract of the HPLC-UV chromatogram from D-08-1 of Fig.27 between around 10 and 22 minutes. The peak representing compound 708 is marked and its area percentage is stated. Fig.29 depicts a complete HPLC-UV chromatogram from D-09-1. A peak representing compound 709 is marked and its area percentage is stated. Fig.30 depicts an extract of the HPLC-UV chromatogram from D-09-1 of Fig.29 between around 14 and 24 minutes. The peak representing compound 709 is marked and its area percentage is stated. Fig.31 depicts a complete HPLC-UV chromatogram from D-10-1. A peak representing compound 710 is marked and its area percentage is stated. Fig.32 depicts an extract of the HPLC-UV chromatogram from D-10-1 of Fig.31 between around 11 and 22 minutes. The peak representing compound 710 is marked and its area percentage is stated. Fig.33 depicts a complete HPLC-UV chromatogram from D-11-1. A peak representing compound 711 is marked and its area percentage is stated. Fig.34 depicts an extract of the HPLC-UV chromatogram from D-11-1 of Fig.33 between around 14 and 22 minutes. The peak representing compound 711 is marked and its area percentage is stated. Fig.35 depicts a complete HPLC-UV chromatogram from B-29-1. A peak representing compound 509 is marked and its area percentage is stated. Fig.36 depicts a complete HPLC-UV chromatogram from B-30-1. A peak representing compound 511 is marked and its area percentage is stated. Fig.37 depicts a complete HPLC-UV chromatogram from B-32-1. A peak representing compound 514 is marked and its area percentage is stated. Fig.38 depicts a complete HPLC-UV chromatogram from B-33-1. A peak representing compound 515 is marked and its area percentage is stated. Fig.39 depicts a complete HPLC-UV chromatogram from B-34-1. A peak representing compound 517 is marked and its area percentage is stated. Fig.40 depicts a complete HPLC-UV chromatogram from B-35-1. A peak representing compound 518 is marked and its area percentage is stated. Fig.41 depicts a complete HPLC-UV chromatogram from B-36-1. A peak representing compound 520 is marked and its area percentage is stated. Sequence Listing Compound 701 KEFIAWLVRGRG (SEQ ID NO:1) K at position 1 = 2-(p-nitrophenylsulfonyl)ethoxycarbonyl-lysine(17-carboxy-heptadecacarbonyl- gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 702 KEFIAWLVRGRG (SEQ ID NO:2) K at position 1 = lysine(17-carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 703 AKEFIAWLVRGRG (SEQ ID NO:3) A at position 1 = 9-fluorenylmethyloxycarbonyl-alanine K at position 2 = lysine(17-carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 704 AKEFIAWLVRGRG (SEQ ID NO:4) K at position 2 = lysine(17-carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 705 (Semaglutide) HXEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:5) X at position 2 = Aib K at position 20 = lysine(17-carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 706 FIAWLVRGRG (SEQ ID NO:6) Compound 707 EFIAWLVRGRG (SEQ ID NO:7) Compound 708 KEFIAWLVRGRG (SEQ ID NO:8) K at position 1 = alpha-azido-lysine(17-carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2- aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 709 KEFIAWLVRGRG (SEQ ID NO:9) K at position 1 = 9-fluorenylmethyloxycarbonyl-lysine(17-carboxy-heptadecacarbonyl-gamma- Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 710 KEFIAWLVRGRG (SEQ ID NO:10) K at position 1 = 2-(phenylsulfonyl)ethoxycarbonyl-lysine(17-carboxy-heptadecacarbonyl- gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl) Compound 711 KEFIAWLVRGRG (SEQ ID NO:11) K at position 1 = 1,1-dioxobenzo[b]thiophene-2-yl-methyloxycarbonyl-lysine(17-carboxy-hepta- decacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]- acetyl) Examples A) general A-1) abbreviations % if not stated differently, a percentage value refers to weight percent ACN acetonitrile AcOH acetic acid Aib 2-aminoisobutyric acid Bsmoc 1,1-dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl (commonly also named: benzo[b]thiophenesulfone-2-methyloxycarbonyl) Boc tert-butyloxycarbonyl CAD charged aerosol detector d day DBU 1,8-diazabicyclo(5.4.0)undec-7-ene DEPBT 3-(diethoxyphosphoryloxy)-3H-benzo[d][1,2,3]triazin-4-one DIC N,N’-diisopropylcarbodiimide DIPEA diisopropylethylamine DMF N,N-dimethylformamide EDT ethane-1,2-dithiol EtOAc ethyl acetate Fmoc 9-fluorenylmethyloxycarbonyl HPLC high performance liquid chromatography HR-MS high resolution mass spectrometry IPA isopropanol IPC in process control IPE diisopropyl ether MeTHF 2-methyltetrahydrofuran Mpe 3-methylpent-3-yl MS mass spectrometry MTBE methyl tert-butyl ether N3azido NMP N-methylpyrrolidone Nsc 2-(p-nitrophenylsulfonyl)ethoxycarbonyl OxymaPure (TM) cyano-hydroxyimino-acetic acid ethyl ester Pbf 2,2,4,6,7-pentamethyl-2,3-dihydrobenzfuran-5-ylsulfonyl Psc 2-(phenylsulfonyl)ethoxycarbonyl Psi(Me,Me)pro 1,1-dimethylmethdiyl, which is covalently linked to the beta oxygen atom of serine or threonine and covalently linked to the alpha-nitrogen of serine or threonine (pseudoproline) RT room temperature TBTU (benzotriazolyl)tetramethyluronium tetrafluoroborate tBu tert-butyl TFA trifluoroacetic acid TIS triisopropylsilane TLC thin layer chromatography Trt trityl TsOH 4-toluenesulfonic acid UV ultraviolet vol.% volume percents If not stated differently, alpha amino acids different to glycine are in L-form. Room temperature means herein a temperature between 22 °C and 25 °C. A-2) chemicals All reagents and solvents are obtained from standard suppliers of raw materials for peptide synthesis and are used as received. A-3) analytical methods A-3-1: HPLC method 1 HPLC method 1 is an analytical HPLC, which is performed on a Dionex (TM) Ultimate (TM) 3000 RS UHPLC system using ACQUITY (TM) UPLC BEH 130 C18 (1.7 μm, 2.1 × 50 mm) column with a flow rate of 0.4 mL / min, an UV detection at 220 nm or a CAD detection and an oven temperature of 25 °C. Buffer A is 0.05 vol.% TFA in ACN / H2O (1:99 v / v) and buffer B is 0.05 vol.% TFA in ACN. At some examples, a gradient program and the detection is stated. At some examples, one of the following general modes A to F is stated. Mode A: 0 min 20% B - 5 min 100% B - 7 min 100% B, with UV detection Mode B: 0 min 5% B - 5 min 100% B - 7 min 100% B, with UV detection Mode C: 0 min 80% B - 5 min 100% B - 7 min 100% B, with CAD detection Mode D: 0 min 20% B - 5 min 100% B - 7 min 100% B, with UV detection and CAD detection Mode E: 0 min 0% B - 5 min 100% B - 7 min 100% B, with UV detection Mode F: 0 min 30% B - 3 min 72% B - 5 min 100% B - 9 min 100 % B, with UV detection A-3-2: HPLC method 2 HPLC method 2 is an analytical HPLC, which is performed on a Thermo Scientific (TM) Vanquish (TM) UHPLC system or a Dionex (TM) Ultimate (TM) 3000 RS UHPLC system using ACQUITY (TM) UPLC BEH 130 C18 (1.7 μm, 2.1 × 150 mm) column with a flow rate of 0.4 mL / min, UV detection at 220 nm and 50 °C oven temperature. In case of a mass spectroscopy, the MS analysis is performed on a UHPLC coupled with Bruker (TM) maXis II (TM) spectrometer with ultra-high resolution QTOF technology equipped with electron-transfer dissociation (ETD) capabilities. Buffer A is 0.05 vol.% TFA in ACN / H2O (1:99 v / v) and buffer B is 0.05 vol.% TFA in ACN. Gradient program at HPLC method 2 time (min) buffer A buffer B 0 100 0 30 0 100 A-3-3: HPLC method 3 HPLC method 3 is an analytical HPLC, which is performed on a Thermo Scientific (TM) Vanquish (TM) UHPLC system or Dionex (TM) Ultimate (TM) 3000 RS UHPLC system using AQUITY (TM) UPLC BEH C18, 130 A (1.7 μm, 2.1 × 150 mm) column with a flow rate of 0.4 mL / min, UV detection at 220 nm and 25 °C oven temperature. Buffer A is 0.05 vol.% TFA in ACN / H2O (1:99, v / v / v) and buffer B is 0.05 vol.% TFA in ACN. Gradient program at HPLC method 3 time (min) buffer A buffer B 0 70 30 5 0 100 5 0 100 A-4) synthetic general procedures A-4-1: general procedure 1 for condensing a lysine derivative 200 mg of compound 612-SP (0.22 mmol / g, 0.044 mmol), which is depicted at example C-06- 1, is pre-swelled two times in DMF (10 mL / g resin) each for 15 min at RT. A respective lysine derivative (0.088 mmol, 2.0 eq.) and OxymaPure (19.4 mg, 0.136 mmol, 3.1 eq.) are dissolved in DMF (10 mL / g resin). To this solution, 17.7 µL DIC (0.114 mmol, 2.6 eq.) are added. The solution is stirred for 15 min at RT and afterwards added to the reaction mixture. After 20 min of reaction time at RT, an additional portion of 8.8 µL DIC (0.057 to 0.143 mmol, 1.3 eq.) is added to the reaction mixture and stirred for typically 24 h at RT. The liquid parts are removed, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). The washed peptide material is dried 24 h in high vacuum at RT to obtain the respective product from the condensing of the lysine derivative with compound 612-SP. For analytical purposes, a small-scale test cleavage can be performed. A-4-2: general procedure 2 for test cleavage Peptide is cleaved from the resin in a 2 mL plastic syringe (50 to 100 mg peptide resin) upon treatment of the peptide resin with 0.5 to 1.0 mL cleavage cocktail (TFA / TIS / H2O = 90 / 5 / 5 based on volume) for 2 h at RT. The cleaved peptide in solution is then precipitated in 5 to 10 mL cold IPE (< -15 °C), centrifuged and washed two additional times with cold IPE. The obtained crude peptide, which is typically solid, is dried in high vacuum. A-4-3: general procedure 3 for Fmoc-Ala-OH condensing followed by removing Fmoc A procedure is described for 200 mg of compound 614-SP as starting material. The procedure can be adjusted to a lower or higher amount of starting material. 200 mg of compound 614-SP (0.21 mmol / g resin), which is depicted at example C-08-1, is pre- swelled two times in DMF (10 mL / g resin) each for 15 min at RT. In case compound 614-SP is already a resin material in contact with DMF, then the pre-swelling can be omitted.27.7 mg Fmoc-Ala-OH (0.084 mmol, 2.0 eq.) and 18.5 mg OxymaPure (0.130 mmol, 3.1 eq.) are dissolved in 2.0 mL DMF. To this solution, 16.9 µL DIC (0.109 mmol, 2.6 eq.) are added, the solution is stirred for 15 min at RT and added afterwards to pre-swelled respectively DMF- contacted compound 614-SP. After 20 min of reaction time at RT, an additional portion of 8.5 µL DIC (0.059 mmol, 1.3 eq.) are to the reaction mixture and stirred for typically 17 h at RT. The liquid parts are removed, and the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin) to obtain compound 615- SP, which is depicted at example C-09-1. Compound 615-SP is treated with 20 vol.% piperidine in DMF (10 mL / g resin) twice with a duration of 20 min for the first treatment and a duration of 60 min for the second treatment. Afterwards, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). The washed resin material can be employed at a further reaction without drying or is dried. A part of the washed resin material is dried for 24 h in high vacuum at RT to obtain compound 616-SP. For analytical purposes, a small-scale test cleavage can be performed to obtain compound 704, which is depicted at example D-04-1. B) synthesis of lysine derivatives and some of their starting materials Example B-01-1: synthesis of compound 101 Compound 101 is obtainable for example from a condensing reaction of compound 102 (CAS- No.21386-32-3) in analogy to molecule II in International Journal Peptide Research (1975) volume 7, p.295-305. Example B-02-1: of 104 Compound 104 is obtainable for example by a condensing reaction of compound 105 (CAS-No. 102093-85-6) in analogy to the preparation of molecule 10 at US 3791830. Example B-02-2: synthesis of compound 104 Compound 104 is obtainable for example by a condensing reaction of compound 102 (CAS-No. 21386-32-3) in analogy to example 5 of US 3936452. Example B-03-1: of 108 Compound 108 is obtainable for example by a condensing reaction of compound 105 (CAS-No. 102093-85-6) with N-hydroxyphthalimide in analogy to molecule IVb in International Journal Peptide Research (1975) volume 7, p.295-305. Example B-04-1: synthesis of compound 109 Compound 109, which is a hydrochloric acid salt (WO 2002-098903 A1, table 1 / entry 19 states Nsc-Lys-OH), is obtainable for example by a deprotecting reaction of compound 110 (CAS-No. 160422-23-1) Example B-05-1: of 110 Compound 110 (CAS-No.160422-23-1) is obtainable for example as described in example 3f in Tetrahedron Letters (1994), vol.35, No.42, p.7821-7824, i.e. by a protecting reaction of compound 111 (CAS-No.2418-95-3) with chlorotrimethylsilane to obtain compound 112 as shown at scheme 1 in Tetrahedron Letters (1994), vol.35, No.42, p.7821-7824, , which is afterwards reacted with compound 105 (CAS-No.102093-85-6). Example B-05-2: synthesis of compound 110 Compound 110 (CAS-No.160422-23-1) is obtainable for example by a protecting reaction of compound 111 (CAS-No.2418-95-3) with compound 101 in analogy to p.302 / general procedure method B in International Journal Peptide Research (1975) volume 7, p.295-305. Example B-05-3: synthesis of compound 110 Compound 110 (CAS-No.160422-23-1) is obtainable for example by a protecting reaction of compound 111 (CAS-No.2418-95-3) with compound 104 in analogy to example 26 of US 3936452. Example B-05-4: synthesis of compound 110 Compound 110 (CAS-No.160422-23-1) is obtainable for example by a protecting reaction of compound 111 (CAS-No.2418-95-3) with compound 108 in analogy to the solid phase synthesis at example 7 of WO 2004-065412. Example B-06-1: of 201 Compound 201 is obtainable for example by a condensing reaction of compound 202 (CAS-No. 1069067-08-8) with N-hydroxysuccinimide supported by dicyclohexylcarbodiimide in analogy to example 3 c) of CN 113121627 A. Example B-06-2: synthesis of compound 201 3.27 g of compound 202 (8.0 mmol) are dissolved in 12 mL MeTHF.1.02 g of N-hydroxy- succinimide (8.9 mmol) are added to the solution. Then, a solution of 1.36 g DIC (8.8 mmol) in 4 mL MeTHF is added. The resulting solution is stirred at room temperature for 7 h to obtain a solution containing compound 201. The solution is directly used as pre-activated carboxy compound for the coupling reaction at example B-28-1. Compound 301 is obtainable for example by a protecting reaction of compound 109 with chlorotrimethylsilane in analogy to step 3b of EP 3819308 A1 to obtain compound 113 , which is afterwards reacted with compound 201 in analogy to step 3b of EP 3819308 A1. Example B-08-1: synthesis of compound 302 Compound 302, which is a hydrochloric acid salt, is obtainable for example by a deprotecting reaction of compound 301 with HCl in dioxane. Example B-09-1: synthesis of compound 303 Compound 303, which is a hydrochloric acid salt, is obtainable for example by a deprotecting reaction of compound 304 (CAS-No.1662688-18-7) with HCl in dioxane. Example B-10-1: synthesis of compound 501 Compound 501 (CAS-No.1662688-20-1) is obtainable for example as described in example 9 of CN 104356224 A, i.e. by a coupling reaction of compound 308 (CAS-No.1662688-19-8) . Example B-10-2: synthesis of compound 501 Compound 501 (CAS-No.1662688-20-1) is obtainable for example by a protecting reaction of compound 303, which is a hydrochloric acid salt, with chlorotrimethylsilane to obtain compound 305 [the structure of compound 305 is depicted as -NH2 x HCl, but a structure of compound 305 with -NH-Si(CH3)3 or -NH-Si(CH3)3 x HCl might also be present - this topic is open], which is afterwards reacted with compound 203 (CAS-No.1188328-22-4) in analogy to step 3b of EP 3819308 A1. Example B-10-3: synthesis of compound 501 Compound 501 (CAS-No.1662688-20-1) is obtainable for example similarly as described in example 6 of WO 2021-205388 A2. Example B-10-4: synthesis of compound 501 4.1 mL ACN, 4.1 mL 1,4-dioxane and 1.0 mL trimethylsilyl chloride (7.9 mmol) are added to 2.0 g of compound 304 (assay 80%, 2.1 mmol). The reaction mixture is heated to 40 °C for 15 min to obtain a solution, which contains 312 . 3.0 mL of a 5.7 M solution of HCl in 1,4-dioxane (17 mmol) are added to the solution. The resulting reaction mixture is kept at 40 °C for 1.5 h. Then, the solvent is removed under vacuum to give an oily residue, which is co-evaporated twice with 20 mL ACN to remove excess HCl. The resulting oil is dissolved in 20 mL of a 1 : 1 mixture of ACN : 1,4-dioxane. The solution contains compound [the structure of compound 313 is depicted as -NH2x HCl, but a structure of compound 313 with -NH-Si(CH3)3 or -NH-Si(CH3)3 x HCl might also be present - this topic is open], which is the silylated amine compound for the following coupling reaction. For the coupling reaction, 1.24 g of compound 203 (1.9 mmol) and 0.4 mL DIPEA (2.3 mmol) are added at RT to the solution containing the silylated amine compound. The reaction mixture is stirred for 17 h, then additional 0.6 mL DIPEA (3.4 mmol) and 0.07 g of compound 203 (0.1 mmol) are added. Stirring is continued for additional 4 h. The reaction mixture is diluted with 12 mL IPE and 3 mL water and acidified with 1 mL 5.5 N aqueous HCl. The phases are separated, the organic phase is washed with 4 x 3 mL water and concentrated under vacuum to give a viscous oil. The oil is three times dissolved in 20 mL EtOAc and again concentrated under reduced pressure to yield 1.72 g (68%) of the compound 501 as a viscous resin. HPLC method 1 mode F: 91.3 area%, retention time 8.19 min. MS: m / z = 1196.7374 [M+H]+. Example B-11-1: synthesis of compound 502 Compound 502 (CAS-No.2682856-38-6) is obtainable for example as described in Organic Process Research and Development (2021), 25 (7), p.1598-1611 for its molecule 10 in its scheme 3, i.e. by a coupling reaction of compound 306 (CAS-No.1118767-16-0) which is afterwards treated with tetrasodium ethylenediaminetetraacetate for dechelating. Example B-11-2: synthesis of compound 502 Compound 502 (CAS-No.2682856-38-6) is obtainable for example by a deprotecting reaction of compound 501 (CAS-No.1662688-20-1) with piperidine. Example B-11-3: synthesis of compound 502 100 g of compound 501 (84 mmol) are dissolved in 600 mL ACN at 40 °C and the clear solution is cooled to RT. To this solution, 33 mL piperidine are added and the resulting suspension stirred for 30 min, then additional 100 mL ACN are added and stirring continued for 1 h. The suspension is filtered over a suction filter and the filter cake washed with 5 x 200 mL and 2 x 300 mL ACN. The solid is dried under vacuum at 35 °C overnight. The resulting crude product (78 g) is dissolved in 600 mL ACN and 85 mL water at 50 °C. From the resulting solution, 200 mL are evaporated under reduced pressure using a rotary evaporator. To the formed emulsion, 400 mL ACN are added, and the same volume evaporated under reduced pressure. The addition / evaporation cycle is repeated twice more. The resulting suspension is then diluted with another 400 mL ACN and filtered over a vacuum filter. The filter cake is washed with 3 x 300 mL ACN and dried under vacuum at 35 °C for 15 h.73.6 g (76 mmol, 90%) of compound 502 are obtained as a white solid. HPLC method 1 with CAD detection: 98.7 area-%, retention time 6.19 min. Gradient program at HPLC method 1 time (min) buffer A buffer B 0 70 30 3 28 72 8 0 100 12 0 100 Example B-12-1: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with compound 105 (CAS-No.102093-85-6) in analogy to example 1 of US 5616788. Example B-12-2: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with chlorotrimethylsilane to obtain compound 505 , which is afterwards reacted with compound 105 (CAS-No.102093-85-6) in analogy to example 3 of US 6165590. Example B-12-3: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with compound 115 (CAS-No.122865-54-7) in analogy to the solid phase synthesis at example 7 of WO 2004-065412. Example B-12-4: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with compound 101 in analogy to p.302 / general procedure method B in International Journal Peptide Research (1975) volume 7, p.295-305. Example B-12-5: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with compound 104 in analogy to example 26 of US 3936452. Example B-12-6: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 502 (CAS-No. 2682856-38-6) with compound 108 in analogy to the solid phase synthesis at example 7 of WO 2004-065412. Example B-12-7: synthesis of compound 504 Compound 504 is obtainable for example by a protecting reaction of compound 302, which is a hydrochloric acid salt, with chlorotrimethylsilane in analogy to step 3b of EP 3819308 A1 to obtain compound 307 , [the structure of compound 307 is depicted as -NH2 x HCl, but a structure of compound 307 with -NH-Si(CH3)3or -NH-Si(CH3)3x HCl might also be present - this topic is open], which is afterwards reacted with compound 203 (CAS-No.1188328-22-4) in analogy to step 3b of EP 3819308 A1. Example B-12-8: synthesis of compound 504 19.5 g of compound 502 (20 mmol, 1.0 eq.) are suspended in 60 mL ACN and then 8.1 mL N- methyl-N-trimethylsilylacetamide (50 mmol, 2.5 eq.) are added. The mixture is heated to 40 °C to form a clear solution and then cooled to RT.300 mL DMF and 1.6 ml pyridine (20 mmol, 1.0 eq.) are added to the solution, then 8.5 g of compound 101 (20 mmol, 1.0 eq.) is added over a period of 30 min. After 5 h, an additional 0.8 mL pyridine (10 mmol, 0.5 eq.) and 8.5 g of compound 101 (20 mmol, 1.0 eq.) are added and stirring is continued for 17 h.120 mL of 0.25 N aqueous hydrochloric acid are added to the mixture and the solvent is evaporated under reduced pressure at 45 °C. The resulting thin oil is dissolved in 250 mL EtOAc and transferred to a separation funnel.50 mL water are added, and the pH is adjusted to 1-2 with 5.5 N aqueous hydrochloric acid. The phases are separated, the organic phase is washed with 3 x 50 mL water and then concentrated under reduced pressure to obtain a viscous oil. The purity of the viscous oil is 88.1 area% according HPLC method 1 and the below stated gradient program. The purity is even worse in case of a desirable extraction with an aqueous sodium hydrogencarbonate solution. The latter one has been left out. An assumption is a relatively high base sensitivity of the Nsc protecting group at the present molecule structure, which comes into play already with during pyridine contact and fortifies at the initially tried extraction with an aqueous sodium hydrogencarbonate solution. A purification of the viscous oil with a first preparative reverse phase HPLC (C4 column, 0.1% TFA – starting with a gradient of 3 vol.% ACN in water and going to 100 vol.% ACN) leads during the lyophilization of the collected and combined fractions to a partial decomposition. An assumption is that the TFA content is detrimental. The lyophilized material is purified with a second preparative HPLC without TFA addition (C4 column, no TFA - starting with a gradient of 3 vol.% ACN in water and going to 100 vol.% ACN). Lyophilization of the collected and combined fractions gives 2.1 g of compound 504 (1.7 mmol, yield 9%). HPLC method 1 with CAD detection: 99.4 area%, retention time 5.14 min. Gradient program at HPLC method 1 time (min) buffer A buffer B 0 40 60 5 0 100 7 0 100 Example B-13-1: synthesis of compound 117 Compound 117 is obtainable for example from a condensing reaction of compound 116 (CAS- No.20611-21-6) with compound 103 in analogy to molecule II in International Journal Peptide Research (1975) volume 7, p.295-305. Example B-14-1: synthesis of compound 506 Preparation of azidation reagent 23.35 g sodium azide (359 mmol, 10 eq.) are dissolved in 82 mL water and cooled in an ice bath. A solution of 12.1 mL trifluoromethanesulfonic anhydride (72 mmol, 2.0 eq.) in 135 mL cyclohexane is slowly added to the cooled solution over a period of 35 min under maintaining the internal temperature below 5 °C. The reaction mixture is stirred under cooling in the ice-bath for 2 h and then transferred to a separation funnel. The phases are separated. The aqueous phase is extracted with 2 x 120 mL cyclohexane. The combined organic phases are used as azidation reagent in the subsequent azide formation. Azide formation 35.0 g of compound 502 (36 mmol, 1.0 eq.) and 8.99 g potassium hydrogencarbonate (90 mmol, 2.5 eq.) are suspended in 65 mL water and 130 mL MeOH. The mixture is heated to 35 °C until remaining solids are dissolved.90 mg CuSO4· 5 H2O (0.4 mmol, 0.01 eq.) are added at 20 °C and then the solution of the azidation reagent is added over a period of 30 min to the mixture. The resulting emulsion is diluted with 56 mL dioxane and stirred for 20 h.130 mL cyclohexane and 50 mL dioxane are added, the phases are separated in a separation funnel, and the aqueous phase is extracted with 3 x 240 mL IPE and 3 x 250 mL MTBE. To the aqueous phase, 400 mL 5-methyl-tetrahydrofurane and 200 mL 5 % aqueous sodium hydrogencarbonate solution are added. The phases are separated, and the organic phase is extracted repeatedly with 5 % aqueous sodium hydrogencarbonate solution, diluted aqueous hydrochloric acid and water. The organic phase is evaporated to a white oil under reduced pressure, which is dissolved in 250 mL 5-methyl-tetrahydrofurane and again evaporated under reduced pressure. This operation is repeated four times and results in a yellow viscous oil that is dried under vacuum overnight.29.5 g of compound 506 (29.5 mmol, yield 82%) are obtained as a yellow viscous oil. HPLC method 1 with CAD detection: 94.8 area%, retention time 7.40 min. Gradient program at HPLC method 1 time (min) buffer A buffer B 0 70 30 3 28 72 8 0 100 12 0 100 Example B-15-1: synthesis of compound 507 Compound 507 is prepared in analogy to compound 508 at example B-16-1 from 19.5 g of compound 502, 9.6 mL N-methyl-N-trimethylsilylacetamide (60 mmol, 3.0 eq.) and 8.3 g of compound 117 (20 mmol, 1.0 eq.).22.8 g of compound 507 (19.2 mmol, yield 96%) are obtained as a viscous oil. HPLC method 1 with CAD detection: 99.3 area%, retention time 7.11 min. Gradient program at HPLC method 1 time (min) buffer A buffer B 0 80 20 5 0 100 10 0 100 Example B-16-1: synthesis of compound 508 15.4 g of compound 502 (15.8 mmol, 1.0 eq.) is suspended in 47 mL ACN and then 6.3 mL N- methyl-N-trimethylsilylacetamide (39.5 mmol, 2.5 eq.) are added. The mixture is heated to 40 °C for 2 h to form a clear solution and then cooled to RT.107 mL ACN and 2.5 mL pyridine (36.3 mmol, 2.3 eq.) are added to the solution and the mixture is cooled to 0 °C. A solution of 4.71 g 1,1-dioxobenzo[b]thiophene-2-yl-methyloxycarbonyl chloride (CAS-No.135204-19-2, 18.2 mmol, 1.15 eq.) in 178 mL ACN are added over a period of 30 min under maintaining the internal temperature at 0 °C. Afterwards, additional 0.4 mL pyridine (5 mmol, 0.3 eq.) and a solution of 0.6 g 1,1-dioxobenzo[b]thiophene-2-yl-methyloxycarbonyl chloride (CAS-No.135204- 19-2, 2.3 mmol, 0.15 eq., also called Bsmoc-Cl) in 26 mL ACN are added and stirring is continued at 0 °C for 15 h. The reaction mixture is then transferred to a separation funnel, 1400 mL MTBE and 320 mL water are added and acidified with 1 N aqueous hydrochloric acid. The phases are separated, and the organic phase is washed 3 times with 350 mL dilute aqueous hydrochloric acid and with 320 mL water. The organic phase is concentrated under reduced pressure to give the crude product as a viscous oil. The crude product is dissolved in a mixture of 170 mL water, 170 mL ACN and 170 mL IPE at 35 °C and transferred to a separation funnel. 31 mL of 10 % aqueous sodium hydrogencarbonate solution are added and the phases are separated. The aqueous phase is washed with 340 mL of a mixture of IPE ether and ACN, the phases are separated, the aqueous phase is acidified by the addition of 5.5 N aqueous hydrochloric acid and then extracted with 1200 mL MTBE. The phases are separated, and the organic phase is washed with 250 mL dilute aqueous hydrochloric acid and 250 mL water. The organic phase is evaporated under reduced pressure and the resulting oil dried under vacuum to give 10.6 g of compound 508 (8.8 mmol, yield 56%) as a very viscous oil. HPLC method 1 with CAD detection: 97.7 area%, retention time 7.16 min. Gradient program at HPLC method 1 time (min) buffer A buffer B 0 80 20 5 0 100 10 0 100 Example B-16-2: synthesis of compound 508 50 mL 1,4-dioxane and 2.0 mL trimethylsilyl chloride are added to 3.5 g of compound 310 (5.0 mmol) at RT. The mixture is heated under stirring to 40 °C. After 1 h, the reaction mixture is cooled to 20 °C. The reaction mixture contains compound 311 [the structure of compound 311 is depicted as -NH2x HCl, but a structure of compound 311 with -NH-Si(CH3)3 or -NH-Si(CH3)3 x HCl might also be present - this topic is open], which is the silylated amine compound for the following coupling reaction. For the coupling reaction, 2.68 g of compound 203 (4.0 mmol) and 3.5 mL DIPEA (20 mmol) are added to the reaction mixture containing the silylated amine compound. Additional 2.25 mL DIPEA (13 mmol) are added over a period of 4 h. The reaction mixture is stirred overnight at RT. Then, the reaction mixture is diluted with 250 mL MTBE and quenched by the addition of 30 mL 0.5 N aqueous HCl.100 mL ACN are added, and the phases are separated. The organic phase is washed with 3 x 25 mL deionized water and concentrated under vacuum to yield 5.5 g of the crude product as viscous oil. The crude product is purified by column chromatography over 75 g silicagel (eluent EtOAc towards EtOAc / MeOH 4:1 towards EtOAc / MeOH / H2O 5:4:1) to yield 2.66 g (54%) of compound 508 as a white foam. HPLC method 1 mode D: 98.1 area% (220nm) and 92.2 area% (CAD), retention time 7.11 min (220 nm) and 7.19 min (CAD). MS: m / z = 1196.6659 [M+H]+, 2392.3167 [2M+H]+. Example B-17-1: synthesis of compound 118 68.4 g of compound 111 (278 mmol, CAS-No.2418-95-3, also called H-Lys(Boc)-OH) is suspended in 1000 mL water and 29.4 g Na2CO3(278 mmol) and 550 mL acetone is added to the suspension. At room temperature, 89.0 g of compound 119 (264 mmol, CAS-No.197244- are added in portions over a period of 2 h. The solution is stirred overnight, and the resulting suspension is filtered over a G4 suction filter. The clear filtrate is concentrated at a rotary evaporator to remove acetone, 1.7 L MeTHF / 340 mL water / 550 mL aqueous 1N HCl are added, and the phases are separated. The organic phase is washed with 680 mL water / 100 mL aqueous 1N HCl and then with 850 mL water. The resulting organic phase is concentrated under vacuum to a thin oil, 4 x 1 L MeTHF is added and each time concentrated to a thin oil, yielding 161.3 g (124%; crude product containing residual solvent) of compound 118 (CAS-No. 197245-37-7, also called Bsmoc-Lys(Boc)-OH) as a beige foam. The material is used in the subsequent deprotection step as is. HPLC method 1 mode A: 96.9 area%, retention time 3.17 min. MS: m / z = 469.1660 [M+H]+, 954.3512 [2M+NH + 4] . Example B-18-1: synthesis of compound 120 1.6 L 3.4 M HCl solution in EtOAc are added to 159 g of compound 118 (max.278 mmol, also called Bsmoc-Lys(Boc)-OH) from example B-17-1. The resulting suspension is stirred at RT for 2 h, then filtered over a G3 suction filter, and washed with 3 x 250 mL EtOAc. The obtained solid is dried under vacuum overnight to yield 94.3 g (88%) of compound 120 (also called Bsmoc-Lys-OH x HCl), which is a hydrochloric acid salt, as a white powder. HPLC method 1 mode B: 98.6 area%, retention time 2.60 min. MS: m / z = 369.1111 [M+H]+, 737.2152 [2M+H]+. Example B-18-1: synthesis of compound 122 1.0 g of compound 120 (2.0 mmol, also called Bsmoc-Lys-OH x HCl) is subjected to an ion exchange column with strongly basic ion exchange resin (acetate form). Upon elution with 20% aqueous AcOH, a solution containing compound 121 (also called Bsmoc-Lys-OH x AcOH) , which is an acetic acid salt, obtained. The solution is subjected to lyophilization, the lyophilizate is dissolved in 30 mL deionized water and subjected to a second lyophilization to yield 0.82 g of compound 122 (also called Bsmoc-Lys-OH) as a white solid. Chloride test is negative and residual AcOH content is 5.2 wt.%. HPLC method 1 mode B: 93.5 area%, retention time 2.60 min. Example B-19-1: synthesis of compound 123 5.0 g of compound 124 (10.7 mmol, CAS-No.71989-26-9, also called Fmoc-Lys(Boc)-OH) is dissolved in 50 mL 3.4 M HCl solution in EtOAc. After 2 h stirring at RT, the resulting suspension is filtered over a G3 suction filter and washed with 3 x 25 mL EtOAc. The obtained solid is dried under vacuum overnight to yield 4.0 g (92%) of compound 123 (CAS-No.139262- 23-0, also called Fmoc-Lys-OH x HCl), which is a hydrochloric acid salt, as a white powder. HPLC method 1 mode A: 99.6 area%, retention time 2.57 min. Example B-20-1: synthesis of compound 125 1.0 g of compound 123 (2.0 mmol, CAS-No.139262-23-0, also called Fmoc-Lys-OH x HCl) is subjected to an ion exchange column with strongly basic ion exchange resin (acetate form). Upon elution with 20% aqueous AcOH, a solution containing compound 126 (also called Fmoc- Lys-OH x AcOH) , which is an acetic acid salt, is obtained. The solution is subjected to lyophilization, the lyophilizate is suspended in 30 mL deionized water and subjected to a second lyophilization to yield 0.92 g of compound 125 (CAS-No.105047-45-8, also called Fmoc-Lys-OH) as a white solid. Chloride test is negative and residual AcOH content is 2.2 wt.%. HPLC method 1 mode B: 99.3 area%, retention time 3.34 min. Example B-21-1: synthesis of compound 127 10.0 g of compound 120 (22 mmol, also called Bsmoc-Lys-OH x HCl) are dissolved in 40 mL deionized water and subjected to an ion exchange column with strongly basic ion exchange resin Amberlite IRN 78 (acetate form). Upon elution with deionized water, 172 g of an aqueous solution containing compound 122 (also called Bsmoc-Lys-OH) is obtained. The aqueous solution is split in four equal portions. 0.54 mL of TFA (7.0 mmol) are added to one portion (43 g) of the aqueous solution containing compound 122 (also called Bsmoc-Lys-OH). The resulting solution is subjected to lyophilization to yield 2.73 g (100%) of compound 127 (also called Bsmoc-Lys-OH x TFA) as a white powder. HPLC method 1 mode B: 98.9 area%, retention time 2.61 min. Example B-22-1: synthesis of compound 128 1.35 g of TsOH (7.0 mmol, CAS-No.104-15-4) are added to one portion (43 g) of the aqueous solution containing compound 122 (also called Bsmoc-Lys-OH) from example B-21-1. The resulting solution is subjected to lyophilization to yield 3.20 g (100%) of compound 128 (also called Bsmoc-Lys-OH x TsOH), which is a para-toluenesulfonic acid salt or a 4-toluenesulfonic acid salt, as a white powder. HPLC method 1 mode B: 98.8 area%, retention time 2.61 min. For stability tests at F), this quality of compound 128 is employed. For a crystallization, 1.0 g of compound 128 (from the previous preparation, also Bsmoc-Lys-OH x TsOH) is suspended in 20 mL deionized water and heated to 45 °C, which results in a clear solution. The water is evaporated under reduced pressure to a final weight of 3 g. To the resulting white suspension, 20 mL IPA are added, and the solvent is partially evaporated. The addition / evaporation cycle is repeated twice. The resulting suspension is diluted with 10 mL IPA, cooled to 4°C and then filtered. The filter cake is washed with 10 mL IPA and 2 x 10 mL IPE and dried under vacuum to yield 0.73 g (73%) of crystallized compound 128 (also called Bsmoc-Lys-OH x TsOH), as white crystals. Crystals are visibly confirmed under a microscope. HPLC method 1 mode B: 99.6 area%, retention time 2.60 min. Example B-23-1: synthesis of compound 129 1.35 g of methanesulfonic acid (7.0 mmol, CAS-No.75-75-2) are added to one portion (43 g) of the aqueous solution containing compound 122 (also called Bsmoc-Lys-OH) from example B- 21-1. The resulting solution is subjected to lyophilization to yield 2.60 g (100%) of compound 129 (also called Bsmoc-Lys-OH x MeSO3H), which is a methanesulfonic acid salt, as a translucent solid resin. HPLC method 1 mode B: 98.9 area%, retention time 2.61 min. Example B-24-1: synthesis of compound 130 0.39 mL of sulfuric acid (7.0 mmol, CAS-No.7664-93-9) are added to one portion (43 g) of the aqueous solution containing compound 122 (also called Bsmoc-Lys-OH) from example B-21-1. The resulting solution is subjected to lyophilization to yield 2.61 g (100%) of compound 130 (also called Bsmoc-Lys-OH x 0.5 H2SO4), which is a hemi sulfuric acid salt, as a translucent solid resin. HPLC method 1 mode B: 98.9 area%, retention time 2.61 min. Example B-25-1: synthesis of compound 203 20.0 g of 17-(t-butoxycarbonyl)-heptadecanoyl-Glu-OtBu (36.0 mmol, CAS-No.1188328-39-3) and 4.97 g N-hydroxy-succinimide (43.2 mmol) are dissolved in a mixture of 120 mL THF and 60 mL toluene. To the resulting clear solution, a solution of 5.85 mL DIC (37.8 mmol) in 20 mL THF is added over a period of 1.5 h under maintaining the internal temperature at 25 °C. Then, the temperature is raised to 35 °C and the reaction mixture is stirred at this temperature overnight. Then, a solution of 0.72 mL DIC (4.6 mmol) in 2 mL THF is added and stirring at 35 °C is continued for 5.5 h. The resulting suspension is filtered over a G4 glass suction filter, and the filtrate is concentrated under reduced pressure. To the resulting oil, 3 x 100 mL toluene are added and each time evaporated under reduced pressure. Then, 100 mL IPE are added and the resulting white suspension is filtered over a G3 glass suction filter. The filter cake is washed with toluene and IPE, then dried under vacuum at 35 °C to yield 19.6 g (83%) of compound 203 (CAS-No.1188328-22-4, also called 17-(t-Butoxycarbonyl)-heptadecanoyl-Glu(OSu)-OtBu) as a white solid. HPLC method 1 mode C: 97.9 area%, retention time 3.66 min. Example B-26-1: of 309 5 mL THF and 2 mL trimethylsilyl chloride (18 mmol) are added to 2.31 g of compound 120 (5.0 mmol, also called Bsmoc-Lys-OH x HCl) at RT. The mixture is heated under stirring to 40 °C.15 mL ACN are added. After 1 h, the resulting heterogenous mixture is cooled to 20 °C. The heterogenous mixture contains compound 131 [the structure of compound 131 is depicted as -NH2 x HCl, but a structure of compound 131 with -NH-Si(CH3)3or -NH-Si(CH3)3x HCl might also be present - this topic is open], which is the silylated amine compound for the following coupling reaction. 2.1 g of compound 202 (5.0 mmol, CAS-No.1069067-08-8) are dissolved in 15 mL ACN at RT. 1.6 g of TBTU (5.0 mmol) and 0.65 mL DIPEA are added and then stirred for 10 min for pre- activation of the carboxy compound for the following coupling reaction. For the coupling reaction, the solution of the pre-activated carboxy compound is added to the mixture containing the silylated amine compound.2.8 mL DIPEA are added to the obtained mixture. After 1.5 h, 100 mL EtOAc are added to the reaction mixture, the reaction mixture is transferred to a separation funnel, and the solution is washed with 20 mL 1N aqueous HCl and 3 x 20 mL semi saturated aqueous NaCl solution. The organic phase is separated and concentrated under vacuum to yield 4.4 g (116%; crude product containing residual solvent) of compound 309 as a beige foam. Compound 309 is used the subsequent deprotection step as is. HPLC method 1 mode B: 94.5 area%, retention time 3.47 min. MS: m / z = 759.3137 [M+H]+. Example B-27-1: synthesis of compound 310 3.6 g of compound 309 (4.7 mmol) are dissolved in 16 mL EtOAc. To the resulting solution, 50 mL of 3.4 N HCl solution in EtOAc is added. A sticky residue forms immediately and after 30 min, the supernatant is discarded. The sticky residue is triturated with 3 x 50 mL MTBE. It is then dried at 30 °C under vacuum to yield 3.70 g (112%; crude product containing residual solvent) of compound 310, which is a hydrochloric acid salt, as a beige resin. Compound 310 is used in the subsequent deprotection step as is. HPLC method 1 mode B: 95.6 area%, retention time 2.75 min. MS: m / z = 659.2590 [M+H]+, 1317.5111 [2M+H]+. Example B-28-1: of 304 3.2 mL THF and 3.2 mL N-methyl-N-trimethylsilyl acetamide (20 mmol) are added to 3.24 g of compound 123 (8.0 mmol, also called Fmoc-Lys-OH x HCl) at RT. The mixture is heated under stirring to 40 °C. After 2 h, the resulting solution is cooled to 20 °C. The solution contains compound 132 [the structure of compound 132 is depicted as -NH2 x HCl, but a structure of compound 132 with -NH-Si(CH3)3 or -NH-Si(CH3)3 x HCl might also be present - this topic is open], which is the silylated amine compound for the following coupling reaction. For the coupling reaction, the solution of the pre-activated carboxy compound from example B- 06-2 is added to the solution containing the silylated amine compound.1.39 mL DIPEA (8.0 mmol) are added to the obtained mixture. After 3 h stirring at RT, 8 mL deionized water are added, and the mixture is acidified to pH 1 by addition of 5.5 N aqueous HCl. The phases are separated, the organic phase is washed with 3 x 10 mL water and then evaporated under reduced pressure. The resulting yellow oil is dissolved in 60 mL MeTHF.12 mL THF and 12 mL water are added. The phases are separated, and the organic phase is washed with 3 x 12 mL water. The washed organic phase is subsequently diluted with 30 mL hexane and extracted with 20 mL 10% aqueous sodium hydrogencarbonate solution. The aqueous phase is washed with 2 x 20 mL IPE. Then, 50 mL MeTHF are added, and the mixture is acidified to pH 1 with 5.5 N aqueous HCl. The phases are separated. The organic phase is washed with 3 x 10 mL water, then evaporated under reduced pressure to yield 2.8 g (46%) of compound 304 as a sticky foam. HPLC method 1 mode E: 83.3 area%, retention time 5.58 min. MS: m / z = 759.380 [M+H]+. Example B-29-1: synthesis of 509 In a temperature-controlled 500 mL double-jacketed reactor with a mechanical stirrer, 10 g of compound 510 (CAS-No.1491158-62-3)

[0004] are dissolved in 100 mL THF, resulting in a clear solution after stirring at 25 °C for 2 min.15.4 mL dodecanethiol and 1.88 mL DBU are added and the solution is stirred at 25 °C for 1 h, resulting in a clear, gel-like solution. IPC by TLC and HPLC shows full conversion of the starting material. Then, 50 mL H2O and 50 mL n-heptane are added to the reaction mixture, the obtained mixture is stirred, the phases are separated, and the organic layer is discarded. To the separated aqueous layer, 50 mL n-heptane, 50 mL THF and 10 mL H2O are added. The obtained mixture is stirred, the phases are separated, and the organic layer is discarded. To the separated aqueous layer, 100 mL MeTHF and 2.4 mL 5.5 N aqueous HCl are added to reach pH 5.1, the mixture is stirred, the phases are separated, and the aqueous layer is discarded. The separated organic layer is concentrated to a volume of 50 mL using a rotary evaporator at 40 °C bath temperature. Water is removed twice by azeotropic distillation with 100 mL MeTHF, then the solution is concentrated to dryness.150 mL IPE are added to the obtained residue and the resulting suspension is stirred at 40 °C for 30 min. The suspension is cooled to RT and filtered. The obtained solid is re-suspended and is washed with 20 mL IPE twice. Drying the washed solid at a reduced pressure at 40 °C for 16 h furnishes 6.37 g (88.5%) of compound 509 (CAS-No.1962161-20-1) as a white solid. HPLC method 3: 72.4 area%. Fig.35 depicts a complete HPLC-UV chromatogram. Example B-30-1: synthesis of compound 511 In a 25 ml round-bottom flask with a magnetic stirrer, 500 mg of compound 510 (CAS-No. 1491158-62-3) are suspended in 5 mL THF.352 µL N-methyl-N-trimethylsilyl acetamide are added. The reaction mixture is stirred at 40 °C for 1 h and results in a clear solution. The solution is cooled to RT and 162.4 µL pyridine, which are dissolved in 3.5 mL THF, are added. The clear solution is cooled to 5 °C.261.3 mg 1,1-dioxobenzo[b]thiophene-2-yl-methyloxy- carbonyl chloride (CAS-No.135204-19-2, also called Bsmoc-Cl), which are dissolved in 6 mL THF, are added dropwise over 5 min. The reaction mixture is stirred at 0 °C for 1 h. IPC by TLC and HPLC shows full conversion of the starting material. The reaction mixture is concentrated to a volume of 50 mL using a rotary evaporator at 25 °C bath temperature. The residue is dissolved in 5 mL Et2O, then 1 mL H2O are added, and the pH is set to 7 with 4.8 mL 2.5 % aqueous NaHCO3. Then, the phases are separated, and the organic layer is discarded. To the separated aqueous layer, 5 mL Et2O are added. The obtained mixture is stirred, the phases are separated, and the organic layer is discarded. To the separated aqueous layer, 5 mL MTBE and 0.4 mL 5.5 N aqueous HCl are added to reach pH 2.0. The obtained mixture is stirred, the phases are separated, and the aqueous layer is discarded. The separated organic layer is concentrated to dryness using a rotary evaporator at 40 °C bath temperature.3 mL Et2O and 8 mL n-hexane are added to the obtained residue and the resulting suspension is again concentrated to dryness.8 mL n-hexane are added to the obtained residue and the resulting suspension is again concentrated to dryness. The previous addition of solely n-hexane is repeated including a concentration to dryness. The obtained residue is dried at a reduced pressure and 30 °C for 16 h to furnish 432 mg (62.2%) of compound 511 as a white solid. HPLC method 3: 90.7 area%. Fig.36 depicts a complete HPLC-UV chromatogram. HR-MS: calc.791.4391 m / z, found 792.4413 m / z [M+H]+. Example B-31-1: synthesis of compound 512 In a 50 mL round-bottom flask with a magnetic stirrer, 2.0 g of compound 513 (CAS-No. 201004-46-8) are dissolved in 20 mL THF, resulting in a clear solution after stirring at 25 °C for 7 min.4.0 mL dodecanethiol and 492 µL DBU are added. Immediately after the addition of DBU, a solid is formed. The white suspension is stirred at 25 °C for 1 h. IPC by TLC and HPLC show full conversion of the starting material. The suspension is filtered, and the solid is washed with 10 mL THF. Drying of the washed solid at a reduced pressure at 40 °C for 64 h furnished 1.50 g (formally 100% yield, i.e., calculated 118% yield) of compound 512 (CAS-No.59012-43-0) as a light pink solid. The solid seems to be insoluble respectively is hardly soluble in common organic solvents. HPLC or TLC analysis seems not to be easily feasible. Example B-32-1: synthesis of 514 In a 10 mL round-bottom flask with a magnetic stirrer, 100 mg of compound 512 (as obtained in Example B-31-1, CAS-No.59012-43-0) are suspended in 2 mL THF.104.4 µL N-methyl-N- trimethylsilyl acetamide are added, and the reaction mixture is stirred at 40 °C for 1 h. The slightly turbid solution is cooled to 25 °C, and 48.2 µL pyridine, which are dissolved in 0.6 mL THF, are added. After cooling to 5 °C, 77.2 mg 1,1-dioxobenzo[b]thiophene-2-yl-methyloxy- carbonyl chloride (CAS-No.135204-19-2, also called Bsmoc-Cl), which are dissolved in 1.2 mL THF, are added dropwise within 5 min. The reaction mixture is stirred at 0 °C for 2 h and concentrated to dryness using a rotary evaporator at 25 °C bath temperature.8 mL Et2O and 3 mL H2O are added to the residue, the pH is adjusted to pH 7 with 1 mL 2.5 % aqueous NaHCO3. A biphasic mixture is formed. The phases are separated, the organic layer is discarded, and the extraction is repeated with 2 x 5 mL Et2O. The aqueous layer is diluted with 15 mL MTBE and the pH is adjusted to pH 2.5 with 30 µL 5.5 N aqueous HCl. The phases are separated, the aqueous layer is discarded, and the organic layer is concentrated to dryness using a rotary evaporator at 40 °C bath temperature. The residue is co-evaporated with 2 x 10 mL MeTHF, 1 x 10 mL IPE and 1 x 5 mL IPE. The obtained residue is dried at a reduced pressure at 30 °C for 16 h to furnish 68 mg (43.1%) of compound 514 as a white solid. HPLC method 3: 68.9 area%. Fig.37 depicts a complete HPLC-UV chromatogram. HR-MS: calc.606.3339 m / z, found 607.3417 m / z [M+H]+. Example B-33-1: synthesis of compound 515 In a 100 mL round-bottom flask with a magnetic stirrer, 5.0 g of compound 516 (CAS-No. 2460751-66-8) are dissolved in 50 mL THF. A clear solution results after stirring at 25 °C for 1 min.5.0 mL dodecanethiol and 609 µL DBU are added, and the colorless clear solution is stirred at 25 °C for 1 h. IPC by TLC and HPLC show full conversion of the starting material. After dilution with 20 mL IPE, 20 mL H2O and 20 mL THF, the phases are separated, and the organic layer is discarded. The aqueous layer is extracted twice with 20 mL IPE and 50 mL THF.100 mL MeTHF and 30 mL H2O are added to the aqueous layer, the pH is adjusted to pH 5 with 720 µL 5.5 N aqueous HCl, the phases are separated, and the aqueous layer is discarded. The organic layer is concentrated to dryness using a rotary evaporator at 40 °C bath temperature. After co- evaporation with 3 x 50 mL MeTHF and 1 x 50 mL ACN, ACN (50 mL) is added. The resulting suspension is stirred at 25 °C for 15 min and is filtered. The obtained solid is washed with 2 x 5 mL ACN. Drying the washed solid at a reduced pressure at 40 °C for 64 h furnishes 2.15 g (52.5%) of compound 515 (CAS-No.2931515-16-9) as a white solid. HPLC method 3: 97.9 area%. Fig.38 depicts a complete HPLC-UV chromatogram. Example B-34-1: synthesis of compound 517 In a 100 mL 3-neck round-bottom flask with a magnetic stirrer, 1.0 g of compound 515 (CAS-No. 2931515-16-9) are suspended in 25 mL THF.401 µL N-methyl-N-trimethylsilyl acetamide are added, and the reaction mixture is stirred at 40 °C for 1 h. The clear solution is cooled to 25 °C and 185 µL pyridine, which are dissolved in 5 mL THF, are added. After cooling to 5 °C, 297 mg 1,1-dioxobenzo[b]thiophene-2-yl-methyloxycarbonyl chloride (CAS-No.135204-19-2, also called Bsmoc-Cl), which are dissolved in 20 mL THF, are added dropwise within 30 min. The reaction mixture is stirred at 0 °C for 1.5 h. IPC by TLC shows full conversion of the starting material. After concentration to dryness using a rotary evaporator at 25 °C bath temperature, 60 mL Et2O and 10 mL H2O are added to the residue and the pH is adjusted to pH 7 with 8 mL 2.5 % aqueous NaHCO3. A biphasic solution is formed. The phases are separated, and the organic layer is discarded. The aqueous layer is extracted with 2 x 25 mL Et2O.150 mL MTBE are added to the aqueous layer, the pH is adjusted to pH 2.0 with 600 µL 5.5 N aqueous HCl, the phases are separated, and the aqueous layer is discarded. Then, the organic layer is extracted with 50 mL H2O. The organic layer is concentrated to dryness using a rotary evaporator at 40 °C bath temperature. The residue is dissolved in 50 mL ACN and co-evaporated with 3 x 50 mL ACN and 30 mL IPE. After evaporation of solvents, the residue is re-dissolved in 20 mL ACN. The thin suspension is filtered and the product containing filtrate is concentrated to dryness. The obtained residue is dried at a reduced pressure and 30 °C for 16 h to furnish 1.05 g (85.8%) of compound 517 as a colorless sticky solid. HPLC method 3: 86.2 area%. Fig.39 depicts a complete HPLC-UV chromatogram. HR-MS: calc.1223.6862 m / z, found 1224.6961 m / z [M+H]+. Example B-35-1: synthesis of compound 518 In a 50 mL round-bottom flask with a magnetic stirrer, 2.0 g of compound 519 (CAS-No. 1931109-48-6) are dissolved in 20 mL THF. A clear solution results after stirring at 25 °C for 10 min.2.7 mL dodecanethiol and 329.4 µL DBU are added, and the yellow solution is stirred at 25 °C for 1 h. IPC by TLC and HPLC show full conversion of the starting material.20 mL n-heptane, 20 mL H2O and 20 mL THF are added to the reaction mixture, the phases are separated, and the organic layer is discarded. The extraction of the aqueous layer is repeated twice using 10 mL n- heptane, 20 mL H2O, 20 mL THF for the second extraction and 10 mL n-heptane (10 mL), 10 mL THF for the third extraction.50 mL MeTHF are added to the aqueous layer, the pH is adjusted to pH 5 with 250 µL 5.5 N aqueous HCl, the phases are separated, and the aqueous layer is discarded. The organic layer is concentrated to a volume of 10 mL using a rotary evaporator at 40 °C bath temperature. The mixture is co-evaporated with 3 x 50 mL MeTHF, then the solution is concentrated to dryness.10 mL ACN are added to the residue and the resulting suspension is concentrated to dryness. After dilution with 10 mL ACN and stirring at 25 °C for 15 min, the suspension is filtered. The obtained solid is washed with 2 mL ACN. The washed solid is dried at a reduced pressure at 40 °C for 64 h. This furnishes 720 mg (47.7%) of compound 518 as a white solid. HPLC method 3: 72.2 area%. Fig.40 depicts a complete HPLC-UV chromatogram. Example B-36-1: synthesis of 520 In a 50 mL round-bottom flask with a magnetic stirrer, 500 mg of compound 518 are suspended in 5 mL ACN.293.7 µL N-methyl-N-trimethylsilyl acetamide are added to the suspension. The reaction mixture is stirred at 40 °C for 1 h. The clear solution is cooled to 25 °C.135.3 µL pyridine, which are dissolved in 2.5 mL ACN, are added. After cooling to 5 °C, 217.5 mg 1,1- dioxobenzo[b]thiophene-2-yl-methyloxycarbonyl chloride (CAS-No.135204-19-2, also called Bsmoc-Cl), which are dissolved in 5 mL ACN, are added dropwise within 6 min to the mixture. The reaction is stirred at 0 °C for 1 h. IPC by TLC and HPLC show full conversion of the starting material. The reaction mixture is concentrated to dryness using a rotary evaporator at 25 °C bath temperature.60 mL Et2O and 25 mL H2O are added to the residue, and the pH is adjusted to pH 7 with 5 mL 2.5 % aqueous NaHCO3. A biphasic solution is formed, the phases are separated, and the organic layer is discarded. The extraction is repeated with 2 x 50 mL Et2O. After dilution with 50 mL MTBE, the pH is adjusted to pH 2.0 with 200 µL 5.5 N aqueous HCl. Then, the phases are separated, the aqueous layer is discarded, and the organic layer is concentrated to dryness using a rotary evaporator at 40 °C bath temperature. The residue is dissolved in 10 mL MeTHF (10 mL), co-evaporated with 3 x 20 mL MeTHF and IPE / MeTHF / n-heptane (45 mL, 2:1:6 v / v / v). After concentration to dryness, the residue is stirred for 30 minutes at 25 °C in 20 mL n-heptane and filtered. Drying the washed solid at a reduced pressure at 30 °C for 16 h furnishes 451 mg (68.1%) of compound 520 as a white solid. HPLC method 3: 75.3 area%. Fig.41 depicts a complete HPLC-UV chromatogram. HR-MS: calc.905.5071 m / z, found 906.5197 m / z [M+H]+. C) synthesis of solid-phase conjugated compounds Example C-01-1: synthesis of solid-phase conjugated compound 601-SP Fmoc-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2- chlorotritylamidomethyl resin] (601-SP) (SEQ ID NO:13) Compound 601-SP is obtainable for example by a solid phase synthesis starting with compound 602-SP H-Gly-[2-chlorotritylamidomethyl resin] (602-SP) A coupling cycle of compound 602-SP with Fmoc-Arg(Pbf)-OH is followed by coupling cycles of Fmoc-Gly-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Val-OH, Fmoc-Leu-OH, Fmoc-Trp(Boc)-OH, Fmoc- Ala-OH, Fmoc-Ile-OH, Fmoc-Phe-OH and Fmoc-Glu(OtBu)-OH. A coupling cycle comprises a deprotecting reaction of the N-terminal alpha amino group of the solid-phase conjugated intermediate unless the N-terminal alpha amino group is already unprotected. The deprotecting reaction for Fmoc is conducted with 20 vol.% piperidine in DMF or when desired with 20 vol.% piperidine in NMP in a typical time range of 0.5 to 4.0 hours. The coupling cycle comprises also a coupling reaction of the solid-phase conjugated intermediate with its unprotected N-terminal alpha amino group, i.e. an acylation of the unprotected N- terminal alpha amino group by an activated alpha carboxylic acid group of respective amino acid derivative, which is activated by either DIC / OxymaPure, TBTU / DIPEA or DEPBT / DIPEA. A typical time range of the acylating reaction is 1.5 to 24 hours. The coupling cycle comprises also one or more washings of the solid phase after the acylating reaction. DMF or IPA is used as a solvent for the one or more washings. The coupling cycle comprises also optionally an acetylating reaction with acetic anhydride after the acylating reaction. The coupling cycle comprises also optionally one or more washings after the acetylating reaction with acetic anhydride. DMF or IPA is used as a solvent for the optional one or more washings after the acetylating reaction with acetic anhydride. Example C-02-1: synthesis of solid-phase conjugated compound 603-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (603-SP) (SEQ ID NO:26) Compound 603-SP (= Nsc-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl])-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val- Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin]) (SEQ ID NO:26) is obtainable for example by a coupling cycle with compound 504 applied to compound 601-SP, i.e. a deprotecting reaction of compound 601-SP with 20 vol.% piperidine in DMF to obtain compound 604-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (604-SP) (SEQ ID NO:14), which is afterwards reacted with compound 504 and DIC / OxymaPure. As used herein, the residue tBu-O-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl may also be designated as O-tert-butyl-17- carboxy-heptadecacarbonyl-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2- aminoethoxy)ethoxy]acetyl. As used herein, the residue HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl- 2-[2-(2-aminoethoxy)ethoxy]acetyl may also be designated as 17-carboxy-heptadecacarbonyl- gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl. Example C-03-1: synthesis of solid-phase conjugated compound 605-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (605-SP) (SEQ ID NO:15) Compound 605-SP (= Fmoc-Ala-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2- aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)- Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin]) (SEQ ID NO:15) is obtainable for example by a coupling cycle with Fmoc-Ala-OH applied to compound 603-SP, i.e. a deprotecting reaction of compound 603-SP with 20 vol.% piperidine in DMF to obtain compound 606-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (606-SP) (SEQ ID NO:28), which is afterwards reacted with Fmoc-Ala-OH and DIC / OxymaPure. Example C-04-1: synthesis of solid-phase conjugated compound 607-SP Boc-His(Trt)-Aib-Glu(OtBu)-Gly-Thr(tBu)-Phe-Thr(Psi(Me,Me)pro)-Ser(tBu)-Asp(OMpe)-Val- Ser(tBu)-Ser(tBu)-Tyr(tBu)-Leu-Glu(OtBu)-Gly-Gln(Trt)-Ala-Ala-Lys(tBuO-CO-(CH2)16-CO- gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)- Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (607-SP) (SEQ ID NO:16) Compound 607-SP (= a protected and solid-phase conjugated derivative of Semaglutide (CAS- No.910463-68-2)) is obtainable for example by several coupling cycles starting at a coupling cycle with Fmoc-Ala-OH applied to compound 605-SP, i.e. a deprotecting reaction of compound 605-SP with 20 vol.% piperidine in DMF to obtain compound 608-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotritylamidomethyl resin] (608-SP) (SEQ ID NO:29), which is afterwards reacted with Fmoc-Ala-OH and DIC / OxymaPure. Coupling cycles with and in the sequence of Fmoc-Gln(Trt)-OH, Fmoc-Gly-OH, Fmoc- Glu(OtBu)-OH, Fmoc-Leu-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Val-OH, Fmoc-Asp(OMpe)-OH, Fmoc-Ser(tBu)-OH, Fmoc-Phe-Thr(Psi(Me,Me))pro)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Gly-OH, Fmoc-Glu(OtBu)-OH and Boc-His(1-Trt)-Aib-OH are following. The coupling cycles are conducted as described in example C-01-1. Example C-05-1: synthesis of solid-phase conjugated compound 611-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (611-SP) (SEQ ID NO:17) Compound 611-SP (= H-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-2-chlorotrityl resin) (SEQ ID NO:17) is synthesized at a 30 mmol scale using an automated synthesizer (Sonata, Gyros Protein Technologies). Compound 610-SP (= H-Gly-2-chlorotrityl resin, 66.7 g, 0.45 mmol / g resin, 30 mmol), i.e. as depicted by H-Gly-[2-chlorotrityl resin] (610-SP), is pre-swelled in two cycles each with 30 min in DMF (10 mL / g resin). The first Fmoc-protected amino acid, i.e. Fmoc-Arg(Pbf)-OH), is pre-activated for 3 min with TBTU / DIPEA (1.8 eq. / 3.0 eq.), added to the resin and the reaction mixture is stirred for 2 h at RT. The following Fmoc- protected amino acid derivatives (2.0 eq.) are pre-activated for 15 min using DIC / OxymaPure (2.6 eq. / 3.1 eq., Fmoc-Arg(Pbf)-OH is pre-activated for 5 min) and added to the resin. After 20 min reaction time, additional DIC (1.3 eq.) is added to the reaction mixture (total reaction volume is 670 mL) and the reaction of the coupling step is continued. The total reaction time of the couplings steps are 1.5 h for Fmoc-Gly-OH, Fmoc-Val-OH, Fmoc-Leu-OH, Fmoc-Trp(Boc)-OH, Fmoc-Ala-OH, 2 h for Fmoc-Arg(Pbf)-OH and 5 h for Fmoc-Ile-OH and Fmoc-Phe-OH. At the end of each coupling step, the resin is drained and an acetylation reaction using a solution 0.05 M acetic acid anhydride / 17 mM 2,4,6-collidine / 1.6 mM OxymaPure (670 mL) in DMF is conducted. This acetylation serves to acetylate remaining unreacted amino-groups and avoids their reaction in a following coupling step (so-called capping). Afterwards, the resin is then filtered and washed with DMF and Fmoc deprotection is carried out using twice or three times 670 mL of a solution of 20 vol.% piperidine in DMF (5 min duration for a first treatment and 10 min duration for a second treatment prior to Fmoc-Trp(Boc)-OH and Fmoc-Ala-OH coupling; 5 min duration for a first treatment, 10 min duration for a second treatment and 15 min duration for a third treatment prior to Fmoc-Gly-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Val-OH, Fmoc-Leu-OH, Fmoc-Ile-OH and Fmoc-Phe-OH). After the Fmoc deprotection, the resin is washed with 670 mL DMF, 670 mL IPA and two times 670 mL DMF. After coupling of Fmoc-Phe-OH, acetylation and Fmoc deprotection, the resin material is washed three times alternatingly with 670 mL DMF, 670 mL IPA and three times with 670 mL IPA. The washed resin material is dried under vacuum at RT for three days to yield 132 g of dried compound 611-SP. For analytical purposes, a small-scale test cleavage from compound 611-SP is conducted. This is described at example D-06-1. Example C-06-1: synthesis of solid-phase conjugated compound 612-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (612-SP) (SEQ ID NO:21) 10.00 g of compound 611-SP (2.2 mmol, 0.22 mmol / g) are pre-swelled two times in 100 mL DMF (10 mL / g resin) each for 15 min at RT.1.95 g Fmoc-Glu(OtBu)-OH (4.40 mmol, 2.0 eq.) and 0.969 g OxymaPure (6.82 mmol, 3.1 eq.) are dissolved in 100 mL DMF (10 mL / g resin). To this solution, 886 µL DIC(5.72 mmol, 2.6 eq.) are added, the solution is stirred for 15 min at RT and the solution is then added to the pre-swelled compound 611-SP. After 20 min of reaction time at RT, an additional portion of 443 µL DIC (2.86 mmol, 1.3 eq.) are added to the reaction mixture and stirred for 1.5 h at RT. After removing the liquid parts from the reaction mixture by drainage, an additional coupling step with the Fmoc-Glu(OtBu)-OH is performed (so- called recoupling). Therefore, 1.95 g Fmoc-Glu(OtBu)-OH (4.40 mmol, 2.0 eq.) and 0.969 g OxymaPure (6.82 mmol, 3.1 eq.) are dissolved in 100 mL DMF (10 mL DMF / g resin). To this solution, 886 µL DIC (5.72 mmol, 2.6 eq.) are added, and the solution is stirred for 15 min at RT and is afterwards added afterwards to the reaction mixture. After 20 min of reaction time at RT, an additional portion of 443 µL DIC (2.86 mmol, 1.3 eq.) are added to the reaction mixture and stirred for 16 h at RT. The liquid parts are removed, the remaining resin material is washed with 20 mL DMF and is then treated for Fmoc-deprotection with 20 vol.% piperidine in DMF (10 mL / g resin) three times with a duration of 5 min for a first treatment, of 10 min for a second treatment and of 60 min for a third treatment. After this Fmoc-deprotection step, the resin material is washed three times with alternatingly 670 mL DMF and 670 mL IPA, then finally with three times 100 mL IPA and then two times 670 mL DMF. The washed resin material is dried under vacuum at RT for three days to yield 11.0 g of compound 612-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-07-1. Example C-07-1: synthesis of solid-phase conjugated compound 613-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (613-SP) (SEQ ID NO:18) 2.00 g of compound 611-SP (0.88 mmol, 0.44 mmol / g) is pre-swelled two times in 20 mL DMF (10 mL / g resin) each for 15 min at RT.0.781 g Fmoc-Glu(OtBu)-OH (1.76 mmol, 2.0 eq.) and 0.388 g OxymaPure (2.728 mmol, 3.1 eq.) are dissolved in 20 mL DMF (10 mL / g resin). To this solution, 354 µL DIC (2.288 mmol, 2.6 eq.) are added, and the solution is stirred for 15 min at RT and added afterwards to the solution is then added to the pre-swelled compound 611-SP. After 20 min of reaction time at RT, an additional portion of 177 µL DIC (1.144 mmol, 1.3 eq.) are added to the reaction mixture and stirred for 5 h at RT. After removing the liquid parts from the reaction mixture by drainage, an additional coupling step with the Fmoc-Glu(OtBu)-OH is performed (so-called recoupling). Therefore, 0.781 g Fmoc-Glu(OtBu)-OH (1.76 mmol, 2.0 eq.) and 0.388 g OxymaPure (2.728 mmol, 3.1 eq.) are dissolved in 20 mL DMF (10 mL / g resin). To this solution, 354 µL DIC (2.288 mmol, 2.6 eq.) are added, the solution is stirred for 15 min at RT and added afterwards to the reaction mixture. After 20 min of reaction time at RT, 177 µL DIC (1.144 mmol, 1.3 eq.) are added to the reaction mixture and stirred for 15 h at RT. The liquid parts are removed, the resin material is washed with 20 mL DMF and is treated with 20 vol.% piperidine in DMF (10 mL / g resin) in three times with a duration of 5 min for a first treatment, of 10 min for a second treatment and of 60 min for a third treatment. Afterwards, 1.76 g of compound 506 (1.760 mmol, 2.0 eq.) and 0.388 g OxymaPure (2.728 mmol, 3.1 eq.) are dissolved in 20 mL DMF (10 mL / g resin). To this solution, 354 µL DIC (2.288 mmol, 2.6 eq.) are added and the solution is stirred for 15 min at RT and added afterwards to the reaction mixture. After 20 min of reaction time at RT, an additional portion of 177 µL DIC (177 µL, 1.144 mmol, 1.3 eq.) are added to the reaction mixture and stirred for 22 h at RT. The liquid parts are removed, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). The washed resin material is dried 24 h in high vacuum at RT to yield 2.22 g of the compound 613-SP (= N3-Lys(tBuO-CO-(CH2)16-CO- gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)- Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin]) (SEQ ID NO:18). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-08-1. Example C-08-1: synthesis of solid-phase conjugated compound 614-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (614-SP) (SEQ ID NO:19) 100 mg of compound 613-SP (0.21 mmol / g, 0.022 mmol) is pre-swelled two times in DMF (10 mL / g resin) each for 15 min at RT.31.5 mg tris(2-carboxyethyl)phosphine (= TCEP, 0.11 mmol, 5.0 eq.) are dissolved in 250 µL of a 10 vol.% aqueous DMF solution (2.5 mL / g resin), 18.8 µL DIPEA (0.11 mmol, 5.0 eq.) are added and the solution was added to the pre-swelled compound 613-SP. The reaction mixture is then stirred for 3 h at RT and additional 16 h at 50 °C. The liquid parts are removed, the resin material is washed three times with 10 vol.% aqueous DMF, three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). A part of the resin material is further processed at example C-09-1. without drying. A part of the resin material is dried 24 h in high vacuum at RT to yield compound 614-SP (= H-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2- [2-(2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly- Arg(Pbf)-Gly-[2-chlorotrityl resin]) (SEQ ID NO:19). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-02-2. Example C-08-2: synthesis of solid-phase conjugated compound 614-SP 100 mg of compound 617-SP (0.022 mmol, 0.21 mmol / g resin) is pre-swelled two times in DMF (10 mL / g resin) each for 10 min RT. The pre-swelled compound 617-SP is treated with 20 vol.% piperidine in DMF solution (10 mL / g resin) in twice with a duration of 20 min for a first treatment and a duration of 60 min for a second treatment. Afterwards, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). The washed resin-material is dried 24 h in high vacuum at RT to obtain compound 614-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-02-3. Example C-08-3: synthesis of solid-phase conjugated compound 614-SP 200 mg of compound 618-SP (0.21 mmol / g resin, 0.042 mmol) is pre-swelled two times in DMF (10 mL / g resin) each for 10 min at RT. The pre-swelled resin material is treated with 2 vol.% DBU in a 20 vol.% piperidine in DMF solution (10 mL / g resin) twice with a duration of 20 min for a first treatment and a duration of 60 min for a second treatment. Afterwards, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). A part of the washed peptide material is further processed without drying according to example C-09-3. A part of the washed peptide material is dried 24 h in high vacuum at RT to obtain compound 614-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-02-4. Example C-08-4: synthesis of solid-phase conjugated compound 614-SP 200 mg of compound 619-SP (0.21 mmol / g resin, 0.042 mmol) is pre-swelled two times in DMF (10 mL / g resin) each for 10 min at RT. The pre-swelled resin material is treated with 2 vol.% DBU in a 20 vol.% piperidine in DMF solution (10 mL / g resin) twice with a duration of 20 min for a first treatment and a duration of 60 min for a second treatment. Afterwards, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). A part of the washed peptide material is further processed without drying according to example C-09-4. A part of the washed peptide material is dried 24 h in high vacuum at RT to obtain compound 614-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-02-5. Example C-08-5: synthesis of solid-phase conjugated compound 614-SP 200 mg of compound 620-SP (0.21 mmol / g resin, 0.042 mmol) is pre-swelled two times in DMF (10 mL / g resin) each for 10 min at RT. The pre-swelled resin material is treated with 20 vol.% piperidine in DMF solution (10 mL / g resin) twice with a duration of 20 min for a first treatment and a duration of 60 min for a second treatment. Afterwards, the resin material is washed three times alternating with DMF / IPA and three times with IPA (each washing step with 10 mL / g resin). A part of the washed peptide material is further processed without drying according to example C-09-5. A part of the washed peptide material is dried 24 h in high vacuum at RT to obtain compound 614-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-02-6. Example C-09-1: synthesis of solid-phase conjugated compound 616-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (616-SP) (SEQ ID NO:27) Compound 616-SP (= H-Ala-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2- aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)- Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin]) (SEQ ID NO:27).is synthesized from compound 614-SP obtained at example C-08-1 according to general procedure 3 via the Fmoc- protected intermediate compound 615-SP (= Fmoc-Ala-Lys(tBuO-CO-(CH2)16-CO-gamma- Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)- Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin]) (SEQ ID NO:20) *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (615-SP) (SEQ ID NO:20). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-04-2. Example C-09-2: synthesis of solid-phase conjugated compound 616-SP Compound 616-SP is synthesized from 100 mg of compound 614-SP (0.022 mmol, 0.22 mmol / g resin) obtained at example C-08-2 according to general procedure 3 via the Fmoc-protected intermediate compound 615-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-04-3. Example C-09-3: synthesis of solid-phase conjugated compound 616-SP Compound 616-SP is synthesized from 100 mg of compound 614-SP (0.022 mmol, 0.22 mmol / g resin) obtained at example C-08-3 according to general procedure 3 via the Fmoc-protected intermediate compound 615-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-04-4. Example C-09-4: synthesis of solid-phase conjugated compound 616-SP Compound 616-SP is synthesized from 100 mg of compound 614-SP (0.022 mmol, 0.22 mmol / g resin) obtained at example C-08-4 according to general procedure 3 via the Fmoc-protected intermediate compound 615-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-04-5. Example C-09-5: synthesis of solid-phase conjugated compound 616-SP Compound 616-SP is synthesized from 100 mg of compound 614-SP (0.022 mmol, 0.22 mmol / g resin) obtained at example C-08-5 according to general procedure 3 via the Fmoc-protected intermediate compound 615-SP. For analytical purposes, a small-scale test cleavage is performed. This is described at example D-04-6. Example C-10-1: synthesis of solid-phase conjugated compound 617-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (617-SP) (SEQ ID NO:22) 200 mg of compound 612-SP (0.044 mmol, 0.22 mmol / g resin) and 105 mg compound 501 (0.088 mmol, 2.0 eq.) are reacted according to general procedure 1 to obtain compound 617-SP (= Fmoc-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2- (2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)- Gly-[2-chlorotrityl resin]) (SEQ ID NO:22). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-09-1. Example C-11-1: synthesis of solid-phase conjugated compound 618-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (618-SP) (SEQ ID NO:24) 200 mg of compound 612-SP (0.044 mmol, 0.22 mmol / g resin) and 105 mg compound 507 (0.088 mmol, 2.0 eq.) are reacted according to general procedure 1 to obtain compound 618-SP (= Psc-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2- aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly- [2-chlorotrityl resin]) (SEQ ID NO:24). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-10-1. Example C-12-1: synthesis of solid-phase conjugated compound 619-SP *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (619-SP) (SEQ ID NO:25) 200 mg of compound 612-SP (0.044 mmol, 0.22 mmol / g resin) and 105 mg compound 504 (0.088 mmol, 2.0 eq.) are reacted according to general procedure 1 to obtain compound 619-SP (= Nsc-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2- aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly- [2-chlorotrityl resin]) (SEQ ID NO:25). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-01-2. Example C-13-1: synthesis of solid-phase conjugated compound 620-SP

[0005] *-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)-Gly-[2-chlorotrityl resin] (620-SP) (SEQ ID NO:23) 200 mg of compound 612-SP (0.044 mmol, 0.22 mmol / g resin) and 105 mg compound 508 (0.088 mmol, 2.0 eq.) are reacted according to general procedure 1 to obtain compound 620-SP (= Bsmoc-Lys(tBuO-CO-(CH2)16-CO-gamma-Glu(OtBu)-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2- (2-aminoethoxy)ethoxy]acetyl)-Glu(OtBu)-Phe-Ile-Ala-Trp(Boc)-Leu-Val-Arg(Pbf)-Gly-Arg(Pbf)- Gly-[2-chlorotrityl resin]) (SEQ ID NO:23). For analytical purposes, a small-scale test cleavage is performed. This is described at example D-11-1. D) cleavage of solid-phase conjugated compounds Example D-01-1: synthesis of compound 701 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (701) (SEQ ID NO:1) Compound 701 (= Nsc-Lys(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl- 2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH) (SEQ ID NO:1) is obtainable for example by a deprotecting reaction of compound 603-SP with a cleavage composition of TFA / EDT / H2O / TIS (90 / 5 / 2.5 / 2.5 in vol.% based on volume of cleavage composition). Example D-01-2: synthesis of compound 701 A small sample of the dried compound 619-SP from example C-12-1 is cleaved according to general procedure 2 to obtain a solid containing compound 701 (SEQ ID NO:1). HPLC method 2: 45.7 area% + 27.8 area%, retention times 18.42 min + 19.39 min / one of both peaks is assumed to be compound 701 and one a decomposition product. Whether the decomposition occurs during TFA-based cleavage, during TFA-containing analytical HPLC method 2 or both, is unknown. TFA-sensitivity of Nsc-protected compound 504 is also observed at Example B-12-8. Fig.1 depicts a complete HPLC-UV chromatogram. Fig.2 depicts an extract of the complete HPLC-UV chromatogram. Example D-02-1: synthesis of compound 702 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (702) (SEQ ID NO:2) Compound 702 (= H-Lys(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2- [2-(2-aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH) (SEQ ID NO:2) is obtainable for example by a deprotecting reaction of compound 606-SP with a cleavage composition of TFA / EDT / H2O / TIS (90 / 5 / 2.5 / 2.5 in vol.% based on volume of cleavage composition). Example D-02-2: synthesis of compound 702 A small sample of the dried compound 614-SP from example C-08-1 is cleaved according to general procedure 2 to obtain a solid containing compound 702 (SEQ ID NO:2). HPLC method 2: 80.9 area%, retention time 16.65 min. Fig.3 depicts a complete HPLC-UV chromatogram. Fig.4 depicts an extract of the complete HPLC-UV chromatogram. Example D-02-3: synthesis of compound 702 A small sample of the dried compound 614-SP from example C-08-2 is cleaved according to general procedure 2 to obtain a solid containing compound 702 (SEQ ID NO:2). HPLC method 2: 76.2 area%, retention time 16.65 min. Fig.5 depicts a complete HPLC-UV chromatogram. Fig.6 depicts an extract of the complete HPLC-UV chromatogram. Example D-02-4: synthesis of compound 702 A small sample of the dried compound 614-SP from example C-08-3 is cleaved according to general procedure 2 to obtain a solid containing compound 702 (SEQ ID NO:2). HPLC method 2: 76.4 area%, retention time 16.66 min. Fig.7 depicts a complete HPLC-UV chromatogram. Fig.8 depicts an extract of the complete HPLC-UV chromatogram. Example D-02-5: synthesis of compound 702 A small sample of the dried compound 614-SP from example C-08-4 is cleaved according to general procedure 2 to obtain a solid containing compound 702 (SEQ ID NO:2). HPLC method 2: 81.4 area%, retention time 16.66 min. Fig.9 depicts a complete HPLC-UV chromatogram. Fig.10 depicts an extract of the complete HPLC-UV chromatogram. Example D-02-6: synthesis of compound 702 A small sample of the dried compound 614-SP from example C-08-5 is cleaved according to general procedure 2 to obtain a solid containing compound 702 (SEQ ID NO:2). HPLC method 2: 81.1 area%, retention time 16.66 min. Fig.11 depicts a complete HPLC-UV chromatogram. Fig.12 depicts an extract of the complete HPLC-UV chromatogram. Example D-03-1: synthesis of compound 703 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (703) (SEQ ID NO:3) Compound 703 (= Fmoc-Ala-Lys(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly- OH) (SEQ ID NO:3) is obtainable for example by a deprotecting reaction of compound 605-SP with a cleavage composition of TFA / EDT / H2O / TIS (90 / 5 / 2.5 / 2.5 in vol.% based on volume of cleavage composition). Example D-04-1: synthesis of compound 704 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (704) (SEQ ID NO:4) Compound 704 (= H-Ala-Lys(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)- ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly- OH) (SEQ ID NO:4) is obtainable for example by a deprotecting reaction of compound 608-SP with a cleavage composition of TFA / EDT / H2O / TIS (90 / 5 / 2.5 / 2.5 in vol.% based on volume of cleavage composition). Example D-04-2: synthesis of compound 704 A small sample of the dried compound 616-SP from example C-09-1 is cleaved according to general procedure 2 to obtain compound 704 (SEQ ID NO:4). HPLC method 2: 73.6 area%. Fig.13 depicts a complete HPLC-UV chromatogram. Fig.14 depicts an extract of the complete HPLC-UV chromatogram. High resolution mass spectroscopy: calculated for [C105H175N24O28]3+ m / z 740.0997, measured 740.1031. Example D-04-3: synthesis of compound 704 A small sample of the dried compound 616-SP from example C-09-2 is cleaved according to general procedure 2 to obtain compound 704 (SEQ ID NO:4). HPLC method 2: 74.6 area%, retention time 16.76 min. Fig.15 depicts a complete HPLC-UV chromatogram. Fig.16 depicts an extract of the complete HPLC-UV chromatogram. High resolution mass spectroscopy: calculated for [C105H175N24O28]3+ m / z 740.0997, measured 740.1021. Example D-04-4: synthesis of compound 704 A small sample of the dried compound 616-SP from example C-09-3 is cleaved according to general procedure 2 to obtain compound 704 (SEQ ID NO:4). HPLC method 2: 74.9 area%, retention time 16.75 min. Fig.17 depicts a complete HPLC-UV chromatogram. Fig.18 depicts an extract of the complete HPLC-UV chromatogram. Example D-04-5: synthesis of compound 704 A small sample of the dried compound 616-SP from example C-09-4 is cleaved according to general procedure 2 to obtain compound 704 (SEQ ID NO:4). HPLC method 2: 80.7 area%, retention time 16.75 min. Fig.19 depicts a complete HPLC-UV chromatogram. Fig.20 depicts an extract of the complete HPLC-UV chromatogram. Example D-04-6: synthesis of compound 704 A small sample of the dried compound 616-SP from example C-09-5 is cleaved according to general procedure 2 to obtain compound 704 (SEQ ID NO:4). HPLC method 2: 78.2 area%, retention time 16.76 min. Fig.21 depicts a complete HPLC-UV chromatogram. Fig.22 depicts an extract of the complete HPLC-UV chromatogram. Example D-05-1: synthesis of compound 705 H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(HO-CO- (CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2-aminoethoxy)ethoxy]acetyl)- Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (705) (SEQ ID NO:5) Compound 705 (= H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln- Ala-Ala-Lys(HO-CO-(CH2)16-CO-gamma-Glu-2-[2-(2-aminoethoxy)ethoxy]acetyl-2-[2-(2- aminoethoxy)ethoxy]acetyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH respectively Semaglutide (CAS-No.910463-68-2)) (SEQ ID NO:5) is obtainable for example by a deprotecting reaction of compound 607-SP with a cleavage composition of TFA / EDT / H2O / TIS (90 / 5 / 2.5 / 2.5 in vol.% based on volume of cleavage composition). Example D-06-1: synthesis of 706 A small sample of the dried compound 611-SP from example C-05-1 is cleaved according to general procedure 2 to obtain compound 706 (SEQ ID NO:6). HPLC method 2: 88.4 area%, retention time 11.18 min. Fig.23 depicts a complete HPLC-UV chromatogram. Fig.24 depicts an extract of the complete HPLC-UV chromatogram. Example D-07-1: synthesis of 707 A small sample of the dried compound 612-SP from example C-06-1 is cleaved according to general procedure 2 to obtain compound 707 (SEQ ID NO:7). HPLC method 2: 84.0 area%, retention time 11.65 min. Fig.25 depicts a complete HPLC-UV chromatogram. Fig.26 depicts an extract of the complete HPLC-UV chromatogram. Example D-08-1: synthesis of compound 708 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (708) (SEQ ID NO:8) A small sample of the dried compound 613-SP from example C-07-1 is cleaved according to general procedure 2 to obtain compound 708 (SEQ ID NO:8). HPLC method 2: 81.6 area%, retention time 21.64 min. Fig.27 depicts a complete HPLC-UV chromatogram. Fig.28 depicts an extract of the complete HPLC-UV chromatogram. Example D-09-1: synthesis of compound 709 *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (709) (SEQ ID NO:9) A small sample of the dried compound 617-SP from example C-10-1 is cleaved according to general procedure 2 to obtain compound 709 (SEQ ID NO:9). HPLC method 2: 80.2 area%, retention time 21.72 min. Fig.29 depicts a complete HPLC-UV chromatogram. Fig.30 depicts an extract of the complete HPLC-UV chromatogram. Example D-10-1: synthesis of compound 710

[0006] *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (710) (SEQ ID NO:10) A small sample of the dried compound 618-SP from example C-11-1 is cleaved according to general procedure 2 to obtain compound 710 (SEQ ID NO:10). HPLC method 2: 76.4 area%, retention time 19.26 min. Fig.31 depicts a complete HPLC-UV chromatogram. Fig.32 depicts an extract of the complete HPLC-UV chromatogram. Example D-11-1: synthesis of compound 711

[0007] *-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH (711) (SEQ ID NO:11) A small sample of the dried compound 620-SP from example C-13-1 is cleaved according to general procedure 2 to obtain compound 711 (SEQ ID NO:11). HPLC method 2: 81.0 area%, retention time 19.45 min. Fig.33 depicts a complete HPLC-UV chromatogram. Fig.34 depicts an extract of the complete HPLC-UV chromatogram. E) comparison of solid phase coupling reactions Results obtained at cleaving small scale samples from solid-phase conjugated compounds under section D) are put into relation to conducted reactions with solid-phase conjugated compounds under section C) at a table E-1. Table E-1 amino protecting group Fmoca)N3a)Psca)Nsca)Bsmocb)cycle I step (c) condensing I [example No.] C-10-1 C-07-1 C-11-1 C-12-1 C-13-1 lysine derivative 501 506 507 504 508 solid-phase conjugated 617-SP 613-SP 618-SP 619-SP 620-SP compound [step cleaved and side chain deprot- 709 708 710 701e)711 (x)c)] ected compound / ([area%])d)(80.2%) (73.5%) (76.4%) (45.7% (81.0%) or 27.8%) step (d) removing amino protecting C-08-2 C-08-1 C-08-3 C-08-4 C-08-5 group I f) [example No.] solid-phase conjugated 614-SP 614-SP 614-SP 614-SP 614-SP compound [step cleaved and fully deprotected 702 702 702 702 702 (x)c)] compound / [area%] 76.2% 80.9% 76.2% 81.4% 81.1% average (c) + (d)g)([area%])d)(78.1%) (77.2%) (76.3%) ( -h)) (81.1%) cycle II step (e) condensing II and removing C-09-2 C-09-1 C-09-3 C-09-4 C-09-5 +…i) Fmoc-group IIj) [example No.] solid-phase conjugated 616-SP 616-SP 616-SP 616-SP 616-SP compound [step cleaved and deprotected com- 704 704 704 704 704 (x) c)] pound / total (e)+…i), k) [area%] 74.6% 73.6% 74.9% 80.7% 78.2% average 702 + 704l)[area%] 75.4% 77.3% 75.6% 81.1% 79.7% Footnotes: a) comparative b) inventive c) for a quantification of an effectiveness of the solid-phase reaction, a cleavage of the solid- phase conjugated reaction product from the resin is conducted and an area percentage for the obtained compound at a HPLC-UV chromatogram determined d) different amino protecting groups have different UV-absorbing properties at 220 nm, which requires some caution at an interpretation and therefore the brackets e) only one of the observed peaks with 45.7 area% or 27.8 area% is compound 701, the other one is a decomposition product f) optimized deprotection conditions are employed for the respective amino protecting group, i.e. a phosphine reduction for N3, 20 vol.% piperidine in DMF for Fmoc and Bsmoc, 2 vol.% DBU and 20 vol.% piperidine in DMF for Psc and Nsc g) due to different deprotection conditions at step (d), a direct comparison of the combined effectiveness of the solid-phase reactions at step (c) and step (d) is formally not possible – however, an averaged cycle I effectiveness is on the one hand a confirmation of a condensing effectiveness at step (c) and shows on the other hand a removing effectiveness for the amino protecting group at step (d) h) decomposition of compound 702 makes an average not possible i) three dots represent a step of removing Fmoc-group at cycle II i) condensing with Fmoc-Ala-OH and removing Fmoc with 20 vol.% piperidine in DMF k) it is noted that the starting resin material is not similar, i.e. synthesis at the previous cycle I has occurred with compounds 501, 504, 506, 507 or 508 and partially different deprotection conditions due to the involved respective amino protecting group l) average over cycle I and cycle II is based on area% of cleaved and fully deprotected compound 702 and on area% of cleaved and fully deprotected compound 704 The results of table E-1 show - that dependent on the amino protecting group of the lysine derivative, which is employed as one reactant of the condensing step (c) at a solid-phase cycle I, an effectiveness of the cycle I as indicated by area-percentages of cleaved and fully deprotected compound 702 and an effectiveness of a subsequent solid-phase cycle II as indicated by area-percentages of cleaved and deprotected compound 704 is influenced as indicated by area-percentages of the peptides cleaved from the solid-phase; - that Nsc provides the highest effectiveness based on area percentages followed closely by Bsmoc, whereas N3 is next and followed by Psc and Fmoc; - that a reasonably presumable influence of a sterical hindrance of the amino proctecting group at the lysine derivative is not decisive, i.e. in view of the least hindered N3, which is followed by Psc / Nsc with two methylene units after the oxy-carbonyl unit and then Fmoc / Bsmoc with one methylene unit after the oxycarbonyl unit; - that compound 701 with Nsc as the amino protecting group has a high sensitivity against TFA and thus confirms the high sensitivity of Nsc as the amino protecting group at compound 504 versus an exposure against TFA (and an exposure against of aqueous sodium hydrogencarbonate) as shown in Example B-12-8. F) stability tests Example F-01-1: compound 122 (Bsmoc-Lys-OH) vs. compound 125 (Fmoc-Lys-OH) in solid form at 80 °C A sample of the respective solid material is stored at 80 °C and analyzed after 4 h and 24 h. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-01-1-1. Table F-01-1-1 compound No. name t = 0 t = 4 h t = 24 h [area%] [area%] [area%] 122 Bsmoc-Lys-OH 93.5 16.7 2.2 125 Fmoc-Lys-OH 99.3 99.0 98.5 The results of table F-01-1-1 show - that compound 122 (Bsmoc-Lys-OH) in solid form has a very low stability at 80 °C and almost completely decomposes within 24 h, whereas compound 125 (Fmoc-Lys-OH) in solid form is rather stable under the same conditions. Example F-02-1: compound 122 (Bsmoc-Lys-OH) vs. compound 125 (Fmoc-Lys-OH) in solid form at 23 °C A sample of the respective solid material is stored at 23 °C and analyzed after 4 h, 24 h and 168 h. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-02-1-1. Table F-02-1-1 Compound name t = 0 t = 4 h t = 24 h t = 168 h No. [area%] [area%] [area%] [area%] 122 Bsmoc-Lys-OH 93.5 93.4 92.5 88.5 125 Fmoc-Lys-OH 99.3 99.2 99.2 98.9 The results of table F-02-1-1 show - that compound 122 (Bsmoc-Lys-OH) in solid form has limited stability at 23 °C and particularly over 168 h (7 days), whereas compound 125 (Fmoc-Lys-OH) in solid form is rather stable under the same conditions. Example F-03-1: compound 120 (Bsmoc-Lys-OH x HCl) vs. compound 123 (Fmoc-Lys-OH x HCl) in solid form at 23 °C A sample of the respective solid material is stored at 23 °C and analyzed after 1 d, 2 d and 5 d. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-03-1-1. Table F-03-1-1 Compound name t = 0 t = 1 d t = 2 d t = 5 d No. [area%] [area%] [area%] [area%] 120a)Bsmoc-Lys-OH x HCl 98.6 98.6 98.6 98.5 123b)Fmoc-Lys-OH x HCl 99.5 99.6 99.6 99.5 Footnotes: a) inventive b) comparative The results of table F-03-1-1 show - that compound 120 (Bsmoc-Lys-OH x HCl) in solid form is stable at 23 °C over 5 days and its stability is corresponding to the stability of compound 123 (Fmoc-Lys-OH x HCl) in solid form under the same conditions. Example F-04-1: compound 122 (Bsmoc-Lys-OH) vs. various compounds (Bsmoc-Lys-OH x acid) in solid form at 23 °C A sample of the respective solid material is stored at 23 °C and analyzed after 1 d, 2 d and 5 d. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-04-1-1. Table F-04-1-1 Compound name t = 0 t = 1 d t = 2 d t = 5 d difference e) No. [area%] [area%] [area%] [area%] [area%] 122a)Bsmoc-Lys-OH 93.5 92.5 n.d.c)(88.5%)d)(- 5.0)f)120b)Bsmoc-Lys-OH x 98.6 98.6 98.6 98.5 - 0.1 HCl 129b)Bsmoc-Lys-OH x 98.9 98.7 98.6 97.7 - 1.2 MeSO3H 128b)Bsmoc-Lys-OH x 98.8 98.6 98.3 98.2 - 0.6 TsOH 130 b) Bsmoc-Lys-OH x 98.5 97.7 97.5 97.3 - 1.2 0.5 H2SO4 127b)Bsmoc-Lys-OH x 98.9 98.8 98.7 98.6 - 0.3 TFA Footnotes: a) comparative b) inventive c) not determined d) determined after 7 d e) decrease of area percentage between t = 0 and t = 5 d f) decrease of area percentage between t = 0 and t = 7 d The results of table F-04-1-1 show - that compounds 120, 127, 128, 129 and 127 (Bsmoc-Lys-OH x acid) in solid form are rather stable at 23 °C over 5 days in comparison to compound 122 (Bsmoc-Lys-OH), which has a low stability; - that compound 120 (Bsmoc-Lys-OH x HCl) and compound 127 (Bsmoc-Lys-OH x TFA) in solid form at 23 °C over 5 days are more stable in comparison to compound 128 (Bsmoc- Lys-OH x TsOH), compound 129 (Bsmoc-Lys-OH x MeSO3H) and compound 130 (Bsmoc- Lys-OH x 0.5 H2SO4); - that the area percentage at t = 0 of compound 122 (Bsmoc-Lys-OH) is relatively low in comparison to the area percentages at t = 0 of compounds 120, 127, 128, 129 and 127 (Bsmoc-Lys-OH x acid) and reference is made to table F-09-1-2 at example F-09-1. Example F-05-1: compound 122 (Bsmoc-Lys-OH) vs. compound 125 (Fmoc-Lys-OH) in DMF solution at 23 °C A DMF solution (50 mg / mL) of compound 122 (Bsmoc-Lys-OH) is stored at 23 °C and analyzed after 15 min, 4 h and 24 h. The preparation of a DMF solution (targeted 50 mg / mL) of compound 125 (Fmoc-Lys-OH) failed, because it turns out that compound 125 (Fmoc-Lys-OH) is not dissolved / not soluble enough for the present purpose under these conditions. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-05-1-1. Table F-05-1-1 Compound name solid t = 15 min t = 4 h t = 24 h No. material a) [area%] [area%] [area%] [area%] 122 Bsmoc-Lys-OH 93.5 69.5 20.8 6.6 125 Fmoc-Lys-OH 99.3 - b) - b) - b) Footnote: a) in view of the observed fast decomposition of compound 122 (Bsmoc-Lys-OH) once it is dissolved in DMF, the area percentages of the employed solid materials are stated b) not dissolved / not soluble enough for the present purpose The results of table F-05-1-1 show - that compound 122 (Bsmoc-Lys-OH) in DMF solution has very low stability at 23 °C and significantly decomposes already within the 15 min period between preparing of the solution and starting a HPLC of the solution; - that a stability of compound 125 (Fmoc-Lys-OH) cannot be measured, since it is not dissolved in DMF under the conditions of dissolving compound 125 (Bsmoc-Lys-OH). Example F-06-1: compound 120 (Bsmoc-Lys-OH x HCl) vs. compound 123 (Fmoc-Lys-OH x HCl) in DMF solution at 23 °C A DMF solution (50 mg / mL) of the respective material is stored at 23 °C and analyzed after 1 d, 2 d and 5 d. HPLC area percentage is determined by HPLC method 1 mode B for compound 120 (Bsmoc-Lys-OH x HCl). HPLC area percentage is determined by HPLC method 1 mode A for compound 123 (Fmoc-Lys-OH x HCl). The results are shown in table F-06-1-1. A part of the prepared DMF solution (50 mg / mL) of the respective material at t = 0 is taken for example F-07-1. Table F-06-1-1 Compound name t = 0 t = 1 d t = 2 d t = 5 d No. [area%] [area%] [area%] [area%] 120a)Bsmoc-Lys-OH x HCl 98.8 98.7 98.6 98.6 123b)Fmoc-Lys-OH x HCl 99.6 99.6 99.6 99.5 Footnotes: a) inventive b) comparative The results of table F-06-1-1 show - that compound 120 (Bsmoc-Lys-OH x HCl) in DMF solution is stable at 23 °C over 5 days and its stability corresponds to the stability of compound 123 (Fmoc-Lys-OH x HCl) under the same conditions. Example F-07-1: compound 120 (Bsmoc-Lys-OH x HCl) + DIPEA vs. compound 123 (Fmoc- Lys-OH x HCl) + DIPEA in DMF solution at 23 °C To the part of the prepared DMF solution (50 mg / mL) of the respective material, which is taken at t = 0 from example F-06-1, at a small scale at 23 °C, DIPEA (diisopropylethylamine) is added to the extend that a drop of the mixture on an wetted pH-paper indicates pH around 7. Samples are taken shortly after the DIPEA addition and then after 1d and 2 d. HPLC area percentage is determined by HPLC method 1 mode B for compound 120 (Bsmoc-Lys-OH x HCl) + DIPEA. HPLC area percentage is determined by HPLC method 1 mode A for compound 123 (Fmoc- Lys-OH x HCl) + DIPEA. The results are shown in table F-07-1-1. Table F-07-1-1 Compound name DIPEA addition No. t = 0c)t ~ 0d)t = 1 d t = 2 d [area%] [area%] [area%] [area%] 120 a) Bsmoc-Lys-OH x HCl 98.8 92.4 e) 31.6 e) 30.3 e) 123 b) Fmoc-Lys-OH x HCl 99.6 98.1 f) (24.9) g) (21) g) Footnotes: a) inventive b) comparative c) from example F-06-1 at t = 0, i.e., prior to DIPEA addition d) taken shortly after DIPEA addition e) no precipitation observed f) precipitation observed after DIPEA addition g) precipitation persists The results of table F-07-1-1 show - that addition of the base diisopropylethylamine to compound 120 (Bsmoc-Lys-OH x HCl) in DMF solution at 23°C leads to decomposition, but the decomposition seems to be not as fast as when compound 122 (Bsmoc-Lys-OH) is directly dissolved in DMF at example F-05- 1; - that addition of the base diisopropylethylamine to compound 123 (Fmoc-Lys-OH x HCl) in DMF solution at 23 °C leads to a precipitation, which is in-line with the low solubility of compound 125 (Fmoc-Lys-OH) in DMF at example F-05-1; - that the low area percentages at 1 day and 2 days after addition of the base diisopropylethylamine to compound 123 (Fmoc-Lys-OH x HCl) in DMF solution at 23 °C might be speculated to be partly caused by a depletion of compound 125 (Fmoc-Lys-OH) from the solution, a ripening / ageing of the initial precipitation over time and a difficulty to take a homogenous analytical sample for HPLC sample from the mixture. Example F-08-1: compound 122 (Bsmoc-Lys-OH) vs. compound 125 (Fmoc-Lys-OH) in THF : H2O = 3 : 1 (v / v) solution at 23 °C A THF : H2O = 3 : 1 (v / v) solution of the respective material (50 mg / mL) is stored at 23 °C and analyzed after 16 h and 70 h. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-08-1-1. Table F-08-1-1 Compound name t = 0 t = 16 h t = 70 h No. [area%] [area%] [area%] 122a)Bsmoc-Lys-OH 92.0 90.6 83.7 125b)Fmoc-Lys-OH 99.1 99.0 98.8 The results of table F-08-1-1 show - that compound 122 (Bsmoc-Lys-OH) in THF : H2O = 3 : 1 (v / v) solution has limited stability at 23 °C over 70 hours in comparison to compound 125 (Fmoc-Lys-OH), which is rather stable under the same conditions. Example F-09-1: compound 120 (Bsmoc-Lys-OH x HCl) vs. compound 123 (Fmoc-Lys-OH x HCl) in THF : H2O = 3 : 1 (v / v) solution at 23 °C A THF : H2O = 3 : 1 (v / v) solution of the respective material (50 mg / mL) is stored at 23 °C and analyzed after 16 h and 70 h. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in table F-09-1-1. Table F-09-1-1 Compound name t = 0 t = 16 h t = 70 h No. [area%] [area%] [area%] 120a)Bsmoc-Lys-OH x HCl 98.8 98.8 98.6 123b)Fmoc-Lys-OH x HCl 99.4 99.4 99.4 Footnotes: a) inventive b) comparative The results of table F-09-1-1 show - that compound 120 (Bsmoc-Lys-OH x acid) in THF : H2O = 3 : 1 (v / v) solution is stable at 23 °C over 70 hours and its stability corresponds to the stability of compound 123 (Fmoc- Lys-OH x HCl) under the same conditions. Example F-10-1: compound 122 (Bsmoc-Lys-OH) vs. various compounds (Bsmoc-Lys-OH x acid) in THF : H2O = 3 : 1 (v / v) solution at 23 °C A THF : H2O = 3 : 1 (v / v) solution of the respective material (50 mg / mL) is stored at 23 °C and analyzed after 16 h and 70 h. HPLC area percentage is determined by HPLC method 1 mode B. The results are shown in tables F-10-1-1 and F-10-1-2. Table F-10-1-1 Compound name t = 0 t = 16 h t = 70 h differencec)No. [area%] [area%] [area%] [area%] 122 a) Bsmoc-Lys-OH 92.0 90.6 83.7 - 8.3 120 b) Bsmoc-Lys-OH x 98.8 98.8 98.6 - 0.2 HCl 129 b) Bsmoc-Lys-OH x 98.8 98.8 98.8 0.0 MeSO3H 128 b) Bsmoc-Lys-OH x 98.6 98.7 98.7 0.1 TsOH 130b)Bsmoc-Lys-OH x 98.2 98.1 98.0 - 0.2 0.5 H2SO4127b)Bsmoc-Lys-OH x 98.8 98.9 98.8 0.0 TFA Footnotes: a) comparative b) inventive c) decrease of area percentage between t = 0 and t = 70 h The results of table F-10-1-1 show - that compounds 120, 127, 128, 129 and 127 (Bsmoc-Lys-OH x acid) in THF : H2O = 3 : 1 (v / v) solution are rather stable at 23 °C over 70 hours in comparison to compound 122 (Bsmoc-Lys-OH), which has a low stability; - that compound 120 (Bsmoc-Lys-OH x HCl) and compound 127 (Bsmoc-Lys-OH x TFA) in THF : H2O = 3 : 1 (v / v) solution at 23 °C over 70 hours 5 are similarly stable in comparison to compound 128 (Bsmoc-Lys-OH x TsOH), compound 129 (Bsmoc-Lys-OH x MeSO3H) and compound 130 (Bsmoc-Lys-OH x 0.5 H2SO4). Table F-10-1-2 Compound name drying(s)c)solid materiale)t = 0 hf)differenceg)No. [amount] [area%] [area%] [area%] 122 a) Bsmoc-Lys-OH 1 + 2 d) 93.5 92.0 - 1.5 120 b) Bsmoc-Lys-OH x 1 98.6 98.8 0.2 HCl 129 b) Bsmoc-Lys-OH x 1 + 1 98.9 98.8 - 0.1 MeSO3H 128 b) Bsmoc-Lys-OH x 1 + 1 98.8 98.6 - 0.2 TsOH 130b)Bsmoc-Lys-OH x 1 + 1 98.9 98.2 - 0.5 0.5 H2SO4 127b)Bsmoc-Lys-OH x 1 + 1 98.9 98.8 - 0.1 TFA Footnotes: a) comparative b) inventive c) overall amount of drying(s): one from the drying of compound 120 (Bsmoc- Lys-OH x HCl) as common starting material of all other compounds plus individual drying(s) (lyophilization) until the respective compound as a solid d) first individual drying (lyophilization) as compound 121 (Bsmoc-Lys-OH x AcOH) and second individual drying (lyophilization) as compound 122 (Bsmoc- Lys-OH) e) in view of the observed decomposition of compound 122 (Bsmoc-Lys-OH) once it is dissolved in THF : H2O = 3 : 1, the area percentages of the employed solid materials are stated f) t = 0 includes a period between preparing a solution and measuring a HPLC of the solution g) decrease of area percentage between solid material and material dissolved in THF : H2O = 3 : 1 at t = 0 The results of table F-10-1-2 show - that the area percentages of compounds 120, 127, 128, 129 and 127 (Bsmoc-Lys-OH x acid) in THF : H2O = 3 : 1 (v / v) solution are rather like to the area percentages of the dissolved starting materials, whereas a difference at compound 122 (Bsmoc-Lys-OH) is observed; - that a comparison of the area percentages of compounds 120, 127, 128, 129 and 127 (Bsmoc-Lys-OH x acid) indicates that a drying from an aqueous solution in the tested acidic salt forms does not change the area percentages, which contrast with a drying of compound 122 (Bsmoc-Lys-OH) in its form of an inner salt. G) summary of stability tests In solid state, compound 122 (Bsmoc-Lys-OH) is shown to be relatively unstable in comparison to compound 125 (Fmoc-Lys-OH) [-> example F-01-1, example F-02-1], whereas compound 120 (Bsmoc-Lys-OH x HCl) is similarly stable than compound 123 (Fmoc-Lys-OH x HCl) at 23 °C [-> example F-03-1-1]. Compounds 120, 127, 128, 129 and 130 (Fmoc-Lys-OH x acid) are similarly stable at 23 °C [-> example F-04-1]. In DMF solution, compound 122 (Bsmoc-Lys-OH) is shown to be very unstable after dissolution at 23 °C and compound 125 (Fmoc-Lys-OH) does not dissolve [-> example F-05-1]. In contrast, compound 120 (Bsmoc-Lys-OH x HCl) is similarly stable than compound 123 (Fmoc-Lys-OH x HCl) [-> example F-06-1]. Addition of diisopropylethylamine to a DMF solution of compound 120 (Bsmoc-Lys-OH x HCl) leads to an unstable situation, whereas addition of diisopropylethylamine to a DMF solution of compound 123 (Fmoc-Lys-OH x HCl) leads to a precipitation and a difficulty for analysis [-> example F-07-1]. In THF : H2O = 3 : 1 (v / v) solution, compound 122 (Bsmoc-Lys-OH) is shown to be relatively unstable in comparison to compound 125 (Fmoc-Lys-OH) [-> example F-08-1], ], whereas compound 120 (Bsmoc-Lys-OH x HCl) is similarly stable than compound 123 (Fmoc-Lys-OH x HCl) at 23 °C [-> example F-09-1-1]. Compounds 120, 127, 128, 129 and 130 (Fmoc-Lys-OH x acid) are similarly stable at 23 °C [-> example F-10-1]. It is noted that compound 120 (Bsmoc-Lys-OH x HCl) is employed as starting material [-> example B-26-1]. It turns out that compound 120 (Bsmoc-Lys-OH x HCl) is sufficiently silylated to allow a coupling reaction with an activated carboxylic acid derivative under formation of an amide group. Thus, compound 122 (Bsmoc-Lys-OH) as starting material is avoided. Further- more, chloride as a released counter anion from compound 120 (Bsmoc-Lys-OH) does not disturb the coupling reaction. It is then shown that compound 123 (Fmoc-Lys-OH x HCl) is also sufficiently silylated to allow a coupling reaction with an activated carboxylic acid derivative under formation of an amide group [-> example B-28-1]. Thus, compound 125 (Fmoc-Lys-OH), which is described in literature as starting material for silylation (e.g. EP 3819308 A1, example 1 / step 1f, example 3 / step 3b), can be substituted by compound 123 (Fmoc-Lys-OH x HCl).

Claims

Bachem Holding AG BAC75079PC April 10, 2024 Claims 1. A compound of formula 1Xwherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5 HY is sulfuric acid.

2. The compound according to claim 1, wherein when n is 1 HY is hydrochloric acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, 2-propane-sulfonic acid, 1-butane- sulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid or nitric acid, when n is 0.5 HY is sulfuric acid.

3. The compound according to claim 1 or 2, wherein when n is 1 HY is hydrochloric acid, trifluoroacetic acid, para-toluenesulfonic acid or methanesulfonic acid, when n is 0.5 HY is sulfuric acid.

4. The compound according to any one of claims 1 to 3, wherein the compound has been stored for at least 12 hours.

5. The compound according to any one of claims 1 to 4, wherein the compound is in a solid state.

6. The compound according to any one of claims 1 to 4, wherein the compound is dissolved or suspended in a solvent composition SolvI-1, which comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2- methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, benzonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane, water, or a mixture thereof.

7. A method of manufacturing a lysine derivative LYSX, which method comprises the steps (aI-1), (cI-1) and (dI-1) or comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2), (aI-1) providing a compound of formula 1Xwherein n is 1 or 0.5, when n is 1 HY is hydrochloric acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, hydrobromic acid, hydroiodic acid, perchloric acid, triflic acid, nitric acid, picric acid, trichloroacetic acid, camphorsulfonic acid, dichloroacetic acid, difluoroacetic acid or phosphoric acid, when n is 0.5HY is sulfuric acid; (cI-1) combining the provided compound of formula 1X and an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-1) reacting the epsilon nitrogen atom of the provided compound of formula 1Xwith the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-1) might partly also take place already during step (cI-1); or (aI-2) providing a compound of formula 1X as defined at (aI-1); (bI-2) silylating the provided compound of formula 1X with a silylation agent to obtain a silylated compound; (cI-2) combining the silylated compound and an activated carboxylic acid derivative, which has one of its one or more carboxylic acid groups changed to a carbonyl group with a covalently linked leaving group, in case of more than one carboxylic acid groups, the other carboxylic acid groups are protected, and in case the activated carboxylic acid derivative has one or more amino or imino groups, the one or more amino or imino groups are protected; (dI-2) reacting the epsilon nitrogen atom of the silylated compound with the carbonyl group of the activated carboxylic acid derivative to form a covalent bond between the epsilon nitrogen atom and the carbonyl group, which leads to an amide group; wherein step (dI-2) might partly also take place already during step (cI-2).

8. A method according to claim 7, wherein the lysine derivative LYSXcontains a structural element of formulaewherein * indicates a covalent connection, R4X-B-N-1 is an amino-protecting group; and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element of formulaewherein * indicates a covalent connection, LG is a leaving group, R5X-B-N-1is an amino protecting group.

9. A method according to claim 8, wherein the lysine derivative LYSXcontains a structural element of formulaewherein * indicates a covalent connection, R6X-A-b-O-1 is a carboxylic acid proctecting group; and at step (cI-1) and at step (cI-2), the activated carboxylic acid derivative contains a structural element ofwherein * indicates a covalent connection, LG is a leaving group, R7X-A-b-O-1is a carboxylic acid protecting group.

10. A method according to any one of claims 7 to 9, wherein the lysine derivative LYSXis a compound of formula, wherein RL-O-1and RL-O-2are independently of each other a carboxylic acid protecting group; compound 309compound 310compound 511compound 514or compound 517.

11. A method according to any one of claims 7 to 10, wherein at step (cI-1) or at step (dI-1), a base, which is free of an unprotected amino group or an unprotected imino group, is added, and at step (cI-2) or step (dI-2), a base, which is free of an unprotected amino group or an unprotected imino group, is added.

12. A method according to any one of claims 7 to 11, wherein at step (aI-1), the compound of formula 1X is provided as a solution or a suspension in a solvent composition SolvI-1, which comprises N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)- 2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2-methyltetrahydrofuran, 1,3- dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, methanol, ethanol, propanol, butanol, diethyl ether, methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane, water, or a mixture thereof; and wherein at step (aI-2), the compound of formula 1X is provided as a solution or a suspension in an anhydrous solvent composition SolvI-2, which comprises N,N-dimethylformamide, N,N- dimethylacetamide, N-methyl-2-pyrrolidone, N-butyl-2-pyrrolidone, N-octyl-2-pyrrolidone, methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate, dimethyl sulfoxide, tetrahydrofuran, 2- methyltetrahydrofuran, 1,3-dioxolane, 1,4-dioxane, ethyl acetate, propyl acetate, butyl acetate, dichloromethane, chloroform, 1,2-dichloroethane, nitromethane, acetonitrile, acetone, methyl ethyl ketone, gamma-butyrolactone, gamma-valerolactone, triethyl phosphate, diethyl ether,methyl tert-butyl ether, diisopropyl ether, benzene, toluene, xylene, chlorobenzene, pentane, hexane, heptane, octane, cyclohexane or a mixture thereof.

13. A method according to any one of claims 7 to 12, wherein the method comprises the steps (aI-2), (bI-2), (cI-2) and (dI-2) and at step (bI-2), the silylation agent is trimethylsilyl chloride, N-methyl-N-trimethylsilyl acetamide, N,O-bis(trimethylsilyl)acetamide, N,O- bis(trimethylsilyl)trifluoroacetamide, trimethylsilyl methanesulfonate or trimethylsilyl triflate.

14. A method of manufacturing a peptide PX, wherein the method comprises a step (cX) (cX) condensing an alpha amino acid derivative S-am, which has one unprotected alpha amino group or one unprotected alpha imino group, with a lysine derivative LYSX, which is obtained according to claim 7, to obtain an intermediate peptide Int-PX.

15. Use of a compound of formula 1X as defined in any one of claims 1 to 6 in the synthesis of a peptide.

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