953 results about "Protecting group" patented technology

The invention provides a solid-liquid combined synthesis method of semeglutide, which belongs to the technical field of semeglutide synthesis, and specifically comprises the following steps: segmenting a main chain of the semeglutide into three shorter polypeptide fragments, namely a fragment 4, a fragment 5 and a fragment 2 at sites 7-14, 15-22 and 23-37, and respectively synthesizing at the same time; performing solid-phase assembly on the fragment 4 and the fragment 5 to form 7-22 peptide fragments, namely a fragment 1, and after the fragment 1 is cut off from the resin, forming NHS ester at a C end; after the fragment 2 is assembled, selectively removing a protecting group A11oc on the Lys26, then connecting with a side chain for fatty acid treatment to form a fragment 3, and cutting off the fragment 3 from the resin; and connecting the NHS ester of the fragment 1 with the fragment 3 in a liquid phase reaction system. The crude semeglutide prepared by the synthetic method is relatively high in yield and purity. The refined semeglutide of which the purity is more than 99.3% and the content of single impurity is less than 0.1% can be obtained at high yield through a conventional purification means.

The invention provides a solid-phase synthesis method of semeglutide, and belongs to the technical field of synthesis of medical intermediates, and the method specifically comprises the following steps: segmenting a semeglutide main chain into three shorter polypeptide fragments, namely a fragment 4, a fragment 5 and a fragment 2, which are 7-14 sites, 15-22 sites and 23-37 sites; and respectively synthesizing and then assembling fragments to obtain a target product. The method specifically comprises the following steps: a) synthesizing a 7-14 peptide fragment and a 15-22 peptide fragment, and assembling the 7-14 peptide fragment and the 15-22 peptide fragment into a 7-22 peptide fragment, namely a fragment 1; b) synthesizing a 23-37 peptide fragment, selectively removing a protecting group A11oc on Lys26, and connecting with a side chain to form a fragment 3; c) connecting the peptide fragment 7-22 with the peptide fragment 23-37, and removing a protecting group to obtain a crude product; and d) separating and purifying to obtain a finished product. According to the invention, the purpose of high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug can be achieved.

The invention discloses an antibacterial peptide simulant based on adamantane modification and application of the antibacterial peptide simulant. The preparation method comprises the following steps: performing amide condensation on Fmoc amino acid to obtain a compound of which the carboxyl terminal is modified by amantadine or Boc protected aliphatic amine, and then removing an Fmoc group by piperidine to obtain a series of amantadine modified crude products and Boc protected aliphatic amine modified intermediate compounds; the intermediate compound is subjected to amide condensation to obtain a compound of which the amino terminal is further modified by adamantanic acid, then other protecting groups are cracked by trifluoroacetic acid to obtain a series of adamantanic acid modified crude products, and the crude products are purified to obtain the adamantane modified peptidomimetic. The adamantane modified peptidomimetic is used for preparing drugs for treating infectious diseases caused by sensitive bacteria and drug-resistant bacteria, has efficient antibacterial activity and low toxicity, and is not influenced by a traditional drug-resistant mechanism.

The present invention provides a method for synthesizing alacastran, comprising reacting an amino compound of formula V with a chiral intermediate of formula VI, reducing the resulting product with a reducing agent capable of providing an ethyl group to produce a compound of formula VII, and then deprotecting the compound to obtain alacastran, as shown in the following reaction formula. The method for synthesizing alacastran of the present invention avoids the low yield caused by amide reduction and the risk of substrate racemization, has a high yield, low material cost, safe operation, and is suitable for industrial production.

The invention discloses a vibeglycolone intermediate, a preparation method thereof and application of the intermediate in preparation of vibeglycolone, and belongs to the technical field of medicinal chemistry. The structural general formula of the vibeglycolone intermediate compound II disclosed by the invention is as follows: # imgabs0 # R1 is a silicon-containing hydroxyl protecting group. The invention also develops a new synthesis route of vibeglycolone by adopting the key intermediate, and by introducing a hydroxyl protecting group at the front end of the reaction, the stability of the intermediate compound is increased, the generation of oxidation impurities in the cyclization and hydrogenation process is effectively reduced, the purification problem in the synthesis process is greatly improved, the cost is saved, and the yield is increased. The synthesis efficiency is also improved, the obtained target compound vibeglycolone has higher purity, and the newly developed synthesis route is more suitable for industrial large-scale production.

The present invention discloses an imidazole derivative, a preparation method thereof, and an application, belonging to the field of organic chemistry. The preparation method of the imidazole derivative of the present invention includes: adding compound 2a and dimethyl sulfate into an organic solvent, heating and reacting to obtain compound 3a; wherein, compound 2a is prepared by adding compound 1a, TrtCl, and a base reagent into a solvent, controlling the temperature at 0-10 °C, mixing evenly and reacting. The present invention also further prepares 2-(1-methylimidazol-5-yl)ethylamine (4a) by using the imidazole derivative. The present invention selects dimethyl sulfate as a methylation reagent and cooperates with a specific protecting group design to achieve the efficient preparation of 2-(1-methylimidazol-5-yl)ethylamine, with a total yield of 82.4%.

The present invention belongs to the technical field of drug synthesis, relating to the synthesis of drugs for the prevention or treatment of diseases such as Alzheimer's disease and Parkinson's disease. Specifically, it relates to pharmaceutical intermediates and synthesis methods and isoquinoline derivatives and synthesis methods therefor. The pharmaceutical intermediate has a chemical structure shown in Formula II, wherein X is a halogen, and R is an amino protecting group. The synthesis of the pharmaceutical intermediate is simple, operates under mild conditions, and results in a high yield. Additionally, the pharmaceutical intermediate can be used to prepare isoquinoline derivatives.

The invention discloses a synthesis process of vitamin C ethyl ether, and belongs to the technical field of vitamin C derivative synthesis. The process comprises the following steps: taking L-ascorbic acid as a raw material, adding acetone, anhydrous cupric sulfate and acetyl chloride, and reacting for 1-2 hours at 38-40 DEG C under the protection of nitrogen to obtain a vitamin C protector; adding alkali, water, an alkylating reagent and absolute ethyl alcohol into the reaction product, reacting for 3 hours at 75-78 DEG C under the protection of nitrogen, and performing reduced pressure distillation to obtain a vitamin C protector etherate; and finally, hydrolyzing by using cationic resin, removing a protecting group, and recrystallizing by using ethyl acetate to obtain the vitamin C ethyl ether. Through the synergistic catalysis of anhydrous cupric sulfate and acetyl chloride, the reaction time is remarkably shortened, and the product purity and yield are improved. Through detection, the product purity is more than 99.5%, the total yield can reach more than 80%, and an efficient and economical method is provided for industrial production of vitamin C ethyl ether.

The invention discloses a synthetic method of glabridin with optical purity, which comprises the following steps: by taking (R)-3-acetoxyl-2-(2, 4-dimethoxyphenyl) propanol and 2-isopentenyl resorcinol as raw materials, carrying out Mitsunobu reaction to obtain a key intermediate compound I, then carrying out hydrolysis and iodination to obtain an intermediate compound II, and then carrying out cyclization to obtain the glabridin with optical purity. Reducing and removing a protecting group to obtain glabridin. By introducing the isopentene side chain, the reaction activity of an olefin functional group is reserved, a key site is provided for subsequent cyclization conversion, the precise spatial configuration of the product is ensured, and finally glabridin with optical purity is prepared. The method is short in route, low in cost, mild in reaction condition and suitable for industrial production.

The invention relates to a method for preparing a nerofloxacin chiral piperidylamine intermediate, which comprises the following steps of: carrying out condensation reaction on 5-hydroxy nicotinic acid which is simple and easy to obtain and is used as a raw material and different alcohols, screening through a series of asymmetric catalytic hydrogenation conditions to obtain optimal reaction conditions, and under the conditions, carrying out reaction on various 3, 3 '-dihydroxy nicotinic acid and 3, 3'-dihydroxy nicotinic acid to obtain the nerofloxacin chiral piperidylamine intermediate. The 2, 5-disubstituted pyridine quaternary ammonium salt is reduced into a tetrahydropyridine product, and the C5 site enantioselectivity of the product is excellent. The preparation method comprises the following steps: selecting methyl (R)-1-benzyl-5-hydroxy-1, 4, 5, 6-tetrahydropyridine-3-carboxylic acid methyl ester as a substrate, completely hydrogenating by using platinum dioxide hydrogen, and then carrying out methyl ester reduction, dehydroxylation, Mitsunobu reaction and protecting group removal to obtain a key chiral intermediate for industrial synthesis of a quinolone antibacterial drug nemonofloxacin with high enantioselectivity and high yield.

The invention belongs to the technical field of polymer synthetic materials, and particularly relates to bio-based MS resin and a preparation method thereof. The bio-based MS resin is a free radical copolymer of a methyl methacrylate monomer and a styrene monomer; the methyl methacrylate monomers comprise bio-based methyl methacrylate, isobornyl methacrylate and 3-pinane methacrylate, and the methyl methacrylate monomers comprise methyl methacrylate, isobornyl methacrylate and 3-pinane methacrylate; the styrene monomers comprise styrene and caffeic acid derivatives; based on 100% of the mass of the bio-based MS resin, the methacrylate monomer accounts for 30%; the molar ratio of caffeic acid derivatives to styrene in the styrene monomers is 1: (1-9). The synthesized bio-based MS resin has the characteristics of greenness and reproducibility, compared with petroleum-based MS resin, the performance of the MS resin can be regulated and controlled by designing a protecting group of a bio-based caffeic acid derivative so as to expand the application range of the MS resin, a specific functional group can be introduced to prepare a functional, advanced and high-performance polymer material, and the MS resin has a good market prospect.

The invention relates to the technical field of polypeptide synthesis, in particular to a synthesis method of retaglutide and the retaglutide prepared by the method. Comprising the following steps: synthesizing retaglutide side chain peptide resin through an Fmoc / tBu solid phase method; removing a Lys17 main chain protecting group Dde or Alloc, and sequentially coupling main chain protected amino acids or protected amino acid fragments to obtain retaglutide peptide resin; cracking the peptide resin by adopting an acidic mixed solution to obtain crude peptide; and performing HPLC (High Performance Liquid Chromatography) purification, salt conversion, concentration and freeze-drying on the crude peptide to obtain refined retaglutide. According to the retaglutide synthesis method provided by the invention, the purity of the obtained retaglutide product is greater than 99.0%, and the purity of a single impurity is less than 0.10%. The synthesis method is simple to operate, high in crude peptide purity, easy to purify and prepare, low in comprehensive synthesis cost and very suitable for industrial production.

The invention discloses a synthesis method of an insulin analogue, which comprises the following steps of: firstly, obtaining A-chain peptide resin by using a solid-phase synthesis method, constructing a disulfide bond between A6 and A11 on a solid phase, and cracking the A-chain peptide resin by using a cracking solution containing a sulfydryl activator to obtain a peptide chain with an activated sulfydryl group and a protected sulfydryl group; then a solid-phase synthesis method is used for obtaining B-chain peptide resin, Lys side chain protecting groups are removed on a solid phase in a fixed-point mode, side chain fatty acid modification is completed, and a peptide chain with an exposed sulfydryl group and a protected sulfydryl group is obtained after cracking is conducted through a cracking solution; and mixing the products in a solution according to a certain proportion to form a first pair of intermolecular disulfide bonds, and constructing and purifying the last pair of disulfide bonds to obtain the insulin analogue. The method disclosed by the invention has the advantages of convenience in synthesis, low cost, simple process and the like, can be used for research on amino acid mutation of insulin compounds, and has important practical significance on development of insulin drugs.

The present disclosure describes novel reagents and processes for preparing oligonucleotides, which have two or more nucleotides. In one embodiment, the reagent is represented by Formula I. wherein: W is O or NH; R1 is -H or a solid support; R2 is a silyl hydroxyl protecting group or an alloc protecting group, R3 is a nucleoside or a group represented by (II) wherein (III) represents the point of attachment for R3.

The invention discloses a preparation method of alplsutentan and an alplsutentan intermediate, alplsutentan is obtained by taking a compound SM1 as a raw material through a one-step method or a multi-step method, and the multi-step method comprises the following steps: reacting the compound SM1 with a compound SM2 to obtain an intermediate I; reacting the intermediate I with 2-[(5-bromo-2-pyrimidinyl) oxy] ethanol to obtain an intermediate II, or reacting the intermediate I with ethylene glycol to obtain an intermediate I-b, and then reacting with 5-bromo-2-chloropyrimidine or 5-fluoro-2-chloropyrimidine to obtain the intermediate II; and finally, removing a protecting group from the intermediate II to obtain alpoxivan. The one-step method comprises the following steps: when X in a compound SM1 is a fluorine atom, the compound SM1 is 5-(4-bromophenyl)-4, 6-difluoropyrimidine, and the compound SM1 reacts with sulfonamide and 2-[(5-bromo-2-pyrimidinyl) oxy] ethanol to directly obtain alpoxivan. The synthesis route is short, and the reaction conditions are mild.

The present invention relates to the field of drug synthesis, and specifically relates to a method for preparing a Zavegepant intermediate and a derivative thereof. Specifically, the method comprises reacting a compound of formula II with a compound of formula III to obtain a compound of formula I, reacting the compound of formula I with isoamyl nitrite to obtain compound V, and removing a protecting group from the compound of formula V to obtain a compound of formula VI or a salt thereof. On the basis of the preparation method provided by the present invention, the raw materials are readily available, the production cost is relatively low, there are fewer synthesis steps, and the operation is simpler and more convenient.

The invention discloses a preparation method of polypeptide with an anti-inflammatory effect. The preparation method comprises the following steps: S1, swelling resin; s2, removing Fmoc protecting groups of the resin; s3, washing the resin, and draining the cleaned resin to ensure that the resin reaches the cleanliness required by the next-step reaction; s4, amino acid coupling; s5, removing an Fmoc protecting group in the amino acid; s6, polypeptide cutting: preparing a cutting reagent, after the last amino acid is synthesized and the Fmoc group is removed, cleaning the resin, adding the cutting reagent, putting a synthesis tube into a shaking table, oscillating, cutting, collecting a cutting liquid into a centrifugal tube, and drying by blowing; s7, polypeptide purification; and S8, polypeptide freeze-drying: performing freeze-drying treatment on the purified polypeptide solution through a low-temperature freeze-drying machine to finally obtain solid powder of the target polypeptide. The anti-inflammatory effect can be improved, adverse reactions are reduced, toxic and side effects on the body in the anti-inflammatory process are reduced or eliminated, and the varieties of anti-inflammatory polypeptides are enriched.

The application discloses a PAG bonding type photosensitive photoresist resin and a preparation method and application thereof. The photoresist resin is as follows: formula. The PAG bonding type resin is prepared through the following reaction process: 1) performing a RAFT polymerization reaction on p-acetoxystyrene, p-styrene sulfonamide trifluoromethyl potassium salt and a RAFT chain transfer agent under the action of an initiator to obtain an intermediate I, 2) performing a hydrolysis reaction on the intermediate I to obtain an intermediate II, 3) performing a protection group introduction reaction on the intermediate II and di-tert-butyl dicarbonate to obtain an intermediate III; and 4) performing an ion exchange reaction on the intermediate III and triphenylsulfonium bromide. The application realizes the bonding of the PAG into the resin skeleton, and improves the problems of poor compatibility between the PAG and the resin, phase separation, uneven distribution of the PAG and the like. Therefore, the photoresist prepared from the resin has the photo-generated acid bound by the polymer main chain and limited diffusion, the resolution is improved, and the photoetching effect is excellent.

The invention belongs to the technical field of organic synthesis and medicinal chemistry, and discloses a total synthesis method of rhododendron heteroterpenin Rhododaurines A-C. The total synthesis method comprises the following steps: carrying out allyl stereoselective addition on a compound 3 and a compound 5 in a toluene solvent under the conditions of catalysis of n-butyllithium and low temperature of-78 DEG C, and constructing a chiral center to obtain a compound 6; removing a methoxy methyl (MOM) protecting group from the compound 6 under an acidic condition, cyclizing, and reacting to generate rhododaurine C (7); the rhododaurine C (7) is subjected to intramolecular [4 + 2] cycloaddition and oxidation reaction in the illumination and oxygen atmosphere of 300-385 nm, and rhododaurine B (8) and an epoxy epimer epinedodaurine B (9) are obtained; and carrying out protonation and rearrangement on the epidodaurine B (9) by virtue of acid catalysis cyclic ether, so as to generate the rhododaurine A (10). The method can overcome the defects that the content of rhododendron miscellaneous terpenoids Rhododaurines A-C in nature is extremely low, and large-scale extraction is difficult.

The invention provides semeglutide, which is synthesized by adopting the following method, and the specific steps are as follows: 1) segmenting the main chain of semeglutide into three polypeptide fragments: 7-14 sites, 15-22 sites and 23-37 sites; (2) respectively preparing the 7-14-site fragments, the 15-22-site fragments and the 23-37-site fragments through solid-phase synthesis; 3) connecting the 7-14-site fragment with the 15-22-site fragment to form a 7-22-site fragment, and activating the C end of the fragment into active ester; (4) selectively removing an Alloc protecting group of Lys26 in the 23-37-site fragment, and then carrying out fatty acid modification to obtain a modified 23-37-site fragment; 5) in a liquid phase system, coupling the activated 7-22-site fragment and the modified 23-37-site fragment according to a molar ratio of 1: (0.6-1.4) to form a complete polypeptide chain; and 6) removing the protecting group and purifying to obtain a semaglutide finished product. The method provided by the invention can effectively realize high-purity, high-yield and low-cost synthesis of the semeglutide bulk drug.

Provided is an adhesive composition comprising: a compound that generates an acid by at least one of heating or irradiation with an active energy ray; and a protected compound that has, in the molecule, a hydrophilic group protected by a protective group, said hydrophilic group being deprotected by the acid.

The invention provides a synthesis method of tilpotide, which comprises the following steps: dividing a target peptide chain into six fragments, and adopting bis (4-C18-C28 alkoxy phenyl) methylamine, 2, 4-bis (18-C28 alkoxy)-benzyl alcohol and NH2-Asp (OTAG)-OR1 as hydrophobic label carriers to assist synthesis. A side chain carboxyl group of aspartic acid is innovatively used as an anchoring position of a hydrophobic label, a new fragment connection route is designed, a full-protection tilpotide conjugate is synthesized through a multi-label synergistic effect, and finally a protecting group and a label are removed by using a TFA lysate. Compared with a solid-phase synthesis method, the method is carried out in a homogeneous reaction, the dosage of amino acid and the condensing agent is reduced to 1-1.2 times from 2-3 times, and the cost is remarkably reduced. Compared with an existing hydrophobic labeling method, the method has the advantages that multiple labels can be introduced to serve as protecting groups, the yield and purity of synthesis of medium-chain and long-chain polypeptides are improved, meanwhile, the problem of hydrophobicity attenuation caused by peptide chain extension is solved, and the green chemical process requirement is met.

The invention discloses a synthesis process of chiral cyclic ether indole. The synthesis process comprises the following steps: reacting 4-bromobenzaldehyde with malonic acid under the catalysis of piperidine to generate olefin carboxylic acid CHP-1; carrying out condensation reaction to prepare CHP-2; under the catalysis of a copper reagent, carrying out Michael addition reaction to obtain CHP-3; preparing a chiral alcohol intermediate CHP-4 through a reduction reaction; trifluoromethanesulfonic acid is used, and a chiral ether intermediate CHP-5 is prepared through ring closing; reacting with protected hydrazine by using a copper ion catalyst to obtain an intermediate CHP-6; the method comprises the following steps: by taking alcohol as a solvent, adding strong acid, and removing a protecting group of hydrazine to obtain an intermediate CHP-7; and carrying out ring closing by taking lewis acid as a catalyst to obtain an indole product CHP-8. The use of a noble metal catalyst palladium is avoided, and the cost is greatly reduced. The chiral center is directly constructed through a chemical method, and SFC is not needed for resolution, so that the cost is remarkably reduced, and industrial production is successfully realized.

The invention discloses a preparation method of protecting group cefdil side chain acid. The preparation method comprises the following reaction steps: step 1, performing oximation reaction on a compound IV to obtain a compound V; 2, cyclizing the compound V and thiourea to obtain a compound VI; 3, condensing the compound VI and tert-butyl alpha-bromoisobutyrate to obtain a compound VII; 4, the compound VII passes through a protective group to obtain a compound VIII; and 5, hydrolyzing the compound VIII to obtain the product protecting group cefdil side chain acid. The raw materials used in the method are simple and easy to obtain, expensive reagents and customized raw and auxiliary materials are not used, the process operation is simple, a major dangerous process is not involved, and the method has industrial advantages.

Provided is a method for producing a protected glycoside derivative, including reacting a sugar in which all hydroxyl groups of the sugar are protected by protective groups and protective groups of a hydroxyl group at a 1-position and a hydroxyl group at a 2-position are acyl groups, with a phenolic compound in the presence of at least one catalyst selected from the group consisting of trifluoromethanesulfonic acid and copper (II) trifluoromethanesulfonate, in which the phenolic compound is bonded to an anomeric position of the sugar and other hydroxyl groups of the sugar are protected.

The present disclosure relates to peptide compounds and conjugate compounds, processes, methods and uses thereof for treating cancer. For example, the compounds can comprise compounds of formula(SEQ ID NO: 1)X1X2X3X4X5GVX6AKAGVX7NX8FKSESY(I)(SEQ ID NO: 2)(X9)nGVX10AKAGVX11NX12FKSESY(II)(SEQ ID NO: 3)YKX13LRRX14APRWDX15PLRDPALRX16X17L(III)(SEQ ID NO: 4)YKX18LRR(X19)nPLRDPALRX20X21L(IV)(SEQ ID NO: 5)IKLSGGVQAKAGVINMDKSESM(V)(SEQ ID NO: 6)IKLSGGVQAKAGVINMFKSESY(VI)(SEQ ID NO: 7)IKLSGGVQAKAGVINMFKSESYK(VII)(SEQ ID NO: 8)GVQAKAGVINMFKSESY(VIII)(SEQ ID NO: 9)GVRAKAGVRNMFKSESY(IX)(SEQ ID NO: 10)GVRAKAGVRN(Nle)FKSESY(X)(SEQ ID NO: 11)YKSLRRKAPRWDAPLRDPALRQLL(XI)(SEQ ID NO: 12)YKSLRRKAPRWDAYLRDPALRQLL(XII)(SEQ ID NO: 13)YKSLRRKAPRWDAYLRDPALRPLL(XIII)wherein X1 to X21 and n can have various different valuesand wherein at least one protecting group and / or at least one labelling agent is optionally connected to said peptide compound at an N- and / or C-terminal end.

The present invention provides a paroxysmal hemoglobinuria indication drug ipropam key intermediate synthesis method, and relates to the technical field of ipropam, the method comprises: taking p-bromobenzaldehyde as an initial raw material, adopting an S-configuration catalyst to obtain an intermediate 03, carrying out protection group removal on the intermediate 03, carrying out automatic ring closing to obtain an intermediate 04, and carrying out post-treatment to obtain the paroxysmal hemoglobinuria indication drug ipropam key intermediate. Reducing the intermediate 04 with sodium borohydride to obtain a single cis-configuration intermediate 05, then carrying out a chiral flip reaction and hydrolysis to remove p-nitrobenzoic acid, then carrying out an etherification reaction with diethyl sulfate to obtain an intermediate 08, reducing amide of the intermediate 08 with sodium borohydride and boron trifluoride diethyl etherate to obtain an intermediate 09, then carrying out an acetylation reaction to protect amino, and finally carrying out a reaction to obtain the chiral cis-configuration intermediate 03. Cuprous cyanide is subjected to a cyanation reaction and a hydrolytic esterification reaction to obtain the ipropam key intermediate TM. The method is low in raw material price, high in chiral control selectivity, easy in reaction condition control and low in equipment requirement, avoids column chromatography and other operations, and is more suitable for industrial production.

The invention provides a deuterium-labeled quetiapine fumarate isotope compound, a preparation method thereof and a food detection method, and relates to the technical field of food detection. The deuterium-labeled quetiapine fumarate isotope compound is obtained by introducing deuterated Boc piperazine to react with 11-chlorodibenzo [b, f] [1, 4] thiazepine, then removing a protecting group and grafting 2-chloroethoxyethanol. According to the preparation method provided by the invention, by screening proper reaction reagents and optimizing the reaction temperature and the reaction duration, the product conversion rate is greatly improved, and stable mass production in the industry is facilitated. The chemical purity of the deuterium-labeled quetiapine fumarate obtained by the preparation method provided by the invention can reach 98.3% or above, the isotope abundance exceeds 97%, and the deuterium-labeled quetiapine fumarate can be used as an internal standard substance in the field of food quality inspection, and has important practical application value.

The invention relates to the technical field of compound synthesis, in particular to an intermediate of gepodalin, a preparation method of the intermediate and a preparation method of gepodalin. The intermediate of gepodamycin is selected from any one of compounds shown in the following structural formula, and in the formula, X represents halogen, and R1 represents a hydroxyl protecting group; r2 represents an amino protecting group, and R3 represents a C1-C10 alkyl group. The intermediate can be synthesized to obtain the core intermediate of gepodamycin through a series of new synthesis steps, and the yield, the purity and the post-treatment difficulty of the core intermediate can be improved, so that the production cost of gepodamycin is greatly reduced.

The invention discloses an oligonucleotide synthesis process of a sulfo-PMO structure. In the oligonucleotide synthesis process of the sulfo-PMO structure, the molecular structural formula of sulfo-PMO is shown in the specification. According to the invention, the molecular structure of thio-PMO is specifically limited, and the synthesis of nucleotide phosphate amide and (thio) phosphoric acid amide in the solid-phase synthesis oligonucleotide is carried out along the direction from 5'to 3 ', that is, in each cycle period, the O5'or O6' position of the nucleotide phosphate amide and (thio) phosphoric acid amide monomer is firstly subjected to coupling reaction, and then the protecting group is removed at the O3 'or N3' position, so that the oligonucleotide phosphate amide and (thio) phosphoric acid amide are obtained. And releasing active hydroxyl or amino / amido to enter the next cycle. The protecting group adopted by the sulfo-PMO molecule is consistent with the protecting groups of other nucleotides, so that the conversion rate of each step of coupling reaction can be conveniently detected on line.