C2-amine boryl substituted adenosine, adenosine monophosphate and analogues thereof, and preparation method and application of C2-amine boryl substituted adenosine and adenosine monophosphate

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to C2-amine boryl substituted adenosine, adenosine monophosphate and analogues thereof, a preparation method and an application of the C2-amine boryl substituted adenosine and adenosine monophosphate. The method comprises the following steps: dissolving a substrate and a boron free radical precursor in a solvent, adding or not adding an acid, adding an oxidizing agent, and carrying out illumination (a photocatalyst needs to be added under the illumination condition) or heating to initiate a reaction, so as to obtain C2-amine borane substituted adenosine, adenosine monophosphate and analogues thereof. The method provided by the invention has the advantages of mild reaction conditions, simple operation, easily available reaction reagents, and wide adaptability to substrates substituted by different groups. The amine borane in the compound structure provided by the invention can be converted through functional groups to synthesize C2-hydroxyl, aryl, deuterated adenosine and adenosine acid compounds. A series of obtained nucleoside compounds have good application prospects and research values.

Description

Technical Field

[0001] The present invention belongs to the technical fields of chemistry and medicine, and particularly relates to a C2-aminoboranyl-substituted adenosine, adenylic acid and analogues thereof, a preparation method and applications thereof. Background Art

[0002] Adenosine widely exists in biological organisms, is a precursor of adenine nucleotides and the basic energy currency in organisms - ATP, can be generated by the degradation of ATP during energy consumption processes, and effectively regulates cell growth, differentiation and death. In addition, adenosine can also act as a signaling molecule to activate adenosine receptors, thereby triggering a series of physiological or pathological changes. Currently, four adenosine receptors have been discovered, namely: A1, A2A, A2B, and A3 receptors, which are closely related to various biological functions, including heart rhythm and circulation regulation, lipid degradation, renal blood flow, immune function, sleep regulation and angiogenesis, as well as inflammatory diseases, ischemia-reperfusion and neurodegenerative diseases, etc. Among them, adenosine A3 receptor (A3AR) is highly expressed in a variety of tumor cell lines and tumor tissues, and under the action of low-concentration agonists, A3AR activation can inhibit the proliferation of a variety of tumor cells while stimulating myelopoiesis. Therefore, low-concentration A3AR natural ligands or synthetic agonists may become a new method for tumor treatment.

[0003] Although adenosine molecules, as natural adenosine receptor agonists, have broad application prospects in disease treatment. However, due to the fact that adenosine molecules are easily metabolized by the body, have an extremely short half-life (less than 10 seconds), and have poor selectivity for AR subtypes, it is particularly important to develop AR agonists with long-lasting effects, strong specificity and low toxicity and side effects for targeted treatment of certain specific diseases. So far, many adenosine analogues with chemical structures similar to adenosine molecules have been synthesized and developed. For example, cladribine, fludarabine phosphate and clofarabine have been officially approved as drugs for the treatment of leukemia; vidarabine has been officially approved for the treatment of hepatitis B and herpes virus infections; adefovir dipivoxil, tenofovir disoproxil fumarate and tenofovir alafenamide have become the most commonly used drugs for the treatment of hepatitis B; remdesivir has been urgently approved for the treatment of severe patients with novel coronavirus infection (SARS-Cov-2); cangrelor and ticagrelor, as ATP analogues, are a class of P2Y12 platelet inhibitors used to prevent coronary artery obstruction or stenosis. In addition, the anti-cancer activities of drugs such as cladribine, 8-chloro-adenosine (8-Cl-Ado), pentostatin, cordycepin, etc. have also been verified in clinical trials.

[0004] Studies on the structure-activity relationship (SAR) of anticancer activity of adenosine analogs with adenine ring modification have shown that C2-modified adenosine analogs have good anticancer activity, such as clofarabine, cladribine, and fludarabine, etc. They all belong to adenosine receptor agonists with halogen atoms introduced at the C2 position of the adenine ring. And the amino group at the C6 position is a necessary group to maintain its anticancer activity. For example, compared with adenosine, N6-cyclopentyladenosine reduces cytotoxicity after amino modification at the C6 position.

[0005] Currently, the names and structures of the marketed adenosine analog drugs are as follows:

[0006]

[0007]

[0008] And the names and structures of the adenosine analog drugs that are entering clinical trials are as follows:

[0009]

[0010] Long-term treatment with nucleoside (nucleotide) analogs can effectively reduce the risk of cancer or infectious diseases, but it also leads to drug resistance in patients. On the other hand, with the emergence of more and more new viruses, such as SARA-Cov-2 that broke out in 2019, the current nucleoside drugs are far from meeting the treatment needs. In order to overcome the problem of drug resistance and create more novel-structured nucleoside analogs, it is extremely necessary to develop new organic synthesis methodologies suitable for further chemical modification of existing nucleoside (nucleotide) drugs. For example, besifovir, a hepatitis B treatment drug in clinical research, is further modified from adefovir or tenofovir. Adenosine analogs with simultaneous modification at C2 and C8 of the adenine ring, or simultaneous modification of the adenine ring and the ribose ring, have even broader research value, and these nucleoside analogs may become important sources of antiviral and antitumor drugs. In addition, adenosine analogs have great potential to be developed into cardiovascular drugs because they can act as agonists or antagonists of purinergic P receptors and adenosine A receptors. A large number of other studies have shown that adenosine analogs with substituents introduced at the 2 position have the effect of resisting degradation by adenosine deaminase or adenosine kinase. Then, once 2-substituted adenosine compounds are developed into drugs, they can exert more lasting drug effects compared with the 2-unsubstituted analogs.

[0011] Although 2-substituted adenosines have various important functions, to date, not only is the type of substituent at the 2-position of adenosine very limited, but also the organic synthesis methods for directly functionalizing the 2-position of adenosine are extremely scarce. In addition to de novo synthesis, the previous methods for introducing substituents at the 2-position of adenosine mainly include the following four: (1) Starting from 2’,3’,5’-OAc-2-aminoadenosine, 2-haloadenosine compounds are prepared by diazotization / halogenation reactions of the amino group at the 2-position; 2-azidoadenosine is also prepared by a similar method ( Figure 1 a) in Figure 1 ). (2) Using a base such as lithium 2,2,6,6-tetramethylpiperidide to deprotonate the 2- and 8-positions of 2’,3’,5’-OTBDMS-6-chloropurine nucleoside, the resulting 2-position carbanion undergoes a nucleophilic substitution reaction with tributyltin chloride (Bu3SnCl), thereby introducing a tributyltin group (-SnBu3) at the 2-position of adenosine. The tin group can be transformed into a series of functional groups such as halogen, aryl, benzyl, allyl, alkenyl, and alkynyl ( Figure 1 b)(1) in Figure 1 ); in addition, the 2-position carbanion can also be directly captured by an electrophile to produce more diverse substituted products at the 2-position ( Figure 1 b)(2) in

[0012] ). (3) 2-Nitroadenosine is synthesized by introducing a nitro group at the 2-position of 2’,3’,5’-OAc-6-chloropurine nucleoside ( Figure 1 c) in Figure 1 ). (4) After oxidation at the N1-position, followed by hydrolysis and ring opening, and then re-cyclization using CS2. On the other hand, the in-situ generated H2S acts as a reducing agent to reduce the nitrogen oxide, producing the final product - 2-mercapto / thioether group-substituted adenosine compounds ( Figure 1 d) in

[0012] ). Most of the above synthesis methods use hydroxyl-protected adenosines, and in order to ensure the smooth progress of the reaction, a -Cl atom is often introduced at the C6-position instead of the final amino -NH2; in addition, the introduction of substituents also depends on the transformation of other pre-introduced functional groups. Therefore, it is extremely necessary to develop more direct and efficient methods for synthesizing C2-substituted adenosines and their analogs.

[0012] The radical Minisci reaction is an effective method for introducing substituents onto heteroarenes and has played a quite important role in the post-modification of drug molecules in recent years. An organic small molecule compound library derived from the same precursor with diverse structures provides a variety of choices for drug screening. The Minisci reaction of the purine ring has also attracted the interest of numerous scholars. However, the methods developed in recent years for the post-modification of the purine ring via the Minisci reaction mainly focus on introducing substituents at the 6-position, and in most cases, an N9-protected purine ring without a glycosyl group is used. For example, substituents such as alkyl, cycloalkyl, aryl, acyl, hydroxymethyl, 1-hydroxyalkyl, etc. are introduced at the 6-position. In addition, there are also some reports involving the introduction of substituents at the 8-position of the purine ring via the Minisci reaction, such as aminoacyl, alkoxy, α-oxyalkyl, difluoromethyl, trifluoromethyl, or polyfluoroalkyl, etc. Although the Minisci reaction of unprotected adenosine at the 2-position can be traced back to the 1970s ( Figure 2 a) in Figure 2 ), however, due to reasons such as poor regioselectivity and low yield at the 2- and 8-positions, no progress has been made in the past 50 years. Introducing an acyl protecting group on the 6-amino group usually only enhances the selectivity at the 8-position ( Figure 2 b) in Figure 2 ). In the Minisci reaction reported by Sherwood in 2018 using carboxylic acid active esters as radical precursors, there is an example of introducing a cyclohexyl group at the 2-position of adenosine, but the yield is extremely low (11%, Figure 2 c) in 6 ). In addition, the Jemielity research group reported the trifluoromethylation reaction of N 6 ,2’,3’,5’-tetraacetyladenosine in 2020. However, this reaction not only has a low overall yield but also has no regioselectivity at all. The reaction produces the following three trifluoromethyl-substituted products: C2-monosubstituted product (10%), C8-monosubstituted product (9%), and C2,C8-disubstituted product (7%) ( Figure 2 d) in Figure 2 ). In the Minisci alkylation reaction reported by Molander in 2017 using alkyl trifluoroborates as radical precursors, there is an example of the alkylation reaction at the 2-position of 6-benzylaminopurine ( Figure 2 e) in Figure 2 ). In addition, in the Minisci alkylation reaction of the amino α-position radical reported by Berthelot in 2018, there is also an example of the selective functionalization at the 2-position of 6-chloropurine ( Figure 2 f) in 3 ). For the above two reactions, although excellent regioselectivity is achieved, the substrates used are not natural adenosines containing glycosyl groups, and only the construction of the C(2)-C(sp 3 ) bond at the 2-position can be realized. Then, there remains a question as to whether excellent C2-position selectivity can be achieved for natural adenosine / deoxyadenosine containing ribose or deoxyribose units.

[0013] So far, no construction of the C-B bond at the 2-position of adenosine has been found. If the C-B bond at the 2-position of adenosine can be successfully constructed, it will be expected to be used in the synthesis of more diverse 2-substituted adenosine compounds and the construction of compound libraries, thus facilitating the research and discovery of new adenosine drugs. Summary of the Invention

[0014] In view of the deficiencies in the prior art, the present invention provides an adenosine analog, namely C2-aminoboryl-substituted adenosine, adenylic acid and their analogs, and also provides a preparation method and application of C2-aminoboryl-substituted adenosine, adenylic acid and their analogs. A series of C2-aminoboryl-substituted adenosine, adenylic acid and their analogs are synthesized for the first time by this method, and the reaction conditions are mild. Compared with the de novo synthesis route of other C2-substituted adenosine analogs, the reaction steps are short and the atom economy is high.

[0015] The object of the present invention is achieved by the following technical solutions:

[0016] In the first aspect, the present invention provides a C2-aminoboryl-substituted adenosine, adenylic acid and their analogs, which have the chemical structures shown in the following general formulas (I), (II), (III), (IV), (V) or (VI):

[0017]

[0018] Among them, R 1 is selected from the following groups:

[0019]

[0020] For the above R 1 in each group, R 6 and R 7 are each selected from OH, H, F, Cl, Br, I, OMe, OEt, OCH2CH2OCH3, OAc, N3, SH; Z is selected from N, O, C, S; R 8 is selected from H, OH, ODMTr, OAc;

[0021] R 2 is selected from the following groups: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;

[0022] R 3 is selected from the following groups:

[0023]

[0024] For the above R 3In each group, Alkyl is a substituted or unsubstituted alkyl group, and Aryl is a substituted or unsubstituted aryl or heteroaryl group;

[0025] R 4 is selected from the following groups: a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or any group represented by the following structures:

[0026]

[0027] R 5 is selected from the following groups: H, F, CN;

[0028] The nitrogen-containing heterocycle in formula (V) is selected from the groups represented by any of the following structures:

[0029]

[0030] L is selected from any of the following neutral molecules:

[0031] NHMe2

[0032]

[0033] Preferably, the R 2 、R 3 、R 4 In the groups, the substituted or unsubstituted alkyl group can be a C1-C6 alkyl group, a C3-C20 cycloalkyl group, a 3- to 20-membered non-aromatic heterocycloalkyl group; the substituted or unsubstituted aryl group can be a C6-C20 aryl group, a C7-C25 alkyl-aryl group; the substituted or unsubstituted heteroaryl group can be a 3- to 20-membered heteroaryl group, a C1-C5 alkyl-3- to 20-membered heteroaryl group. Among them, the heteroaryl or heterocyclic group has 1-5 heteroatoms selected from the following: N, O or S; the cycloalkyl or heterocyclic group can be a monocyclic, polycyclic, spirocyclic or bridged ring structure.

[0034] In a second aspect, the present invention provides a method for preparing a C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs, the method comprising the following steps: dissolving a substrate (1) and a boron radical precursor (2) in a solvent, then adding or not adding an acid, adding an oxidant, and reacting under light or heating conditions to obtain a C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs (3). The reaction formula is as follows:

[0035]

[0036] Preferably, the substrate is selected from adenosine, adenylic acid or adenosine analogs;

[0037] The boron radical precursor is selected from the compounds shown in the following structures:

[0038]

[0039] Preferably, the molar ratio of the substrate to the boron radical precursor is 1:3 to 8.

[0040] Preferably, the acid is selected from Lewis acids or Bronsted acids;

[0041] Preferably, the Lewis acid is at least one of zinc chloride, magnesium chloride, lithium chloride, silver nitrate, scandium trifluoromethanesulfonate, and yttrium trifluoromethanesulfonate; more preferably, the Lewis acid is at least one of magnesium chloride, lithium chloride, and zinc chloride.

[0042] Preferably, the Bronsted acid is at least one of formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, and trifluoromethanesulfonic acid; more preferably, the Bronsted acid is at least one of formic acid and acetic acid.

[0043] Preferably, the solvent is at least one of acetonitrile, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, and water; more preferably, the solvent is a mixed solvent composed of water and any other solvent; most preferably, the solvent is a mixed solvent of acetonitrile and water.

[0044] Preferably, the oxidant is at least one of ammonium persulfate, potassium persulfate, sodium persulfate, tert-butyl peroxybenzoate, tert-butyl hydroperoxide, and di-tert-butyl peroxide; more preferably, the oxidant is ammonium persulfate.

[0045] Preferably, the molar ratio of the Lewis acid to the substrate is 0.8 to 2:1;

[0046] The molar ratio of the Bronsted acid to the substrate is 2 to 15:1;

[0047] The molar ratio of the oxidant to the substrate is 2 to 4:1;

[0048] The ratio of the solvent to the substrate is 20 to 40 mL:1 mmol.

[0049] Preferably, when the reaction is carried out under light conditions, the specific reaction conditions are: at room temperature for 48 to 72 hours under a protective atmosphere and in the presence of a photocatalyst, with a light condition of 10 to 100 W blue light irradiation. If the blue light lamp used is lower than 10 W, the yield will be reduced.

[0050] Preferably, the photocatalyst is at least one of Ir(ppy)3, Ru(bpy)3(PF6)2, MesAcr(BF4), Ir[dF(CF3)ppy]2(dtbbpy)(PF6), Ru(bpz)3(PF6)2, Ru(DMB)3(PF6)2, Eosin Y, 4CzIPN, 3CzClIPN, Rosebengal. More preferably, the photocatalyst is at least one of 4CzIPN, Ru(bpy)3(PF6)2, Ru(bpz)3(PF6)2, Ru(DMB)3(PF6)2. Most preferably, the photocatalyst is 4CzIPN.

[0051] Preferably, when the reaction is carried out under heating conditions, the specific reaction conditions are: under a protective atmosphere, reacting at 35-55 °C for 8-36 hours.

[0052] Preferably, the protective atmosphere is nitrogen or argon.

[0053] The present invention also provides an application of the aforementioned C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs in the preparation of C2-hydroxy, aryl, deuterated adenosine, adenylic acid and their analogs, and the C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs are synthesized into the C2-hydroxy, aryl, deuterated adenosine, adenylic acid and their analogs by converting the C2-aminoboranyl functional group in their structures.

[0054] Compared with the prior art, the present invention has the following beneficial effects:

[0055] 1) The present invention synthesizes a series of C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs with a C-B bond at the 2-position for the first time. And due to the boron functional group can undergo rich functional group conversions through a series of chemical reactions such as oxidation reaction, fluorination reaction, Chan-Lam coupling reaction and Suzuki-Miyaura coupling reaction, etc., and thus be converted into a series of functional groups such as hydroxyl, fluorine, amino, alkoxy, thioether, aryl, etc. (constructing C-C bonds or C-heteroatom bonds), and then it is expected to be used in the synthesis of more diverse 2-substituted adenosine compounds and the construction of compound libraries, which is conducive to the research and discovery of new adenosine drugs.

[0056] 2) The present invention relates to a method for boron modification of adenine nucleoside compounds. The starting materials used are inexpensive and readily available, do not require protecting groups, and can omit a series of cumbersome operations such as introducing protecting groups and removing protecting groups. It has extremely high step economy and atom economy, convenient experimental operation, and high yield. When the boron radical precursor used in the reaction undergoes a Minisci reaction with the adenine ring in the adenosine compound, unexpectedly excellent 2-position selectivity is achieved, thereby obtaining a specific adenosine product with boron modification at the 2-position. Compared with the existing de novo synthesis methods of 2-substituted adenosine compounds, it can reduce the investment of funds and labor, and provides a new, simple and efficient route method for the preparation of 2-functionalized adenosine compounds. Therefore, the present invention has good practical value and has great reference significance for the process development of adenine nucleoside derivatives and downstream products. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] By reading the detailed description of the non-limiting embodiments with reference to the following drawings, other features, objects, and advantages of the present invention will become more apparent:

[0058] Figure 1 is the existing preparation route for introducing a substituent group at the 2-position of adenosine;

[0059] Figure 2 is the existing method for introducing a substituent group on the purine ring based on the Minisci reaction;

[0060] Figure 3 is the reaction mechanism for the preparation of C2-aminoborylated adenosine, adenosine monophosphate, and their analogs under light conditions in the present invention;

[0061] Figure 4 is the reaction mechanism for the preparation of C2-aminoborylated adenosine, adenosine monophosphate, and their analogs under heating conditions in the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0062] The present invention will be described in detail below with reference to specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that those of ordinary skill in the art can make several modifications and improvements without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0063] The following examples provide a method for C2-borylation modification of adenosine, adenylate and their analogs, including the following steps: Dissolve the substrate and the boron radical precursor in a solvent, then add a photocatalyst, an oxidant, a Lewis acid or a Bronsted acid, and react under light irradiation for 48 to 72 hours to obtain C2-aminoborane-modified adenosine, adenylate and their analogs; or, dissolve the substrate and the boron radical precursor in a solvent, then add an oxidant, a Lewis acid or a Bronsted acid, and react at 35 to 55 °C for 8 to 36 hours to obtain C2-aminoborane-modified adenosine, adenylate and their analogs.

[0064] Under the above conditions, the corresponding C2-aminoboranylated adenosine, adenylate and adenosine analogs can be prepared.

[0065] The reaction mechanism for preparing C2-aminoboranylated adenosine, adenylate and their analogs in the present invention is divided into two types: light irradiation condition and heating condition:

[0066] (I) Reaction mechanism under light irradiation condition (as shown in Figure 3 ): The reaction is initiated by the irradiation of blue light on the photocatalyst. After the photosensitizer obtains light energy, it becomes an excited state with a longer lifetime; the excited photosensitizer performs single-electron reduction on the persulfate (S2O8 2- ), thereby causing S2O8 2- to cleave into one molecule of sulfate (SO4 2- ) and one molecule of sulfate anion radical species (SO4 ·- ); after a polar-matched H atom transfer process (HAT) occurs between the aminoborane (such as Me3N-BH3) and the sulfate anion radical (SO4 ·- ), boron radical and hydrogen sulfate are generated; the boron radical undergoes 2-position selective addition to the adenine ring activated by metal ions or protons, generating a cation radical species with a C-B bond; after being single-electron oxidized by the oxidized photosensitizer, this cation radical eliminates a proton and releases the product; in addition, the C2-borylated adenosine cation radical can also be single-electron oxidized by the persulfate (S2O8 2- ) (radical chain reaction), and then generates the product after eliminating a proton; or, after the C2-borylated adenosine cation radical is abstracted by the hydrogen radical of the sulfate anion radical (SO4 ·- ), the product is generated.

[0067] (II) Reaction mechanism under heating condition (without photocatalyst, without light irradiation, as shown in Figure 4 ): The peroxide bond in the persulfate (S2O8 2- ) undergoes homolytic cleavage under heating, generating sulfate anion radical species (SO4 ·-); After a polarity-matched hydrogen atom transfer process (HAT) occurs between amine borane (such as Me3N-BH3) and sulfate anion radical (SO4 ·- ), borane radical and hydrogen sulfate are generated; the borane radical undergoes a 2-position selective addition to the adenine ring activated by metal ions or protons, generating a cation radical species with a C-B bond; this cation radical is monoelectron oxidized by persulfate (S2O8 2- ) and eliminates a proton to form a product; alternatively, it is directly abstracted by sulfate anion radical (SO4 ·- ) to extract a hydrogen radical, generating hydrogen sulfate (HSO4 - ), and releasing the product.

[0068] Based on the above methods and reaction mechanisms, C2-aminoboranylated modified adenosine, adenosine monophosphate or their analogs with structures shown in the following general formulas (I), (II), (III), (IV) or (V) can be prepared:

[0069]

[0070] Among them, R 1 is selected from the following groups:

[0071]

[0072] In each of the above R 1 groups, R 6 and R 7 each is selected from OH, H, F, Cl, Br, I, OMe, OEt, OCH2CH2OCH3, OAc, N3, SH; Z is selected from N, O, C, S; R 8 is selected from H, OH, ODMTr, OAc;

[0073] R 2 is selected from the following groups: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl;

[0074] R 3 is selected from the following groups:

[0075]

[0076] In each of the above R 3 groups, Alkyl is substituted or unsubstituted alkyl, Aryl is substituted or unsubstituted aryl or heteroaryl;

[0077] R 4 is selected from the following groups: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or any of the following groups:

[0078]

[0079] R 5 is selected from the following groups: H, F, CN;

[0080] The nitrogen-containing heterocycle in formula (V) is selected from any one of the following groups:

[0081]

[0082] L is selected from any one of the following neutral molecules:

[0083] NHMe2

[0084]

[0085] Example 1 (photoreaction conditions):

[0086] Synthesis of (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0087]

[0088] Add adenosine (0.20 mmol, 54 mg) shown in formula 1a, borane-trimethylamine complex (1.1 mmol, 81 mg) shown in formula 2a, 4CzIPN (0.01 mmol, 8 mg), magnesium chloride (0.2 mmol, 19 mg), ammonium persulfate (0.4 mmol, 92 mg), 2 mL of ultrapure water and 2 mL of acetonitrile into a 25 mL Schlenk tube with a magnetic stir bar. The reaction mixture was frozen into a solid under a nitrogen atmosphere, evacuated, and purged with N2 for protection, and then thawed. After repeating three times, the reaction tube was placed under two 20 W blue light lamps and irradiated at room temperature for 72 hours. The reaction was monitored by LC-MS. After stopping the reaction, the pH value of the reaction solution was adjusted to 9-10 with 1 M aqueous NaOH solution, and the solvent was removed by a freeze dryer. The obtained residue was purified by column chromatography to obtain 58.0 mg of the target compound C2-trimethylamine boranyl-substituted adenosine shown in formula I-1, with a yield of 86%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results were as follows: 11H NMR (400 MHz, D2O) δ 8.43 (s, 1H), 6.15 (d, J = 5.6 Hz, 1H), 4.47 - 4.40 (m, 1H), 4.27 (dd, J = 6.8, 3.6 Hz, 1H), 3.90 (dd, J = 12.8, 2.8 Hz, 1H), 3.82 (dd, J = 12.8, 3.8 Hz, 1H), 2.74 (s, 9H); 13 13C NMR (125 MHz, D2O) δ 149.8, 148.5, 142.3, 117.0, 88.4, 85.6, 73.9, 70.3, 61.2, 51.9; 11 11B NMR (160 MHz, DMSO) δ -5.20.

[0089] Example 2 (Heating reaction conditions):

[0090]

[0091] Add adenosine (0.20 mmol, 54 mg) shown in formula 1a, borane - trimethylamine complex (1.1 mmol, 81 mg) shown in formula 2a, magnesium chloride (0.2 mmol, 19 mg) and ammonium persulfate (0.4 mmol, 92 mg) into a 25 mL Schlenk tube with a magnetic stir bar. After sealing with a rubber stopper, evacuate with a double - manifold for 5 minutes, replace with N2 gas for protection, and repeat the evacuation and replacement operation 3 times. Add 4 mL of pre - deoxygenated mixed solvent (containing 2 mL of ultrapure water and 2 mL of acetonitrile) using a syringe. Place the reaction tube in an oil bath at 50 °C and heat with stirring for 36 hours. Monitor the reaction by LC - MS. After stopping the reaction, adjust the pH value of the reaction solution to 9 - 10 with 1 M aqueous NaOH solution, remove the solvent with a freeze - dryer, and purify the obtained residue by column chromatography to obtain 54.0 mg of the target compound C2 - trimethylamine boranyl - substituted adenosine shown in formula I - 1, with a yield of 80%. The characterization results of the obtained target compound are the same as those in Example 1.

[0092] Example 3 (Gram - scale reaction):

[0093]

[0094] Add adenosine shown in Formula 1a (4 mmol, 1.08 g), borane-trimethylamine complex shown in Formula 2a (22 mmol, 1.62 g), 4CzIPN (0.2 mmol, 158 mg), magnesium chloride (4 mmol, 0.38 g), ammonium persulfate (8 mmol, 1.84 mg), 40 mL of ultrapure water and 40 mL of acetonitrile into a 250 mL round-bottom flask equipped with a magnetic stir bar. The reaction mixture was frozen into a solid under a nitrogen atmosphere, evacuated, and purged with N2 for protection, and then thawed. After repeating this three times, the reaction tube was placed under two 20 W blue light lamps and irradiated at room temperature for 72 hours. The reaction was monitored by LC-MS. After stopping the reaction, the pH value of the reaction solution was adjusted to 9 - 10 with 1 M aqueous NaOH solution, and the solvent was removed by a freeze dryer. The obtained residue was purified by column chromatography to obtain 0.82 g of the target compound C2-trimethylamine boranyl-substituted adenosine shown in Formula I-1, with a yield of 61%.

[0095] Example 4:

[0096] Synthesis of (2R,3R,4R,5R)-5-(6-amino-2-boraneyl-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol trimethylamine complex

[0097]

[0098] For the specific operation, refer to Example 1. The substrate used was 2'-deoxy-2'-fluoroadenosine shown in Formula 1b, and the boron radical precursor was borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-2 was 72%. The obtained target compound was analyzed by 1H NMR, 13C NMR, 19F NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results were as follows: 1 1H NMR (400 MHz, MeOD) δ 8.44 (s, 1H), 6.30 (dd, J = 16.4, 2.4 Hz, 1H), 5.28 (ddd, J = 52.8, 4.4, 2.4 Hz, 1H), 4.48 (ddd, J = 18.0, 6.8, 4.4 Hz, 1H), 4.07 - 4.03 (m, 1H), 3.86 (dd, J = 12.4, 2.4 Hz, 1H), 3.69 (dd, J = 12.6, 3.0 Hz, 1H), 2.77 (s, 9H); 13 13C NMR (125 MHz, MeOD) δ 168.7, 150.5, 148.4, 141.0, 116.6, 94.0 (d, J C-F= 188.9 Hz), 86.9 (d, J C-F = 33.8 Hz), 84.3, 68.5 (d, J C-F = 16.2 Hz), 59.8, 51.6 (3C); 19 F NMR (377 MHz, MeOD) δ -206.36; 11 B NMR (160 MHz, D2O) δ -6.79.

[0099] Example 5:

[0100] (2R,3R,4R,5R)-5-(6-amino-2-boraneyl-9H-purin-9-yl)-2-(hydroxymethyl)-4-(2-methoxyethoxy)tetrahydrofuran-3-ol trimethylamine complex synthesis

[0101]

[0102] For the specific operation, refer to Example 1. The substrate used is 2'-O-(2-methoxyethyl)adenosine shown in Formula 1c, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-3 is 83%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.40 (s, 1H), 6.17 (d, J = 5.6 Hz, 1H), 4.60 - 4.55 (m, 1H), 4.54 - 4.49 (m, 1H), 4.25 (dd, J = 6.4, 3.2 Hz, 1H), 3.88 (dd, J = 12.8, 2.8 Hz, 1H), 3.84 - 3.75 (m, 2H), 3.71 - 3.64 (m, 1H), 3.54 - 3.46 (m, 2H), 3.19 (s, 3H), 2.73 (d, J = 3.5 Hz, 1H); 13 13C NMR (125 MHz, D2O) δ 171.0, 149.9, 148.6, 142.3, 117.0, 86.9, 85.8, 81.9, 71.1, 69.7, 69.2, 61.2, 58.0, 52.0; 11 11B NMR (160 MHz, D2O) δ -6.70.

[0103] Example 6:

[0104] (2R,3R,4R,5R)-5-(6-amino-2-boranyl-9H-purin-9-yl)-2-(hydroxymethyl)-4-methoxytetrahydrofuran-3-ol trimethylamine complex Synthesis

[0105]

[0106] For the specific operation, refer to Example 1. The substrate used is 2'-O-methyladenosine shown in Formula 1d, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-4 is 92%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ8.40(s,1H),6.17(d,J=5.2Hz,1H),4.58-4.53(m,1H),4.47-4.41(m,1H),4.26-4.19(m,1H),3.88(dd,J=12.8,2.0Hz,1H),3.80(dd,J=12.8,3.6Hz,1H),3.42(s,3H),2.72(s,9H); 13 13C NMR(125MHz,DMSO)δ166.5,152.2,148.9,140.7,117.2,86.7,86.3,83.5,69.1,61.5,58.0,52.3; 11 11B NMR(160MHz,DMSO)δ-6.08.

[0107] Example 7:

[0108] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex Synthesis

[0109]

[0110] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1e, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-5 is 91%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 1 1H NMR(400MHz,MeOD)δ8.37(s,1H),6.41(d,J=4.0Hz,1H),4.23-4.17(m,2H),3.92(dd,J=8.0,4.0Hz,1H),3.80(dd,J=12.0,3.6Hz,1H),3.75(dd,J=12.0,4.8Hz,1H),2.79(s,9H); 13 13C NMR(100MHz,MeOD)δ169.1,150.4,148.9,142.5,115.6,85.1,84.9,76.2,75.6,60.9,51.6(3C); 11 11B NMR(160MHz,D2O)δ-6.94。

[0111] Example 8:

[0112] (2R,3R,5S)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3-ol trimethylamine complex synthesis

[0113]

[0114] For the specific operation, refer to Example 1. The substrate used is cordycepin shown in Formula 1f, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-6 is 78%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ8.37(s,1H),6.08(d,J=2.0Hz,1H),4.63-4.57(m,1H),3.91(d,J=12.4,2.8Hz,1H),3.71(dd,J=12.8,4.4Hz,1H),2.72(s,9H),2.29-2.21(m,1H),2.15(ddd,J=13.8,6.4,3.0Hz,1H); 13¹³C NMR (125 MHz, D₂O) δ 171.0, 149.7, 148.3, 141.6, 116.7, 91.2, 81.5, 75.3, 62.5, 52.0 (3C), 33.0; 11 ¹¹B NMR (160 MHz, D₂O) δ -6.94.

[0115] Example IX:

[0116] Synthesis of (2R,3R,4S,5S)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0117]

[0118] For the specific operation, refer to Example I. The substrate used is 5'-chloro-5'-deoxyadenosine shown in Formula 1g, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-7 is 70%. The obtained target compound was analyzed by ¹H NMR, ¹³C NMR, and ¹¹B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Corporation, Germany. The characterization results are as follows: 1 ¹H NMR (400 MHz, D₂O) δ 8.39 (s, 1H), 6.15 (d, J = 4.8 Hz, 1H), 4.48 (t, J = 5.2 Hz, 1H), 4.40 (dd, J = 8.4, 4.4 Hz, 1H), 3.95 (dd, J = 12.4, 4.0 Hz, 1H), 3.88 (dd, J = 12.4, 4.4 Hz, 1H), 2.73 (s, 9H); 13 ¹³C NMR (125 MHz, D₂O) δ 171.0, 149.8, 148.9, 141.8, 116.6, 87.8, 83.3, 73.7, 70.6, 52.0 (3C), 44.1; 11 ¹¹B NMR (160 MHz, D₂O) δ -7.19.

[0119] Example X:

[0120] Synthesis of ((2R,3S,4R,5R)-5-(6-amino-2-boranyl-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate trimethylamine complex

[0121]

[0122] For the specific operation, refer to Example 1. The substrate used is adenosine monophosphate shown in Formula 1h, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-8 is 75%. The obtained target compound was analyzed by 1H NMR, 13C NMR, 31P NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ8.51(s,1H),6.19(d,J=5.6Hz,1H),4.69(t,J=5.2Hz,1H),4.47(t,J=4.6Hz,1H),4.38-4.33(m,1H),4.19-4.12(m,1H),4.12-4.05(m,1H),2.73(s,9H); 13 13C NMR(100MHz,D2O)δ149.6,148.9,141.4,116.2,87.4,84.1(d,J C-P =8.7Hz),74.7,70.3,64.2(d,J C-P =5.3Hz),52.0(3C); 31 31P NMR(162MHz,D2O)δ0.41; 11 11B NMR(160MHz,D2O)δ-7.25。

[0123] Example 11:

[0124] (4aR,6R,7R,7aS)-6-(6-amino-2-boraneyl-9H-purin-9-yl)-2,7-dihydroxytetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinine 2-oxide trimethylamine complex synthesis

[0125]

[0126] For the specific operation, refer to Example 1. The substrate used is cyclic adenosine monophosphate shown in Formula 1i, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-9 is 69%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 11H NMR (400 MHz, MeOD) δ 8.18 (s, 1H), 6.03 (s, 1H), 4.63 - 4.56 (m, 2H), 4.34 - 4.25 (m, 1H), 4.21 - 4.13 (m, 2H), 2.79 (s, 9H); 13 13C NMR (125 MHz, MeOD) δ 148.6, 140.3, 140.22, 116.5, 92.3, 77.8 (d, J = 4.6 Hz), 72.7 (d, J = 8.2 Hz), 72.0 (d, J = 4.1 Hz), 66.8 (d, J = 7.0 Hz), 51.61 (3C); 11 11B NMR (160 MHz, MeOD) δ -6.49.

[0127] Example XII:

[0128] Synthesis of 2-boraneyl-9-methyl-9H-purin-6-amine trimethylamine complex

[0129]

[0130] For the specific operation, refer to Example I. The substrate used is 9-methyladenine shown in Formula 1j, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-10 is 62%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.17 (s, 1H), 3.87 (s, 3H), 2.74 (s, 9H); 13 13C NMR (100 MHz, DMSO) δ 167.1, 151.2, 149.6, 143.8, 116.3, 52.4 (3C), 30.2; 11 11B NMR (160 MHz, D2O) δ -6.74.

[0131] Example XIII:

[0132] Synthesis of ((2-(6-amino-2-boraneyl-9H-purin-9-yl)ethoxy)methyl)phosphonic acid trimethyl amine complex

[0133]

[0134] For the specific operation, refer to Example 1. The substrate used is adefovir shown by Formula 1k, and the boron radical precursor is borane-trimethylamine complex shown by Formula 2a. The total yield of the target compound shown by Formula I-11 is 74%. The obtained target compound was analyzed by hydrogen spectrum, carbon spectrum, phosphorus spectrum, and boron spectrum using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 H NMR(400MHz,D2O)δ8.24(s,1H),4.42(t,J=4.8Hz,2H),3.91(t,J=4.8Hz,2H),3.57(d,J=8.8Hz,2H),2.66(s,9H); 13 C NMR(125MHz,D2O)δ149.3,148.9,145.1,115.6,70.2(d,J C-P =11.7Hz),66.9(d,J C-P =157.0Hz),51.9(3C),42.7; 31 P NMR(202MHz,D2O)δ15.17; 11 B NMR(160MHz,D2O)δ-6.99。

[0135] Example 14:

[0136] (R)-(((1-(6-amino-2-boraneyl-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonic acid trimethylamine complex synthesis

[0137]

[0138] For the specific operation, refer to Example 1. The substrate used is tenofovir shown by Formula 1l, and the boron radical precursor is borane-trimethylamine complex shown by Formula 2a. The total yield of the target compound shown by Formula I-12 is 70%. The obtained target compound was analyzed by hydrogen spectrum, carbon spectrum, and boron spectrum using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 H NMR(400MHz,D2O)δ8.31(s,1H),4.46(dd,J=14.4,3.6Hz,1H),4.31(dd,J=14.8,6.4Hz,2H),4.04-3.96(m,1H),3.71(dd,J=13.2,9.2Hz,1H),3.53(dd,J=13.2,9.6Hz,1H),2.73(s,9H),1.16(d,J=6.0Hz,1H);13 C NMR (125 MHz, D2O) δ 149.4, 149.2, 145.0, 115.5, 75.7 (d, J C-P = 11.9 Hz), 64.7 (d, J C-P = 157.3 Hz), 52.0, 47.7, 16.0; 11 B NMR (160 MHz, D2O) δ -6.98.

[0139] Example 15:

[0140] Synthesis of 3'-O,5'-O-Diacetyl-2'-deoxyadenosine trimethylamine complex

[0141]

[0142] For the specific operation, refer to Example 1. The substrate used is 3’,5’-diacetyl-2’-deoxyadenosine shown in Formula 1m, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula I-13 is 68%. The obtained target compound was analyzed by 1H NMR, 13C NMR and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.41 (s, 1H), 6.58 (t, J = 6.8 Hz, 1H), 5.57 - 5.51 (m, 1H), 4.51 (dd, J = 7.8, 3.8 Hz, 1H), 4.38 (dd, J = 12.0, 3.6 Hz, 1H), 4.33 (dd, J = 12.4, 5.2 Hz, 1H), 3.13 - 3.03 (m, 1H), 2.84 - 2.78 (m, 1H), 2.76 (s, 9H), 2.16 (s, 3H), 2.02 (s, 3H); 13 13C NMR (125 MHz, D2O) δ 173.6, 173.5, 141.9, 116.7, 84.5, 82.2, 74.2, 63.8, 52.0, 36.2, 20.32, 20.04; 11 11B NMR (160 MHz, D2O) δ -7.50.

[0143] Example 16:

[0144] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-8-methyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex Synthesis

[0145]

[0146] For the specific operation, refer to Example 1. The substrate used is 8-methyladenosine shown in Formula 3a, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula II-1 is 49%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 6.01 (d, J = 7.2 Hz, 1H), 5.02 (t, J = 6.4 Hz, 1H), 4.47 (dd, J = 5.6, 2.8 Hz, 1H), 4.29 (dd, J = 5.6, 2.8 Hz, 1H), 3.90 (dd, J = 12.8, 2.4 Hz, 1H), 3.81 (dd, J = 12.8, 3.2 Hz, 1H), 2.72 (s, 9H), 2.68 (s, 3H); 13 13C NMR (125 MHz, D2O) δ 170.9, 153.8, 116.0, 88.7, 86.1, 72.6, 70.6, 61.7, 52.0, 13.8; 11 11B NMR (160 MHz, D2O) δ -6.49.

[0147] Example XVII:

[0148] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-8-phenyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex Synthesis

[0149]

[0150] For the specific operation, refer to Example 1. The substrate used is 8-phenyladenosine shown in Formula 3b, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula II-2 is 40%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Corporation, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ7.70-7.49(m,5H),5.94(d,J=6.4Hz,1H),5.24-5.16(m,1H),4.45(dd,J=5.4,3.0Hz,1H),4.20(d,J=2.4Hz,1H),3.90(dd,J=12.8,2.4Hz,1H),3.81(dd,J=12.8,3.6Hz,1H),2.76(s,9H); 13 13C NMR(125MHz,D2O)δ131.1,129.4,128.9,127.1,116.8,89.2,85.8,71.8,70.6,61.8,52.0; 11 11B NMR(160MHz,D2O)δ-5.97。

[0151] Example 18:

[0152] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-8-(p-tolyl)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex synthesis

[0153]

[0154] For the specific operation, refer to Example 1. The substrate used is 8-(4-methylphenyl)adenosine shown in Formula 3c, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula II-3 is 46%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Corporation, Germany. The characterization results are as follows: 11H NMR (400 MHz, D2O) δ 7.37 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.0 Hz, 1H), 5.88 (d, J = 6.0 Hz, 1H), 5.22 (t, J = 6.0 Hz, 1H), 4.52 (dd, J = 5.6, 4.0 Hz, 2H), 4.21 (dd, J = 6.8, 4.0 Hz, 1H), 3.95 (dd, J = 12.6, 2.6 Hz, 1H), 3.84 ((dd, J = 12.6, 4.2 Hz, 1H), 2.79 (s, 9H), 2.32 (s, 1H); 13 13C NMR (125 MHz, D2O) δ 170.7, 153.3, 148.4, 141.4, 128.9, 128.1, 123.1, 115.7, 89.2, 84.6, 71.3, 70.4, 61.8, 51.9 (3C), 20.6; 11 11B NMR (160 MHz, D2O) δ -7.21.

[0155] Example XIX:

[0156] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-8-(4-methoxyphenyl)-9H-purin-9-yl)-5-

[0157] (hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex synthesis

[0158]

[0159] For the specific operation, refer to Example 1. The substrate used is 8-(4-methoxyphenyl)adenosine shown in Formula 3d, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula II-4 is 40%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 7.54 - 7.36 (m, 2H), 6.96 - 6.75 (m, 2H), 5.93 - 5.81 (m, 1H), 5.26 - 5.16 (m, 1H), 4.52 (dd, J = 9.2, 4.8 Hz, 1H), 4.24 - 4.18 (m, 1H), 3.98 - 3.91 (m, 1H), 3.88 - 3.77 (m, 4H), 2.78 (m, 9H); 1313C NMR (125 MHz, D2O) δ 170.9, 160.7, 130.5, 119.0, 116.2, 113.9, 89.2, 85.0, 71.6, 70.4, 61.7, 55.4, 52.0; 11 11B NMR (160 MHz, D2O) δ -6.26.

[0160] Example 20: Synthesis of (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-8-(4-fluorophenyl)-9H-purin-9-yl)-5-

[0161] (hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0162]

[0163] For the specific operation, refer to Example 1. The substrate used was 8-(4-fluorophenyl)adenosine shown in Formula 3e, and the boron radical precursor was borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula II-5 was 37%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results were as follows: 1 1H NMR (400 MHz, D2O) δ 7.69 (dd, J = 8.2, 5.4 Hz, 1H), 7.25 (t, J = 8.6 Hz, 1H), 5.90 (d, J = 6.8 Hz, 1H), 5.20 (t, J = 6.2 Hz, 1H), 4.46 (dd, J = 4.8, 2.8 Hz, 1H), 4.21 - 4.16 (m, 1H), 3.90 - 3.76 (m, 2H), 2.74 (s, 9H); 13 13C NMR (125 MHz, MeOD) δ 170.6, 166.6, 164.6, 154.3, 151.6 (d, J C-F = 153.0 Hz), 133.4 (d, J C-F = 8.9 Hz), 125.81 (d, J C-F = 3.4 Hz), 118.1, 117.1 (d, J C-F = 22.4 Hz), 91.0, 87.4, 73.2, 72.1, 63.2, 53.1 (3C); 11 11B NMR (160 MHz, D2O) δ -6.01.

[0164] Example 21:

[0165] Synthesis of (2R,3R,4S,5R)-2-(2-boraneyl-6-(propylamino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0166]

[0167] For the specific operation, refer to Example 1. The substrate used is N-propyladenosine shown in Formula 4a, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula III-1 is 65%. The obtained target compound was analyzed by 1H NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 6 1H NMR (400 MHz, D2O) δ 8.46 (s, 1H), 6.08 (s, 1H), 4.77 - 4.72 (m, 1H), 4.44 - 4.39 (m, 1H), 4.28 (dd, J = 6.4, 3.2 Hz, 1H), 3.96 - 3.78 (m, 3H), 2.76 (s, 9H), 1.81 - 1.66 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H). 1 H NMR(400 MHz,D2O)δ8.46(s,1H),6.08(s,1H),4.77-4.72(m,1H),4.44-4.39(m,1H),4.28(dd,J=6.4,3.2 Hz,1H),3.96-3.78(m,3H),2.76(s,9H),1.81-1.66(m,2H),0.99(t,J=7.4 Hz,3H).

[0168] Example 22:

[0169] Synthesis of (2R,3R,4S,5R)-2-(6-(benzylamino)-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0170]

[0171] For the specific operation, refer to Example 1. The substrate used is N-benzyladenosine shown in Formula 4b, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula III-2 is 50%. The obtained target compound was analyzed by 1H NMR, 13C NMR and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 6 1H NMR (400 MHz, D2O) δ 8.46 (s, 1H), 6.08 (s, 1H), 4.77 - 4.72 (m, 1H), 4.44 - 4.39 (m, 1H), 4.28 (dd, J = 6.4, 3.2 Hz, 1H), 3.96 - 3.78 (m, 3H), 2.76 (s, 9H), 1.81 - 1.66 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H). 11H NMR (400 MHz, D2O) δ 8.32 (s, 1H), 7.42 - 7.28 (m, 5H), 6.12 (d, J = 6.0 Hz, 1H), 5.02 (brs, 2H), 4.42 (dd, J = 5.2, 3.2 Hz, 1H), 4.30 (dd, J = 5.8, 3.0 Hz, 1H), 3.90 (dd, J = 12.8, 2.4 Hz, 1H), 3.83 (dd, J = 12.8, 3.6 Hz, 1H), 2.64 (s, 9H); 13 13C NMR (175 MHz, D2O) δ 171.0, 128.8, 127.8, 126.9, 74.0, 61.2, 51.9; 11 11B NMR (160 MHz, D2O) δ -6.01.

[0172] Example 23:

[0173] (2R,3R,4S,5R)-2-(2-boraneyl-6-(phenethylamino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex synthesis

[0174]

[0175] For the specific operation, refer to Example 1. The substrate used is N- 6 -(2-phenylethyl)adenosine, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula III-3 is 50%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.20 (s, 1H), 7.12 - 6.95 (m, 5H), 5.95 (d, J = 5.6 Hz, 1H), 4.56 (t, J = 5.4 Hz, 1H), 4.27 (dd, J = 4.8, 4.0 Hz, 1H), 4.14 (dd, J = 6.6, 3.4 Hz, 1H), 4.05 (brs, 1H), 3.78 (dd, J = 12.6, 2.6 Hz, 1H), 3.71 (dd, J = 12.8, 3.6 Hz, 1H), 2.84 (t, J = 6.5 Hz, 2H), 2.59 (s, 9H); 1313C NMR (125 MHz, D2O) δ 171.0, 141.0, 137.9, 129.0, 128.3, 126.6, 88.4, 85.6, 74.0, 70.4, 61.2, 52.0 (3C); 11 11B NMR (160 MHz, D2O) δ -6.68.

[0176] Example 24:

[0177] Synthesis of (2R,3R,4S,5R)-2-(2-boraneyl-6-methoxy-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0178]

[0179] For the specific operation, refer to Example 1. The substrate used is O-methyl inosine shown in Formula 4d, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula III-4 is 43%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 6 1H NMR (400 MHz, D2O) δ 8.24 (s, 1H), 6.43 (d, J = 7.6 Hz, 1H), 5.02 (dd, J = 7.6, 5.6 Hz, 1H), 4.43 (dd, J = 5.2, 2.0 Hz, 1H), 4.19 (dd, J = 4.6, 2.2 Hz, 1H), 4.01 (s, 3H), 3.82 (dd, J = 13.0, 2.2 Hz, 1H), 3.77 (dd, J = 12.8, 2.8 Hz, 1H), 2.58 (s, 9H); 1 13C NMR (125 MHz, D2O) δ 162.1, 153.5, 153.0, 122.8, 92.2, 89.0, 74.6, 73.8, 64.8, 57.2, 54.6 (3C); 13 11B NMR (160 MHz, D2O) δ -7.47. 11 Example 25:

[0180] Example 25:

[0181] (2R,3R,4S,5R)-2-(2-boraneyl-6-ethoxy-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex Synthesis

[0182]

[0183] The specific operation refers to Example 1. The substrate used is O shown in Formula 4e 6 -ethylinosine, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula III-5 is 34%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Corporation, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.34 (s, 1H), 6.56 (d, J = 7.2 Hz, 1H), 5.18 (dd, J = 7.4, 5.4 Hz, 1H), 4.50 - 4.52 (m, 3H), 4.31 (dd, J = 4.8, 2.4 Hz, 1H), 3.94 (dd, J = 12.8, 2.4 Hz, 1H), 3.89 (dd, J = 13.0, 3.0 Hz, 1H), 2.70 (s, 9H), 1.49 (t, J = 7.0 Hz, 3H); 13 13C NMR (125 MHz, D2O) δ 159.0, 150.9, 150.2, 120.1, 89.8, 86.6, 72.1, 71.5, 64.2, 62.3, 52.1, 13.5; 11 11B NMR (160 MHz, D2O) δ -9.48.

[0184] Example 26:

[0185] Synthesis of N-benzyl-2-boraneyl-9H-purin-6-amine trimethylamine complex

[0186]

[0187] The specific operation refers to Example 1. The substrate used is N shown in Formula 5a 6-Benzyladenine, with the boron radical precursor being the borane-trimethylamine complex shown in Formula 2a, the total yield of the target compound shown in Formula IV-1 is 55%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, DMSO) δ 13.87 (brs, 1H), 9.19 (brs, 1H), 8.38 (s, 1H), 7.43 - 7.33 (m, 4H), 7.33 - 7.25 (m, 1H), 4.87 (d, J = 5.2 Hz, 2H), 2.67 (s, 9H); 13 13C NMR (125 MHz, DMSO) δ 138.8, 129.6, 128.3, 52.8, 45.3; 11 11B NMR (160 MHz, DMSO) δ -2.46.

[0188] Example 27:

[0189] (2R,3R,4S,5R)-2-(4-amino-2-boraneyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-

[0190] (hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex synthesis

[0191]

[0192] For the specific operation, refer to Example 1. The substrate used is 7-deazoadenosine shown in Formula 6a, and the boron radical precursor is the borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula V-1 is 44%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 7.41 (d, J = 3.6 Hz, 1H), 6.67 (d, J = 3.6 Hz, 1H), 6.23 (d, J = 6.4 Hz, 1H), 4.63 (t, J = 5.8 Hz, 1H), 4.35 (dd, J = 5.0, 3.4 Hz, 1H), 4.20 (dd, J = 6.6, 3.4 Hz, 1H), 3.85 (dd, J = 12.6, 3.0 Hz, 1H), 3.78 (dd, J = 12.6, 4.2 Hz, 1H), 2.69 (s, 9H);13 C NMR (125 MHz, D2O) δ 171.1, 150.8, 124.2, 101.6, 100.7, 87.4, 85.0, 73.9, 70.5, 61.5, 52.0 (3C); 11 B NMR (160 MHz, D2O) δ -6.95.

[0193] Example 28:

[0194] (2R,3R,4S,5R)-2-(7-amino-5-boraneyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-

[0195] Synthesis of (hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0196]

[0197] For the specific operation, refer to Example 1. The substrate used is 8-azidoadenosine shown in Formula 6b, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula V-2 is 59%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 6.51 (d, J = 4.0 Hz, 1H), 5.07 (t, J = 4.4 Hz, 1H), 4.68 (t, J = 5.2 Hz, 1H), 4.32 (dd, J = 8.0, 4.8 Hz, 1H), 3.88 (dd, J = 12.4, 3.2 Hz, 1H), 3.77 (dd, J = 12.8, 4.8 Hz, 1H), 2.82 (s, 1H); 13 13C NMR (125 MHz, D2O) δ 171.0, 156.8, 148.1, 122.7, 89.6, 85.7, 73.7, 70.6, 61.3, 52.0 (3C); 11 11B NMR (160 MHz, D2O) δ -6.80.

[0198] Example 29:

[0199] (2R,3R,4S,5R)-2-(4-amino-6-boraneyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-5-

[0200] Synthesis of (hydroxymethyl)tetrahydrofuran-3,4-diol trimethylamine complex

[0201]

[0202] For the specific operation, refer to Example 1. The substrate used is 8-aza-7-deazaadenosine shown in Formula 6c, and the boron radical precursor is borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula V-3 is 62%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ8.27(s,1H),6.38(d,J=4.8Hz,1H),4.85-4.81(m,1H),4.49(t,J=4.8Hz,H),4.20(dd,J=8.2,4.6Hz,1H),3.83(dd,J=12.6,3.4Hz,1H),3.73(dd,J=12.4,5.6Hz,1H),2.75(s,9H); 13 13C NMR(125MHz,D2O)δ171.0,152.3,151.6,135.9,98.3,88.0,84.9,73.4,70.5,61.6,52.0(3C); 11 11B NMR(160MHz,D2O)δ-7.26。

[0203] Example 30:

[0204] (2R,3R,4S,5R)-2-(4-amino-2-boraneylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-

[0205] Synthesis of (hydroxymethyl)tetrahydrofuran-2-carbonitrile trimethylamine complex

[0206]

[0207] For the specific operation, refer to Example 1. The substrate used is the important intermediate GS-441524 of the antiviral drug remdesivir shown in Formula 6d, and the boron radical precursor is the borane-trimethylamine complex shown in Formula 2a. The total yield of the target compound shown in Formula V-4 is 25%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR(400MHz,D2O)δ6.98(d,J=4.8Hz,1H),6.88(d,J=4.8Hz,1H),4.76(d,J=5.6Hz,1H),4.30(dd,J=7.8,4.6Hz,1H),4.21(t,J=5.2Hz,1H),3.78(dd,J=12.8,2.8Hz,1H),3.68(dd,J=12.8,4.8Hz,1H),2.71(s,9H); 13 13C NMR(125MHz,D2O)δ148.6,127.2 116.7,112.8,112.1,108.1,85.5,77.8,75.4,70.1,60.9,52.1(3C); 11 11B NMR(160MHz,D2O)δ-7.30。

[0208] Example 31:

[0209] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol triethylamine complex synthesis

[0210]

[0211] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is the borane-triethylamine complex shown in Formula 2b. The total yield of the target compound shown in Formula VI-1 is 53%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 11H NMR (400 MHz, MeOD) δ 8.54 (s, 1H), 6.13 (d, J = 5.2 Hz, 1H), 4.65 (t, J = 5.2 Hz, 1H), 4.35 (t, J = 4.6 Hz, 1H), 4.16 (dd, J = 7.0, 3.4 Hz, 1H), 3.88 (dd, J = 12.2, 3.0 Hz, 1H), 3.79 (dd, J = 12.2, 3.4 Hz, 1H), 3.22 (q, J = 7.2 Hz, 6H), 1.22 (t, J = 7.2 Hz, 9H); 13 13C NMR (125 MHz, MeOD) δ 169.1, 150.5, 149.0, 141.3, 116.2, 88.5, 85.7, 75.0, 70.5, 61.1, 50.5 (3C), 7.2 (3C); 11 11B NMR (160 MHz, MeOD) δ -12.17.

[0212] Example 32:

[0213] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol N,N-dimethylethylamine complex synthesis

[0214]

[0215] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-N,N-dimethylethylamine complex shown in Formula 2c. The total yield of the target compound shown in Formula VI-2 is 79%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.41 (s, 1H), 6.13 (d, J = 5.6 Hz, 1H), 4.81 (s, 1H), 4.42 (dd, J = 5.10, 4.2 Hz, 1H), 4.26 (dd, J = 7.0, 3.8 Hz, 1H), 3.89 (dd, J = 12.8, 2.8 Hz, 1H), 3.81 (d, J = 12.8, 4.0 Hz, 1H), 3.04 (q, J = 7.3 Hz, 2H), 2.66 (s, 6H), 1.21 (t, J = 7.2 Hz, 3H); 1313C NMR (125 MHz, D2O) δ 171.0, 142.4, 117.1, 88.4, 85.5, 73.9, 70.3, 61.2, 57.6, 48.4, 8.0; 11 11B NMR (160 MHz, D2O) δ -8.01.

[0216] Example 33:

[0217] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol N,N-dimethylcyclohexanamine complex synthesis

[0218]

[0219] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-N,N-dimethylcyclohexylamine complex shown in Formula 2d. The total yield of the target compound shown in Formula VI-3 is 68%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.42 (s, 1H), 6.15 (d, J = 5.6 Hz, 1H), 4.84 - 4.80 (m 1H), 4.43 - 4.39 (m, 1H), 4.24 (dd, J = 7.2, 3.6 Hz, 1H), 3.89 (dd, J = 12.8, 2.8 Hz, 1H), 3.81 (dd, J = 12.8, 4.0 Hz, 1H), 3.08 - 2.99 (m, 1H), 2.66 (s, 3H), 2.66 (s, 3H), 2.26 - 2.17 (m, 2H), 1.88 - 1.77 (m, 1H), 1.63 - 1.54 (m, 1H), 1.45 - 1.31 (m, 2H), 1.28 - 1.15 (m, 2H), 1.14 - 1.05 (m, 1H); 13 13C NMR (175 MHz, D2O) δ 171.0, 142.2, 116.9, 88.2, 85.3, 73.7, 70.2, 69.2, 61.1, 53.8, 46.7, 46.7, 26.4, 25.5, 25.5, 24.9; 11 11B NMR (160 MHz, D2O) δ -9.82.

[0220] Example 34:

[0221] Synthesis of (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 1-methylpyrrolidine complex

[0222]

[0223] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-N-methylpyrrolidine complex shown in Formula 2e. The total yield of the target compound shown in Formula VI-4 is 75%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.43 (s, 1H), 6.16 (d, J = 5.6 Hz, 1H), 4.84 - 4.80 (m, 1H), 4.46 – 4.42 (m, 1H), 4.28 (dd, J = 7.0, 3.8 Hz, 1H), 3.92 (dd, J = 12.8, 2.8 Hz, 1H), 3.83 (dd, J = 12.8, 4.0 Hz, 1H), 3.34 - 3.24 (m, 2H), 3.12 - 3.03 (m, 2H), 2.71 (s, 3H), 2.09 - 2.01 (m, 4H); 13 13C NMR (125 MHz, D2O) δ 171.0, 149.8, 142.2, 116.9, 88.3, 85.5, 73.9, 70.3, 61.6, 61.6, 61.2, 47.6, 21.7; 11 11B NMR (160 MHz, D2O) δ -8.34.

[0224] Example 35:

[0225] Synthesis of (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 1-methylpiperidine complex

[0226]

[0227] For the specific operation, refer to Example 1. The substrate used is adenosine represented by Formula 1a, and the boron radical precursor is borane-N-methylpiperidine complex represented by Formula 2f. The total yield of the target compound represented by Formula VI-5 is 58%. The obtained target compound was analyzed by 1H NMR, 13C NMR and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.44 (s, 1H), 6.15 (d, J = 5.6 Hz, 1H), 4.81 (s, 1H), 4.23 (t, J = 4.6 Hz, 1H), 4.27 (dd, J = 7.2, 4.0 Hz, 1H), 4.06 - 3.99 (m, 2H), 3.99 - 3.94 (m, 2H), 3.93 - 3.88 (m, 1H), 3.83 (dd, J = 12.8, 4.0 Hz, 2H), 3.45 - 3.37 (m, 1H), 3.07 - 3.00 (m, 2H), 2.87 (s, 3H); 13 13C NMR (125 MHz, D2O) δ 142.5, 117.1, 88.5, 85.6, 73.9, 70.4, 61.3, 58.7, 58.6, 21.8, 19.6; 11 11B NMR (160 MHz, D2O) δ -7.34.

[0228] Example 36:

[0229] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 1-ethylpiperidine complex synthesis

[0230]

[0231] For the specific operation, refer to Example 1. The substrate used is adenosine represented by Formula 1a, and the boron radical precursor is borane-N-ethylpiperidine complex represented by Formula 2g. The total yield of the target compound represented by Formula VI-6 is 69%. The obtained target compound was analyzed by 1H NMR, 13C NMR and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 11H NMR (400 MHz, D2O) δ 8.36 (s, 1H), 6.07 (d, J = 5.2 Hz, 1H), 4.38 (d, J = 4.8 Hz, 1H), 4.22 (dd, J = 6.8, 3.6 Hz, 1H), 3.87 (dd, J = 12.6, 2.6 Hz, 1H), 3.78 (dd, J = 12.8, 4.0 Hz, 1H), 3.05 (q, J = 7.2 Hz, 2H), 3.02 - 2.92 (m, 4H), 1.73 - 1.53 (m, 5H), 1.44 - 1.32 (m, 1H), 1.11 (t, J = 7.2 Hz, 3H); 13 13C NMR (125 MHz, D2O) δ 171.0, 150.0, 148.7, 142.2, 116.8, 88.4, 85.3, 73.8, 70.2, 61.2, 56.1, 56.0, 50.2, 21.8, 19.2, 7.9; 11 11B NMR (160 MHz, D2O) δ -9.62.

[0232] Example 37:

[0233] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 4-methylmorpholine complex synthesis

[0234]

[0235] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-N-methylmorpholine complex shown in Formula 2h. The total yield of the target compound shown in Formula VI-7 is 54%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 11H NMR (400 MHz, D2O) δ 8.44 (s, 1H), 6.15 (d, J = 5.6 Hz, 1H), 4.82 - 4.80 (m, 1H), 4.45 - 4.41 (m, 1H), 4.26 (dd, J = 7.2, 4.0 Hz, 1H), 4.06 - 3.99 (m, 2H), 3.99 - 3.93 (m, 2H), 3.93 - 3.88 (m, 1H), 3.91 (dd, J = 12.6, 3.0 Hz, 2H), 3.82 (dd, J = 12.8, 4.0 Hz, 2H), 3.45 - 3.37 (m, 2H), 3.07 - 2.99 (s, 2H), 2.87 (s, 1H); 13 13C NMR (125 MHz, D2O) δ 171.0, 155.5, 152.4, 148.3, 140.5, 88.3, 85.7, 73.6, 70.6, 64.0 (2C), 61.5, 53.2 (2C), 43.2; 11 11B NMR (160 MHz, D2O) δ -9.06.

[0236] Example 38:

[0237] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol quinuclidine complex synthesis

[0238]

[0239] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is the borane - quinuclidine complex shown in Formula 2i. The total yield of the target compound shown in Formula VI - 8 is 65%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.18 (s, 1H), 6.01 (d, J = 7.2 Hz, 1H), 4.90 (dd, J = 6.8, 5.2 Hz, 1H), 4.42 (dd, J = 5.0, 1.8 Hz, 1H), 4.31 (d, J = 2.0 Hz, 1H), 3.87 (dd, J = 13.2, 2.0 Hz, 1H), 3.79 (dd, J = 13.2, 2.8 Hz, 1H), 3.01 (t, J = 7.8 Hz, 6H), 1.90 - 1.85 (m, 1H), 1.70 - 1.61 (m, 6H);13 CNMR(125MHz, D2O) δ 153.7, 148.5, 140.9, 117.6, 89.1, 86.5, 73.2, 71.3, 61.8, 52.0, 24.0, 19.8; 11 B NMR(160MHz, D2O) δ -6.21.

[0240] Example 39:

[0241] (2R,3R,4S,5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol quinuclidine-4-carbonitrile complex synthesis

[0242]

[0243] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-4-cyanoquinuclidine complex shown in Formula 2j. The total yield of the target compound shown in Formula VI-9 is 42%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 H NMR(400MHz, D2O) δ 8.32(s, 1H), 6.08(d, J = 6.4Hz, 1H), 4.84 - 4.81(m, 1H), 4.42(dd, J = 5.2, 3.2Hz, 1H), 4.29(dd, J = 6.0, 3.2Hz, 1H), 3.89(dd, J = 12.8, 2.4Hz, 1H), 3.81(dd, J = 13.0, 3.4Hz, 1H), 3.21(t, J = 7.8Hz, 6H), 2.14(r, J = 7.6Hz, 6H); 13 C NMR(125MHz, D2O) δ 171.0, 148.5, 141.7, 133.7, 123.3, 117.2, 88.6, 85.9, 73.7, 70.7, 61.4, 50.8, 27.0, 24.7; 11 B NMR(160MHz, D2O) δ -8.25. Example 40:

[0244] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol quinuclidin-3-ol complex Synthesis

[0245]

[0246] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane - quinuclidin - 3 - ol complex shown in Formula 2k. The total yield of the target compound shown in Formula VI - 10 is 66%. The obtained target compound was analyzed by hydrogen spectrum, carbon spectrum, and boron spectrum using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Company, Germany. The characterization results are as follows: 1 H NMR(400 MHz,D2O)δ8.26(s,1H),6.06(d,J=13.0,2.4 Hz,1H),4.89 - 4.84(m,1H),4.43(dd,J=5.0,2.6 Hz,1H),4.32 - 4.28(m,1H),4.13 - 4.07(m,1H),3.90(dd,J=13.2,2.4 Hz,1H),3.81(dd,J=13.2,3.2 Hz,1H),3.11 - 2.85(m,5H),2.07 - 2.02(m,1H),2.01 - 1.94(m,1H),1.89 - 1.79 m,1H),1.71 - 1.58(m,2H); 13 C NMR(125 MHz,D2O)δ171.0,152.4,148.5,141.4,117.4,88.8,86.2(isomer A),86.1(isomer B),73.5,70.9(isomerA),70.9(isomer B),65.4,61.6,60.4(isomer A),60.4(isomer B),52.0(isomer A),52.0(isomer B),51.1,26.6(isomerA),26.6(isomer B),21.9,17.4; 11 B NMR(160 MHz,D2O)δ - 6.90。

[0247] Example 41:

[0248] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 3-methoxyquinuclidine complex Synthesis

[0249]

[0250] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-3-methoxyquinuclidine complex shown in Formula 2l. The total yield of the target compound shown in Formula VI-11 is 62%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR(400 MHz,D2O)δ8.23(s,1H),6.03(d,J=6.8 Hz,1H),4.88-4.84(m,1H),4.43-4.39(m,1H),4.28(dd,J=5.2,2.8 Hz,1H),3.87(dd,J=13.2,2.4 Hz,1H),3.79(dd,J=12.8,2.8 Hz,1H),3.68-3.61(m,1H),3.32-3.25(m,4H),3.08–2.98(m,1H),2.99-2.88(m,4H),2.26-2.19(m,1H),1.87-1.76(m,2H),1.63-1.50(m,2H); 13 13C NMR(126 MHz,D2O)δ171.0,152.5,148.5,141.3,117.3,88.9,86.2,74.9,73.4(isomer A),73.4(isomerB),71.0,61.7,58.7(isomer A),58.6(isomer B),55.4(isomer A),55.4(isomer B),52.0(isomer A),52.0(isomer B),51.4(isomer A),51.4(isomer B),23.1,21.5,17.4; 11 11B NMR(160 MHz,D2O)δ-6.17.

[0251] Example 42:

[0252] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 3-(prop-2-yn-1-yloxy)quinuclidine complex Synthesis

[0253]

[0254] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-3-(2-propynyloxy)quinuclidine complex shown in Formula 2m. The total yield of the target compound shown in Formula VI-12 is 33%. The obtained target compound was analyzed by 1H NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.36 (s, 1H), 6.11 (d, J = 6.4 Hz, 1H), 4.86 (t, J = 5.8 Hz, 1H), 4.47–4.42 (m, 1H), 4.33 - 4.28 (m, 1H), 4.24 (dd, J = 7.8, 1.8 Hz, 1H), 4.09 - 4.02 (m, 1H), 3.92 (dd, J = 12.8, 2.4 Hz, 1H), 3.83 (dd, J = 12.8, 3.2 Hz, 1H), 3.50 - 3.37 (m, 1H), 3.20 - 2.98 (m, 5H), 2.35 - 2.28 (m, 1H), 1.99 - 1.83 (m, 2H), 1.76 - 1.61 (s, 2H).

[0255] Example 43:

[0256] (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol dimethylamine complex Synthesis

[0257]

[0258] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-dimethylamine complex shown in Formula 2n. The total yield of the target compound shown in Formula VI-13 is 50%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows:1 H NMR (400 MHz, D2O) δ 8.39 (d, J = 8.8 Hz, 1H), 6.14 (d, J = 5.6 Hz, 1H), 4.78 - 4.74 (m, 1H), 4.43 (t, J = 4.6 Hz, 1H), 4.27 (dd, J = 7.2, 4.0 Hz, 1H), 3.93 (dd, J = 12.8, 2.8 Hz, 1H), 3.84 (dd, J = 12.8, 4.0 Hz, 1H), 2.60 - 2.54 (m, 6H); 13 C NMR (125 MHz, D2O) δ 171.0, 149.6, 141.6, 116.4, 88.1, 85.3, 74.1, 70.2, 61.1, 42.1, 42.1; 11 B NMR (160 MHz, D2O) δ -11.25.

[0259] Example Forty-Four:

[0260] (2R, 3R, 4S, 5R)-2-(6-amino-2-boraneyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol piperidine complex synthesis

[0261]

[0262] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-piperidine complex shown in Formula 2o. The total yield of the target compound shown in Formula VI-14 is 58%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 1 H NMR (400 MHz, D2O) δ 8.11 (s, 1H), 5.95 (d, J = 6.4 Hz, 1H), 4.75 (dd, J = 6.0, 5.2 Hz, 1H), 4.33 (dd, J = 5.2, 3.2 Hz, 1H), 4.19 (q, J = 2.8 Hz, 1H), 3.81 (dd, J = 13.0, 2.6 Hz, 1H), 3.71 (dd, J = 13.2, 3.2 Hz, 1H), 3.10 - 3.01 (m, 2H), 2.51 - 2.38 (m, 2H), 1.70 - 1.60 (m, 3H), 1.55 - 1.40 (m, 2H), 1.35 - 1.20 (m, 1H); 1313C NMR (125 MHz, D2O) δ 173.5, 155.5, 151.2, 143.1, 119.5, 91.1, 88.5, 75.9, 73.4, 64.1, 54.0, 54.0, 27.0, 24.7; 11 11B NMR (160 MHz, D2O) δ -7.36.

[0263] Example 45:

[0264] Synthesis of (2R,3R,4S,5R)-2-(6-amino-2-boranyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol morpholine complex

[0265]

[0266] For the specific operation, refer to Example 1. The substrate used is adenosine shown in Formula 1a, and the boron radical precursor is borane-morpholine complex shown in Formula 2p. The total yield of the target compound shown in Formula VI-15 is 63%. The obtained target compound was analyzed by 1H NMR, 13C NMR, and 11B NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer of Bruker Corporation, Germany. The characterization results are as follows: 1 1H NMR (400 MHz, D2O) δ 8.31 (s, 1H), 6.06 (d, J = 5.4 Hz, 1H), 4.67 (d, J = 5.4 Hz, 1H), 4.34 (t, J = 4.8 Hz, 1H), 4.18 (dd, J = 7.0, 4.0 Hz, 1H), 3.95 - 3.88 (d, J = 12.2 Hz, 2H), 3.83 (dd, J = 12.8, 3.2 Hz, 1H), 3.78 - 3.66 (m, 3H), 3.16 (d, J = 13.6 Hz, 2H), 2.83 (t, J = 12.5 Hz, 2H); 13 13C NMR (125 MHz, D2O) δ 149.9, 148.8, 141.3, 116.4, 87.9, 85.2, 74.0, 70.2, 65.0, 61.0, 50.0, 50.0; 11 11B NMR (160 MHz, D2O) δ -12.10.

[0267] Example 46:

[0268] This example provides a method for preparing C2-trimethylaminoboranyl-substituted adenosine. The specific steps are basically the same as those in Example 1, except that: various additives (Bronsted acid, Lewis acid or base) shown in Table 1 are used instead of magnesium chloride in Example 1, and other conditions remain unchanged. The yield results of the target compound C2-trimethylaminoboranyl adenosine shown in Formula I-1 are shown in Table 1. Among them, the experiment numbered 6 represents the experimental result without adding magnesium chloride.

[0269] Table 1

[0270] Serial number Additive Equivalent Yield (%) Serial number Additive Equivalent Yield (%) 1 HCOOH 10 87 7 <![CDATA[Y(OTf)3]]> 1 68 2 HOAc 10 82 8 <![CDATA[Sc(OTf)3]]> 1 77 3 <![CDATA[MeSO3H]]> 10 74 9 <![CDATA[AgNO3]]> 1 53 4 TFA 10 69 10 LiCl 1 88 5 TEA 10 75 11 <![CDATA[ZnCl2]]> 1 85 6 - - 79 12 <![CDATA[Potassium carbonate]]> 1 4

[0271] Note: The yields described in this table are determined by LC-MS.

[0272] Example Forty-Seven:

[0273] This example provides a method for preparing C2-trimethylaminoboranyl-substituted adenosine. The specific steps are basically the same as those in Example 1, except that: various photocatalysts shown in Table 2 are used instead of 4CzIPN in Example 1, and other conditions remain unchanged. The yield results of the target compound C2-trimethylaminoboranyl adenosine shown in Formula I-1 are shown in Table 2.

[0274] Table 2

[0275] Serial number Photocatalyst Yield (%) 1 3CzClIPN 45 2 <![CDATA[Ir(ppy)3]]> 53 3 <![CDATA[{Ir[dF(CF3)ppy]2(dtbbpy)}(PF6)]]> 58 4 <![CDATA[MesAcr(BF4)]]> 49 5 <![CDATA[Ru(bpy)3(PF6)2]]> 67 6 <![CDATA[Ru(bpz)3(PF6)2]]> 70 7 <![CDATA[Ru(DMB)3(PF6)2]]> 73 8 Eosin Y 56 9 Rose Bengal 52

[0276] Note: The yields described in this table are determined by LC-MS.

[0277] The structural formulas of the photocatalysts in Example 1 and Table 2 are as follows:

[0278]

[0279]

[0280] Application Example 1:

[0281] Synthesize deuterated adenosine from C2-trimethylaminoboranyl-substituted adenosine (Compound I-1).

[0282]

[0283] In a 25 mL Schlenk tube equipped with a magnetic stir bar, add C2-trimethylaminoboranyl-substituted adenosine shown in Formula I-1 (0.10 mmol, 34 mg), palladium acetate (0.005 mmol, 1 mg), and cesium carbonate (0.40 mmol, 130 mg). After sealing with a rubber stopper, evacuate with a double manifold for 5 minutes, replace with N2 gas for protection, and repeat the evacuation and gas replacement operation 3 times. Add 5 mL of a pre-deoxygenated mixed solvent (containing 4 mL of tetrahydrofuran and 1 mL of deuterium water) using a syringe. Place the reaction tube in an 80 °C oil bath, heat and stir for 2 hours. LC-MS monitored the complete conversion of the starting material. Evaporate the solvent under reduced pressure, and the resulting residue was purified by column chromatography to obtain 2,8-dideuterated adenosine (the compound shown in Formula 7) 24.0 mg, with a yield of 89%. The obtained target compound was analyzed by 1H NMR and 13C NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results were as follows: 1 1H NMR (400 MHz, D2O) δ 8.20 (s, 0.17H), 8.06 (s, 0.16H), 5.94 (d, J = 6.0 Hz, 1H), 4.33 (dd, J = 5.2, 3.6 Hz, 1H), 4.20 (dd, J = 6.4, 3.2 Hz, 1H), 3.83 (dd, J = 13.0, 2.6 Hz, 1H), 3.75 (dd, J = 12.8, 3.6 Hz, 1H); 13 13C NMR (100 MHz, D2O) δ 157.9, 154.5, 150.8, 142.7, 121.5, 90.6, 88.2, 76.0, 73.0, 63.8.

[0284] Application Example 2:

[0285] Synthesize isoguanosine from C2-trimethylaminoboranyl-substituted adenosine (Compound I-1).

[0286]

[0287] In a 25 mL reaction tube equipped with a magnetic stir bar, add C2-trimethylaminoboranyl-substituted adenosine shown in Formula I-1 (0.20 mmol, 68 mg), oxone (0.80 mmol, 492 mg), and 2 mL of water. Place the reaction tube in an 80 °C oil bath, heat and stir for 12 hours. LC-MS monitored the complete conversion of the starting material. Evaporate the solvent under reduced pressure, and the resulting residue was purified by column chromatography to obtain isoguanosine (the compound shown in Formula 8) 46.0 mg, with a yield of 81%. The obtained target compound was analyzed by 1H NMR and 13C NMR using a 400 MHz (or 500 MHz) nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results were as follows: 11H NMR (400 MHz, DMSO) δ 7.94 (s, 1H), 7.76 (s, 1H), 5.72 (s, 1H), 5.64 (d, J = 6.5 Hz, 1H), 5.39 (s, 1H), 5.13 (s, 1H), 4.52 (s, 1H), 4.07 (s, 1H), 3.92 (d, J = 2.5 Hz, 1H), 3.63 (dd, J = 12.2, 2.9 Hz, 1H), 3.52 (d, J = 10.2 Hz, 1H); 13 13C NMR (100 MHz, DMSO) δ 156.1, 147.6, 142., 120.0, 116.2, 90.7, 75.8, 71.7, 87.3, 62.6.

[0288] Application Example 3:

[0289] Synthesis of 2-phenyladenosine from C2-trimethylamine boranyl-substituted adenosine (Compound I-1).

[0290]

[0291] Add C2-trimethylamine boranyl-substituted adenosine (0.20 mmol, 68 mg) shown in Formula I-1, tris(dibenzylideneacetone) dipalladium (Pd2(dab)3, 0.01 mmol, 10 mg), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos, 0.024 mmol, 12 mg) and lithium hydroxide (1.0 mmol, 24 mg) into a 25 mL reaction tube equipped with a magnetic stir bar. After sealing with a rubber stopper, evacuate with a double manifold for 5 minutes, replace with N2 gas for protection, and repeat the evacuation and replacement operation 3 times. Sequentially add bromobenzene (0.40 mmol, 42 μL) and 4 mL of a pre-deoxygenated mixed solvent (containing 3.2 mL of tetrahydrofuran and 0.8 mL of water) using a syringe. Place the reaction tube in an oil bath at 55 °C, heat and stir for 18 hours. LC-MS monitored the complete conversion of the starting material. Evaporate the solvent under reduced pressure, and the resulting residue was purified by column chromatography to obtain 25.0 mg of 2-phenyladenosine (the compound shown in Formula 9a) with a yield of 36%. The target compound was analyzed by 1H NMR using a 400 MHz nuclear magnetic resonance spectrometer from Bruker, Germany, and the characterization results were: 11H NMR (400 MHz, DMSO) δ 8.41 (s, 1H), 8.39 - 8.34 (m, 2H), 7.52 - 7.43 (m, 3H), 6.01 (d, J = 6.0 Hz, 1H), 4.74 (t, J = 5.4 Hz, 1H), 4.25 - 4.20 (m, 1H), 3.98 (dd, J = 7.6, 4.0 Hz, 1H), 3.71 (dd, J = 11.8, 4.2 Hz, 1H), 3.59 (dd, J = 11.8, 4.2 Hz, 1H); The hydrogen spectrum is consistent with the literature (Synthesis, 1984, 11, 963 - 965).

[0292] Application Example 4:

[0293] Synthesize C2-(4-methoxyphenyl)adenosine from C2-trimethylamine boranyl-substituted adenosine (Compound I-1).

[0294]

[0295] Add C2-trimethylamine boranyl-substituted adenosine (0.20 mmol, 68 mg) shown in Formula I-1, tris(dibenzylideneacetone)dipalladium (Pd2(dab)3, 0.01 mmol, 10 mg), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos, 0.024 mmol, 12 mg) and lithium hydroxide (1.0 mmol, 24 mg) into a 25 mL reaction tube with a magnetic stir bar. After sealing with a rubber stopper, evacuate with a double-tube for 5 minutes, replace with N2 gas for protection, and repeat the evacuation and replacement operation 3 times. Add 4-bromoanisole (0.40 mmol, 51 μL) and 4 mL of a pre-deoxygenated mixed solvent (containing 3.2 mL of tetrahydrofuran and 0.8 mL of water) successively using a syringe. Place the reaction tube in an oil bath at 55 °C, heat and stir for 18 hours. LC-MS monitored the complete conversion of the raw material. Evaporate the solvent by rotary evaporation, and the obtained residue was purified by column chromatography to obtain 36.0 mg of 2-phenyladenosine (the compound shown in Formula 9b) with a yield of 48%. The target compound was analyzed by 1H NMR and 13C NMR using a 400 MHz nuclear magnetic resonance spectrometer from Bruker, Germany. The characterization results are as follows: 11H NMR (400 MHz, DMSO) δ 8.35 (s, 1H), 8.29 (d, J = 8.4 Hz, 2H), 7.27 (brs, 2H), 7.01 (d, J = 8.8 Hz, 2H), 5.98 (d, J = 4.8 Hz, 1H), 5.60 - 5.45 (m, 1H), 5.34 - 5.21 (m, 1H), 5.13 - 5.02 (m, 1H), 4.77 - 4.65 (m, 1H), 4.26 - 4.18 (m, 1H), 4.01 - 3.92 (m, 1H), 3.82 (s, 3H), 3.73 - 3.64 (m, 1H), 3.61 - 3.52 (m, 1H); 13 13C NMR (125 MHz, DMSO) δ 161.0, 158.4, 156.2, 131.4, 129.7, 114.0, 87.7, 85.9, 73.8, 71.1, 62.1, 55.7.

[0296] It should be noted that based on the same method for preparing C2-trimethylaminoboranyl-substituted adenosine under the heating reaction conditions of the aforementioned Example 2, the substrate raw materials of other examples can also adopt the same heating reaction conditions to prepare the corresponding C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs, and the present invention will not list them one by one.

[0297] It should be noted that based on the aforementioned Application Examples 1 to 4, the same reaction can be used to prepare the corresponding products (C-2 hydroxy, aryl, deuterated adenosine, adenylic acid and their analogs) using the C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs prepared in the aforementioned other examples as raw materials, and the present invention will not list them one by one.

[0298] The above description of the embodiments is for the convenience of those of ordinary skill in the art to understand and use the invention. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative labor. Therefore, the present invention is not limited to the above embodiments, and the improvements and modifications made by those skilled in the art without departing from the scope of the present invention should be within the protection scope of the present invention.

Claims

1. A C2-aminoboranyl-substituted adenosine, adenylic acid and their analogues, characterized in that, having a chemical structure represented by the following general formula (I), (II), (III), (IV), (V) or (VI): wherein, R 1 is selected from the following groups: The above-mentioned R 1 Among each group, R 6 and R 7 each independently selected from OH, H, F, Cl, Br, I, OMe, OEt, OCH2CH2OCH3, OAc, N3, SH; Z is selected from N, O, C, S; R 8 is selected from H, OH, ODMTr, OAc; R 2 selected from the following groups: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl; R 3 selected from the following groups: The above-mentioned R 3 In each group, Alkyl is a substituted or unsubstituted alkyl group, and Aryl is a substituted or unsubstituted aryl or heteroaryl group; R 4 selected from the following groups: substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or any group represented by the following structure: R 5 selected from the following groups: H, F, CN; The nitrogen-containing heterocycle in formula (V) Selected from the groups represented by any of the following structures: L is selected from any one of the following neutral molecules:

2. A method for preparing a C2-aminoboranyl-substituted adenosine, adenylic acid, and analogs thereof according to claim 1, characterized in that, The method comprises the following steps: dissolving a substrate and a boron radical precursor in a solvent, then adding or not adding an acid, adding an oxidant, and reacting under light irradiation or heating conditions to obtain C2-aminoboranidyl-substituted adenosine, adenylic acid and their analogues.

3. The preparation method of the C2-amine borane group-substituted adenosine, adenylic acid and their analogs according to claim 1, characterized in that, The substrate is selected from adenosine, adenylic acid or adenosine analogues; The boron radical precursor is selected from compounds represented by the following structures:

4. The preparation method of the C2-amine borane-substituted adenosine, adenylic acid and their analogs according to claim 2 or 3, characterized in that, The molar ratio of the substrate to the boron radical precursor is 1:3 to 8.

5. The method for preparing a C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs according to claim 2 or 3, characterized in that, The acid is selected from Lewis acids or Bronsted acids; The Lewis acid is at least one of zinc chloride, magnesium chloride, lithium chloride, silver nitrate, scandium trifluoromethanesulfonate, yttrium trifluoromethanesulfonate; The Bronsted acid is at least one of formic acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid; The solvent is at least one of acetonitrile, dimethyl sulfoxide, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, water; The oxidant is at least one of ammonium persulfate, potassium persulfate, sodium persulfate, tert-butyl peroxybenzoate, tert-butyl hydroperoxide, di-tert-butyl peroxide; 6. The preparation method of the C2-amine borane-substituted adenosine, adenylic acid and their analogs according to claim 5, characterized in that, The molar ratio of the Lewis acid to the substrate is 0.8 to 2:1; The molar ratio of the Bronsted acid to the substrate is 2 to 15:1; The molar ratio of the oxidant to the substrate is 2 to 4:1; The ratio of the solvent to the substrate is 20 to 40 mL:1 mmol.

7. The preparation method of the C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs according to claim 2, characterized in that, When the reaction is carried out under light irradiation conditions, the specific reaction conditions are: reacting at room temperature for 48 to 72 hours under a protective atmosphere and in the presence of a photocatalyst, with the light irradiation condition being 10 to 100 W blue light irradiation.

8. The method for preparing C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs according to claim 7, characterized in that, The photocatalyst is at least one of Ir(ppy)3, Ru(bpy)3(PF6)2, MesAcr(BF4), Ir[dF(CF3)ppy]2(dtbbpy)(PF6), Ru(bpz)3(PF6)2, Ru(DMB)3(PF6)2, Eosin Y, 4CzIPN, 3CzClIPN, Rose bengal; 9. The method for preparing C2-aminoboranyl-substituted adenosine, adenylic acid and their analogues according to claim 2, characterized in that, When the reaction is carried out under heating conditions, the specific reaction conditions are: reacting at 35 to 55 °C for 8 to 36 hours under a protective atmosphere; The protective atmosphere is nitrogen or argon.

10. Use of the C2-aminoboranyl-substituted adenosine, adenylic acid and their analogs according to claim 1 in the preparation of C2-hydroxy, aryl, deuterated adenosine, adenylic acid and their analogs, characterized in that, The C2-aminoboranidyl-substituted adenosine, adenylic acid and their analogues are synthesized into the C2-hydroxy, aryl, deuterated adenosine, adenylic acid and their analogues by converting the C2-aminoboranidyl functional group in their structures.

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