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Preparation method of pyrimidine nucleoside compound or purine nucleoside compound

A technology of nucleoside compounds and purines, which is applied in the field of preparation of pyrimidine nucleoside compounds or purine nucleoside compounds, and can solve the problems of severe and harsh reaction conditions and limited types of applicable nucleosides

Active Publication Date: 2011-07-20
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to provide a pyrimidine-type nucleoside compound or a purine-type The preparation method of nucleoside compound

Method used

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  • Preparation method of pyrimidine nucleoside compound or purine nucleoside compound
  • Preparation method of pyrimidine nucleoside compound or purine nucleoside compound
  • Preparation method of pyrimidine nucleoside compound or purine nucleoside compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Synthesis of whole Bz uridine:

[0052]

[0053] Reagents and conditions: a) DCC / DMAP, CH 2 Cl 2 , rt; b) BSTFA, AuPPh 3 NTf, CH 3 CN, rt.

[0054] Specific experimental process and data:

[0055] Under the protection of argon, the anomeric exposed fully Bz-protected ribose (1 g, 2.3 mmol) and o-alkynylbenzoic acid (697 mg, 3.5 mmol) were dissolved in dry CH 2 Cl 2 (2 mL), then DCC (950 mg, 4.6 mmol) and a catalytic amount of DMAP were added to the system and stirred at room temperature for 4 h. The solvent was evaporated to dryness under reduced pressure to obtain a crude product, followed by column chromatography to obtain ribose alkynyl ester donor (1.3 g, 90%).

[0056] The product identification data are as follows: [α] D 25 =+37.6(c1.05, CHCl 3 ); 1 H NMR (300MHz, CDCl 3 ): δ8.05(d, J=7.5Hz, 2H), 7.96(d, J=7.2Hz, 2H), 7.90(m, 3H), 7.63(t, J=7.5Hz, 1H), 7.55(m , 2H), 7.48(m, 4H), 7.35(m, 5H), 6.68(s, 1H), 6.04(m, 2H), 4.88(m, 1H), 4.76(dd, J=12.6, 5...

Embodiment 2

[0060] Synthesis of glucothymidine:

[0061]

[0062] Reagents and conditions: a) EDC / DIEPA, CH 2 Cl 2 , rt; b) BSTFA, AuPPh 3 NTf, CH 3 CN, rt.

[0063] Specific experimental process and data:

[0064] The anomeric exposed whole Bz glucose (2160mg, 4.0mmol), alkynoic acid (970mg, 4.8mmol, 1.2eq), DMAP (488mg, 4.0mmol, 1.2eq), EDCI (955mg, 5.0mmol, 1.25eq) and DIPEA (1.3mL, 7.2mmol, 1.8eq) was put into a 25mL egg bottle, injected with 4mL dry DCM, stirred at room temperature for 3h, diluted with DCM, washed with saturated saline, dried over anhydrous sodium sulfate, filtered, concentrated, and flash column chromatography (PE / EA=5:1), the product (2815 mg, 97%, β / α=1:1.3) was obtained.

[0065] The product identification data are as follows: α configuration: [α] D 27 =98.3(c 4.1, CHCl 3 ). 1 HNMR (300MHz, CDCl 3 ): δ8.097.22(m, 24H), 6.93(d, 1H, J=3.3Hz), 6.32(t, 1H, J=10.2Hz), 5.90(t, 1H, J=9.9Hz), 5.73(dd , 1H, J=10.2, 2.7Hz), (m, 2H), 4.52(dd, 1H, J=12.3, 3...

Embodiment 3

[0070] Synthesis of glucocytosine:

[0071]

[0072] Reagents and conditions: a) EDC / DIEPA, CH 2 Cl 2 , rt; b) BSTFA, AuPPh 3 NTf, CH 3 CN, rt.

[0073] Specific experimental process and data:

[0074] The preparation method of the whole acetyl group-protected glucoynyl ester donor is the same as that of the whole benzoyl-protected glucose.

[0075] The product identification data are as follows: α configuration: [α] D 29 =96.7(c 2.5, CHCl 3 ). 1 H NMR (300MHz, CDCl 3 ): δ7.96(d, 1H, J=8.1Hz), 7.59(d, 1H, J=7.8Hz), 7.51(t, 1H, J=7.5Hz), 7.41(t, 1H, J=7.5 Hz), 6.63(d, 1H, J=3.6Hz), 5.62(t, 1H, J=9.6Hz), 5.25(m, 2H), 4.33(d, 1H, J=9.6Hz), 4.12(d, 1H, J=10.2Hz), 4.26(m, 1H), 2.10(s, 3H), 2.05(s, 3H), 2.04(s, 3H), 2.01(s, 3H), (m, 4H), 0.96(t, 1H, J=7.2Hz). 13 C NMR (75MHz, CDCl 3 ): δ170.5, 170.0, 169.6, 169.2, 163.9, 135.0, 132.3, 130.6, 129.6, 127.2, 125.1, 97.0, 89.7, 79.5, 70.1, 69.9, 69.2, 67.8, 61.2, 30.6, 21.9, 20.5, 2 20.3, 19.4, 19.0, 13.5. HRMS (MALDI...

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Abstract

The invention discloses a preparation method of a pyrimidine nucleoside compound shown in a formula 1 or a purine nucleoside compound shown in a formula 2, comprising the following steps of: performing glucosidation on a compound 3 and a compound 4 to obtain the pyrimidine nucleoside compound 1; or performing glucosidation on the compound 3 and a compound 5 to obtain the purine nucleoside compound 2. The preparation method disclosed by the invention is applicable to preparation of many kinds of nucleoside compounds, and has the advantages of mild reaction conditions, greenness, environmental friendliness and higher yield and purity of the product.

Description

technical field [0001] The present invention specifically relates to a preparation method of a pyrimidine nucleoside compound or a purine nucleoside compound. Background technique [0002] Nucleosides and analogs play important roles in life processes, such as their involvement in cell division, virus replication, etc. Therefore, nucleosides and their analogs can be used as drugs to intervene in these processes, so as to achieve the purpose of anti-virus and anti-tumor [(a) Otová, B.; J.; Votruba, I.; A. Anticancer Res. 2009, 29, 1295. (b) De Clercq, E. Med. Res. Rev. 2009, 29, 571.]. [0003] Currently clinically used antineoplastic drugs include 5-F-2'-deoxyuridine, etc.; antiviral drugs, especially anti-HIV virus drugs, are of a great variety such as: AZT (3'-azido-3'-deoxythymidine), ddC ( 2', 3'-dideoxycytidine), ddI (2', 3'-dideoxyinosine), etc. There are also some nucleoside analogues that are in Phase I, Phase II or Phase III clinical studies because of their e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/067C07H19/09C07H19/167C07H1/00
Inventor 俞飚孙建松张庆举李瑶
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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