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可持续合成 2',3'-二脱氧核苷和 2',3'-二脱氢-2',3'-二脱氧核苷衍生物的方法。

Sustainable Protocol for the Synthesis of 2',3'-Dideoxynucleoside and 2',3'-Didehydro-2',3'-dideoxynucleoside Derivatives.

机构信息

Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo, 33006 Oviedo, Spain.

Rasayan Inc., Encinitas, CA 92024, USA.

出版信息

Molecules. 2022 Jun 21;27(13):3993. doi: 10.3390/molecules27133993.

DOI:10.3390/molecules27133993
PMID:35807233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9268517/
Abstract

An improved protocol for the transformation of ribonucleosides into 2',3'-dideoxynucleoside and 2',3'-didehydro-2',3'-dideoxynucleoside derivatives, including the anti-HIV drugs stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), was established. The process involves radical deoxygenation of xanthate using environmentally friendly and low-cost reagents. Bromoethane or 3-bromopropanenitrile was the alkylating agent of choice to prepare the ribonucleoside 2',3'-bisxanthates. In the subsequent radical deoxygenation reaction, tris(trimethylsilyl)silane and 1,1'-azobis(cyclohexanecarbonitrile) were used to replace hazardous BuSnH and AIBN, respectively. In addition, TBAF was substituted for camphorsulfonic acid in the deprotection step of the 5'--silyl ether group, and an enzyme (adenosine deaminase) was used to transform 2',3'-dideoxyadenosine into 2',3'-dideoxyinosine (ddI) in excellent yield.

摘要

建立了一种将核糖核苷转化为 2',3'-二脱氧核苷和 2',3'-二脱氢-2',3'-二脱氧核苷衍生物的改良方法，包括抗 HIV 药物司他夫定（d4T）、扎西他滨（ddC）和去羟肌苷（ddI）。该过程涉及使用环保且低成本的试剂对黄原酸盐进行自由基脱氧。溴乙烷或 3-溴丙腈是制备核糖核苷 2',3'-双黄原酸盐的首选烷基化剂。在随后的自由基脱氧反应中，分别使用三（三甲基硅基）硅烷和 1,1'-偶氮双（环己甲腈）代替危险的 BuSnH 和 AIBN。此外，在 5'--硅醚基团的脱保护步骤中用 TBAF 代替樟脑磺酸，并且使用酶（腺苷脱氨酶）将 2',3'-二脱氧腺苷转化为 2',3'-二脱氧肌苷（ddI），产率优异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/3bd99e8a843a/molecules-27-03993-sch005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/636456aee574/molecules-27-03993-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/f9986ffefffe/molecules-27-03993-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/9f5b4ee71597/molecules-27-03993-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/f54333c76b64/molecules-27-03993-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/02287a8dda5c/molecules-27-03993-sch004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/3bd99e8a843a/molecules-27-03993-sch005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/636456aee574/molecules-27-03993-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/f9986ffefffe/molecules-27-03993-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/9f5b4ee71597/molecules-27-03993-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/f54333c76b64/molecules-27-03993-sch003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/02287a8dda5c/molecules-27-03993-sch004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e9/9268517/3bd99e8a843a/molecules-27-03993-sch005.jpg

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