Improved synthetic approaches toward 2′-O-methyl-adenosine and guanosine and their N-acyl derivatives
Improved synthetic approaches toward 2′-O-methyl-adenosine and guanosine and their N-acyl derivatives
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DOI：
10.1016/s0040-4020(00)00002-8
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发表时间：
2000-02-18
期刊：
影响因子：
2.1
通讯作者：
Karpeisky, A
中科院分区：
文献类型：
--
作者：
Beigelman, L;Haeberli, P;Karpeisky, A
我们开发了几种改进的方法来获得2 '-O-甲基腺苷和鸟苷及其N-酰基衍生物。(a)N-4-乙酰基-5 ′，3 ′-二-O-乙酰基-2 ′-O-甲基胞苷与N-6-Bz-腺嘌呤转糖基化得到N-6-苯甲酰基-5 ′，3 ′-二-O-乙酰基-2 ′-O-甲基腺苷，产率50%。(b)2-氨基-6-氯嘌呤核苷经MeI/NaH区域选择性甲基化后水解，高产率地得到2 '-O-Me-鸟苷。相同的2 ′-O-Me-前体转化为2 ′-O-Me-腺苷，产率为58%。(c)通过5 '，3'-O-TIPDSi衍生物的甲基化，随后选择性地N-2-酰化、脱氨基和去酰化，非常有效地将2，6-二氨基嘌呤核苷转化为N-2-异丁酰基（异丙基苯氧基乙酰基）2 '-O-Me-鸟苷，以70%的总收率提供目标化合物。(d)Mg ~（2+）和Ag ~（2+）对N-1-Bzl-鸟苷的甲基化反应产率>80%，2 ′-O-Me/3 ′-O-Me=9：1。腺苷与Ag+和Sr 2+乙酰丙酮化物的相同甲基化以75-80%产率提供2 '-O-Me-腺苷。(C)2000爱思唯尔科技有限公司版权所有。
We developed several improved approaches toward 2'-O-methyl adenosine and guanosine and their N-acyl derivatives. (a) Transglycosylation of N-4-acetyl-5', 3'-di-O-acetyl-2'-O-methyl cytidine with N-6-Bz-adenine provided N-6-benzoyl-5'3'-di-O-acetyl-2'-O-methyl adenosine in 50% yield. (b) Regioselective methylation of 2-amino-6-chloro purine riboside with MeI/NaH followed by hydrolysis provided 2'-O-Me-guanosine in high yield. The same 2'-O-Me-precursor was transformed into 2'-O-Me-adenosine in 58% yield. (c) Very efficient transformation of 2,6-diamino-purine riboside into N-2-isobutyryl (isopropylphenoxyacetyl) 2'-O-Me-guanosine through methylation of 5',3'-O-TIPDSi derivative followed by selective N-2-acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg2+ and Ag+ directed methylation of N-1-Bzl-guanosine proceeded in >80% yield with ratio of 2'-O-Me/3'-O-Me=9:1. The same methylation of adenosine with Ag+ and Sr2+ acetylacetonates provided 2'-O-Me-adenosine in 75-80% yield. (C) 2000 Elsevier Science Ltd. All rights reserved.