脱氮嘌呤固相合成：在带有半胱胺连接基的交联聚苯乙烯上构建3-取代的吡咯并[3,2-d]嘧啶-6-羧酸酯。

Deazapurine solid-phase synthesis: construction of 3-substituted pyrrolo[3,2-d]pyrimidine-6-carboxylates on cross-linked polystyrene bearing a cysteamine linker.

作者信息

Rombouts Frederik J R, Fridkin Gil, Lubell William D

机构信息

Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.

出版信息

J Comb Chem. 2005 Jul-Aug;7(4):589-98. doi: 10.1021/cc050002l.

DOI:10.1021/cc050002l

PMID:16004503

Abstract

The first solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidines is presented. Merrifield resin bearing a cysteamine "traceless" linker was treated with 4-oxo-N-(PhF)proline benzyl ester (10; PhF = 9-(9-phenylfluorenyl)) to provide resin-bound aminopyrrole 20, which was treated with ethyl, phenyl, 4-phenoxyphenyl, and 2,4-dimethoxyphenyl isocyanates to furnish resin-bound ureidopyrroles 21a-d. Resin-bound pyrrolo[3,2-d]pyrimidines 22a-d were then obtained by acylation of 21 using trichloroacetyl chloride in dioxane followed by treatment with Cs2CO3 in DMF. Cleavage of pyrrolo[3,2-d]pyrimidines 22a-d from the resin was achieved in two steps, by oxidation of the sulfur to the sulfone followed by beta-elimination in the presence of t-BuONa. Four pyrrolo[3,2-d]pyrimidines, 24a-d, with different alkyl and aryl substituents at the N3 pyrimidine nitrogen, were thus obtained in overall yields of 42-50% and purities of 90-100%.

摘要

本文介绍了制备吡咯并[3,2 - d]嘧啶的首个固相方法。将带有半胱胺“无痕”连接基的 Merrifield 树脂用 4 - 氧代 - N - (PhF)脯氨酸苄酯（10；PhF = 9 - (9 - 苯基芴基)）处理，得到树脂结合的氨基吡咯 20，再用乙基、苯基、4 - 苯氧基苯基和 2,4 - 二甲氧基苯基异氰酸酯处理，得到树脂结合的脲基吡咯 21a - d。然后通过在二氧六环中用三氯乙酰氯对 21 进行酰化，接着在 DMF 中用碳酸铯处理，得到树脂结合的吡咯并[3,2 - d]嘧啶 22a - d。通过两步从树脂上裂解吡咯并[3,2 - d]嘧啶 22a - d，即先将硫氧化为砜，然后在叔丁醇钠存在下进行β - 消除反应。由此得到了四个在嘧啶氮的 N3 位带有不同烷基和芳基取代基的吡咯并[3,2 - d]嘧啶 24a - d，总收率为 42 - 50%，纯度为 90 - 100%。