Synthesis of novel thienonorbornylpurine derivatives

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• 作者：Hubert H艡ebabecký ; ^a ; Milan Dejmek^a ; Michal &Scaron ; á ; la^a ; Helena Mertl&iacute ; ková ; -Kaiserová ; ^a ; Martin Dra膷&iacute ; nský ; ^a ; Pieter Leyssen^b ; Johan Neyts^b ; Radim Nencka^a ; ^{nencka@uochb.cas.cz}
• 关键词：Sulfur heterocycles ; Purines ; Mitsunobu reaction ; Aldol reaction ; Coxsackie virus ; Hepatitis C virus
• 刊名：Tetrahedron
• 出版年：2012
• 期刊代码：107_00404020
• 类别：ch
• 出版时间：15 April, 2012
• 卷：68
• 期：15
• 页码：3195-3204
• 文件大小：510 K

摘要

The synthesis and antiviral evaluation of 6-amino- and 6-chloro-9-(exo-bicyclo[2.2.1]hept-2yl)-9H-purine derivatives with thiophene and tetrahydrothiophenes annelated to a norbornane moiety are described. The key step in the synthesis of derivatives with the symmetrically annelated thiophene was the Mitsunobu reaction of endo-4-thiatricyclo[5.2.1.0^2,6]deca-2,5-dien-8-ol with 6-chloropurine. The key alcohol was obtained by DDQ mediated aromatization of the corresponding tetrahydro derivatives, which were used for the preparation of the target tetrahydrothieno analogs. The key intermediate for the synthesis of derivatives with the asymmetrically annelated thiophene was 8-exo-azido-3-thiatricyclo[5.2.1.0^2,6]deca-2(6),4-diene, which was prepared from 5-exo-azido[2.2.1]heptan-2-one by aldol condensation with O-ethyl S-(2-oxoethyl) carbonodithioate, deprotection and cyclization. The target compounds were obtained by the construction of the purine base on an amine, which was obtained by LAH reduction of the key azide. The synthesized compounds were evaluated for antiviral and cytostatic activity.