Efficient microwave-assisted solid phase coupling of nucleosides, small library generation, and mild conditions for release of nucleoside derivatives

TETRAHEDRON LETTERS

卷:54

Article

Paritala, Hanumantharao¹  Suzuki, Yuta²  Carroll, Kate S.¹ 

[1] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA

[2] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA

关键词: Solid phase synthesis;    Microwave assisted;    Nucleoside;    Combinatorial library;   

DOI  :  10.1016/j.tetlet.2013.01.109

来源: Elsevier

【 摘 要 】

Nucleosides are essential bio-molecules that participate in a wide array of biological processes involved in maintaining physiologic homeostasis. Recent efforts geared toward the synthesis of nucleoside analogues and development of nucleoside combinatorial libraries using solid phase synthesis have contributed invaluable information toward drug design and development. These studies have provided information concerning the structural requirements of substrate binding pockets of enzymes and evaluation of enzyme kinetics. However, the synthesis of nucleosides and its corresponding analogues remains a challenging and time consuming process. Herein, we report an efficient, microwave assisted solid phase coupling of nucleosides, combinatorial chemistry on the coupled nucleosides to generate small library, and mild cleavage conditions to release nucleoside derivatives from its solid support. We anticipate these findings will accelerate the development of synthetic methods or combinatorial library design of nucleoside analogues in similar settings. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

Free