1-Boc-3-氟氮杂环丁烷-3-羧酸的合成。

Synthesis of 1-Boc-3-fluoroazetidine-3-carboxylic acid.

机构信息

Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.

出版信息

J Org Chem. 2009 Mar 6;74(5):2250-3. doi: 10.1021/jo802791r.

DOI:10.1021/jo802791r

PMID:19216497

Abstract

Synthetic strategies toward 3-fluoroazetidine-3-carboxylic acid, a new cyclic fluorinated beta-amino acid with high potential as building block in medicinal chemistry, were evaluated. The successful pathway includes the bromofluorination of N-(diphenylmethylidene)-2-(4-methoxyphenoxymethyl)-2-propenylamine, yielding 1-diphenylmethyl-3-hydroxymethyl-3-fluoroazetidine after reduction of the imino bond, ring closure, and removal of the 4-methoxybenzyl group. Changing the N-protecting group to a Boc-group allows further oxidation to 1-Boc-3-fluoroazetidine-3-carboxylic acid, a new fluorinated heterocyclic amino acid.

摘要

评估了合成 3-氟氮杂环丁烷-3-羧酸的策略，这是一种新型环状氟化β-氨基酸，具有作为药物化学中构建块的巨大潜力。成功的途径包括 N-（二苯甲基亚胺）-2-（4-甲氧基苯氧甲基）-2-丙烯基胺的溴氟化，还原亚胺键、环化和去除 4-甲氧基苄基后得到 1-二苯甲基-3-羟甲基-3-氟氮杂环丁烷。将 N-保护基改为 Boc-基允许进一步氧化得到 1-Boc-3-氟氮杂环丁烷-3-羧酸，这是一种新型氟化杂环氨基酸。