From L-Ascorbic Acid to Protease Inhibitors: Practical Synthesis of Key Chiral Epoxide Intermediates for Aspartyl Proteases

Bulletin of the Korean chemical society

Sang Min Lee¹  Dong Joon Choo¹  Jae sung Kang¹  Jae Yeol Lee¹  B. Moon Kim¹  Sung Min Kim¹  Kyoung Mee Seol¹  Sun Ki Chang¹  Min Kyu Kim¹  Soon Mog So¹ 

关键词: L-Ascorbic acid;    Protease inhibitors;    Aziridine opening;    HIV protease;    Epoxide;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

Efficient synthetic routes were developed to prepare a sizable amount (4-15 grams) of the chiral epoxides 4-6 as versatile intermediates for the synthesis of aspartyl protease inhibitors of therapeutic interest such as HIV protease and β-secretase. Oxidative cleavage of the C(2)-C(3) double bond of L-ascorbic acid followed by functional group manipulation led to the preparation of the epoxide 10, which was opened with an azide to yield a common aziridine intermediate 12. Through opening of the aziridine ring of 12 with either a carbon or a sulfur nucleophile, chiral epoxide precursors 4-6 could be prepared for various HIV protease inhibitors. Except for the final low melting epoxides 5 and 6, all intermediates were obtained as crystalline solids, thus the synthetic pathway can be easily applied to a large-scale synthesis of the chiral epoxides.

【 授权许可】

Unknown