4.6 Article

Development of a synthetic equivalent of α,α-dicationic acetic acid leading to unnatural amino acid derivatives via tetrafunctionalized methanes

期刊

ORGANIC & BIOMOLECULAR CHEMISTRY
卷 20, 期 11, 页码 2282-2292

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ob02482e

关键词

-

向作者/读者索取更多资源

Diethyl mesoxalate (DEMO) reacts with acid amide to form N,O-hemiacetal. Dehydration is more favored than amide elimination upon treatment with a base, which is overcome by the presence of acetic anhydride. N-acylimine formed reacts with pyrrole or indole to form α,α-disubstituted malonates, followed by hydrolysis and decarboxylation to form (α-indolyl-α-acylamino)acetic acid.
Diethyl mesoxalate (DEMO) exhibits high electrophilicity and accepts the nucleophilic addition of a less nucleophilic acid amide to afford N,O-hemiacetal. However, our research showed that elimination of the amide moiety proceeded more easily than dehydration upon treatment with a base. This problem was overcome by reacting DEMO with an acid amide in the presence of acetic anhydride to efficiently obtain N,O-acetal. Acetic acid was eliminated leading to the formation of N-acylimine in situ upon treatment with the base. N-Acylimine is also electrophilic, accepting the second nucleophilic addition by pyrrole or indole to form alpha,alpha-disubstituted malonates. Subsequent hydrolysis followed by decarboxylation resulted in (alpha-indolyl-alpha-acylamino)acetic acid formation; homologs of tryptophan. Through this process, DEMO serves as a synthetic equivalent of alpha,alpha-dicationic acetic acid to facilitate nucleophilic introduction of the two substituents.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据