期刊
SCIENCE
卷 340, 期 6129, 页码 180-182出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1234756
关键词
-
资金
- National Institute of General Medical Sciences [R01 GM084927]
- American Chemical Society Division of Organic Chemistry
- NSF
Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.
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。
推荐
暂无数据