Open Access11-Step Total Synthesis of Araiosamines
Author(s) -
Maoqun Tian,
Ming Yan,
Phil S. Baran
Publication year - 2016
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.6b09701
Subject(s) - chemistry , guanidine , reagent , total synthesis , combinatorial chemistry , stereochemistry , polarity (international relations) , sponge , chemical synthesis , organic chemistry , biochemistry , in vitro , biology , cell , botany
A concise route to a small family of exotic marine alkaloids known as the araiosamines has been developed, and their absolute configuration has been assigned. The dense array of functionality, high polarity, and rich stereochemistry coupled with equilibrating topologies present an unusual challenge for chemical synthesis and an opportunity for innovation. Key steps involve the use of a new reagent for guanidine installation, a remarkably selective C-H functionalization, and a surprisingly simple final step that intersects a presumed biosynthetic intermediate. Synthetic araiosamines were shown to exhibit potency against Gram-positive and -negative bacteria despite a contrary report of no activity.