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Total Synthesis of Bistramide A and Its 36( Z ) Isomers: Differential Effect on Cell Division, Differentiation, and Apoptosis
Author(s) -
Tomas Loïc,
Boije af Gennäs Gustav,
Hiebel Marie Aude,
Hampson Peter,
Gueyrard David,
Pelotier Béatrice,
YliKauhaluoma Jari,
Piva Olivier,
Lord Janet M.,
Goekjian Peter G.
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102462
Subject(s) - tetrahydropyran , apoptosis , cell division , chemistry , stereochemistry , ether , fragment (logic) , enol ether , cell growth , enol , cell , biochemistry , organic chemistry , ring (chemistry) , catalysis , computer science , programming language
The total synthesis of bistramide A and its 36( Z ),39( S ) and 36( Z ),39( R ) isomers shows that these compounds have different effects on cell division and apoptosis. The synthesis relies on a novel enol ether‐forming reaction for the spiroketal fragment, a kinetic oxa‐Michael cyclization reaction for the tetrahydropyran fragment, and an asymmetric crotonylation reaction for the amino acid fragment. Preliminary biological studies show a distinct pattern of influence of each of the three compounds on cell division, differentiation, and apoptosis in HL‐60 cells, thus suggesting that these effects are independent activities of the natural product.