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The Total Synthesis of Inostamycin A
Author(s) -
Yu Guangri,
Jung Byunghyuck,
Lee HeeSeung,
Kang Sung Ho
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201510852
Subject(s) - ketone , stereocenter , aldol reaction , aldehyde , stereoselectivity , aldol condensation , transmetalation , chemistry , total synthesis , coupling reaction , quaternary carbon , methyl ketone , organic chemistry , stereochemistry , enantioselective synthesis , catalysis
The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8 , respectively, in which the use of LaCl 3 for transmetallation was critical for high coupling efficiency.