Total synthesis of (+)-sarain A.
This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (+)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4'-C3'-C7' stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late-stage installation of the tertiary amine-aldehyde proximity interaction.
Becker
Michael H
MH
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
Chua
Peter
P
Downham
Robert
R
Douglas
Christopher J
CJ
Garg
Neil K
NK
Hiebert
Sheldon
S
Jaroch
Stefan
S
Matsuoka
Richard T
RT
Middleton
Joy A
JA
Ng
Fay W
FW
Overman
Larry E
LE
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D000473:Alkanes / Q000138:chemical synthesis; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008958:Models, Molecular; D011161:Porifera; D013237:Stereoisomerism
D000470:Alkaloids; D000473:Alkanes; D001952:Bridged-Ring Compounds; C410431:sarain A; C022884:undecane