Total synthesis of (+)-crocacin C using hidden symmetry.
A highly convergent and protecting-group-free synthesis of (+)-crocacin C, featuring an enzymatic enantioselective desymmetrization of a meso-diol, a base-induced ring opening of a THP ring, and a one-pot hydrostannylation/Stille coupling as the key steps, is reported. The natural product was obtained in 11 steps and 22.3% overall yield starting from readily available oxabicycle 1. Finally, a unique enantioselective step, an enzymatic desymmetrization, revealed four stereogenic centers and created one in C4 of the THP furnishing the dense building block 4 with high enantioselectivity (ee >98%).
Candy
Mathieu
M
Aix-Marseille Université, Institut des Sciences Moléculaires de Marseille, iSm2 CNRS UMR 6263-équipe STeRéO, Campus Saint-Jérôme, 13397 Marseille cedex 20, France.
Audran
Gérard
G
Bienaymé
Hugues
H
Bressy
Cyril
C
Pons
Jean-Marc
JM
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000475:Alkenes; D000577:Amides; C500918:crocacin C