Total synthesis of (+)-ambruticin S: probing the pharmacophoric subunit.
An enantioselective synthesis of the antifungal natural product (+)-ambruticin S has been accomplished starting with the readily available methyl alpha-d-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which encompassed seven of the 10 stereogenic centers of the target molecule. The remaining three centers were set by a highly diastereoselective, asymmetric cyclopropanation employing a chiral, nonracemic phosphonamide reagent. Our strategy for the construction of the dihydropyran subunit involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization. Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, Canada H3C 3J7. stephen.hanessian@umontreal.ca
Focken
Thilo
T
Mi
Xueling
X
Oza
Rupal
R
Chen
Bin
B
Ritson
Dougal
D
Beaudegnies
Renaud
R
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001685:Biological Factors / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D006031:Glycosylation; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000935:Antifungal Agents; D001685:Biological Factors; D011714:Pyrans; C553537:ambruticin S; C014964:ambruticin