Beta-lactam antifungals. II. Enantiocontrolled synthesis of (2R,5S)-2-hydroxymethyl-1-carbapenam, the carba-analog of a clavam antifungal.
(2R,5S)-2-Hydroxymethyl-1-carbapenam (3), the carba-analog of an antifungal beta-lactam (2R,5S)-2-(hydroxymethyl)calvam (1), was synthesized in an enantiocontrolled manner, starting from the coupling reaction of an optically active phthalimido-acetate (3S,4S)-4 and an allylsilane 7, followed by removal of the phthalimido group that was crucial for asymmetric induction. Hydroboration, protecting-group interconversion, and cyclization gave 3 stereoselectively.
Konosu
T
T
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Furukawa
Y
Y
Hata
T
T
Oida
S
S
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism
D000935:Antifungal Agents; D015780:Carbapenems; C073503:2-hydroxymethyl-1-carbapenam