Catalytic enantioselective synthesis of key intermediates for triazole antifungal agents.
[reaction: see text] A short-step synthesis of versatile chiral building blocks for triazole antifungal agents such as ZD0870 and Sch45450 was developed via catalytic enantioselective cyanosilylation of electron-deficient ketones as the key step. High enantioselectivity was produced using a catalyst prepared from Gd(HMDS)(3) and ligand 5 in a 2:3 ratio. This new catalyst preparation method was superior to the previous method using Gd(O(i)Pr)(3) as a metal source. A rationale for the difference is proposed on the basis of structural studies of the catalyst complexes using ESI-MS.
Suzuki
Masato
M
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Kato
Nobuki
N
Kanai
Motomu
M
Shibasaki
Masakatsu
M
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000935:Antifungal Agents; C508849:Sch45450; D014230:Triazoles; C105015:ZD 0870