C-Si結合開裂に伴うＤ化反応

抄録

4-[3,5-Bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) is being developed as a novel anticancer drug which is a synthetic retinobenzoic acid with selective affinity for RAR-a receptor.
During pre-clinical and clinical studies, three metabolites, oxidized at the trimethylsilyl group of TAC-101, were found, and we developed and reported synthetically efficient routes of these metabolites.
In these snthetic studies, we found that the C-Si bond of hydroxymethyldimethyl arylsilane was easily cleaved by weak base such as K₂CO₃. After detailed optimization of the reaction condition, we selected NaOMe as base and MeOD as reaction medium for introducing the deuterium atom into the ipso-position of hydroxymethyldimethyl arylsilane. Herein, we wish to report the details of scope and limitaion of applicable substrates for the desilylation reaction.