Diastereoselective synthesis of gamma-amino-delta-hydroxy-alpha,alpha-difluorophosphonates: a vehicle for structure-activity relationship studies on SMA-7, a potent sphingomyelinase inhibitor.
A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.
Yamagishi
Takehiro
T
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Muronoi
Shin
S
Hikishima
Sadao
S
Shimeno
Hiroshi
H
Soeda
Shinji
S
Yokomatsu
Tsutomu
T
D000473:Alkanes / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013109:Sphingomyelins / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000473:Alkanes; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C552381:SMA-7 compound; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase