School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
J Org Chem. 2009 Aug 21;74(16):6350-3. doi: 10.1021/jo9008782.
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.
通过 LiAlH(O-t-Bu)(3)介导的相应α-氨基酮还原反应，实现了在 3 位带有二氟甲基膦硫酯基团的 2-氨基醇衍生物的高度非对映选择性合成。产物的膦硫酯部分可通过用 m-CPBA 氧化轻易转化为相应的膦酸酯，然后进行水相处理。所开发的方法对于 SMases 的有效抑制剂 SMA-7 的 SAR 研究应该是有用的。
