Kaltenbach R F, Nugiel D A, Lam P Y, Klabe R M, Seitz S P
DuPont Merck Pharmaceutical Company, P.O. Box 80500, Wilmington, Delaware 19880-0500, USA.
J Med Chem. 1998 Dec 3;41(25):5113-7. doi: 10.1021/jm980255b.
We have synthesized stereoisomers of cyclic urea HIV-1 protease inhibitors to study the effect of varying configurations on binding affinities. Four different synthetic approaches were used to prepare the desired cyclic urea stereoisomers. The original cyclic urea synthesis using amino acid starting materials was used to prepare three isomers. Three additional isomers were prepared by synthetic routes utilizing L-tartaric acid and D-sorbitol as chiral starting materials. A stereoselective hydroxyl inversion of the cyclic urea trans-diol was used to prepare three additional isomers. In all 9 of the 10 possible cyclic urea stereoisomers were prepared, and their binding affinities are described.
我们合成了环状尿素HIV-1蛋白酶抑制剂的立体异构体，以研究不同构型对结合亲和力的影响。采用了四种不同的合成方法来制备所需的环状尿素立体异构体。使用氨基酸起始原料的原始环状尿素合成法制备了三种异构体。利用L-酒石酸和D-山梨醇作为手性起始原料的合成路线又制备了三种异构体。通过环状尿素反式二醇的立体选择性羟基转化制备了另外三种异构体。总共制备了10种可能的环状尿素立体异构体中的9种，并描述了它们的结合亲和力。
