Asymmetric synthesis of 1,2,3,4,5,6-hexahydro-5-hydroxypyrimidin-2-ones aspotential HIV-protease inhibitors

The first asymmetric synthesis of potential cyclic urea HIV protease inhibi tors of Type 2 is reported. The synthesis is short and highly versatile in the choice of the substitution pattern and absolute configuration of the pr oducts starting from readily available materials. Nonchiral central buildin g block was synthesized and subsequently asymmetrically alkylated under (R) -/(S)-1-amino-2-(methoxymethyl)pyrrolidine (RAMP/SAMP)-auxiliary control to provide 8a-e. The alkylated ketones then were reduced to the target compou nds 9a-e, with good-to-excellent overall yields, as well as diastereoisomer ic and enantiomeric purities.