Synthesis and reactions of Biginelli-compounds. Part 23. Chemoenzymatic syntheses of enanttiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1H)-ones

Enantiomerically pure dihydropyrimidones (DHPMs) were prepared by lipase-ca tlyzed enzymatic resolution of two types of activated DHPM esters. In the f irst model series, pivaloyloxymethyl-activated DHPM C5-esters 10a-c were re solved on an analytical scale by various lipases in two different solvent s ystems with selectivities E < 50. Alternatively, attachment of an acetoxyme thyl residue at the N3 position of the DHPM scaffold led to activated ester 15, which was selectively cleaved by Thermomyces lanuginosus lipase (E > 2 00) to furnish, after depretection, DHPMs (R)- and (S)-13 on a semi-prepara tive scale. Treatment of (R)-13 with trichloroacetyl isocyanate produced th e antihypertensive agent (R)-SQ 32926.