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

Abstract

Enantiomerically pure dihydropyrimidones (DHPMs) were prepared by lipase-catalyzed enzymatic resolution of two types of activated DHPM esters. In the first model series, pivaloyloxymethyl-activated DHPM C5-esters 10a–c were resolved on an analytical scale by various lipases in two different solvent systems with selectivities E < 50. Alternatively, attachment of an acetoxymethyl residue at the N3 position of the DHPM scaffold led to activated ester 15, which was selectively cleaved by Thermomyces lanuginosus lipase (E > 200) to furnish, after deprotection, DHPMs (R)- and (S)-13 on a semi-preparative scale. Treatment of (R)-13 with trichloroacetyl isocyanate produced the antihypertensive agent (R)-SQ 32926.