Synthesis and reactions of Biginelli-compounds. Part 23. Chemoenzymatic syntheses of enanttiomerically 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.

Synthesis and Biological Activity of Ethyl 2‐(substituted benzylthio)‐4‐(3′‐(ethoxycarbonyl)biphenyl‐4‐yl)‐6‐methyl‐1,4‐dihydropyrimidine‐5‐carboxylate Derivatives

“…These Biginelli compounds possess several pharmaceutical properties like antibacterial, antiviral, antiinflammatory, antihypertensive and antitumor agents [14]. In continued quest of new antimicrobial agents, we designed and synthesized novel biphenylpyrimidines having substituted benzylthio groups.…”

Activated Anilide in Heterocyclic Synthesis: Synthesis of New Dihydropyridines, Dihydropyridazines and Thiourea Derivatives

“…18 Generally, 1,4-DHPs are synthesized by the Hantszch method, which involves one pot condensation of an aldehyde with ethyl acetoacetate, and ammonia either in acetic acid or refluxing in alcohol. 19 However, the yields of 1,4-dihydropyridines obtained by this method are generally low and several methods have been described for the synthesis of 1,4-dihydropyridine.…”

Synthesis and anticoagulant activity of a new series of 1,4-dihydropyridine derivatives

“…1,4-Dihydropyridine derivatives are of interest because of their potential biological activity and use in therapeutics such as antihypertensive [1e4], hypnotic, anti-inflammatory [5], antihypoxic and antiischemic drugs [6] and calcium channel modulators of the nifedipine type [7]. Several methods have been described for the synthesis of 1,4-dihydropyridine [8e12].…”