Three-component Biginelli cyclocondensation reaction using C-glycosylated substrates. Preparation of a collection of dihydropyrimidinone glycoconjugates and the synthesis of C-glycosylated monastrol analogues

J Org Chem. 2002 Oct 4;67(20):6979-94. doi: 10.1021/jo0202076.

Abstract

The aldehyde-ketoester-urea cyclocondensation reaction has been revisited using C-glycosylated reagents with the aim of exploring a potential entry to a library of dihydropyrimidinone glycoconjugates. A collection of 13 mono- and bis-C-glycosylated dihydropyrimidinones has been prepared by a parallel synthesis approach using the three-component promoter CuCl/AcOH/BF(3) x Et(2)O. The sugar residues have been installed at either N1, C4, or C6 in the monoglycosylated derivatives and at both the C4 and C6 in the bisglycosylated products. The mono- and bisglycosylated products at C4 and C6 were obtained as mixtures of diastereoisomers with good to excellent selectivities due to the asymmetric induction by the sugar residue in the formation of the C4 stereocenter of the dihydropyrimidinone ring. Individual stereoisomers were isolated as pure compounds and their structures assigned with the aid of X-ray crystallography and chiroptical properties. As a demonstration of this new concept in the Biginelli reaction, the synthesis of two C4 epimer monastrol analogues bearing the ribofuranosyl moiety at C6 has been described.