Three-Component Synthesis of Polysubstituted Homoproline Analogs 英文参考文献.docVIP

Molecules 2005, 10, 755-761 molecules ISSN 1420-3049 Three-Component Synthesis of Polysubstituted Homoproline Analogs Konstantin V. Kudryavtsev* and Veronika V. Irkha Department of Chemistry, Moscow State University, Lenin’s Hills, Moscow, 119992, Russian Federation. Tel. (+7) 095-939-3564, Fax (+7) 095-932-8846 * Author to whom correspondence should be addressed; e-mail: kudr@org.chem.msu.su Received: 16 July 2004; in revised form 28 December 2004 / Accepted: 1 January 2005 / Published: 31 August 2005 Abstract: Tetrasubstituted pyrrolidines representing analogs of homoproline were synthesized by three-component condensation of aryl(heteroaryl)aldehydes, asparagine and N-methylmaleimide (NMM). Compounds with (1S*, 3R*, 3aS*, 6aR*)-configuration at the corresponding carbon positions of the bicyclic pyrrolidine ring could be isolated on a preparative scale. Keywords: Multicomponent reactions, 1,3-dipolar cycloaddition, homoproline. Introduction β-Amino acids receive considerable interest due to their biologically important properties, their occurrence in natural products, and as potential precursors for β-lactams. Substitution of proline fragment in tetrapeptides with homoproline leads to increased resistance to enzymatic hydrolysis and preserving of μ-opioid agonists properties of tetrapeptides [1]. Homoproline and its derivatives were the targets of some recent synthetic examinations including Kowalski ester homologation protocol [2], sequential conjugate addition - ring closing metathesis [3], asymmetric hydrogenation of cyclic β-enaminoacid derivatives [4], retro-Dieckmann reaction of 7-azabicyclo[2.2.1]heptan-2-one- carboxylic acid esters [5], 1,3-dipolar cycloaddition of nitrones with phenyl vinyl ether [6]. Functionalized homoprolines have been used for pyrrolizidines and indolizidines syntheses via Dieckmann condensation [7]. To access a diversit