Part I: Thiourea organocatalysts for enantioselective reactions Part II: Syntheses of a tyrosine analogue for novel opioid peptides

Abstract

In Part I, a novel chiral amine-thiourea bifunctional organocatalyst was developed. It has been demonstrated to promote the asymmetric MBH reactions of cyclohexenone with a variety of aromatic aldehydes to afford highly functionalised, synthetically useful chiral allylic alcohols. In this process, the thiourea organocatalyst exhibited low catalytic activity and poor to moderate levels of enantioselectivity toward this reaction. The catalyst also exhibited low levels of enantioselectivity towards the Michael Thiol addition of tert-butyl thiolphenol to cyclohexenone, but displayed non-enantioselectivity in the hydrophosphonylation reaction.In Part II, 3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid (Dcp), a 2a??,6a??-dimethyltyrosine containing a carbamoyl group in place of the hydroxyl function and lacking the amino group was prepared. Replacement of Tyr1 in an enkephalin analogue resulted in the first opioid peptide-derived antagonist that does not contain a phenolic hydroxyl group at the 1-position residue. The cyclic peptide Dcp-c[D-Cys-Gly-Phe(pNO2)-D-Cys]NH2 represents a novel, potent I? opioid antagonist.