Monoterpene-based chiral β-amino acid derivatives prepared from natural sources: syntheses and applications

Natural monoterpenes have proved to be good starting materials for the synthesis of beta-amino acid derivatives. In the past decade, a number of well-known synthetic procedures have been applied for the preparation of monoterpene-based beta-amino acid derivatives, e.g. from beta-lactams via the 1,2-dipolar cycloaddition of chlorosulfonyl isocyanate to commercial or readily available monoterpenes [e.g. (+)- and (-)-alpha- or delta-pinene, (+)-3- and 2-carene, (+)- and (-)-apopinene], the conjugate addition of amides to monoterpene-based alpha,beta-unsaturated esters or the transformations of (-)-cis-pinonoic acid prepared by the oxidative cleavage of (+)- and (-)-verbenone. beta-Amino acid derivatives are excellent building blocks for versatile transformations, e.g. multicomponent reactions resulting in beta-lactams, syntheses of 1,3-heterocycles and diaminopyrimidine derivatives or the formation of peptides containing an H12 helix. 1,3-Amino alcohol derivatives prepared from beta-amino esters have been applied as chiral catalysts in enantioselective transformations. Several of these compounds are of noteworthy pharmacological importance, such as tyrosine kinase Axl inhibitor diaminopyrimidine-coupled beta-aminocarboxamides, MDR inhibitor thiourea derivatives of beta-amino esters or 2-imino-1,3-oxazines, which exhibit marked growth inhibitory activity on multiple cancer cell lines. The present review summarizes recent developments relating to the syntheses, applications and pharmaceutical importance of monoterpene-based beta-amino acids and their derivatives.