Synthesis of chiral oligopeptides by means of catalytic asymmetric hydrogenation of dehydropeptides

Asymmetric hydrogenations of Ac-ΔTyr(Ac)-(S)-Ala-Gly-OMe (6), Ac-ΔTyr(Ac)-(R)-AlaGly-(S)-Phe-OMe (7), Ac-ΔPhe-NH-CH(R) CH₂-OCH₂Ph (10), HCO-ΔPhe-(S)-Leu-OMe (16), X-AA-ΔPhe-AA'-OMe (5: X ^tBOC, CBZ, CF₃CO; AA, AA' = α-amino acid), and ^tBOC-AA-ΔPhe-AA'-NH-Y (21: Y=H, NH-AA'-ΔPhe-AA-^tBOC, NHPh), catalyzed by cationic Rh complexes, [L*Rh(NBD)]⁺ClO₄ (L* = chiral diphosphine), were performed to give the corresponding chiral oligopeptides with high stereoselectivities. It was found that the nature of the N-protecting group of dehydrotripeptides (5) exerted a significant influence on the asymmetric induction as well as catalyst efficiency. The chiral centers in AA' and AA' amino acid residues in 5 were also found to have some influence on the catalytic asymmetric induction. Possible mechanism which can accommodate these effects are discussed. Asymmetric reduction of RCOCO-AA-OMe (13) via hydrosilylation was carried out to give chiral depsipeptide units. The asymmetric hydrogenation of dehydropeptides was successfully applied to the synthesis of enkephalin analogs, Ac-(R)Tyr-(R) -Ala-Gly-(S)-Phe-(S)-Leu-OMe (23) and Ac-(S)Tyr-(R) -Ala-Gly-(S)-Phe-(S)- Leu-OMe (29).