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Synthesis of constrained analogues of cholecystokinin/opioid chimeric peptides.

ABSTRACT: In our ongoing research on the synthesis of constrained analogues of CCK/opioid chimeric peptides, a bicyclic dipeptide mimetic for Nle-Asp was designed and synthesized. Starting from ?-allyl substituted aspartic acids, the terminal double bond was oxidized resulting in spontaneous cyclization to form racemic hemiaminals. Allylation of the hemiaminals afforded 5-allyl substituted proline analogues, which on oxidation, Horner-Emmons olefination, asymmetric hydrogenation, and bicyclization afforded bicyclic dipeptide mimetics for Nle-Asp. Constrained CCK/opioid peptide analogues containing bicyclic dipeptide mimetics for Nle-Gly, Nle-Asp, and homoPhe-Gly were then synthesized and analyzed at both the CCK and opioid receptors.

SUBMITTER: Ndungu JM

PROVIDER: S-EPMC1761685 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Synthesis of constrained analogues of cholecystokinin/opioid chimeric peptides.

Ndungu John M JM Cain James P JP Davis Peg P Ma Shou-W SW Vanderah Todd W TW Lai Josephine J Porreca Frank F Hruby Victor J VJ

Tetrahedron letters 20060301 13

In our ongoing research on the synthesis of constrained analogues of CCK/opioid chimeric peptides, a bicyclic dipeptide mimetic for Nle-Asp was designed and synthesized. Starting from β-allyl substituted aspartic acids, the terminal double bond was oxidized resulting in spontaneous cyclization to form racemic hemiaminals. Allylation of the hemiaminals afforded 5-allyl substituted proline analogues, which on oxidation, Horner-Emmons olefination, asymmetric hydrogenation, and bicyclization afforde ...[more]

PMID: 17203138

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