Amino-zinc-ene-enolate cyclization: a short access to cis-3-substituted prolino-homotryptophane derivatives.

C. Mothes, (1, 2, 3) , S. Lavielle, (1, 2) , P. Karoyan (1, 2)

1 SSFMB - Synthèse, Structure et Fonction de Molécules Bioactives
2 LCMCP (site Paris VI) - Laboratoire de Chimie de la Matière Condensée de Paris (site Paris VI)
3 Genzyme Pharmaceuticals

Proline chimeras are useful tools for medicinal chemistry and/or biological applications. The asymmetric synthesis of cis-3-substituted prolines can be easily achieved via amino-zinc-ene-enolate cyclization followed by transmetalation of the cyclic zinc intermediate for further functionalization. Syntheses of prolino-homotryptophane derivatives were achieved through Negishi cross-coupling of the zinc intermediate with indole rings. The use of Pd catalyst derived from Fu's [(t-Bu3)PH]-BF4 was required to avoid the undesired beta-hydride elimination. Optically pure and orthogonally protected compounds were obtained readily usable for peptide synthesis.

Domaines: Chimie organique

C. Mothes,, S. Lavielle,, P. Karoyan. Amino-zinc-ene-enolate cyclization: a short access to cis-3-substituted prolino-homotryptophane derivatives.. Journal of Organic Chemistry, 2008, 73 (17), pp.6706-10. ⟨10.1021/jo801006a⟩. ⟨hal-00583597⟩