“Carba” peptide bond surrogates: synthesis of Boc-L-Leu-…(CH2-CH2)-L-Phe-OH and Boc-LLeu-ψ-(CH2-CH2)-D-Phe-OH through a horner-emmons reaction.

✍ Scribed by Marc Rodriguez; Annie Heitz; Jean Martinez

• Book ID: 104221872
• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 265 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)88554-8

✦ Synopsis

Abstra

A synthesis of Boc-L-Leu-\r(CHz-CHz&Phe-OH and Boc-~-L~u-u~(CH~-CH~)-Q-Phe-OH from Boc-ghomo-L-leucinal, through a Horner-Emmons reaction with ethyl 2-(diethylphosphono)-3-phenylpropionate is described. Intermediate cyclisation into lactames (3S,6R)-3-benzyl6-isobutyl-piperidin-2-one and (3R,6R)-3-benzyl6-isobutyl-piperidin-2-one allowed a facile and unambiguous identification of diastereomers.

We recently reported on a general route leading to "carba" peptide bonds replacements, which involved the reaction of a phosphorus ylide with a N-Boc-protected g-substituted g-aminoaldehydel.

As an example, we described the unambiguous synthesis of the two diastereomeric pseudodipeptides Boc-L-Phe-'r(CHz-CHz)-L-Ala-OH and Boc-LPhe-Y(CH2-CH$-D-Ala-OH.