Homoserine-derived cyclic sulfamidate as chiral educt for the diversity-oriented synthesis of lactam-bridged dipeptides
✍ Scribed by Fabrice Galaud; William D. Lubell
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2005
- Tongue
- English
- Weight
- 190 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
Introduction of structural constraint into peptides is an effective way for studying their conformation–activity relationships. Conformationally restrained dipeptidyl lactams, important building blocks for the synthesis of peptidomimetics, have now been synthesized from N‐[9‐(9‐phenylfluorenyl)]‐L‐aspartic acid α‐cumyl β‐methyl diester as an inexpensive chiral educt. After selective reduction of the β‐methyl ester with diisobutylaluminum hydride (DIBAL‐H), homoserine 6 was treated with thionyl chloride, imidazole, and triethylamine to give sulfamidites 7. Diastereoisomers 7 were separated by chromatography and oxidation of the major sulfamidite (2R,4S)‐7 with catalytic ruthenium trichloride afforded sulfamidate 8. A series of γ‐lactam‐bridged dipeptides was then obtained by ring opening of sulfamidate cumyl ester 8 with a series of amino esters, selective cumyl ester removal, and lactam formation. The resulting dipeptidyl lactams possessed aliphatic, aromatic, amino, thioether, and carboxylate side chains. A γ‐lactam analog of Pro–Leu–Gly–NH~2~ (PLG), 16, was synthesized to illustrate the potential for using this approach in the synthesis of biologically active peptide mimics. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005