ORGN 885 |
| Efficient convergent synthesis of trans-vinyl dipeptide isosteres where the amide bond has been replaced by an (E)-alkene (5) requires control of the stereochemistry of both side chain centres as well as that of the double bond. A protocol for the preparation of such compounds has been devised where two amino acid-like building blocks are joined in a Wittig-type reaction. The P1 fragment 2 was prepared from the amino alcohol 1 with the desired stereochemistry by conversion to a phosphonium salt. The P1' synthon was derived from 1,3-propane diol 4, which was desymmetrized by lipase catalyzed transesterification, and subsequently modified to the α-chiral aldehyde 3. The two fragments were coupled after deprotonation of the phosphonium salt 2, where the presence of the lithiated trifluoroacetate may facilitate induction of (E)-selectivity, in the reaction with aldehyde 3.
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 131, Oral
Division of Organic Chemistry |
