| Budget Amount *help |
¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
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| Research Abstract |
I have found that the new method for stereoselective peptide synthesis by reduction of α-oxim amides connecting with N-terminal of peptides. A variety of starting α-oxim amides were prepared by condensation of pyruvic acid, phenyl pyruvic acid, or 4-methyl-2-oxovaleric acid oxim with L-phenylalanine, L-leucine, or L-proline peptide (n = 1〜4 residues) methyl ester, N-methylamide, or N,N-dimethylamide. The reduction was carried out using Zn as a reducing agent in the presence of methanesulfonic acid in THF solvent at room temperature. The resulting amines were transformed to N-BOC peptides by treatment with (BOC)_2O in situ. The N-BOC peptides were obtained in good yields and their stereoselectivities were determined by ^1H NMR analysis. The stereoselectivity was not affected by the substituents in α-oxim acids, but much affected by the number of the residue (n) in peptides. In the cases of the L-phenylalanine and L-leucine peptide (n = 1〜4) methyl esters, R-formed products were produced preferentially from the α-oxim amides prepared from L-amino acid methyl esters (n =1) and, in contrast, S-formed products were yielded selectively from the substrates derived from di-, tri, tetrapeptide methyl esters (n = 2〜4). In addition, the S-selectivity increased with an increase in the number of the residues. On the other hand, in the cases of the L-proline peptide (n = 1〜3) methyl esters, and L-phenylalanine peptide (n = 1〜3) N-methylamides and N,N-dimethylamides, S-formed products were obtained selectively in all cases, even from the substrates in which n = 1.
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