Charge-Transfer Effect in Solid Phase Peptide Synthesis:Kinetic Studies in Peptide Bond Formation between Nitrobenzophenone Oxime Resin Esters and Amino Acid Esters

Byeong-Deog Park; Eui-Deok Kim; Yoon-Sik Lee

Journal of Industrial and Engineering Chemistry, Vol.3, No.3, 229-234, September, 1997

Byeong-Deog Park, Eui-Deok Kim¹, and Yoon-Sik Lee¹

Aekyung Central Research Center, Taejeon 300-200, Korea
¹Department of Chemical Technology, Seoul National University, Seoul 151-742, Korea

The effects of charge-transfer complex formation on the rate of peptide bond formation in solid-phase peptide synthesis (SPPS) were examined. 4-Nitro and 3-nitrobenzophenone oxime resins which can act as electron acceptors were prepared. Amino acid 4-(methylthio)phenyl [MTP] esters and 4-methoxyphenyl [PMP] esters which can act as electron donors were prepared. Amino acid pheny[Ph] esters were also prepared for comparison. The aminolysis reactions of the oxime resin esters with amino acid MTP, PMP, and Ph esters were compared in dipeptide formation reactions. The reactions were followed by reverse phase HPLC and their pseudo first-order rate constants were calculated. The results showed that the charge transfer interactions largely depended on the steric hindrance between the electron donors and acceptors. When there is little steric hindrance like Gly esters, MTP and PMP esters revealed fast reactions due to charge-transfer interactions. But, in case of other amino acid esters, the aminolysis reactions were influenced by other factors, such as nucleophilicity, orientation, and bulkiness of the nucleophiles.

[References]

Yajima H, Fujii N, J. Chem. Soc.-Chem. Commun., 115 (1980)
Degrado WF, Kaiser ET, J. Org. Chem., 45, 1295 (1980)
Degrado WF, Kaiser ET, J. Org. Chem., 47, 3258 (1982)
Nakagawa SH, Kaiser ET, J. Org. Chem., 48, 678 (1983)
Kaiser ET, Accounts Chem. Res., 22, 47 (1989)
Osapay G, Taylor JW, J. Am. Chem. Soc., 112, 6046 (1990)
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Park DH, Ph.D. Thesis, Seoul National University (1991)
Park DH, Jung JK, Lee YW, Bull. Korean Chem. Soc., 9, 394 (1988)
Roh KW, Park DH, Lee YS, Proceedings of the 5th Korea-Japan Seminar, 9th Symposium on Organic Chemistry, 73 (1990)
Park DH, Roh KW, Lee YS, Bull. Korean Chem. Soc., 18, 3 (1997)
Park DH, Lee YS, Bull. Korean Chem. Soc., 14, 419 (1993)
Tam JP, Heath WF, Merrifield RB, J. Am. Chem. Soc., 105, 6442 (1983)
Gisin BF, Anal. Chim. Acta, 58, 248 (1972)
Galpin IJ, Hardy PM, Kenner GW, McBermott JR, Ramage R, Selly JH, Tyson RG, Tetrahedron, 35, 2577 (1979)

[Related Articles]

[1] Yajima H, Fujii N, J. Chem. Soc.-Chem. Commun., 115 (1980)

[2] Degrado WF, Kaiser ET, J. Org. Chem., 45, 1295 (1980)

[3] Degrado WF, Kaiser ET, J. Org. Chem., 47, 3258 (1982)

[4] Nakagawa SH, Kaiser ET, J. Org. Chem., 48, 678 (1983)

[5] Kaiser ET, Accounts Chem. Res., 22, 47 (1989)

[6] Osapay G, Taylor JW, J. Am. Chem. Soc., 112, 6046 (1990)

[7] Osapay G, Profit A, Taylor JW, Tetrahedron Lett., 31, 6121 (1990)

[8] Park DH, Ph.D. Thesis, Seoul National University (1991)

[9] Park DH, Jung JK, Lee YW, Bull. Korean Chem. Soc., 9, 394 (1988)

[10] Roh KW, Park DH, Lee YS, Proceedings of the 5th Korea-Japan Seminar, 9th Symposium on Organic Chemistry, 73 (1990)

[11] Park DH, Roh KW, Lee YS, Bull. Korean Chem. Soc., 18, 3 (1997)

[12] Park DH, Lee YS, Bull. Korean Chem. Soc., 14, 419 (1993)

[13] Tam JP, Heath WF, Merrifield RB, J. Am. Chem. Soc., 105, 6442 (1983)

[14] Gisin BF, Anal. Chim. Acta, 58, 248 (1972)

[15] Galpin IJ, Hardy PM, Kenner GW, McBermott JR, Ramage R, Selly JH, Tyson RG, Tetrahedron, 35, 2577 (1979)