Preparation of Oxime Cesium Salts and Its Function as Cleaving Agents in Peptide Synthesis†

doi:10.7503/cjcu20160062

Abstract

Abstract:

This paper aimed at preparation of side chain protected peptides. Modified Wang resin loaded with 2-bromoacetyl linker was selected for syntheses of three kinds of model peptides by the method of solid phase peptide synthesis(SPPS). These model peptides were used to examine the cleave function of some oximates with alkalescence and strong nucleophilicity. Five oxime cesium salts with different structures were designed and synthesized for the cleavage of model peptides from the resin. The optimal cleave conditions of 2-pyridine aldoxime cesium which had the best performance in the cleavage, was studied in detail. The experimental results showed that model peptides with side chain fully protected could be obtained with high yields in mild conditions using oxime cesium salts as cleave reagents in SPPS.

Key words: Side chain fully protected, Solid phase peptide synthesis(SPPS), Oxime cesium salt, Cleavage

TrendMD:

ZONG Liang, DONG Junjun, CHEN Jing, LI Jian, SUI Shaohui, WEI Yifei, ZHANG Ming. Preparation of Oxime Cesium Salts and Its Function as Cleaving Agents in Peptide Synthesis^†[J]. Chem. J. Chinese Universities, 2016, 37(7): 1328.

Figures/Tables 5

References 20

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Peak	Product	Peak	Product
449.9	Boc-Ala-Phe-Leu-OH+H⁺	631.9	Boc-Ser(Bzl)-Leu-Ser(tBu)-O-CH₂-COOH+Na⁺
471.7	Boc-Ala-Phe-Leu-OH+Na⁺	594.8	Boc-Ser(Bzl)-Asp(OtBu)-Lys-OH+H⁺
529.8	Boc-Ala-Phe-Leu-O-CH₂-COOH+Na⁺	628.8	Ser(Bzl)-Asp(OtBu)-Lys-OH+H⁺
573.9	Boc-Ser(Bzl)-Leu-Ser(tBu)-OH+Na⁺	751.0	Boc-Ser(Bzl)-Asp(OtBu)-Lys(Z)-OH+Na⁺

Peak	Product	Peak	Product
449.9	Boc-Ala-Phe-Leu-OH+H⁺	631.9	Boc-Ser(Bzl)-Leu-Ser(tBu)-O-CH₂-COOH+Na⁺
471.7	Boc-Ala-Phe-Leu-OH+Na⁺	594.8	Boc-Ser(Bzl)-Asp(OtBu)-Lys-OH+H⁺
529.8	Boc-Ala-Phe-Leu-O-CH₂-COOH+Na⁺	628.8	Ser(Bzl)-Asp(OtBu)-Lys-OH+H⁺
573.9	Boc-Ser(Bzl)-Leu-Ser(tBu)-OH+Na⁺	751.0	Boc-Ser(Bzl)-Asp(OtBu)-Lys(Z)-OH+Na⁺

Cleaving agent	Saturation concentration/(mol·L^-1)	pH	m/mg			Yield(%)
Cleaving agent	Saturation concentration/(mol·L^-1)	pH	P1	P2	P3	P1	P2	P3
2-Pyridyl oxime cesium	0.12	9	125	141	156	78.2	70.8	61.8
3-Pyridyl oxime cesium	0.10	9	128	145	159	80.1	72.8	63.0
4-Pyridyl oxime cesium	0.11	9	119	126	147	74.4	63.3	58.2
Cyclohexanone oxime cesium	0.05	8	89	100	135	55.7	50.2	53.5
4-Dimethylamino benzaldehyde oxime cesium	0.09	9	108	122	138	67.6	61.3	54.7

Cleaving agent	Saturation concentration/(mol·L^-1)	pH	m/mg			Yield(%)
Cleaving agent	Saturation concentration/(mol·L^-1)	pH	P1	P2	P3	P1	P2	P3
2-Pyridyl oxime cesium	0.12	9	125	141	156	78.2	70.8	61.8
3-Pyridyl oxime cesium	0.10	9	128	145	159	80.1	72.8	63.0
4-Pyridyl oxime cesium	0.11	9	119	126	147	74.4	63.3	58.2
Cyclohexanone oxime cesium	0.05	8	89	100	135	55.7	50.2	53.5
4-Dimethylamino benzaldehyde oxime cesium	0.09	9	108	122	138	67.6	61.3	54.7

Cleaving time/h	m(P1)/mg	Yield(%)	Cleaving time/h	m(P1)/mg	Yield(%)
4	60	37.5	10	124	77.6
6	126	78.8	12	125	78.2
8	129	80.7