3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Th...3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Thr with unprotected hydroxyl group on their side chain.Thus,DEPBT is useful for the synthesis of peptide alcohols,which have attracted much attention not only as the ligands but also as the enzyme inhibitors.A side reaction of DEPBT was found in the synthesis of Boc-β-Ala-HisOMe with unprotected imidazolyl group.In this paper,the discovery of this side reaction and the confirmation of the structure of this side product were reported.In addition,the influence of different reaction conditions on the side reaction were studied.Imidazolyl group was a key factor to cause the side reaction,excess DEPBT and high reaction temperature promoted the side reaction.展开更多
3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing T...3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing histi-dine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of his-tidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%-81%). However, when the carboxyl components were N -protected acidic amino acids, the yields were relatively low (47%-48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.展开更多
A cyclic heptapeptide, c(Gly-Ile-Pro-Tyr-Ile-Ala-Ala), which was isolated and identified from Stellaria yumumensis French (M), was synthesized by solution method for the first time. Protected heptapeptide Z-Gly-Ile-Pr...A cyclic heptapeptide, c(Gly-Ile-Pro-Tyr-Ile-Ala-Ala), which was isolated and identified from Stellaria yumumensis French (M), was synthesized by solution method for the first time. Protected heptapeptide Z-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OBzl was synthesized with 3-(diethoxy-phosphoryloxy)-l,2,3-benzotriazin-4(3H)-one (DEPBT) as a coupling reagent. After deprotection of benzyl and benzyloxycarbonyl groups, a free linear heptapeptide H-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OH was cyclized in DMF (2 × 10?3 mol/L) in the presence of nine different metal ions, i. e., Li+, Na+, K+, Cs+, Mg2+, Ca2+, Bai2+, Nr2+ and Cr5+ respectively, using DEPBT as a coupling reagent. Univalent metal ion Cs+ enhanced both the cyclization yield and cyclization rate of H-Gly-De-Pro-Tyr-Ile-Ala-AlaOH, while some bivalent metal ions, such as Mg2+, Ca2+ and Ni2+ decreased the yields of c (Gly-Ile-Pro-Tyr-De-Ala-Ala) drastically. Trivalent metal ion Cr3+ even inhibited the cyclization reaction completely.展开更多
A series of dipeptide derivatives containing non-coded amino acids, N-Boc-4-X-Phe-Ala-NHNHPh (X = Cl, Br, I, NO2), were synthesized by using thermoase in organic solvents. The physical data were consistent with the sa...A series of dipeptide derivatives containing non-coded amino acids, N-Boc-4-X-Phe-Ala-NHNHPh (X = Cl, Br, I, NO2), were synthesized by using thermoase in organic solvents. The physical data were consistent with the same samples prepared by 3-(diethoxyphosphoryloxy)-1, 2,3-benzotriazin-4 (3H)-one (DEPBT). Influence of different substituted groups of the noncoded amino acids and different organic solvents on the enzymatic peptide synthesis was studied.展开更多
文摘3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one(DEPBT) condensation developed by our group is an effective organophosphorus condensation reagent for the synthesis of protected peptides containing Tyr,Ser and Thr with unprotected hydroxyl group on their side chain.Thus,DEPBT is useful for the synthesis of peptide alcohols,which have attracted much attention not only as the ligands but also as the enzyme inhibitors.A side reaction of DEPBT was found in the synthesis of Boc-β-Ala-HisOMe with unprotected imidazolyl group.In this paper,the discovery of this side reaction and the confirmation of the structure of this side product were reported.In addition,the influence of different reaction conditions on the side reaction were studied.Imidazolyl group was a key factor to cause the side reaction,excess DEPBT and high reaction temperature promoted the side reaction.
基金Project supported by the National Natural Science Foundation of China(No.20242006).
文摘3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing histi-dine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of his-tidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%-81%). However, when the carboxyl components were N -protected acidic amino acids, the yields were relatively low (47%-48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.
文摘A cyclic heptapeptide, c(Gly-Ile-Pro-Tyr-Ile-Ala-Ala), which was isolated and identified from Stellaria yumumensis French (M), was synthesized by solution method for the first time. Protected heptapeptide Z-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OBzl was synthesized with 3-(diethoxy-phosphoryloxy)-l,2,3-benzotriazin-4(3H)-one (DEPBT) as a coupling reagent. After deprotection of benzyl and benzyloxycarbonyl groups, a free linear heptapeptide H-Gly-Ile-Pro-Tyr-Ile-Ala-Ala-OH was cyclized in DMF (2 × 10?3 mol/L) in the presence of nine different metal ions, i. e., Li+, Na+, K+, Cs+, Mg2+, Ca2+, Bai2+, Nr2+ and Cr5+ respectively, using DEPBT as a coupling reagent. Univalent metal ion Cs+ enhanced both the cyclization yield and cyclization rate of H-Gly-De-Pro-Tyr-Ile-Ala-AlaOH, while some bivalent metal ions, such as Mg2+, Ca2+ and Ni2+ decreased the yields of c (Gly-Ile-Pro-Tyr-De-Ala-Ala) drastically. Trivalent metal ion Cr3+ even inhibited the cyclization reaction completely.
文摘A series of dipeptide derivatives containing non-coded amino acids, N-Boc-4-X-Phe-Ala-NHNHPh (X = Cl, Br, I, NO2), were synthesized by using thermoase in organic solvents. The physical data were consistent with the same samples prepared by 3-(diethoxyphosphoryloxy)-1, 2,3-benzotriazin-4 (3H)-one (DEPBT). Influence of different substituted groups of the noncoded amino acids and different organic solvents on the enzymatic peptide synthesis was studied.
