Patellamide A类似物的全合成研究  

Studies on the Synthesis of Patellamide-A Derivatives

作　　者：龙康侯[1] 简志刚[1] 蹇敦龙[1] 

机构地区：[1]中山大学化学系

出　　处：《中山大学学报（自然科学版）》1989年第1期44-50,共7页Acta Scientiarum Naturalium Universitatis Sunyatseni

摘　　要：本文从D-(缬)噻唑氨基酸、L-异亮氨酸、L-丝氨酸、1-苏氨酸出发合成了PatellamideA类似物环肽(1)。D-(缬)噻唑氨基酸由D-缬氨酸和L-半胱氨酸按亚胺酯法合成。丝氨酸噁唑啉(11)由三苯基膦法合成,苏氮酸噁唑啉(17)由亚胺酯法合成。11和17去保护基后经DCC/HOBT法转变为线性肽(19a),19a用五氟苯酯法环化得得1.1和其丝氨酸噁唑啉的开环产物环肽都具有抗肿瘤活性。The reported patellamide-A(1) was synthesized from D-(Val)Thz-OH, L-isoleucine, L-threonine, and L-serine. Bz-D-(Val)-Thz-OEt(7) was synthesized by imino ester method. The serine derived oxazoline methylester(11) was produced by the ph_3P. Et_3N.CCl_4 procedure and hydrolysis of 11 yielded the oxazoline acid(12). The threonine derived oxazoline(17) was synthesized by imino ester method and deprotection of 17 gave rise to the N-deblocked oxazoline(18). The coupling of 12 with 18 yielded linear peptide methyl ester(19a), which was then converted to pentafluoro phenyl ester(19c). Deprotection and cyclization of 19c produced 1.1 is an unstable compound and can be hydrolyzed to cyclic peptide(20) by water in solvents. Both 1 and 20 showed antineoplastic activity.

关 键 词：肽类 PatellamideA 噻唑 恶唑啉 

分 类 号：R979.1[医药卫生—药品]