全保护RGD三肽的合成方法研究  

Synthesis of Protected RGD Tripeptide

作　　者：杨大成[1] 范莉[1] 钟裕国[2] 

机构地区：[1]西南师范大学化学化工学院,重庆400715 [2]四川大学华西药学院,成都610041

出　　处：《有机化学》2003年第5期493-498,共6页Chinese Journal of Organic Chemistry

摘　　要：以两条路线、多种偶联试剂 (DCC ,EDCI ,CDI ,EEDQ)合成了全保护三肽Arg Gly Asp (RGD) .Boc Arg(Tos) OH经上述偶联剂短时活化 ,于合适条件下与TsOH·Gly OBzl缩合 ,均获得良好收率 ( 4 3 %～ 97% ) .经Pd(OH) 2 /H2 还原得到的Boc Arg(Tos) Gly OH于 2 2～ 2 7℃与HCl·Asp(OcHex) OBzl偶联得到全保护三肽Boc Arg(Tos) Gly Asp(OcHex) OBzl (TM) ,反应收率分别为 76 4% (DCC/HOSu) ,64 7%～ 78 3 % (DCC/HOBt) ,66 7%～ 77 9% (EDCI/HOBt) .Boc Gly OH和HCl·Asp (OcHex) OBzl经DCC/HOBt或CDI活化 ,可得到碳端二肽Boc Gly Asp(OcHex) OBzl(收率分别为 81 2 % ,89 5 % ) ,该二肽脱Boc后与Boc Arg(Tos) OH反应 ,经DCC/HOBt,EDCI/HOBt,CDI,DCC/HOSu活化 ,均可生成目标分子TM ,其反应收率分别为 40 4% ,73 8% ,67 8% ,84 4% .Complete protected Arg-Gly-Asp (RGD) tripeptide, Boc-Arg(Tos)-Gly-Asp(OcHex)-OBzl (TM), was synthesized via two synthetic routes and with different, coupling reagents. After activated by coupling reagents such as DCC, EDCI, CDI and EEDQ in short time, Boc-Arg (Tos)-OH was coupled with TsOH . Gly-OBzl to produce N-terminal dipeptide Boc-Arg(Tos)-Gly-OBzl (1) in suitable reactive condition in 43% similar to 97% yield. Boc-Arg(Tos)-Gly-OH (2), obtained from the,catalytic hydrogenation of 1, reacted. with HCl . Asp(OcHex)-OBzl (3a) to give the protected RGD tripeptide in the yields of 76.4% (DCC/HOSu) 64.7% similar to 8.3% (DCC/HOBt) and 66.7% similar to 77.9% (EDCL/HOBt) respectively. C-Terminal dipeptide. Boc-Gly-Asp(OcHex)-OBzl (4) was prepared by the coupling of Boc-Gly-OH with HCl . Asp (OcHex)-OBzl (3a) with the coupling reagents of DCC/HOBt and CDI (81.2%, 89.5% yield). Deprotecting Boc group, 4 reacted with Boc-Arg(Tos)-OH through the coupling reagents of DCC/HOBt, EDCI/HOBt, CDI and DCC/HOSu to form, the target fiiolecule iris the yields of 40.4%, 73.8%, 67.8% and 84.44, respectively.

关 键 词：RGD三肽 合成 精氨酰-甘氨酰-天冬氨酸 β-环己基天冬氨酸苄酯 

分 类 号：O629.72[理学—有机化学]