全保护RGD三肽的合成方法研究

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Ts0H- G1y-OBzl缩合，均获得良好收率(43％-97％)．经Pd(OH)2／H2还原得到的Boc-Arg (Tos)-G1y-0H于22-27℃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-Asp(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％．

Synthesis of Protected RGD Tripeptide

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, GDI and EEDQ in short time, Boc-Arg(Tos)-OH was coupled with TsOH o Gly-OBzl to produce N-terminal dipeptide Hoc-Arg(Tos)-Gly- OBzl (1) in suitable reactive condition in 43% ~ 97% yield. Boc-Arg(Tos) -Gly-OH (2), obtained from the catalytic hydrogenation of 1, reacted with HC1-Asp(OcHex)-OBzl (3a) to give the protected RGD tripeptide in the yields of 76.4% (DCC/HOSu), 64.7% ~ 8.3% (DCC/HOBt) and 66.7% -77. 9% (EDCI/HOBt), respectively. C-Terminal dipeptide Boc-Gly-Asp(OcHex)- OBzl (4) was prepared by the coupling of Boc-Gly-OH with HC1 o Asp (OcHex)-OBzl (3a) with the coupling reagents of DCC/HOBt and GDI (81.2%, 89.5% yield ). Deprotecting Boc group, 4 reacted with Boc-Arg(Tos)-OH through the coupling reagents of DCC/HOBt, EDCI/HOBt, GDI and DCC/HOSu to form the target molecule in the yields of 40.4%, 73.8%, 67.8% and 84.4%, respectively.