PTR-3046
Chemical Name: [3S-(3alpha,6alpha,9beta,12alpha,15alpha)]-2(S)-[6-(4-Aminobutyl)-15-benzyl-12-(4-hydroxybenzyl)-9-(1H-indol-3-ylmethyl)-3-isopropyl-2,5,8,11,14,20-hexaoxo-1,4,7,10,13,16,19-heptaazacyclotricosan-1-yl]-3-phenylpropionyl-L-threoninamide
CAS No. 203200-47-9
项目整合开发状态: Preclinical
项目研究机构: Peptor (Originator), Yissum (Originator)
合成路线:Compound (XI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin.After removal of Fmoc protecting group from the resin with 20% piperidine in N-methyl-2-pyrrolidinone (NMP),a coupling cycle was carried out with Fmoc-Thr(O-t-Bu)OH (I) using bromotripyrrolidino phosphonium hexafluorophosphate (PyBroP) and diisopropylethylamine (DIEA) in NMP,followed by Fmoc removal with 20% piperidine in NMP.To the Thr-bound resin (II) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc- (N-allyloxycarbonylpropyl)PheOH (IV),Fmoc-ValCl (VI),Fmoc-Lys(Boc)OH (VIII),and Fmoc-D-TrpOH (X) to yield the corresponding peptide-bound resins (V),(VII),(IX) and (XI),respectively.
合成路线:Compound (XVI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin.To the Thr-bound resin (XI) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc-Tyr(t-Bu)OH (XII),and Fmoc- (N-allyloxycarbonylaminoethyl)PheOH (XIV) to yield the corresponding peptide-bound resins (XIII) and (XV),respectively.Then,allyl and allyoxycarbonyl protecting groups were both removed from the linear peptide-bound resin (XV) by treatment with tetrakis(triphenylphosphine)palladium,acetic acid,and N-methylmorpholine (NMM) in chloroform to yield compound (XVI).
合成路线:The cyclization between free amino and acid groups of compound (XVI) was effected by reaction with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (PyBOP) to give the cyclic peptide (XVII).Finally,treatment with moist trifluoroacetic acid (TFA) containing a trace of ethanedithiol (EDT) and triisopropylsilane (TIS) at 0 C removed all protecting groups and liberated from the resin the peptide amide,which was finally purified by reversed-phase preparative HPLC.
📌 参考资料/链接：
参考文献标题:Conformationally constrained backbone cyclized somatostatin analogs
文献作者:Hornik,V.; Seri-Levy,A.; Gellerman,G.; Gilon,C.(Yissum Research Development Co.)
参考来源:WO 9804583
📄 详细内容
合成路线:Compound (XI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin.After removal of Fmoc protecting group from the resin with 20% piperidine in N-methyl-2-pyrrolidinone (NMP),a coupling cycle was carried out with Fmoc-Thr(O-t-Bu)OH (I) using bromotripyrrolidino phosphonium hexafluorophosphate (PyBroP) and diisopropylethylamine (DIEA) in NMP,followed by Fmoc removal with 20% piperidine in NMP.To the Thr-bound resin (II) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc- (N-allyloxycarbonylpropyl)PheOH (IV),Fmoc-ValCl (VI),Fmoc-Lys(Boc)OH (VIII),and Fmoc-D-TrpOH (X) to yield the corresponding peptide-bound resins (V),(VII),(IX) and (XI),respectively.
合成路线:Compound (XVI) was prepared by solid phase peptide synthesis on a Rink amide 4-methylbenzhydrylamine (MBHA) resin.To the Thr-bound resin (XI) they were stepwise coupled in subsequent coupling and deprotecting cycles the following amino acids: Fmoc-Tyr(t-Bu)OH (XII),and Fmoc- (N-allyloxycarbonylaminoethyl)PheOH (XIV) to yield the corresponding peptide-bound resins (XIII) and (XV),respectively.Then,allyl and allyoxycarbonyl protecting groups were both removed from the linear peptide-bound resin (XV) by treatment with tetrakis(triphenylphosphine)palladium,acetic acid,and N-methylmorpholine (NMM) in chloroform to yield compound (XVI).
合成路线:The cyclization between free amino and acid groups of compound (XVI) was effected by reaction with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (PyBOP) to give the cyclic peptide (XVII).Finally,treatment with moist trifluoroacetic acid (TFA) containing a trace of ethanedithiol (EDT) and triisopropylsilane (TIS) at 0 C removed all protecting groups and liberated from the resin the peptide amide,which was finally purified by reversed-phase preparative HPLC.
参考文献标题:A backbone-cyclic,receptor 5-selective somatostatin analogue: Synthesis,bioactivity,and nuclear magnetic resonance conformational analysis
文献作者:Gilon,C.; Huenges,M.; Matha,B.; Gellerman,G.; Hornik,V.; Afargan,M.; Amitay,O.; Ziv,O.; Feller,E.; Gamliel,A.; Shohat,D.; Wanger,M.; Arad,O.; Kessler,H.
参考来源:J Med Chem 1998,41(6),919