Cilengitide, NSC-707544, EMD-85189, EMD-121974
西仑吉肽Chemical Name: Cyclo(L-arginyl-glycyl-L-aspartyl-D-phenylalanyl-N-methyl-L-valyl)
CAS No. 188968-51-6, 188969-00-8 (monoHCl), 199807-38-0 (monomethanesulfonate), 199807-35-7 (monotrifluoroacetate)
项目整合开发状态: Phase II
项目研究机构: Merck KGaA (Orphan Drug), Merck KGaA (Originator), National Cancer Institute (Codevelopment)
合成路线:Cilengitide is synthesized using solid-phase Merrifield-type methods by sequentially adding N-Boc-N-Me-L-Val (I),N-Boc-D-Phe (III),N-Boc-4-O-t-Bu-L-Asp (V),N-Boc-Gly (VII) and Nalpha-Fmoc-Nomega-Mtr-L-Arg (IX) in a stepwise manner to a 4-hydroxymethylphenoxymethyl-polystyrene resin (Wang type resin),yielding peptide-resin intermediates (II),(IV),(VI),(VIII) and (X),respectively.Elimination of the resin from the peptide chain with a 1:1 mixture of TFA/dichloromethane results in the linear peptide (XI),which is then deprotected at the amino-terminal group by removing the Fmoc group with a 1:1 mixture of piperidine/DMF,to give peptide (XII).
合成路线:Cyclization of (XII) by means of DPPA in DMF/dichloromethane affords the cyclic peptide (XIII),which is finally deprotected by treatment with TFA/water 98:2.
📌 参考资料/链接：
参考文献标题:Cyclic adhesion inhibitors
文献作者:Jonczyk,A.; Goodman,S.; Diefenbach,B.; Sutter,A.; H鰈zmann,G.; Kessler,H.; Dechantsreiter,M.(Merck Patent GmbH)
参考来源:DE 19534177; EP 0770622; JP 1997132593; US 6001961
📄 详细内容
合成路线:Cilengitide is synthesized using solid-phase Merrifield-type methods by sequentially adding N-Boc-N-Me-L-Val (I),N-Boc-D-Phe (III),N-Boc-4-O-t-Bu-L-Asp (V),N-Boc-Gly (VII) and Nalpha-Fmoc-Nomega-Mtr-L-Arg (IX) in a stepwise manner to a 4-hydroxymethylphenoxymethyl-polystyrene resin (Wang type resin),yielding peptide-resin intermediates (II),(IV),(VI),(VIII) and (X),respectively.Elimination of the resin from the peptide chain with a 1:1 mixture of TFA/dichloromethane results in the linear peptide (XI),which is then deprotected at the amino-terminal group by removing the Fmoc group with a 1:1 mixture of piperidine/DMF,to give peptide (XII).
合成路线:Cyclization of (XII) by means of DPPA in DMF/dichloromethane affords the cyclic peptide (XIII),which is finally deprotected by treatment with TFA/water 98:2.
参考文献标题:Cilengitide
文献作者:Graul,A.; Sorbera,L.A.; Castar,J.
参考来源:Drugs Fut 2000,25(7),674