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L-MTP-PE, MLV-19835A, CGP-19835A, MTP-PE, MEPACT, ACT

米法莫肽Chemical Name: N-Acetylmuramyl-L-alanyl-D-isoglutamine-L-alanine 2-(1',2'-dipalmitoyl-sn-glycero-3'-hydroxyphosphoryloxy)ethylamide
CAS No. 83461-56-7
项目整合开发状态: Phase III
项目研究机构: IDM (Proprietary), IDM (Orphan Drug), Novartis (Originator), Jenner (Licensee)
合成路线:1) The esterification of N-acetylmuramyl-L-alanyl-D-glutaminyl-L-alanine (I) with N-hydroxysuccinimide (II) by means of dicyclohexylcarbodiimide in dimethylacetamide gives the corresponding N-hydroxysuccinimide ester (III),which is then to condensed with O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (IV) by means of triethylamine in the same solvent.
📌 参考资料/链接:
参考文献标题:Phosphorylmuramyl peptides,process for their preparation and use
文献作者:Baschang,G.; Carcsay,L.; Hartmann,A.; Stanek,J.(Novartis AG)
参考来源:EP 0027258

📄 详细内容


合成路线:1) The esterification of N-acetylmuramyl-L-alanyl-D-glutaminyl-L-alanine (I) with N-hydroxysuccinimide (II) by means of dicyclohexylcarbodiimide in dimethylacetamide gives the corresponding N-hydroxysuccinimide ester (III),which is then to condensed with O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (IV) by means of triethylamine in the same solvent.

合成路线:The reaction of N-(tert-butoxycarbonyl)-3-hydroxyvaline (I) with O-benzylhydroxylamine (II) by means of hydroxybenzotriazole (HBT) and dicyclohexylcarbodiimide (DCC) in THF gives the corresponding benzyloxyamide (III),which is treated with the pyridine.SO3 complex (IV) in pyridine to yield N-(tert-butoxycarbonyl)-3-(sulfooxy)-N2-(benzyloxy)valinamide (V).The cyclization of (V) by means of K2CO3 in ethyl acetate - water affords 1-(benzyloxy)-3-(tert-butoxycarbonylamino)-4,4-dimethylazetidin-2-one (VI),which is debenzylated by hydrogenation with H2 over Pd/C in methanol to give the N-hydroxyazetidine (VII).The reaction of (VII) with the sulfonating complex (IV) affords the 1-azetidinyl sulfuric ester (VIII),which is deprotected by reaction with trifluoroacetic acid in anisole - dichloromethane yielding 3-amino-4,4-dimethyl-2-oxoazetidinyl-1-sulfate (IX).The condensation of (IX) with 2-(2-aminothiazol-4-yl)-2(Z)-(diphenylmethoxycarbonylmethoxyimino)acetic acid (X) by means of diphenyl chlorophosphate (PCP) and triethylamine in DMF gives the diphenylmethyl ester (XI) of the final product,which is finally deprotected by hydrolysis with trifluoroacetic acid and anisole.

参考文献标题:Preparation of 4,4-dialkyl-2-azetidinones
文献作者:Slusarchyk,W.A.; Dejneka,T.; Kostes,W.H.(Bristol-Myers Squibb Co.)
参考来源:AU 8652460; BE 090411; DE 3602347; ES 8706112; ES 8800897; FR 2576596; GB 2170201; US 4638061


合成路线:1) The esterification of N-acetylmuramyl-L-alanyl-D-glutaminyl-L-alanine (I) with N-hydroxysuccinimide (II) by means of dicyclohexylcarbodiimide in dimethylacetamide gives the corresponding N-hydroxysuccinimide ester (III),which is then to condensed with O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (IV) by means of triethylamine in the same solvent.

合成路线:2) The esterification of N-acetyl-L-alanyl-D-glutamine (V) with N-hydroxysuccinimide (II) as before gives the corresponding N-hydroxysuccinimide ester (VI),which is then condensed with N-alanyl-O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (VII) by means of triethylamine as before.

参考文献标题:ENV 2-3/MTP-PE
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1989,14(3),220


合成路线:2) The esterification of N-acetyl-L-alanyl-D-glutamine (V) with N-hydroxysuccinimide (II) as before gives the corresponding N-hydroxysuccinimide ester (VI),which is then condensed with N-alanyl-O-(1,2-dipalmitoyl-sn-glycero-3-phosphoryl)ethanolamine (VII) by means of triethylamine as before.
参考文献标题:Synthesis of N-[2-3H]acetyl-D-muramyl-L-alanyl-D-iso-glutaminyl-L-alanyl-2-(1',2'-dipalmitoyl-sn-glycero-3'-phosphoryl)ethylamide of high specific radioactivity
文献作者:Brundish,D.E.; Wade,R.
参考来源:J Label Compd Radiopharm 1985,22(1),29-35


产品链接: CAS No. 83461-56-7››