合成路线:1) The cyclization of ethyl 3(S)-hydroxybutanoate (I) with N-anisylcinnamylideneamine (II) gives 1-(4-anisyl)-3alpha-[1(S)-hydroxyethyl]-4-(2-phenylvinyl)azetidin-2-one (III),which is esterified with thiocarbonyldiimidazole (IV) yielding the thioester (V).The reduction of (V) with NaBH4 in hot DMSO affords 1-(4-anisyl)-3alpha-ethyl-4-(2-phenylvinyl)azetidin-2-one (VI),which is oxidized with KMnO4 - NaClO4,giving the carboxylic acid (VII).The oxidative decarboxylation of (VII) with lead tetraacetate yields 4-acetoxy-1-(4-anisyl)-3alpha-ethylazetidin-2-one (VIII),which is submitted to dearylation with ammonium cerium (IV) nitrate to afford 4-acetoxy-3alpha-ethylazetidin-2-one (IX).The condensation of (IX) with 4-nitrobenzyl 2-diazo-3-(tert-butyldimethylsilyloxy)-3-butenoate (X) gives the diazo keto ester (XI),which is cyclized yielding 4-nitrobenzyl 6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (XII).The reaction of (XII) with diphenyl chlorophosphate affords the enol phosphate (XIII),which is condensed with N-acetylcysteamine (XIV) to give 4-nitrobenzyl ester of PS-5 (XV).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C.
合成路线:2) The hydroxyethylazetidinone (III) is esterified with p-toluenesulfonyl chloride to the corresponding tosylate (XVI),which is reduced with NaBH4 to the ethylazetidinone (VI),which is oxidized with KMnO4 - NaClO4,giving the carboxylic acid (VII).The oxidative decarboxylation of (VII) with lead tetraacetate yields 4-acetoxy-1-(4-anisyl)-3alpha-ethylazetidin-2-one (VIII),which is submitted to dearylation with ammonium cerium (IV) nitrate to afford 4-acetoxy-3alpha-ethylazetidin-2-one (IX).The condensation of (IX) with 4-nitrobenzyl 2-diazo-3-(tert-butyldimethylsilyloxy)-3-butenoate (X) gives the diazo keto ester (XI),which is cyclized yielding 4-nitrobenzyl 6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (XII).The reaction of (XII) with diphenyl chlorophosphate affords the enol phosphate (XIII),which is condensed with N-acetylcysteamine (XIV) to give 4-nitrobenzyl ester of PS-5 (XV).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C.
合成路线:3) The reduction of (III) to (VI) can also be performed by treatment of (III) with methanesulfonyl chloride giving mesylate (XVII),which is treated with NaI to yield iodo derivative (XVIII).This compound is reduced to (VI) with NaBH4,which is oxidized with KMnO4 - NaClO4,giving the carboxylic acid (VII).The oxidative decarboxylation of (VII) with lead tetraacetate yields 4-acetoxy-1-(4-anisyl)-3alpha-ethylazetidin-2-one (VIII),which is submitted to dearylation with ammonium cerium (IV) nitrate to afford 4-acetoxy-3alpha-ethylazetidin-2-one (IX).The condensation of (IX) with 4-nitrobenzyl 2-diazo-3-(tert-butyldimethylsilyloxy)-3-butenoate (X) gives the diazo keto ester (XI),which is cyclized yielding 4-nitrobenzyl 6-ethyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate (XII).The reaction of (XII) with diphenyl chlorophosphate affords the enol phosphate (XIII),which is condensed with N-acetylcysteamine (XIV) to give 4-nitrobenzyl ester of PS-5 (XV).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C.
参考文献标题:An asymmetric synthesis of carbapenem antibiotic (+)-PS-5 from ethyl 3-hydroxybutanoate
文献作者:Georg,G.I.; Kant,J.
参考来源:J Org Chem 1988,53(3),692-5
合成路线:5) The esterification of olivanic acid MM-17880 (XLI) with 4-nitrobenzyl chloride (XLII) gives the corresponding ester (XLIII),which is ethoxylated with triethyloxonium tetrafluoroborate yielding the ethyl sulfate (XLIV).Elimination of sulfuric acid affords the ethylidene derivative (XLV),which is finally reduced to PS-5 4-nitrobenzyl ester (XV) by means of NaBH4.
参考文献标题:Conversion of the olivanic acids into antibiotics of the PS-5 type: Use of a new carboxy protecting group
文献作者:Corbett,D.F.; Eglington,A.J.
参考来源:J Chem Soc Chem Commun 1980,1083-4
合成路线:A new and stereoselective synthesis of (3R-trans)-3-ethyl-1-(tert-butyldimethylsilyl)-4-[2-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one (XVII),a key intermediate in the synthesis of PS-5 has been developed:The oxidation of 3-benzyloxy-1-propanol (I) with oxalyl chloride in DMSO gives the corresponding aldehyde (II),which is condensed with the phosphonate (III) by means of NaH yielding a mixture of the (Z)- and (E)-isomers of 5-benzyloxy-2-ethyl-2-pentenoic acid ethyl ester (IV) and (V).The undesired (Z)-isomer (IV) is isomerized by treating the mixture with diphenyldisulfide in refluxing THF.The hydrolysis of (V) with LiOH in THF/methanol/water gives the expected free acid (VI),which is treated with SOCl2 in refluxing benzene to afford the acid chloride (VII).The condensation of (VII) with the chiral oxazolidinone (VIII) by means of butyllithium in THF gives the acylated compound (IX),which is treated with benzenethiol and butyllithium in THF to give the addition compound (X) that is purified by medium pressure column chromatography to eliminate the undesired diastereomer.The elimination of the oxazolidinone group of (X) by reaction with trimethylaluminum,benzylthiol and butyllithium in THF yields the thioester (XI),which is treated with silver trfluoroacetate and water to afford the corresponding free acid (XII).The reaction of (XII) with methoxyamine and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDPC) in water affords the methoxyamide (XIII),which is methylated by means of methyl iodide and silver perchlorate to give the sulfonium salt (XIV).The cyclization of (XIV) by means of K2CO3 yields the azetidinone (XV),which is debenzylated by means of calcium in liquid ammonia affording (3R-trans)-3-ethyl-4-(2-hydrxyethyl)azetidin-2-one (XVI).Finally,this compound is silylated with tert-butyldimethylsilyl (TBDMS) trifluoromethanesulfonate affording (3R-trans)-3-ethyl-1-(tert-butyldimethylsilyl)-4-[2-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one (XVII),the desired target key intermediate in the synthesis of PS-5.
参考文献标题:Efficient stereoselective route to beta-lactams and their application to the stereoselective synthesis of a key intermediate for carbapenem antibiotic (+)-PS-5
文献作者:Fujiwara,Y.; Ninomiya,I.; Miyata,O.; Naito,T.
参考来源:J Chem Soc - Perkins Trans I 1998,14(14),2167
产品链接: CAS No. 67007-79-8››