合成路线:The reaction of p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)acetamido]penicillanate (IX) with PCl5 and pyridine in benzene gives p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)ketenimino]penicillanate (X),which is treated with Cl2 (or Br2) at -70 C in THF,followed by addition of lithium methoxide (or NaHCO3) in methanol to yield p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)ketenimino]-6alpha-methoxypenicillanate (XI).The treatment of (XI) with H3PO4 in THF yields p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)acetamido-6alpha-methoxypenicillanate (XII),which is debenzylated with H2 over Pd/C in ethanol to the corresponding free penicillanate (XIII).Finally,the p-methylphenyl ester is hydrolyzed with Na2B4O7 in water and treated with sodium 2-ethylhexanoate in isobutyl ketone (B).
参考文献标题:Ketenimine intermediates for 6 alpha-methoxy-alpha-carboxy penicillins
文献作者:Taylor,A.W.; Burton,G.; Clayton,J.P.(SmithKline Beecham plc)
参考来源:BE 0856121; FR 2370748; GB 1578748; JP 53002496; US 4182710; US 4185014
合成路线:The formylation of benzyl 6beta-aminopenicillanate (I) with formic acid and dicyclohexylcarbodiimide in ethyl acetate gives the corresponding formamido derivative (II),which is treated with phosgene in methylenechloride containing triethylamine to yield benzyl 6beta-isocyanopenicillanate (III).The reaction of (III) with methyl methoxycarbonyl disulfide (A) by means of K2CO3 in DMF affords benzyl 6beta-isocyano-6alpha-methylthiopenicillanate (IV),which is treated with p-toluenesulfonic acid hydrate in CHCl3,giving benzyl 6beta-amino-6alpha-methylthiopenicillanate (V).The treatment of (V) with HgCl2 pyridine in methanol yields benzyl 6beta-amino-6alpha-methoxypenicillanate (VI) ,which is condensed with 2-benzyloxycarbonyl-2-(thien-3-yl)acetyl chloride (VII) by means of pyridine in methylene chloride to afford benzyl 6beta-[2-(benzyloxycarbonyl)-2-(thien-3-yl)acetamido]-6alpha-methoxypenicillanate (VIII).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in aqueous ethanol,and treated with NaHCO3.
合成路线:The reaction of p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)acetamido]penicillanate (IX) with PCl5 and pyridine in benzene gives p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)ketenimino]penicillanate (X),which is treated with Cl2 (or Br2) at -70 C in THF,followed by addition of lithium methoxide (or NaHCO3) in methanol to yield p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)ketenimino]-6alpha-methoxypenicillanate (XI).The treatment of (XI) with H3PO4 in THF yields p-nitrobenzyl 6beta-[2-(p-methylphenoxycarbonyl)-2-(thien-3-yl)acetamido-6alpha-methoxypenicillanate (XII),which is debenzylated with H2 over Pd/C in ethanol to the corresponding free penicillanate (XIII).Finally,the p-methylphenyl ester is hydrolyzed with Na2B4O7 in water and treated with sodium 2-ethylhexanoate in isobutyl ketone (B).
参考文献标题:Temocillin sodium
文献作者:Neuman,M.; Serradell,M.N.; Blancafort,P.; Castar,J.
参考来源:Drugs Fut 1982,7(4),273
合成路线:The formylation of benzyl 6beta-aminopenicillanate (I) with formic acid and dicyclohexylcarbodiimide in ethyl acetate gives the corresponding formamido derivative (II),which is treated with phosgene in methylenechloride containing triethylamine to yield benzyl 6beta-isocyanopenicillanate (III).The reaction of (III) with methyl methoxycarbonyl disulfide (A) by means of K2CO3 in DMF affords benzyl 6beta-isocyano-6alpha-methylthiopenicillanate (IV),which is treated with p-toluenesulfonic acid hydrate in CHCl3,giving benzyl 6beta-amino-6alpha-methylthiopenicillanate (V).The treatment of (V) with HgCl2 pyridine in methanol yields benzyl 6beta-amino-6alpha-methoxypenicillanate (VI) ,which is condensed with 2-benzyloxycarbonyl-2-(thien-3-yl)acetyl chloride (VII) by means of pyridine in methylene chloride to afford benzyl 6beta-[2-(benzyloxycarbonyl)-2-(thien-3-yl)acetamido]-6alpha-methoxypenicillanate (VIII).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in aqueous ethanol,and treated with NaHCO3.
参考文献标题:Transformations using benzyl 6-isocyanopenicillanate
文献作者:Girven,R.J.; Bentley,P.H.; Clayton,J.P.; Boles,M.O.
参考来源:J Chem Soc - Perkins Trans I 1979,2455-67
产品链接: CAS No. 61545-06-0›› 产品链接: CAS No.66148-78-5››