合成路线:Two related syntheses of a known intermediate of carumonam are presented:1) The reaction of calcium L-threonate (I) with HBr in acetic acid - acetic anhydride and then with refluxing methanol gives methyl (2S,3S)-2,4-dibromo-3-hydroxybutanoate (II),which by reaction with concentrated NH4OH is converted into (2S,3R)-3-(bromomethyl)oxiranecarboxamide (III).The reaction of (III) with KI and potassium acetate in hot DMF affords (2R,3S)-3-(acetoxymethyl)oxiranecarboxamide (IV),which is treated with concentrated NH4OH at 60 C and then with benzyl chloroformate (V) to give (2S,3R)-2-(benzyloxycarbonylamino)-3,4-dihydroxybutanamide (VIII),an intermediate compound previously obtained in the synthesis described in Drugs Fut 1985,10: 967.2) The treatment of dibromide (II) with KI and potassium acetate in hot DMF gives methyl (2S,3S)-4-acetoxy-2,3-epoxybutanoate (VI),which is treated first with NaOH in methanol and then with hot NH4OH to yield (2S,3R)-2-amino-3,4-dihydroxybutanamide (VII).Finally,this compound is treated with benzyl chloroformate (V) as before to give the intermediate (VIII) previously mentioned.
参考文献标题:A novel synthesis of the monobactam antibiotic carumonam
文献作者:Manchand,P.S.; Luk,K.-C.; Belica,P.S.; Choudhry,S.C.; Wei,C.C.; Soukup,M.
参考来源:J Org Chem 1988,53(23),5507
合成路线:L-threonic acid (XI),which is readily available from L-ascorbic acid (IX),is converted to L-N-benzyloxycarbonyl-4-hydroxyallothreoninamide (VIII).This in turn is transformed to (3S,4S)-cis-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfonic acid (XVIII).Condensation of the azetidinone (XVIII) with the activated aminothiazole portion (XIX) followed by a necessary deprotection step affords the monocyclic beta-lactam.Dissolution of the beta-lactam in aqueous sodium acetate yields the disodium salt,carumonam.Other routes of synthesis have been discussed.
参考文献标题:Chemical modification of sulfazecin: Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives
文献作者:Sendai,M.; Hachiguchi,S.; Tomimoto,M.; Kishimoto,S.; Matsuo,T.; Kondo,M.; Ochiai,M.
参考来源:J Antibiot 1985,38(3),346-371
合成路线:L-threonic acid (XI),which is readily available from L-ascorbic acid (IX),is converted to L-N-benzyloxycarbonyl-4-hydroxyallothreoninamide (VIII).This in turn is transformed to (3S,4S)-cis-3-amino-4-carbamoyloxymethyl-2-azetidinone-1-sulfonic acid (XVIII).Condensation of the azetidinone (XVIII) with the activated aminothiazole portion (XIX) followed by a necessary deprotection step affords the monocyclic beta-lactam.Dissolution of the beta-lactam in aqueous sodium acetate yields the disodium salt,carumonam.Other routes of synthesis have been discussed.
参考文献标题:Ro-172301 (AMA-1080),a new monocyclic beta-lactam antibiotic: Stereorational synthesis
文献作者:Weigele,M.; Wei,C.; Tengi,J.
参考来源:Intersci Conf Antimicrob Agents Chemother 1983,Abst 324
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