MEN-10700
Chemical Name: (+)-(5R,6S)-2-[N-(Carbamoylmethyl)-N-methylaminomethyl]-6-[1(R)-hydroxyethyl]-2-penem-3-carboxylic acid
CAS No. 156662-18-9, 156662-23-6 (monoNa salt)
项目整合开发状态: Preclinical
项目研究机构: Lusofarmaco (Originator), Menarini (Originator)
合成路线:The 2-(hydroxymethyl)penem (I) is transformed into the corresponding mesylate (II),which is then condensed with sarcosinamide (III),to afford adduct (IV).The O-silyl group of (IV) is removed by treatment with tetrabutylammonium fluoride,yielding alcohol (V).Finally,the allyl ester group of (V) is cleaved in the presence of palladium and triphenylphosphine to furnish the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:Penem derivs.,their preparation and pharmaceutical compsns.containing them
文献作者:Altamura,M.; Arcamone,F.M.; Perrotta,E.; Pestellini,V.; Sbraci,P.; Cascio,G.(Lusofarmaco; Menarini Industrie Farma Riunite Srl)
参考来源:EP 0660837; JP 1996501543; WO 9406803
📄 详细内容
合成路线:The 2-(hydroxymethyl)penem (I) is transformed into the corresponding mesylate (II),which is then condensed with sarcosinamide (III),to afford adduct (IV).The O-silyl group of (IV) is removed by treatment with tetrabutylammonium fluoride,yielding alcohol (V).Finally,the allyl ester group of (V) is cleaved in the presence of palladium and triphenylphosphine to furnish the target carboxylic acid.
参考文献标题:Synthesis and antibacterial activity of MEN 10700,a new penem antibiotic
文献作者:Altamura,M.; et al.
参考来源:Bioorg Med Chem Lett 1995,5(6),555
合成路线:The 2-(hydroxymethyl)penem (I) is transformed into the corresponding mesylate (II),which is then condensed with sarcosinamide (III),to afford adduct (IV).The O-silyl group of (IV) is removed by treatment with tetrabutylammonium fluoride,yielding alcohol (V).Finally,the allyl ester group of (V) is cleaved in the presence of palladium and triphenylphosphine to furnish the target carboxylic acid.
参考文献标题:2-Substituted penems with amino acid-related side chains: Synthesis and antibacterial activity of a new series of beta-lactam antibiotics
文献作者:Altamura,M.; Perrotta,E.; Sbraci,P.; Pestellini,V.; Arcamone,F.; Cascio,G.; Lorenzi,L.; Satta,G.; Morandotti,G.; Sperning,R.
参考来源:J Med Chem 1995,38(21),4244
合成路线:In a related method,the 4-acetoxy-azetidinone (I) is reacted with 2-chlorothioacetic acid (II) in the presence of ZnI2 to give the (chloroacetylthio)azetidinone (III).Nitrogen acylation in (III) by means of allyl oxalyl chloride produces (IV),which undergoes ring closure to the penem (V) in the presence of triethyl phosphite in boiling toluene.Displacement of chloride (V) with sarcosinamide (VI) yields adduct (VII).After desilylation of (VII) to (VIII) by means of tetrabutylammonium fluoride,palladium-catalyzed allyl ester cleavage leads to the title compound.
参考文献标题:Synthesis and biological activity of the penem antibiotic MEN 10700 and its orally absorbed ester MEN 11505
文献作者:Arcamone,F.M.; Altamura,M.; Perrotta,E.; Crea,A.; Manzini,S.; Poma,D.; Salimbeni,A.; Triolo,A.; Maggi,C.A.
参考来源:J Antibiot 2000,53(10),1086