合成路线:By acylation of 9-amino-6-demethyl-6-deoxytetracycline (I) with sarcosyl chloride (II) by means of Na2CO3 in acetonitrile with or without dimethylpropylenurea.
合成路线:This compound can be obtained by two related ways:1) The nitration of minocycline (I) by means of NaNO3 and H2SO4 gives the 9-nitro derivative (II),which is hydrogenated with H2 over Pd/C in 2-methoxyethanol to yield the 9-amino derivative (III).Finally,this compound is acylated with sarcosyl chloride (IV) by means of Na2CO3 in acetonitrile/dimethylpropylenurea.2) The acylation of the 9-amino derivative (III) with N-(succinimidyloxycarbonyl)carbamic acid tert-butyl ester (V) by means of sodium acetate in THF gives the 9-(tert-butoxycarbonyl)glycylamino substituted compound (VI),which is deprotected with trifluoroacetic acid to afford the 9-glycylamino compound (VII).Finally,this compound is methylated with formaldehyde and simultaneous hydrogenation with H2 over Pd/C in 2-methoxyethanol.
合成路线:Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II),which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III).Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V).Finally,this compound is treated with tert-butylamine (VI) to yield,after purification,GAR-936.
参考文献标题:Glycylcyclines.1.A new generation of potent antibacterial agents through modification of 9-aminotetracyclines
文献作者:Sum,P.-E.; Lee,V.J.; Testa,R.T.; Hlavka,J.J.; Ellestad,G.A.; Bloom,J.D.; Gluzman,Y.; Tally,F.P.
参考来源:J Med Chem 1994,37(1),184-8
合成路线:Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II),which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III).Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V).Finally,this compound is treated with tert-butylamine (VI) to yield,after purification,GAR-936.
参考文献标题:Synthesis and structure-activity relationship of novel glycylcline derivatives leading to the discovery of GAR-936
文献作者:Sum,P.-E.; Petersen,P.
参考来源:Bioorg Med Chem Lett 1999,9(10),1459
合成路线:Nitration of minocycline (I) with KNO3 and H2SO4 gives the 9-nitro derivative (II),which is reduced with H2 over Pd/C in 2-methoxyethanol/2N H2SO4 to provide 9-aminominocycline (III).Acylation of compound (III) with 2-bromoacetyl bromide (IV) in N,N-dimethylpropyleneurea (DMPU) affords 9-(2-bromoacetamido)minocycline (V).Finally,this compound is treated with tert-butylamine (VI) to yield,after purification,GAR-936.
参考文献标题:GAR-936
文献作者:Hunter,P.A.; Castar,J.
参考来源:Drugs Fut 2001,26(9),851
产品链接: CAS No. 220620-09-7››