【药物名称】
化学结构式(Chemical Structure):
参考文献No.762553
标题:Synthesis of novel C2 and C2-C8 linked pyrrolo[2,1-c][1,4]benzodiazepine-naphthalimide hybrids as DNA-binding agents
作者:Kamal, A.; Srinivas, O.; Ramulu, P.; Ramesh, G.; Kumar, P.P.
来源:Bioorg Med Chem Lett 2003,13(20),3577
合成路线图解说明:

4-Benzyloxy-5-methoxy-2-nitrobenzoic acid (I) is converted to the corresponding acid chloride with SOCl2 and subsequently coupled to trans-4-hydroxy-L-proline methyl ester (II) to yield the benzamide (III). After protection of the hydroxyl group of (III) as the t-butyldimethylsilyl ether (IV), reduction of the ester function by means of DIBAL provides aldehyde (V). Simultaneous protection of the aldehyde function in (V) and O-desilylation in the presence of ethanethiol and chlorotrimethylsilane gives rise to thioacetal (VI). The secondary alcohol (VI) is oxidized to ketone (VII) by treatment with TPAP/NMMO. Then, Horner-Emmons olefination of (VII) with methyl diethylphosphonoacetate (VIII) affords the unsaturated ester (IX), which is further hydrolyzed to acid (X) under alkaline conditions.

合成路线图解说明:

Alkylation of 1,8-naphthalimide (XI) with N-Boc-1-amino-3-bromopropane (XII) provides (XIII), which is further deprotected with trifluoroacetic acid to yield the aminopropyl naphthalimide (XIV). Coupling between amine (XIV) and acid (X) affords amide (XV). After nitro group reduction in (XV) with SnCl2 in MeOH, the resultant amino thioacetal (XVI) is deprotected and cyclized by means of HgCl2/CaCO3 to furnish the title compound.

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