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Bioorg Med Chem Lett. 2016 Apr 1;26(7):1738-41. doi: 10.1016/j.bmcl.2016.02.049. Epub 2016 Feb 18.

Synthesis of tetracyclic iminosugars fused benzo[e][1,3]thiazin-4-one and their HIV-RT inhibitory activity.

Author information

1
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
2
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China. Electronic address: hua-todd@163.com.
3
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, China. Electronic address: lixl@hbu.cn.

Abstract

Several aza-C-pseudonucleosides bearing 1,3-benzothiazin-4-one (6 and 7) were prepared by the one-pot three-component condensation from the iminosugar aldehyde 3, amino acid ethyl/methyl ester hydrochlorides 4(a-c), and 2-mercaptobenzoic acid 5. After removal of Boc and the isopropylidene groups, the target novel tetracyclic iminosugars fused benzo[e][1,3]thiazin-4-one 1(a-c) and 2(a-b) were first afforded by the intramolecular cyclo-amidation reaction. Their structures were determined by their (1)H, (13)C NMR, and HRMS (ESI) spectra and X-ray. The tetracyclic iminosugars 1(a-c) and 2(a-b) were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that all compounds could effectively inhibit RT activity. Among them, compound 2a was the best one with the IC50 value of RT inhibitory activity of 0.82μM. Structure-activity relationship analysis suggested that 1'R configuration in the tetracyclic azasugars was of benefit to their anti-HIV RT activity.

KEYWORDS:

Anti-HIV RT activity; Aza-C-pseudonucleoside; Benzo[e][1,3]thiazin-4-one; One-pot three-component reaction; Tetracyclic iminosugar

PMID:
26944616
DOI:
10.1016/j.bmcl.2016.02.049
[Indexed for MEDLINE]

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