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

Zhuqing Yin; Mo Zhu; Sinan Wei; Jie Shao; Yuheng Hou; Hua Chen; Xiaoliu Li

doi:10.1016/j.bmcl.2016.02.049

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

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

Authors

Zhuqing Yin¹, Mo Zhu¹, Sinan Wei¹, Jie Shao¹, Yuheng Hou¹, Hua Chen², Xiaoliu Li³

Affiliations

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.

PMID: 26944616
DOI: 10.1016/j.bmcl.2016.02.049

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology*
Crystallography, X-Ray
HIV Infections / drug therapy
HIV Infections / virology
HIV Reverse Transcriptase / antagonists & inhibitors*
HIV Reverse Transcriptase / metabolism
HIV-1 / drug effects
HIV-1 / enzymology
Humans
Models, Molecular
Reverse Transcriptase Inhibitors / chemical synthesis
Reverse Transcriptase Inhibitors / chemistry*
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship
Thiazines / chemical synthesis
Thiazines / chemistry*
Thiazines / pharmacology*

Substances

Anti-HIV Agents
Reverse Transcriptase Inhibitors
Thiazines
HIV Reverse Transcriptase