title: Synthesis of tetracyclic iminosugars fused benzo[e][1,3]thiazin-4-one and their HIV-RT inhibitory activity.
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.
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Sinan
authors.initials: S
authors.lastname: Wei
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Hou
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Li
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D013843:Thiazines; D054303:HIV Reverse Transcriptase
keywords: Anti-HIV RT activity; Aza-C-pseudonucleoside; Benzo[e][1,3]thiazin-4-one; One-pot three-component reaction; Tetracyclic iminosugar