Synthesis of pentacyclic iminosugars with constrained butterfly-like conformation and their HIV-RT inhibitory activity. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Yan, Lianhai; Yin, Zhuqing; Niu, Liping; Shao, Jie; Chen, Hua; Li, Xiaoliu
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 3(2018)
• Page Start: 425
• Page End: 428
• Publication Date: 2018-02-01
• Subjects: Pentacyclic iminosugar -- Constrained butterfly-like conformation -- Homomorpholine fused triazole -- Intra molecular click reaction -- Anti-HIV RT activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.025
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Novel pentacyclic iminosugars1 and2 with the constrained butterfly-like conformation were first synthesized by the key intramolecular click reaction from the tricyclic iminosugars fused benzo[ e ][1, 3]thiazin-4-one3 and4 . The pentacyclic iminosugar was constructed by fusing both benzo[ e ][1, 3]thiazin-4-one and triazolo[5, 1- c ][1, 4]oxazepine scaffolds. Their structures were determined by their 1 H, 13 C NMR, and HRMS (ESI) spectra and X-ray. The pentacyclic iminosugars1 (a –c ), 2 (a –b ) and their corresponding protected precursors13 (a –c ) and14 (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, compound13c was the best one with the IC50 value of RT inhibitory activity of 0.69 μM. Structure-activity relationship analysis suggested that the improvement of the hydrophilicity of the pentacycles was of benefit to their anti-HIV RT activity.