title: Synthesis of kifunensine thioanalogs and their inhibitory activities against HIV-RT and α-mannosidase.
abstract: An efficient and practical synthesis of kifunensine thioanalogs 1a-c was reported. The bicyclic azasugars fused thiazolidin-4-one 4a-c as key intermediates were first synthesized in good yields of 74-80% via one-pot tandem Staudinger/aza-Wittig/cyclization by using the pivotal azidosugars 3a and 3b derived from D-mannose. Followed by double Pummerer rearrangements and deprotection, the target thiokifunensine 1a and its epimers 1b and 1c were obtained in good yields. Compounds 1a-c were preliminary evaluated for their HIV-RT and α-mannosidase (Jack bean) inhibitory activities. The results showed that such compounds exhibited significant anti-HIV-RT inhibitory activity but poor inhibitory against α-mannosidase. To gain further insight into the inhibitory mechanism of compounds 1a-c, the analog compounds 9a-c were also prepared after deprotection from 4a-c, respectively. Activity comparison between compounds 1a-c and 9a-c suggests that the better activities of 1a-c than those of the 9a-c is possibly due to the additional carbonyl at thiazolidine-4-one ring in fused bicyclic azasugars.
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Zhenying
authors.initials: Z
authors.lastname: Liu
authors.forename: Sinan
authors.initials: S
authors.lastname: Wei
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D032449:Canavalia / Q000737:chemistry / Q000201:enzymology; D002723:Chlorobenzoates / Q000737:chemistry; D003500:Cyclization; D004789:Enzyme Activation; D057075:Enzyme Assays; D015497:HIV-1 / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009943:Organophosphorus Compounds / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors*
chemical_list: D000470:Alkaloids; D002723:Chlorobenzoates; D009943:Organophosphorus Compounds; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D045162:Thiazolidinediones; C065629:kifunensine; C061896:triphenylphosphine; C089946:2,4-thiazolidinedione; D043323:alpha-Mannosidase; C000433:3-chloroperbenzoic acid; D008358:Mannose