Qingmei Yin

Design, microwave-assisted synthesis and HIV-RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(4,6-dimethyl-5-(un)substituted-pyrimidin-2-yl)thiazolidin-4-ones

A series of novel thiazolidin-4-ones bearing a hydrophobic substituent at 5-position on the 4,6-dimethyl-pyrimidine ring at N-3 (5c-i and 6c-i) were designed on the prediction of QSAR studies, synthesized in good yields of 60.1-85.3% by microwave-assisted one-pot protocol with the combination of using dicyclohexylcarbonimide (DCC) as the promotor, and evaluated as HIV-1 reverse transcriptases inhibitors. The results of in vitro HIV-1 RT kit assay showed that some of the new compounds, such as 5c, 6c, 5d, 6d, 5g, 5h and 6i, could effectively inhibit RT activity. Among them, compounds 5c and 6c where ethyl group existed at 5-position on N-3 pyrimidine ring were the best ones with the IC(50) value of 0.26 microM and 0.23 microM, respectively. Structure-activity relationship analysis of these analogues suggested that the overall hydrophobicity and steric factor were important to the anti-HIV RT activity. The mechanism of the intramolecular cycloamidation promoted by DCC was also investigated with the key uncyclized intermediate 13.

Synthesis and biological activities of novel isoxazoline-linked pseudodisaccharide derivatives

A series of novel isoxazoline linked pseudodisaccharide derivatives were regiospecifically synthesized by 1,3-dipolar cycloaddition of α-allyl-C-glycopyranosides and sugar-derived nitrile oxides with good yields. The structures of the compounds were characterized by NMR spectroscopy and MS spectrometry and confirmed by the X-ray crystallographic analysis of compound ((5S)-3-(2,3-O-isopropylidene-5-deoxy-d-lyxofuranose-4-yl)isoxazoline-5-yl) methyl α- C-D-galactopyranoside. Their biological activities against glycosidases (α-amylase, α-glucosidase, and β-glucosidase) and HIV-RT, and antitumor activity were preliminarily evaluated. Some of them exhibited potent inhibitory activity to HIV-RT.

A convenient synthesis of novel thiazolidin-4-one-linked pseudodisaccharides by tandem Staudinger/aza-Wittig/cyclization and their biological evaluation.

Novel thiazolidin-4-one-linked pseudodisaccharides 3-6 were synthesized by the one-pot tandem Staudinger/aza-Wittig/cyclization reaction at room temperature. The deacetylation of 3-6 afforded compounds 7-10, respectively. The structures of the new compounds were determined using single crystal X-ray crystallography, (1)H, (13)C, and 2D NMR spectroscopy, and HR mass spectrometry. The preliminary biological evaluation of compounds 7-10 showed that compounds 7aa, 8aa, 7ab, 8ab, 7bb and 8bb were found to have significant immunopotentiating activity. Yet none of these tested compounds have obvious inhibition against glycosidases or HIV reverse transcriptase, or show cancer cell growth inhibition.

Synthesis of C-Pseudonucleosides Bearing Thiazolidin-4-one as a Novel Potential Immunostimulating Agent.

Several novel C-pseudonucleosides bearing thiazolidin-4-one were synthesized by one-pot three-component condensation using unprotected sugar aldehyde at room temperature, and their effects on T cells, B cells, the cytokine secretion of IL-2, IL-4, and IFN-γ, T cell-associated molecules (CD3, CD4, CD8), and B cell-associated molecules (CD19) were first evaluated. The experimental data demonstrated that such thiazolidin-4-one C-pseudonucleosides hold potential as immunostimulating agents.

Microwave-assisted synthesis of dinucleoside analogues containing a thiazolidin-4-one linkage via one-pot tandem Staudinger/aza-Wittig/cyclization

Dinucleosides containing a thiazolidin-4-one linkage were prepared by one-pot tandem Staudinger/aza-Wittig/intermolecular cyclization under microwave irradiation and their structures were confirmed. Preliminary examination of HIV-RT inhibition showed that the dinucleosides containing (R)-thiazolidin-4-one linkage are significantly more active than those containing (S)-thiazolidin-4-one linkage.