Tze-Ming Chan

Structure of Sch 68631: A new hepatitis C virus proteinase inhibitor from Streptomyces sp.

Abstract A novel hepatitis C virus (HCV) proteinase inhibitor, Sch 68631 ( 1 ), was isolated from the fermentation culture broth of Streptomyces sp. The structure of 1 was elucidated by analyses of spectroscopic data and shown to be a new member of the phenanthrenequinone family of compounds.

Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC-NMR and LC-MS.

LC-NMR and LC-MS were used to characterize the structures of four major degradation products of SCH 56592, an antifungal drug candidate in clinical trials. These compounds were formed under stress conditions in which the bulk drug substance was heated in air at 150 degrees C for 12 days, and were separated from SCH 56592 as a mixture using a semi-preparative HPLC method. The data from LC-NMR, LC-ESI-MS (electrospray ionization mass spectrometry) and LC-ESI-MS/MS indicate that the oxidation occurred at the piperazine ring in the center of the drug molecule. The structures of the degradation products were determined from the 1H NMR spectra obtained via LC-NMR, which were supported by LC-ESI-MS and LC-ESI-MS/MS analyses. A novel degradation pathway of SCH 56592 was proposed based on these characterized structures.

Solution- and solid-phase synthesis of enantiomerically pure spiro oxindoles

A convenient synthesis of enantiomerically pure oxindoles using a three component reaction involving 1:3 dipolar cycloaddition reaction has been achieved using solution and solid phase chemistry.

Two novel diketopiperazines isolated from the fungus Tolypocladium sp.

Abstract Diketopiperazines, Sch 54794 and Sch 54796, have been isolated from a fungal fermentation. The structures of these compounds have been established based on spectroscopic data analysis. Sch 54794 exhibited inhibitory activity in the platelet activating factor (PAF) assay.

Synthesis of heterocyclic compounds using radical reactions

A generalised radical reaction has been used to synthesise heterocyclic compounds which could serve as ligands for drug discovery. Attempt also have been made to rationalise the formation of oxidation products formed during TBTH reaction.

A new sterol sulfate, Sch 572423, from a marine sponge, Topsentia sp.

Bioassay-guided fractionation of an active fraction from a marine sponge Topsentia sp. in our marine fraction library (MFL) led to the isolation and identification of halistanol sulfate (1) and a new sterol sulfate Sch 572423 (2). Compounds 1 and 2 were identified as P2Y(12) inhibitors with IC(50) of 0.48 and 2.2 microM, respectively. The general method of purification for the MFL library and the structure elucidation of compound 2 are described.

Enantioselective syntheses of carbocyclic ribavirin and its analogs: linear versus convergent approaches

Abstract The first enantioselective syntheses of carbocyclic ribavirin by both convergent and linear approaches are described. The linear approach from chiral nonracemic 2-azabicyclo[2.2.1]hept-5-en-3-one proves to be a highly efficient route to carbocyclic analogs of ribavirin.

Structure Elucidation of Sch 725674 from Aspergillus sp.

A new macrolide Sch725674 (1) was isolated and identified from the culture of an Aspergillus sp. The structure elucidation of 1 was accomplished based on extensive NMR spectroscopic analyses. Compound 1 showed inhibitory activity against Saccharomyces cerevisiae (PM503) and Candida albicans (C43) with MICs of 8 and 32 µg/ml, respectively.

Two antiviral compounds from the plant Stylogne cauliflora as inhibitors of HCV NS3 protease

The 70% aq methanolic extract of the Peruvian plant Stylogne cauliflora was found to contain two novel oligophenolic compounds SCH 644343 (1) and SCH 644342 (2), which were identified as inhibitors of HCV NS3 protease. The structure of 1 and 2 was established based on high-resolution NMR studies. Compound 1 inhibited HCV NS3 protease with an IC(50) of 0.3 microM, while compound 2 showed an IC(50) of 0.8 microM.

Two selective novel triterpene glycosides from sea cucumber, Telenata Ananas: inhibitors of chemokine receptor-5.

The aqueous methanolic extract of a sea cucumber was found to contain two triterpene glycosides 1 and 2. The structures of 1 and 2 were established based on high-resolution NMR studies. Compounds 1 and 2 exhibited inhibitory activity (K(i)) of 30 and 5microM, respectively, in a chemokine receptor subtype 5 (CCR5) assay. Both compounds did not show any significant inhibition in a CXCR2 assay at 50microM, suggesting their selectivity for the CCR5 receptor.