Yi-Tsung Liu

Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals SCH 51048 and SCH 56592

Two complimentary approaches to the key (−)-(2R)-cis-tosylate 1 and its (+)-(2S)-enantiomer 15 via generation of chiral imide enolates having a 2,2-disubstituted olefin functionality in the β-position, are described. In a “protecting group free” sequence, reaction of the titanium enolate generated from (4R)-benzyl-2-oxazolidinone derived imide 5b with s-trioxane provided a convenient intermediate 19 which could be directly subjected to 2,4-diastereoselective iodocyclization.

Detection and structural characterization of ras oncoprotein-inhibitors complexes by electrospray mass spectrometry

MS based methodology employing electrospray ionization (ESI) is described for the detection of ternary complexes in which SCH 54292 or SCH 54341 and GDP are noncovalently bound to oncogenic ras protein. The observed molecular weights of 19,816 and 19,570 Da confirmed the presence of noncovalent complexes of ras-GDP-SCH 54292 and ras-GDP-SCH 54341, respectively. We have also performed selective chemical modification of lysine residues of the ras protein complex followed by enzymatic digestion and on-line LC-ESI MS peptide mapping to determine protein-drug binding topography. There was a good correlation between nucleotide exchange inhibition as determined by the enzyme assay and evidence of complex formation as determined by MS.

Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034

Crystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials.

Synthesis of 20-dihydro-20-deoxy derivatives of 16-membered macrolide antibiotics

The use of bis(triphenylphosphine)copper(I) tetrahydroborate for selective reduction of aldehyde tosylhydrazones in the presence of other reducible and sensitive functions, as present in macrolide antibiotics, is described.

Chemical degradation of AR-5 antibiotics (mycinamicins): X-ray crystal structure analysis of the aglycone from AR-5#2

The structures and stereochemistry of AR-5 antibiotics (mycinamicins) by X-ray analysis are disclosed; a novel degradative procedure for the preparation of the aglycones of the above antibiotics is also described.

Mutasynthesis of 23-O-mycinosyl-12,13-desepoxy-12,13-didehydro-rosaramicin from tylosin

A hybrid structure of rosaramicin and mycinamicin has been mutasynthesised and found to be highly active against gram positive organisms.