Stella Huang

The chemistry of taxanes: unexpected rearrangement of baccatin III during chemoselective debenzoylation with Bu3SnOMe/LiCl

Abstract Chemoselective debenzoylation of 7,13-diacetyl baccatin III was achieved with tributyltin methoxide in NMP in the presence of lithium chloride as an activating agent. Surprisingly, the debenzoylation reaction was followed by rapid intramolecular cleavage of the oxetane ring to produce a novel taxane structure featuring a tetrahydrofuran ring.

The chemistry of taxanes: reaction of taxol and baccatin derivatives with Lewis acids in aprotic and protic media

Abstract Several Lewis acids were shown to cleanly open the oxetane ring of taxol and baccatin derivatives. The reaction is shown to proceed via anchimeric assistance by the C-4 acetate group. Several minor products, including a novel derivative possessing a bridged C-ring, were also isolated. A mechanistic rationale is provided for all compounds formed. When taxol derivatives were treated with Lewis acids in methanol, ester cleavage reactions were observed. We provide conditions that are selective for C-10 acetate cleavage and for C-13 side-chain methanolysis.

Diastereoselective addition of Grignard reagents to azetidine-2,3-dione: Synthesis of novel Taxol® analogues

Abstract Synthesis and cytotoxicity properties of novel C-2′ analogues of paclitaxel are described. The analogues were synthesized using Holtons β-lactam approach to append the side chain on baccatin III. The key intermediate to the synthesis of novel analogues was prepared employing an unprecedented stereocontrolled addition of Grignard reagent to a chiral azetidine-2,3-dione.

Studies toward structure-activity relationships of taxol®: synthesis and cytotoxicity of taxol® analogues with C-2′ modified phenylisoserine side chains☆

Abstract Analogues of taxol with a modified phenylisoserine side chains were synthesized and evaluated as potential cytotoxic agents.

Synthesis and activity of a C-8 keto pleuromutilin derivative

A C-8 keto pleuromutilin derivative has been synthesized from the biotransformation product 8-hydroxy mutilin. A key step in the process was the selective oxidation at C-8 of 8-hydroxy mutilin using tetrapropylammonium perruthenate. The presence of the C-8 keto group precipitated interesting intramolecular chemistry to afford a compound (10) with a novel pleuromutilin-derived ring system.

The isolation and structures of unusual 1, 4-polyketides from the dinoflagellate, Amphidinium sp.

Abstract Unusual 1,4-polyketides with cytotoxic activity against human colon tumor cells were isolated from the dinoflagellate, Amphidinium sp. and their significance with respect to the mode of dinoflagellate polyketide biosynthesis was discussed.

On the reaction of taxol with DAST

Treatment of 2′Cbz taxol (2) with DAST yields several interesting new products, including 7-α-fluoro derivative 3a and a cyclopropane - containing product, 4a.

Sordarin oxazepine derivatives as potent antifungal agents

The synthesis and biological activity of sordarin oxazepine derivatives are described. The key step features a regioselective oxidation of an unprotected triol followed by double reductive amination to afford the ring-closed products. The spectrum of antifungal activity for these novel derivatives includes coverage of Candida albicans, Candida glabrata, and Cryptococcus neoformans.

Orevactaene,1 a novel binding inhibitor of HIV-1 rev protein to Rev response element (RRE) from Epicoccum nigrum WC47880

Orevactaene (1), a novel oxopolyene, was isolated from Epicoccum nigrum WC47880 during the screening of microbial fermentation extracts for their ability to inhibit the binding between HIV-1 regulatory protein Rev and its viral RNA-binding site, Rev response element (RRE). The structure of 1 was elucidated by spectroscopic methods. Compound 1 displayed inhibitory activity against the Rev/RRE binding with an IC50 value of 3.6 μM.

An approach to the identification of potent inhibitors of influenza virus fusion using parallel synthesis methodology

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.