Cytotoxic hypothemycin analogues from Hypomyces subiculosus.

Three new hypothemycin analogues were isolated from the fungal strains Hypomyces subiculosus DSM 11931 and DSM 11932. The structures of these compounds were elucidated by spectroscopic methods, chemical conversion, and X-ray crystallographic analysis. One of the analogues, 4-O-demethylhypothemycin, exhibited potent and selective cytotoxic activity against cell lines with a BRAF mutation.

A series of 23,24-dihydrodiscodermolide analogues with simplified lactone regions.

A collection of seven new 23,24-dihydrodiscodermolide analogues have been synthesized with modifications to the lactone ring, some of which show antiproliferative activities similar to discodermolide.

Toward understanding how the lactone moiety of discodermolide affects activity.

A series of simplified discodermolide analogues have been designed and synthesized in an attempt to understand the role of the lactone ring. These synthetic efforts have led to an unsubstituted butyrolactone 9 being generated, which shows improved activity over the natural product.

Design, synthesis, and evaluation of analogues of (+)-14-normethyldiscodermolide.

[Structure: see text] The design, syntheses, and biological evaluation of nine totally synthetic analogues of the microtubule-stabilizing agent (+)-14-normethyldiscodermolide (2) are reported. Simplification at the C(21)-C(24) terminal diene and at the C(1)-C(5) lactone moieties reveals significant structure-activity relationships.

Design, synthesis, and evaluation of carbamate-substituted analogues of (+)-discodermolide.

[Structure: see text] The design, syntheses, and biological evaluation of 22 totally synthetic analogues of the potent microtubule-stabilizing agent (+)-discodermolide (1) have been achieved. Structure-activity relationships of the C(19) carbamate were defined, exploiting two synthetically simplified scaffolds, as well as the parent (+)-discodermolide framework.

Design, synthesis and cytotoxicity of 7-deoxy aryl discodermolide analogues.

A series of 7-deoxy discodermolide analogues in which the lactone fragment 'C' was replaced by aryl substituents were designed, synthesized, and evaluated for cytotoxicity.

Synthesis, conformational analysis, and bioassay of 9,10-didehydroepothilone D.

[reaction: see text] 9,10-Didehydroepothilone D was synthesized, its conformation was studied, and its tubulin polymerization and antiproliferative activity were compared with that of epothilone D and certain analogues.