pd-113271 and fostriecin

Fostriecin and related natural products present a significant challenge for synthetic chemists due to their structural complexity and chemical sensitivity. This review will chronicle the successful efforts of synthetic chemists in the construction of these biologically active molecules. Key carbon-carbon bond forming reactions will be highlighted, as well as the methods used to install the numerous stereocenters present in this class of compounds.

Topics: Alkenes; Biological Products; Cyclization; Cycloaddition Reaction; Hydroxylation; Lactones; Polyenes; Pyrones; Stereoisomerism

The novel fermentation products fostriecin and analogs PD 113,270 and PD 113,271 are structurally related polyene lactone phosphates that have antitumor activity in vitro and in vivo. They have no antibacterial effects, but they were inhibitory to yeasts (agar diffusion method) with MICs of 3 approximately 300 micrograms/ml. Fostriecin or its analogs were active vs. 29 of 46 yeast species (11 genera). Ten of 12 cultures of Candida sp. were not sensitive to any of the analogs, while 11 of 14 cultures of Saccharomyces sp. were inhibited by one or more of the agents. Sensitivity patterns were of three types: Twelve cultures were sensitive only to PD 113,270; fostriecin and PD 113,271 (but not PD 113,270) were active vs. 7 cultures; and 9 cultures were sensitive to all three compounds. Dephosphorylation of the compounds resulted in the loss of antimycotic effects. Activity vs. the yeasts was related to studies of uptake and activity against cancer cells.

Topics: Alkenes; Animals; Antibiotics, Antineoplastic; Antifungal Agents; Candida; Chemical Phenomena; Chemistry; Leukemia L1210; Mice; Microbial Sensitivity Tests; Mitosporic Fungi; Polyenes; Pyrones; Saccharomyces

CI-920 (PD 110,161) and two analogues (PD 113,270 and PD 113,271) are novel antitumor compounds produced by a new actinomycete characterized as Streptomyces pulveraceus subsp. fostreus ATCC 31906. The antitumor compounds are predominantly produced during the stationary (idiophase) growth phase of the organism. CI-920 is active versus the murine P388 lymphocytic and L1210 lymphoid leukemia with T/C values of 246 and 207, respectively. This compound has no significant antimicrobial activity.

Topics: Alkenes; Animals; Antibiotics, Antineoplastic; Drug Evaluation, Preclinical; Fermentation; Leukemia L1210; Leukemia P388; Mice; Microbial Sensitivity Tests; Polyenes; Pyrones; Streptomyces; Structure-Activity Relationship

A complex of structurally related compounds that exhibit in vivo antileukemic activity was isolated from fermentation broths of a new streptomycete. The components of this complex are water soluble phosphate esters containing a conjugated triene system. The isolation and characterization of three of these components are described.

Topics: Alkenes; Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Fermentation; Magnetic Resonance Spectroscopy; Polyenes; Pyrones; Spectrophotometry; Streptomyces; Structure-Activity Relationship