Design, synthesis, and biological evaluation of simplified analogues of (+)-discodermolide. Additional insights on the importance of the diene, the C7 hydroxyl, and the lactone.
[structure: see text] The design, synthesis, and biological evaluation of seven totally synthetic analogues of the antitumor agent (+)-discodermolide are reported. Saturation of the terminal diene system, alteration of the substituents on the lactone, and alkylation of the C7-hydroxyl group reveal significant structure-activity relationships.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Xian
Ming
M
D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000473:Alkanes; D000970:Antineoplastic Agents; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; C071229:discodermolide