Toward Understanding How the Lactone Moiety of Discodermolide Affects Activity

• Published in: Journal of the American Chemical Society Vol. 127; no. 18; pp. 6532 - 6533
• Main Authors: Shaw, Simon J, Sundermann, Kurt F, Burlingame, Mark A, Myles, David C, Freeze, B. Scott, Xian, Ming, Brouard, Ignacio, Smith, Amos B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.05.2005; Amer Chemical Soc
• Subjects: Alkanes - chemistry; Alkanes - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Carbamates - chemistry; Carbamates - pharmacology; Cell Line, Tumor; Chemistry; Chemistry, Multidisciplinary; Drug Screening Assays, Antitumor; General pharmacology; Humans; Lactones - chemistry; Lactones - pharmacology; Medical sciences; Molecular Conformation; Pharmacology. Drug treatments; Physical Sciences; Physicochemical properties. Structure-activity relationships; Pyrones; Science & Technology; Stereoisomerism; Structure-Activity Relationship; MEDIATED ALDOL REACTIONS; DESIGN; MICROTUBULES; TAXOL; (-)-DISCODERMOLIDE; FRAGMENT; STABILIZING AGENT (+)-DISCODERMOLIDE; LARGE-SCALE SYNTHESIS; INDUCTION; SYNTHETIC ANALOGS; Antineoplastic agent; Structure activity relation; Polyenic compound; Six membered ring; Animal origin; Cytotoxicity; Lactone; Polyol; Oxygen heterocycle; Antimitotic; Biological activity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja051185i

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.