Modular Synthesis of Radicicol A and Related Resorcylic Acid Lactones, Potent Kinase Inhibitors

• Published in: Angewandte Chemie (International ed.) Vol. 46; no. 36; pp. 6899 - 6902
• Main Authors: Dakas, Pierre-Yves, Barluenga, Sofia, Totzke, Frank, Zirrgiebel, Ute, Winssinger, Nicolas
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.01.2007; WILEY-VCH Verlag; WILEY‐VCH Verlag; Wiley
• Subjects: Chemistry; Chemistry, Multidisciplinary; inhibitors; Lactones - chemical synthesis; Macrolides - chemical synthesis; Physical Sciences; Protein Kinase Inhibitors - chemical synthesis; resorcylic acid lactones; Science & Technology; solid-phase extraction; total synthesis; LL-Z1640-2; inhibitors; ACTIVATION; DESIGN; solid-phase extraction; FLUOROUS MIXTURE-SYNTHESIS; BIOLOGICAL EVALUATION; STEREOSPECIFIC SYNTHESIS; STEREOISOMER LIBRARIES; resorcylic acid lactones; total synthesis; MACROLIDES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200702406

Short and sweet: A concise and modular synthesis of radicicol A and related resorcylic acid lactones using fluorous isolation technology and immobilized reagents is reported (see scheme, RF=C3H6C6F13, TMSE=2‐(trimethylsilyl)ethyl). The compounds are found to be potent (low‐nanomolar) inhibitors of selected kinases. Despite their irreversible inactivation of kinases, they show good selectivity amongst a panel of 127 kinases.