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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Antineoplastic agents. 561. Total synthesis of respirantin
George R Pettit1, Thomas H Smith, Song Feng
1Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA. bpettit@asu.edu
Abstract:
Total synthesis of the 18-membered ring cyclodepsipeptide believed to be respirantin (1b) has been achieved. The key step in the synthesis is an intramolecular transesterification of the beta-ketoester alcohol 6 to afford the protected macrocycle 5. The synthetic product was shown to be identical to a natural product presumed to be respirantin (1b), and the absolute stereochemistry of six of the seven asymmetric centers of cyclodepsipeptide 1b was unequivocally established. Respirantin (1b) was found to be a remarkable inhibitor of cancer cell growth and related to the antimycin family of antibiotics.
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