Total synthesis of biselide A. Issue 15 (12th March 2021)

• Record Type: Journal Article
• Authors: Challa, Venugopal Rao; Kwon, Daniel; Taron, Matthew; Fan, Hope; Kang, Baldip; Wilson, Darryl; Haeckl, F. P. Jake; Keerthisinghe, Sandra; Linington, Roger G.; Britton, Robert
• Is Part Of: Chemical science. Volume 12:Issue 15(2021)
• Page Start: 5534
• Page End: 5543
• Publication Date: 2021-03-12
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc06223e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A total synthesis of the marine macrolide biselide A is described that relies on an enantiomerically enriched α-chloroaldehyde as the sole chiral building block. Abstract : A total synthesis of the marine macrolide biselide A is described that relies on an enantiomerically enriched α-chloroaldehyde as the sole chiral building block. Several strategies to construct the macrocycle are presented including a macrocyclic Reformatsky reaction that ultimately provides access to the natural product in a longest linear sequence of 18 steps. Biological testing of synthetic biselide A suggests this macrolide disrupts cell division through a mechanism related to the regulation of microtubule cytoskeleton organization. Overall, this concise synthesis and insight gained into the mechanism of action should inspire medicinal chemistry efforts directed at structurally related anticancer marine macrolides.