Structural corroboration of two important building blocks of the anticancer drug eribulin mesylate through two‐dimensional NMR and single‐crystal X‐ray diffraction studies. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Pullela, Srinivas Venkata; Acharya, Vinod; Reddy, Nagarjuna; Harlikar, Jayvant; Kulkarni, Amar; Chavan, Rakesh; Yadav, Ajay; Manna, Shuvendu; Ghosh, Angshuman
• Is Part Of: Acta crystallographica. Volume 72:Issue 1(2016)
• Page Start: 14
• Page End: 20
• Publication Date: 2016-01-01
• Subjects: Halichondrin B -- eribulin mesylate -- double stereodiffrentiation -- asymmetric dihydroxylation -- crystal structure -- Karplus equation -- anticancer drug -- two‐dimensional NMR -- NOESY -- COSY; Crystallography -- Periodicals; Crystals -- Periodicals; 548.3
• DOI: 10.1107/S2053229615022305
• Languages: English
• ISSNs: 2053-2296

Abstract

Abstract : Eribulin mesylate, one of the most synthetically challenging drugs to date, possesses 19 stereocentres in its structure and ascertaining the absolute stereochemistry at every stage of the 64‐stage synthesis is crucial. In our quest to synthesize eribulin, we identified two critical building blocks of this molecule, namely 3, 4:6, 7‐di‐ O ‐cyclohexylidene‐D‐ glycero ‐α‐L‐ talo ‐heptopyranose methanol monosolvate, C19 H30 O7 ·CH3 OH, and (2 R, 3 R, 4 R, 5 S )‐5‐allyl‐2‐[( S )‐2, 3‐dihydroxypropyl]‐4‐[(phenylsulfonyl)methyl]tetrahydrofuran‐3‐ol, C17 H24 O6 S, for which two‐dimensional NMR (2D‐NMR) data were not sufficient to prove the absolute configuration. To ensure structural integrity, single‐crystal X‐ray diffraction data were obtained to confirm the structures. This information provides useful insights into the structural framework of the large eribulin mesylate molecule.