Structural corroboration of two important building blocks of the anticancer drug eribulin mesylate through two-dimensional NMR and single-crystal X-ray diffraction studies

Srinivas Venkata Pullela, Vinod Acharya, Nagarjuna Reddy, Jayvant Harlikar, Amar Kulkarni, Rakesh Chavan, Ajay Yadav, Shuvendu Manna, Angshuman Ghosh

Research output: Contribution to journalArticlepeer-review

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, C19H30O7·CH3OH, and (2R,3R,4R,5S)-5-allyl-2-[(S)-2,3-dihydroxypropyl]-4-[(phenylsulfonyl)methyl]tetrahydrofuran-3-ol, C17H24O6S, 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.

Original languageEnglish (US)
Pages (from-to)14-20
Number of pages7
JournalActa Crystallographica Section C: Structural Chemistry
Volume72
DOIs
StatePublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 International Union of Crystallography.

Keywords

  • anticancer drug
  • asymmetric dihydroxylation
  • COSY
  • crystal structure
  • double stereodiffrentiation
  • eribulin mesylate
  • Halichondrin B
  • Karplus equation
  • NOESY
  • two-dimensional NMR

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