title: Structural corroboration of two important building blocks of the anticancer drug eribulin mesylate through two-dimensional NMR and single-crystal X-ray diffraction studies.
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.
authors.affiliation: API R&D, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Srinivas Venkata
authors.initials: SV
authors.lastname: Pullela
authors.affiliation: API R&D, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Acharya
authors.affiliation: API R&D, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Nagarjuna
authors.initials: N
authors.lastname: Reddy
authors.affiliation: API-ADL, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Jayvant
authors.initials: J
authors.lastname: Harlikar
authors.affiliation: API-ADL, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Amar
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: API-ADL, Cipla Ltd, MIDC Patalganga, Rasayani, Maharashtra 410 220, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Chavan
authors.affiliation: Block BN, Plot 7, TCG Life Sciences, Salt Lake, Sector V, Kolkata, West Bengal 700 091, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Yadav
authors.affiliation: Block BN, Plot 7, TCG Life Sciences, Salt Lake, Sector V, Kolkata, West Bengal 700 091, India.
authors.forename: Shuvendu
authors.initials: S
authors.lastname: Manna
authors.affiliation: Block BN, Plot 7, TCG Life Sciences, Salt Lake, Sector V, Kolkata, West Bengal 700 091, India.
authors.forename: Angshuman
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry* / Q000145:classification*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D053138:Cyclohexenes / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009005:Monosaccharides / Q000737:chemistry*; D014961:X-Ray Diffraction; D000095662:Polyether Polyketides
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D053138:Cyclohexenes; D005663:Furans; D007659:Ketones; D009005:Monosaccharides; C048401:1,4-cyclohexadiene; C018674:tetrahydrofuran; C490954:eribulin; D000095662:Polyether Polyketides
keywords: COSY; Halichondrin B; Karplus equation; NOESY; anticancer drug; asymmetric dihydroxylation; crystal structure; double stereodiffrentiation; eribulin mesylate; two-dimensional NMR