title: Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A.
abstract: Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected formation of a 10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C. As a result, a thermodynamically stable structure was obtained. The structures of two new diastereomeric, unsaturated spiroketals, their configurations and conformations, were determined by means of NMR spectroscopy and molecular modelling. The reaction kinetics and mechanistic aspects of this transformation are discussed. These rearrangements provide a facile synthesis of novel macrolide scaffolds.
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Čikoš
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Irena
authors.initials: I
authors.lastname: Ćaleta
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Dinko
authors.initials: D
authors.lastname: Žiher
authors.affiliation: GlaxoSmithKline, New Frontiers Science Park, Harlow, CM19 5AW, United Kingdom.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Vine
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Ivaylo J
authors.initials: IJ
authors.lastname: Elenkov
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Dukši
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Gembarovski
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ilijaš
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Snježana
authors.initials: S
authors.lastname: Dragojević
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Malnar
authors.affiliation: GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
authors.forename: Sulejman
authors.initials: S
authors.lastname: Alihodžić
keywords: 6-O-methyl-9(E)-hydroxyiminoerythronolide A; configuration; conformation; reaction mechanism; spiroketal