Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.
Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.
Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.
Chris
C
Lorenc
Process & Analytical Chemistry, NMR Structure Elucidation, Merck Research Laboratories Rahway, NJ, 07065, USA.
Josep
J
Saurí
Advanced Chemistry Development, Inc. 8 King Street E. Suite 107, Toronto, ON, M5C 1B5, Canada.
Arvin
A
Moser
Process & Analytical Chemistry, NMR Structure Elucidation, Merck Research Laboratories Rahway, NJ, 07065, USA.
Alexei V
AV
Buevich
ChemConector, Inc. 904 Tamaras Circle, Wake Forest, NC, 27587, USA.
Antony J
AJ
Williams
Process & Analytical Chemistry, NMR Structure Elucidation, Merck Research Laboratories Rahway, NJ, 07065, USA.
R Thomas
RT
Williamson
Process & Analytical Chemistry, NMR Structure Elucidation, Merck Research Laboratories Rahway, NJ, 07065, USA.
Gary E
GE
Martin
Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.
Mark W
MW
Peczuh
NMR spectroscopy; cheminformatics; computer-assisted structure elucidation; rearrangement; spiro compounds; spiroketals