Divergent Total Synthesis of the Antimitotic Agent Leiodermatolide

Abstract

Subtle but distinctive: The stereostructure of the biologically highly promising antimitotic agent leiodermatolide was uncertain. A short, efficient, and flexible total synthesis based on ring-closing alkyne metathesis as the key step has now solved the puzzle. Subtle differences in the ¹H NMR spectra of the structure shown and the conceivable isomer proved invaluable for the assignment

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

“…54 As shown in Scheme 10, the synthesis began with the asymmetric aldol reaction of 80 and propanal yielding chiral ketone 81, that was submitted to a Sn(OTf) 2 …”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…Construction of a cyclic alkyne-bis(lactone) system was a key event in the synthesis of oxygenated metabolites of n-3 polyunsaturated fatty acids [1331]. Ring closing alkyne metathesis using a conjugated enyne (1570) substrate was employed for a scalable total synthesis of leiodermatolide and leiodermatolide analogs [1332,1333]. Formation of a macrocycle-bridged biphenyl system (e.g.…”

Synthesis of the C(1)–C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C–C Bond Formation

“…To date, total synthesis of leiodermatolide have been reported by Fürstner (2012) 4 and Paterson (2014). 5 Additionally, several leiodermatolide substructures were prepared by Maier.…”

“…5 Additionally, several leiodermatolide substructures were prepared by Maier. 6 Despite this progress, existing routes to leiodermatolide are on the order of roughly 20 steps (LLS) or more, 4,5 warranting further work toward strategies that might streamline its synthesis and broaden access to structural analogues.…”