McMaster Chemists Achieve Total Synthesis of Complex Polyketide Macrolactone Print

Senior Chemistry graduate student David McLeod, working in the McNulty research group, has recently completed a total synthesis of the naturally occurring fungal-derived polyketide Phomolide G.  The original structure assigned to the natural product was prepared in 19 chemical steps but proved to be non-identical to natural Phomolide G. This synthesis and stereochemistry was confirmed by single crystal X-ray analysis carried out by Dr. Hilary Jenkins.  With some detective work and chemical intuition, a diastereomer of the proposed structure was prepared which proved to be identical with natural Phomolide G. David’s synthesis is a landmark of protecting group manipulations, stereocontrol and chemoselective transformations required to prepare the single enantiomer of this natural product that contains four stereogenic centres. The Phomolide macrolactones belong to an expanding group of polyketides that exhibit a wide spectrum of biological activities. The work is to be published in an upcoming issue of the European Journal of Organic Chemistry (http://dx.doi.org/10.1002/ejoc.201501592).