Total synthesis of biselide A.

A total synthesis of the marine macrolide biselide A is described that relies on an enantiomerically enriched α-chloroaldehyde as the sole chiral building block. Several strategies to construct the macrocycle are presented including a macrocyclic Reformatsky reaction that ultimately provides access to the natural product in a longest linear sequence of 18 steps. Biological testing of synthetic biselide A suggests this macrolide disrupts cell division through a mechanism related to the regulation of microtubule cytoskeleton organization.

Diversity-oriented synthesis of glycomimetics.

Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups.

A counterintuitive stereochemical outcome from a chelation-controlled vinylmetal aldehyde addition leads to the configurational reassignment of phormidolide A.

As part of our ongoing studies towards the total synthesis of phormidolide A (1), we explored the chelation-controlled vinylmetal addition of iodide 2 to aldehyde 3 to install the reported 17S configuration. While the stereochemical outcome of this reaction was opposite to that expected, detailed NMR comparisons with the previously reported triacetonide derivative of phormidolide A (18) highlighted that the major adduct was a better match to the natural product. The synthesis of three model acetonides and detailed spectroscopic comparisons to the triacetonide derivative of phormidolide A supports a reassignment of seven of the 11 stereocentres in phormidolide A (1a).