Stereoselective synthesis of the Halaven C14-C26 fragment from D-quinic acid: crystallization-induced diastereoselective transformation of an α-methyl nitrile.

Crystallization-induced diastereoselective transformation (CIDT) of an α-methyl nitrile completes an entirely non-chromatographic synthesis of the halichondrin B C14-C26 stereochemical array. The requisite α-methyl nitrile substrate is derived from D-quinic acid through a series of substrate-controlled stereoselective reactions via a number of crystalline intermediates that benefit from a rigid polycyclic template. Therefore, all four stereogenic centers in the Halaven C14-C26 fragment were derived from the single chiral source D-quinic acid.

Cyclooctatrienes from pyran-2-ones via a tandem [4+4]-photocycloaddition/decarboxylation process.

Irradiation of pyran-2-ones bearing pendent furans in aqueous MeOH followed by heating furnished fused bicyclic products containing a cyclooctatriene ring.

Macrocyclic ketone analogues of halichondrin B.

Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.