Charles E. Chase

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.