title: Stereoselective synthesis of the Halaven C14-C26 fragment from D-quinic acid: crystallization-induced diastereoselective transformation of an α-methyl nitrile.
abstract: 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.
authors.affiliation: Current address: PCAS BioMatrix, 725 Trotter St., Saint-Jean-sur-Richelieu, Quebec J3B 8 J8 (Canada).
authors.forename: Francis
authors.initials: F
authors.lastname: Belanger
authors.forename: Charles E
authors.initials: CE
authors.lastname: Chase
authors.forename: Atsushi
authors.initials: A
authors.lastname: Endo
authors.forename: Francis G
authors.initials: FG
authors.lastname: Fang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Steven R
authors.initials: SR
authors.lastname: Mathieu
authors.forename: Annie Z
authors.initials: AZ
authors.lastname: Wilcoxen
authors.forename: Huiming
authors.initials: H
authors.lastname: Zhang
keywords: antitumor agents; asymmetric synthesis; chiral pool; green chemistry; total synthesis