Advancing Small-Molecule Synthesis
Chemocatalytic and biocatalytic routes play an important role in improving the manufacture of intermediates and active pharmaceutical ingredients.
Apr 02, 2011
Volume 35, Issue 4
Catalysis plays a crucial role in small-molecule synthesis, whether it is in making an intermediate or the final active pharmaceutical ingredient (API). The effective development and application of a catalyst system can improve reaction conditions, yield, and optical purity as well as produce more efficient chemical transformations. As recent developments show, chemocatalysis and biocatalysis continue to be an active area of academic research and business investments.
IMAGE: MIRIAM MASLO/SPL, GETTY IMAGES
Advances from academia
Oxidative enamine catalysis
. Researchers at the East China University of Science and Technology, the Shanghai Institute of Materia Medica, and the University of New Mexico recently reported on a new chemical transformation, oxidative enamine catalysis, a potentially valuable approach in synthesizing chiral intermediates. The researchers noted that although iminium catalysis, which involves the transformation of iminium ions to enamines, has been extensively studied, the reverse process, converting enamines to iminium species, has not been well examined. In their work, the researchers described oxidative enamine catalysis, or the direct oxidation of an enamine, to produce an iminium species. The researchers showed that the use of o-iodoxybenzoic acid as an oxidant in the presence of a secondary amine catalyst is an effective system for converting enamines to iminium ions. The work was carried out for the direct asymmetric -functionalization of simple aldehydes. The research was used in other enantioselective cascade transformations, including triple and quadruple cascades, for a one-pot synthesis of chiral building blocks and structural frameworks that begin with aldehydes (1, 2).
Light-driven molecular motors in asymmetric reactions
. Researchers at the University of Groningen in The Netherlands recently reported on a light-driven molecular motor with a switchable catalytic function in catalytic asymmetric reactions. Specifically, the researchers reported on a light-driven molecular motor with integrated catalytic functions in which the stepwise change in the configuration during a 360° unidirectional rotary cycle dictated the catalyst performance with respect to activity and absolute stereocontrol. During one full rotary cycle, catalysts were formed that produced either racemic (R, S) or preferentially the R or the S enantiomer of the chiral product of a conjugate addition reaction. The researchers noted that in
situ switching of the chiral preference of a catalytic system had been difficult to achieve. The catalytic system in their work showed that different molecular tasks can be performed in a sequential manner and the sequence was controlled by the directionality of the rotary cycle (3, 4).
Patricia Van Arnum