Over 100 years of vitamin E: An overview from synthesis and formulation to application in animal nutrition.

The groundbreaking discovery of vitamin E by Evans and Bishop in 1922 was an important milestone in vitamin research, inspiring further investigation into its crucial role in both human and animal nutrition. Supplementing vitamin E has been proved to enhance multiple key physiological systems such as the reproductive, circulatory, nervous and muscular systems. As the main antioxidant in the blood and on a cellular level, vitamin E maintains the integrity of both cellular and vascular membranes and thus modulates the immune system. This overview showcases important and innovative routes for synthesizing vitamin E on a commercial scale, provides cutting-edge insights into formulation concepts for successful product form development and emphasizes the importance and future of vitamin E in healthy and sustainable animal nutrition.

A Decade of Successful Collaborations in Nutritional Compound Process Research and Development.

Collaborations between academia and industry are vital for modern industrial research and development projects, combining the best of both worlds to develop sustainable chemical processes. Herein we summarize a number of successful cooperations between DSM Nutritional Products and Swiss academic institutions that have been carried out over approximately the past decade. A wide variety of reactions and processes have been investigated with experts located in Switzerland. New synthetic routes, chemical transformations and reactor concepts have been developed to produce industrially relevant compounds. Additionally the scope of known catalytic systems has been probed and new catalysts showing improved selectivity have been designed, synthesized and tested. We describe how the research was supported by DSM, the parallel in-house investigations and also how the projects were continued and further developed.

From Sugars to Nutritional Products - Active Ingredients.

A modern trend to carbon dioxide neutral production processes is based on renewable raw materials derived from sugars. Herein, an overview on modern approaches to fine chemicals for the nutritional industry is presented. In comparison to the traditional fossil-fuel-based processes the development of sustainable alternative transformations is necessary to enable the full potential of the new sustainable feedstocks.

A highly stereoselective and flexible strategy for the convergent synthesis of long-chain polydeoxypropionates: application towards the synthesis of the glycolipid membrane components hydroxyphthioceranic and phthioceranic acid.

A highly stereocontrolled and flexible access to biologically relevant polydeoxypropionates in optically pure form has been developed. Taking advantage of our previously established strategy for the asymmetric and stereodivergent synthesis of trideoxypropionate building blocks, we have now been able to assemble large polydeoxypropionate chains with defined configuration in a highly convergent manner. Central steps of this approach include two Suzuki-Miyaura cross-coupling reactions with subsequent highly diastereoselective hydrogenations to join three advanced synthetic intermediates in excellent yield and with full stereochemical control. We have applied this strategy successfully towards the asymmetric synthesis of glycolipid membrane components phthioceranic acid and hydroxyphthioceranic acid, the latter of which was synthesized on a half-gram scale.

Asymmetric hydrogenation of α,ß-unsaturated nitriles with base-activated iridium N,P ligand complexes.

Although many chiral catalysts are known that allow highly enantioselective hydrogenation of a wide range of olefins, no suitable catalysts for the asymmetric hydrogenation of α,ß-unsaturated nitriles have been reported so far. We have found that Ir N,P ligand complexes, which under normal conditions do not show any reactivity towards α,ß-unsaturated nitriles, become highly active catalysts upon addition of N,N-diisopropylethylamine. The base-activated catalysts enable conjugate reduction of α,ß-unsaturated nitriles with H2 at low catalyst loadings, affording the corresponding saturated nitriles with high conversion and excellent enantioselectivity. In contrast, alkenes lacking a conjugated cyano group do not react under these conditions, making it possible to selectively reduce the conjugated C=C bond of an α,ß-unsaturated nitrile, while leaving other types of C=C bonds in the molecule intact.

Asymmetric hydrogenation of maleic acid diesters and anhydrides.

Asymmetric hydrogenation of maleic and fumaric acid derivatives with iridium catalysts based on N,P ligands provides an efficient route to chiral enantioenriched succinates. A new catalyst derived from a 2,6-difluorophenyl-substituted pyridine-phosphinite ligand was developed and enables the conversion of a wide range of 2-alkyl and 2-arylmaleic acid diesters into the corresponding succinates in high enantiomeric purity. Mixtures of cis/trans substrates can be hydrogenated in an enantioconvergent fashion with high enantioselectivity, and further enhances the scope of this transformation. The products are valuable chiral building blocks with a structural motif found in many bioactive compounds, such as metalloproteinase inhibitors.

Asymmetric hydrogenation of α,ß-unsaturated carboxylic esters with chiral iridium N,P ligand complexes.

Enantioselective conjugate reduction of a wide range of α,ß-unsaturated carboxylic esters was achieved using chiral Ir N,P complexes as hydrogenation catalysts. Depending on the substitution pattern of the substrate, different ligands perform best. α,ß-Unsaturated carboxylic esters substituted at the α position are less problematic substrates than originally anticipated and in some cases α-substituted substrates actually reacted with higher enantioselectivity than their ß-substituted analogues. The resulting saturated esters with a stereogenic center in the α or ß position were obtained in high enantiomeric purity.