Going Green in Process Chemistry: Optimizing an Asymmetric Oxidation Reaction To Synthesize the Antiulcer Drug Esomeprazole.

Sustainable practices in process chemistry are highlighted by a novel, 9 week team project of 8-12 students, in collaboration with AstraZeneca chemists, in an organic chemistry laboratory. Students synthesize the antiulcer medicine esomeprazole, which involves the asymmetric oxidation of pyrmetazole. To provide insight into the modern process chemistry industry, they propose environmentally friendly modifications to the asymmetric oxidation. Students first synthesize pyrmetazole and then follow a standard oxidation procedure and carry out modified, greener reactions of their choice. They investigate how a change in reaction conditions affects both the yield and enantioselectivity of esomeprazole. Positive student feedback was received and student postlab reports were analyzed over a 4 year period (2015-2018). Results consistently showed that the project provided students with the key tools to develop greener syntheses. This contextual approach not only offers the opportunity to develop valuable communication and team-working skills, but it also gives students creative input into their experimental work. It teaches the important research skills involved in sustainable process chemistry, from reproducing and modifying a literature procedure to identifying green metrics.

The first synthesis of the ABC-ring system of 'upenamide.

The first synthetic route to the spirooxaquinolizidinone core (ABC core) of the macrocyclic marine alkaloid 'upenamide (1) has been developed. All five stereocenters were introduced with complete stereocontrol. The hydroxyl group at C-11 was introduced by a regio- and stereoselective SeO(2)-mediated allylic oxidation. The spirocyclic skeleton was formed by a stannous chloride induced deacetalization-bicyclization procedure. Further stereocenters were introduced by an enzymatic desymmetrization and by incorporation of an (S)-malic acid derived building block.

The Ramberg-Bäcklund reaction for the synthesis of C-glycosides, C-linked-disaccharides and related compounds.

The discovery of the Ramberg-Bäcklund procedure for preparing exo-glycals from S-glycoside dioxides, developed independently in (Old) York and New York, is reviewed. The methodology is successful with glucose, galactose, mannose, xylose, fucose, ribose, altrose, 2-deoxy-arabino-hexose (2-deoxy-glucose) and daunosamine derivatives, and has been used to prepare di-, tri- and tetra-substituted exo-glycals. More recent developments, such as one-pot variants, and protecting group-free procedures, are also covered. Synthetic applications of the exo-glycals, for example, to prepare beta-glycosidase inhibitors, spirocyclic glucose derivatives, beta-C-glycosides, C-glycosyl porphyrin glycoconjugates and C-glycosyl amino acids, are also discussed. Finally, applications of the Ramberg-Bäcklund process for the synthesis of known and novel C-glycosides, and in natural product synthesis, are reviewed.