An Asymmetric Synthesis of (2S,5S)-5-Substituted Azepane-2-Carboxylate Derivatives

Abstract

To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.

A Practical, Component-Based Synthetic Route to Methylthiolincosamine Permitting Facile Northern-Half Diversification of Lincosamide Antibiotics

“…When amide bond formation was complete, desilylation was performed by the addition of acetic acid and methanol. Removal of the N-Boc group of 36 and diastereoselective azepene hydrogenation with palladium on carbon 32 furnished azepanamide 37 in 50% yield from 34. Scheme 5.…”

Facile and Green Synthesis of Saturated Cyclic Amines

“…Wishka and his colleagues presented a successful method for the synthesis of (2 S ,5 S )-5-substituted-azepane-2-carboxylate derivatives starting from known hydroxyl ketone ( Scheme 50 ) [ 66 ].…”

Synthesis and investigation of antioxidant and antimicrobial activity of new pyrazinopyrroloazepine derivatives using Fe3O4/CuO/ZnO@MWCNT MNCs as organometallic nanocatalyst by new MCRs

“…Some representatives of this class of azaheterocycles are known as antiviral agents, glycosidase inhibitors, anticancer agents, or antidiabetics. [9][10][11][12][13] Therefore, in view of their medicinal relevance, an increasing number of synthetic methods have been described in recent years for the construction of highly substituted azepine derivatives. [14][15][16][17][18] Also, pyrrole and its derivatives are among the most important nitrogen-containing heterocyclic compounds that exist in the structure of many natural products including bile pigments, heme, cytochromes, vitamin B 12 , and alkaloids.…”