Multicomponent Ligation of Steroids: Creating Diversity at the Linkage Moiety of Bis-spirostanic Conjugates by Ugi Reactions

摘要

The diversity-oriented synthesis of novel bis-spirostanic conjugates utilizing two different Ugi four-component reactions (Ugi-4CR) is described. Spirostanic steroids were functionalized with Ugi-reactive groups, that is, amines, isocyanictes, and carboxylic acids, and next were subjected to multicomponent ligation approaches leading to bis-steroidal; conjugates featuring pseudo-peptidic and heterocyclic linkage moieties. Both the classic Ugi-4CR and its hydrazoic add variant were implemented, proving good emciency for the, ligatioh of isocyanosteroids to spirostanic adds and equatorial amines. Axially oriented amines showed poorer results, although model studies proved that chemical emdeney could be significantly improved while increasing reaction times. Overall, the method comprises the rapid generation of molecular diversity at the bis-steroid linkage moiety and, consequently, shows promise toward the production of combinatorial libraries of bis-spirostanes for biological screening.