title: Multicomponent ligation of steroids: creating diversity at the linkage moiety of bis-spirostanic conjugates by Ugi reactions.
abstract: 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, isocyanides, 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 acid variant were implemented, proving good efficiency for the ligation of isocyanosteroids to spirostanic acids and equatorial amines. Axially oriented amines showed poorer results, although model studies proved that chemical efficiency 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.
authors.affiliation: Center for Natural Products Study, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba. karel@ifal.uh.cu
authors.forename: Karell
authors.initials: K
authors.lastname: Pérez-Labrada
authors.forename: Yanira
authors.initials: Y
authors.lastname: Méndez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Brouard
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rivera
mesh_terms: D002626:Chemistry, Pharmaceutical; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013150:Spirostans / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D054852:Small Molecule Libraries; D013150:Spirostans