Carbohydrate–steroid conjugation by Ugi reaction: one-pot synthesis of triple sugar/pseudo-peptide/spirostane hybrids

The one-pot synthesis of novel molecular chimeras incorporating sugar, pseudo-peptide, and steroidal moieties is described. For this, a new carbohydrate–steroid conjugation approach based on the Ugi four-component reaction was implemented for the ligation of glucose and chacotriose to spirostanic steroids. The approach proved wide substrate scope, as both mono and oligosaccharides functionalized with amino, carboxy, and isocyano groups were conjugated to steroidal substrates in an efficient, multicomponent manner. Two alternative strategies based on the hydrazoic acid variant of the Ugi reaction were employed for the synthesis of tetrazole-based chacotriose–diosgenin conjugates resembling naturally occurring spirostan saponins. This is the first time that triple sugar/pseudo-peptide/steroid hybrids are produced, thus opening up an avenue of opportunities for applications in drug discovery and biological chemistry.

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► A new multicomponent approach for the conjugation of carbohydrates to steroids.
► Mono and oligosaccharides are conjugated to spirostanes by the Ugi reaction.
► Unique type of triple sugar/pseudo-peptide/spirostane hybrids are formed in one pot.
► Applications in the synthesis of tetrazole-based spirostan saponin are described.