Synthesis of dimeric steroid-glycylglycine conjugates by Ugi four-component reaction. NMR and X-ray diffraction characterization

Ugi-four component reaction of bile acids, formaldehyde, ethyl isocyanoacetate and 1,4-phenylenediamine produced dimeric steroid-glycylglycine conjugates in low yields. The structure of the new compounds consists of two steroid-dipeptide conjugate units linked by a 1,4-phenylene bridge. Detailed NMR characterization provided sufficient evidence on the obtained structures that were confirmed by single crystal X-ray diffraction. Interestingly X-ray crystallography revealed that the dimeric lithocholic acid-glycylglycine conjugate crystalizes in a conformation having the tertiary and secondary amides in the E and Z rotamers respectively.