Synthesis and crystal structures of ring A modified glycyrrhetinic acid derivatives derived from 2,3-oxirane and 2,3-thiirane intermediates

A general method for the introduction of thiol groups at positions 1, 2, and 3 of glycyrrhetinic acid has been developed starting from a protected 2α,3α-oxido-derivative. Conversion into the corresponding 2β,3β-epithio-derivative was followed by ring-opening leading to either 2- or 3-substituted thio derivatives. Conversely, 3α-configured allylic alcohol intermediates derived from the 2,3-epoxide provided efficient access to both diastereoisomeric 3-thio derivatives as well as 1α-thio derivatives. The stereochemistry of the newly formed stereogenic centers was rigorously proven using X-ray crystallography.