Following the previous literature, 3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one derivatives were the new GABAA inhibitors. We were also synthesized 21-Imidazolyl-3α-hydroxy-3β-ethoxymethyl-5α-pregnan-20-one and investigated the reaction mechanism and bioactivity.
When the bioactivity was determined the animal study, we found the amounts of daily dosage is more than 200mg/day. As a result, we will modified the skeleton of 3α-hydroxy-3β-methoxy-methyl-5α-pregnan-20-one derivatives to improve the metabolism by the intermolecular hydrogen bonding.
This investigation contains three sections: In first section, we have synthesized the moni- and di- substituted 21-piperazinyl-3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one . In second section, 21-bromo-3α-hydroxy-3β-methoxy-
methyl-5α-pregnan-20-one was treated with amino acid and guanidine to perform substituted reaction on the C-21 position. Finally, we developed a new hydrolysis ethodology by used HCO2Cs to give 21-hydroxy-3α-hydroxy-3β-methoxy-
methyl-5α-pregnan-20-one. Then 21-hydroxy-3α-hydroxy-3β-meth-oxymethyl-5α-pregnan-20-one was reacted with β-D-Galactose to give the corresponding product β-D-
galacto-pyranoside. Those 3α-hydroxy-3β-methoxymethyl-5α-pregnan-20-one derivatives will be perform the bioactivity study in the future work.
