Synthesis routes to access MDMA prodrugs by using controlled and non-controlled intermediates
A method of synthesizing a pharmacological compound substance by attaching a psychoactive base substance to an amino acid and creating a prodrug with modified pharmacological behavior. A prodrug made by the method. A pharmaceutical composition comprising a prodrug of a psychoactive base substance attached to an amino acid and a pharmaceutically acceptable salt.
1. A method of synthesizing a pharmacological compound substance including the steps of:
performing an aldol condensation on 3,4-dibenzyloxybenzaldehyde to obtain 1-(3,4-Dibenzyloxyphenyl)-2-nitropropene;
dissolving 1-(3,4-Dibenzyloxyphenyl)-2-nitropropene in an inert solvent, adding the solution to a suspension of alane, and obtaining 3,4-Dibenzyloxyamphetamine hydrochloride;
reacting 3,4-Dibenzyloxyamphetamine hydrochloride with an activated lysine derivative to obtain Boc-L-Lys(Boc)-3,4-dibenzyloxyamphetamine;
dissolving Boc-L-Lys(Boc)-3,4-dibenzyloxyamphetamine in a solvent and performing a hydrogenolytic removal of O-benzyl groups to obtain Boc-L-Lys(Boc)-3,4-dihydroxyamphetamine;
O,O′—methylating Boc-L-Lys(Boc)-3,4-dihydroxyamphetamine to obtain Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine; and
performing a step chosen from the group consisting of
(A) deprotecting Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine to obtain L-Lys-(R,S)-MDA, and
(B) alkylating an amide nitrogen of Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine to obtain Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine, and deprotecting Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine to obtain L-Lys-(R,S)-MDMA.
2. A method of synthesizing a pharmacological compound substance including the steps of:
reducing 1-(3,4-Dibenzyloxyphenyl)-2-nitropropene to a ketone 3,4-Dibenzyloxyphenylacetone;
applying reductive amination conditions to 3,4-Dibenzyloxyphenylacetone to obtain 3,4-Dibenzyloxymethamphetamine hydrochloride;
reacting 3,4-Dibenzyloxymethamphetamine hydrochloride with an activated lysine derivative to obtain Boc-L-Lys(Boc)-3,4-dibenzyloxymethamphetamine;
performing a hydrogenolytic removal of O-benzyl groups on Boc-L-Lys(Boc)-3,4-dibenzyloxymethamphetamine to obtain Boc-L-Lys(Boc)-3,4-dihydroxymethamphetamine;
O,O′—methylating Boc-L-Lys(Boc)-3,4-dihydroxymethamphetamine to obtain Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine; and
deprotecting Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine to obtain L-Lys-(R,S)-MDMA.