Process for making morphine-6-glucuronide and its analogues using haloglucuronate ester intermediates
AssigneeUFC Corporation
InventorsFeodor Scheinmann, Andrew Valentine Stachulski, John Ferguson, Jane Louise Law
Life of this patent
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Abstract
A process for manufacturing morphine-6-glucuronide and related compounds of the general structure of Formula 1: wherein optionally substituted morphine is conjugated with an optionally substituted member of a new class of intermediates, namely, 1-haloglucuronate esters, in the presence of iodine or an iodinium compound. The conjugation may be followed by conversion of R1 of Formula 1 into hydrogen and/or the removal of the ester groups from the glucuronic residue at R2 of Formula 1.
Claims17
A process for the production of compounds of the general structure of Formula 1:
- in which:
- R1=alkyl both branched and unbranched, aryl, allyl or acyl;
- R2=glycoside ester;
- R3=alkyl, aryl, hydrogen or (CH2)nX, where n is an integer and X=NRR4, where R and R4 are hydrogen, alkyl, aryl or acyl;
- and in which the C(7)-C(8) linkage is olefin, dihydro, dihydroxy, hydroxyhalo, epoxy, dihalo, hydrohalo, hydrohydroxy, or olefin adducts CHX-CHY, where X and Y are epoxy, halogen or hydrohalogen;
- comprising conjugating 1-iodoglucuronate ester or a substituted 1-iodoglucuronate ester with morphine or substituted morphine in the presence of iodine or an iodonium compound;
- said substituted 1-iodoglucuronate ester having the general structure shown in Formula 2:
- in which:
- R1=alkyl or aryl;
- R2=acyl, silyl, alkyl, benzyl or aryl;
- X=iodine in the α or β configuration;
- and
- said substituted morphine having the general structure of Formula 1 in which:
- R1=hydrogen, acyl, trialkylsilyl, lower alkyl, or methyl-β-D-(2,3,4-tri-O-acyl)glucuronate;
- R2=hydrogen;
- R3=methyl, methyl N-oxide (NMeo), or (CH2)nX, where X=NRR4, R and R4 each being one of hydrogen, alkyl, aryl, acyl and a halogen.
1-iodo-derivatives of glucuronate esters having the general structure of Formula 2:
- wherein:
- R1=alkyl or aryl;
- R2=isobutyryl, pivaloyl, silyl, alkyl, benzyl or aryl;
- X=iodine in the α or β configuration.
Dependencies are inferred from the claim text.