US 9,920,342 B2Granted

Process for the preparation of Droxidopa

AssigneeDivi's Laboratories, Ltd.

InventorsSatchandra Kiran Divi, Mysore Aswatha Narayana Rao, Ponnekanti Purnachandra Rao, Shaik Nowshuddin

Life of this patent

Estimating the term…

Loading patent…

Abstract

A novel process for the preparation of L-threo-dihydroxyphenylserine (Droxidopa) is described. It comprises of enantioselective hydrolysis of racemic (DL)-threo-N-acetyl-3-(3,4-methylenedioxyphenyl)-serine using commercially available L-amino acylase from Aspergillus sp. (EC 3.5.1.14) in the presence of cobalt ions, to obtain (L)-threo-3-(3,4-methylenedioxyphenyl)-serine followed by dealkylation to obtain Droxidopa. Protecting the amino group of (L)-threo-3-(3,4-methylenedioxyphenyl)-serine using either benzyloxycarbonyl or phthaloyl group before dealkylation followed by deprotection of the amino group results in obtaining Droxidopa in high yields and purity.

Claims7

Dependent claims

A process for the preparation of (L)-threo-3-(3,4-methylenedioxyphenyl)serine (Droxidopa) comprising:

a) acetylation of (DL)-threo-3-(3,4-methylenedioxyphenyl)serine of formula II with an acetylating agent
to obtain (DL)-threo-N-acetyl-3-(3,4-methylenedioxyphenyl)serine of the formula III, followed by
(b) enantioselective hydrolysis of racemic (DL)-threo compound of the formula (III) using
L-aminoacylase from Aspergillus sp.(EC 3.5.1.14) in the presence of cobalt ionstoobtain(L)-threo-3-(3,4-methylenedioxyphenyl)-serine of formula (IV) and
(c) converting (L)-threo isomer of formula (IV) to Droxidopa of formula (I)
(d) optionally protecting the amino group of (L)-threo isomer of formula (IV) with a protecting agent followed by demethylation and deprotection of the amino group to obtain Droxidopa of formula I.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/413,989Filed 24 Jan 2017
Priority: IN 20164101701917 May 2016
Published: US 2017/0335357 A123 Nov 2017
Granted: 20 Mar 2018
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C12P 13/001
Preparation of nitrogen-containing organic compounds: amines; Imines
C07C 227/16
From compounds containing already amino and carboxyl groups or derivatives thereof: by reactions not involving the amino or carboxyl groups
C12P 13/04
Preparation of nitrogen-containing organic compounds: alpha- or beta- amino acids
C12P 17/04
Oxygen as only ring hetero atoms: containing a five-membered hetero ring, e.g. griseofulvin , vitamin C