# US 5,352,801 A · Process for the production of optically-active 4-amino-3-hydroxycarboxylic acids

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- Number: US 5,352,801 A
- Document ID: US5352801A
- Status: Granted
- Kind: A
- Application number: 08/120,793
- Filed: 1993-09-15
- Granted: 1994-10-04
- Earliest claimed: 1991-08-22
- Assignees: Lonza Ltd.
- Inventors: Markus Banziger; John McGarrity; Thomas Meul
- Web page: https://patentgrep.com/patent/US5352801A

## CPC

- C07D 207/267: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
- C07C 227/22: from lactams, cyclic ketones or cyclic oximes, e.g. by reactions involving Beckmann rearrangement
- C07C 269/00: Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups [IMAGE cpc-sch-C07C-0964.gif], the nitrogen atom not being part of nitro or nitroso groups
- C07D 207/26: 2-Pyrrolidones
- C12P 17/10: Nitrogen as only ring hetero atom
- C12P 41/004: {by esterification of alcohol- or thiol groups in the enantiomers or the inverse reaction}
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

Starting from 5-alkylidene or 5-benzylidenetetramic acid optically-active 4-amino-3-hydroxy-carboxylic acids are produced in the (rel-3R,4R) configuration, especially statine. The synthesis process includes the O-acylation of the tetramic acid to the corresponding 4-acyloxy-3-pyrrolin-2-one, a stereoselective hydrogenation to (rel-4R,5R)-4-acyloxy-5-alkyl or 5-benzylpyrrolidin-2-one and an enantioselective enzymatic hydrolysis of the (4R,5R)-enantiomer to the corresponding 4-hydroxypyrrolidin-2-one. The nonhydrolyzed enantiomer is separated and converted into the target compound with (3S,4S) configuration by hydrolytic cleavage of the lactam ring and the ester function and optionally introduction of an amino protective group. Analogously the (3R,4R)-enantiomer can be obtained from the 4-hydroxypyrrolidin-2-one from the enzymatic hydrolysis. The 4-amino-3-hydroxycarboxylic acids producible according to the invention are the structural elements of enzyme inhibitors.

## Claims

### Claim 1

(4S, 5S)-4-Acyloxypyrrolidin-2-one of formula: ##STR15## wherein R.sup.1 is a branched or a straight chain alkyl group with 1 to 10 C atoms or an aryl, an arylalkyl or a cycloalkyl group and R.sup.2 is a branched or a straight chain alkyl group with 1 to 10 C atoms or an aryl group.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein R.sup.1 is isopropyl, phenyl or cyclohexyl.

### Claim 3 (depends on 2)

The compound according to claim 2 wherein R.sup.2 is propyl.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein R.sup.2 is propyl.