Optically active amino acid sulphoxide and amino acid sulphone derivatives, their preparation, their polymerisation and use as adsorbents for chromatographic resolution of racemates

• US 5,357,001 A
• Filed: 06/23/1993
• Issued: 10/18/1994
• Est. Priority Date: 07/02/1992
• Status: Expired due to Term

• Current Assignee: Daicel Chemical Industries Limited
• Original Assignee: Bayer AG
• Inventors: Grosser, Rolf, Arlt, Dieter, Lange, Walter, Grosse-Bley, Michael, Hoever, Franz-Peter, Bomer, Bruno
• Primary Examiner(s): Michl, Paul R.
• Assistant Examiner(s): Yoon, Tae H.
• Application Number:
  US08/081,537
• Time in Patent Office: 482 Days
• Field of Search: 526/238.1, 526/243, 526/245, 526/248, 526/249, 526/288, 526/304, 526/199, 526/220, 526/258, 526/166, 526/194, 525/328.2, 525/328.5, 525/330.7, 525/326.1, 525/326.3, 525/326.7, 525/330.4, 525/330.5, 525/330.3, 210/656
• US Class Current: 525/326.1
• CPC Class Codes: C07B 57/00 Separation of optically-active compounds
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2602/42 the bicyclo ring system containing seven carbon atoms
• CPC Class Codes: C07C 317/50 at least one of the nitrogen atoms being part of any of the groups , X being a hetero atom, Y being any atom
• CPC Class Codes: C07D 277/06 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C08F 20/54 Amides , e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/17 Nitrogen containing
• CPC Class Codes: Y10T 436/18 Sulfur containing

Abstract

The invention relates to new optically active amino acid derivatives of the general formula (I) ##STR1## in which n, R, R₁, R₂, R₃, X and A have the meaning given in the description, which amino acid derivatives contain sulphoxide or sulphone groups, to two basic synthetic routes for the preparation from sulphur-containing amino acids, to the polymerization of these monomers and to the use of the polymers as optically active adsorbents for chromatographic resolution of racemates to give the enantiomers.

Claims

1. An optically pure crosslinked insoluble polymer containing at least 40 mol % of structural units of the formula ##STR13## in which n is 1 or 2,

R represents hydrogen, methyl or fluorine,

R₁ represents hydrogen or C₁ -C₄ -alkyl or together with R₂ forms a methylene group or a dimethylene group, each of which can be mono- or disubstituted by C₁ -C₄ -alkyl,

R₂ represents a straight-chain, branched or cyclic alkyl radical having up to 10 C atoms, C₆ -C₁₄ -aryl, ##STR14## C₂ -C₁₀ -acyl, substituted or unsubstituted benzoyl or benzyl or together with R₁ forms a bridge,

R₃ represents a straight-chain, branched or cyclic alkyl radical having up to 20 C atoms which is unsubstituted or mono- to trisubstituted by halogen, alkoxy having 1 to 4 C atoms, aralkoxy having 7 to 16 C atoms or aryl having 6 to 10 C atoms,

X denotes oxygen or an NR₄ group in which R₄ represents hydrogen or C₁ -C₄ -alkyl or together with R₃ forms a nitrogen-containing 5- to 7-membered ring which may be mono- or disubstituted by C₁ -C₄ -alkyl- or C₁ -C₆ -alkoxycarbonyl, and

A represents a methylene or dimethylene group which is unsubstituted or mono- or disubstituted by C₁ -C₄ -alkyl.

2. A polymer according to claim 1, in which

R represents hydrogen, methyl or fluorine,

R₁ denotes hydrogen or methyl or together with R₂ forms a methylene group, which can be mono- or disubstituted by methyl or monosubstituted by tertiary-butyl, or a dimethylene group,

R₂ represents alkyl having up to 8 C atoms, phenyl, benzyl, benzoyl and ##STR15## or together with R₁ forms a bridge, R₃ represents a C₁₀ -terpenyl radical, an adamantyl radical, a decahydronaphthyl radical, a 1-phenylethyl radical, a C₅ -C₁₂ -cycloalkyl radical, such as cyclopentyl, cyclohexyl or cycloheptyl, or a branched C₃ -C₁₂ -alkyl radical, such as isopropyl, 3-pentyl or 5-heptyl,

X denotes oxygen or an NR₄ group in which R₄ represents hydrogen or C₁ -C₄ -alkyl or together with R₃ forms a nitrogen-containing 5- to 7-membered ring which may be unsubstituted or mono- or disubstituted by C₁ -C₄ -alkyl- or C₁ -C₆ -alkoxycarbonyl, and

A represents a methylene, dimethylmethylne or dimethylene unit.

3. A polymer according to claim 1, containing the amino acid sequence of the optically active sulphur-containing amino acids, cysteine, homocysteine, penicillamine whose SH function is first alkylated, arylated, alkoxycarbonylmethylated or linked to the amino group via an alkylene bridge and secondly has been oxidized to the sulphoxide or sulphone.

4. A polymer according to claim 1, in the form of beads or bound to a finely divided inorganic support.

5. A process for the preparation of a crosslinked bead polymer according to claim 1, which comprises polymerizing an optically active S-oxide-containing amino acid of the formula ##STR16## in suspension in the presence of 0.5 to 50 mol % of a crosslinking agent.

6. A process according to claim 5, wherein the polymerization is effected in the presence of at least one of a free radical former and an inert organic solvent.

7. A process for the preparation of a crosslinked polymer according to claim 1 bound to an inorganic support material, which comprises polymerizing an optically active S-oxide-containing amino acid of the formula ##STR17## in the presence of a (meth)acryloyl-substituted silica gel/diol phase or a silica gel/vinyl phase.

8. A process according to claim 7, wherein the polymerization is effected in the presence of at least one of a free radical former and an inert organic solvent.

9. In the resolution of a racemic mixture of a compound into its optical antipodes by contacting such mixture with an optically active adsorbent, the improvement wherein such adsorbent comprises a polymer according to claim 1.