Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Reexamination Certificate
1999-12-03
2003-03-25
Low, Christopher S. F. (Department: 1653)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C530S325000, C530S326000, C530S327000, C549S523000, C514S002600, C514S012200, C514S013800, C514S014800, C514S015800
Reexamination Certificate
active
06538105
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATION
This application claims priority from German Application No. 198 55 859.7, filed on Dec. 3, 1998, the complete disclosure of which is hereby incorporated herein by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel supported, diastereomer-enriched and enantiomer-enriched homopolyamino acids, to a process for the production thereof, to the use thereof in a process for the enantioselective epoxidation of C═C double bonds and to preferred intermediates.
2. Background Information
Enantioselective epoxidation reactions are important reactions for the synthesis of chiral intermediates for organic synthesis. In particular, asymmetrical epoxidation of allyl alcohols according to Sharpless et al. and manganese-salen mediated enantioselective epoxidation according to Jacobsen et al. are well established in synthetic organic chemistry for the synthesis of chiral molecules (Sharpless et al.,
J. Am. Chem. Soc
. 1980, 102, 5974
; J. Am. Chem. Soc
. 1987, 109, 5765
; J. Org. Chem
. 1986, 51, 1922; Jacobsen et al.,
J. Am. Chem. Soc
. 1990, 112, 2801
; J. Am. Chem. Soc
. 1991, 113, 7063).
Another possibility for the asymmetric epoxidation of C═C double bonds has been discovered in the reaction of chalcones with hydrogen peroxide in the presence of enantiomer-enriched polyamino acids (Colonna et al.,
Org. Synth.; Mod. Trends
, Proc. IUPAC Symp. 6th, 1986, 275; Julia et al.,
Angew. Chem., Int. Ed. Engl
., 1980, 19, 929).
The synthesis methods just stated all have the disadvantage that they are applicable to a relatively narrowly restricted range of substrates. On the basis of this fact and the continuing research activities in this area, it may be concluded that there is a need to discover further improved epoxidation processes.
To date, two different variants of the Julia/Colonna epoxidation reaction are known in the prior art, namely the two-phase and three-phase variants (S. M. Roberts et al.
Chem. Commun
. 1998, 1159; WO 96/33183). The two-phase variant makes use of an organic solvent and operates with oxidizing agents soluble in these solvents in the presence of the insoluble homopolyamino acids. The three-phase variant also makes use of water as the third phase in addition to the water-insoluble organic solvent. Water-soluble oxidizing agents may accordingly advantageously be used for the reaction, optionally in the presence of phase transfer catalysts.
However, it is clear from the last-stated publications relating to epoxidation reactions that the low space-time yields (reaction times of the order of days) and the sometimes poor ee values for many substrates are major deficiencies of these epoxidation methods with regard to their use in an industrial process.
On the other hand, it has been found that using immobilization techniques for enzyme mediated reactions may be advantageous with regard, for example, to the recoverability of the catalyst and raising the optical and chemical yield (EP 0 799 894 A2 and
Tetrahedron Asymmetry
1991, 2, 931).
SUMMARY OF THE INVENTION
In the light of the prior art stated and discussed above, the object of the invention was accordingly to provide supported, diastereomer-enriched and enantiomer-enriched homopolyamino acids which allow the epoxidation of C═C double bonds in the presence of an oxidizing agent. In comparison with prior art supported catalysts, it was the intention that the novel compounds should in particular exhibit a higher rate of reaction combined with better chiral induction. Another object of the invention was to be able to produce the supported catalysts in the simplest and thus lowest cost manner possible and to ensure better handling characteristics with regard to recovery of the catalyst after the reaction, so resulting in advantages for use on an industrial scale.
These and further objects which are not stated in greater detail but may be derived in an obvious manner from the prior art are achieved by homopolyamino acids which are adsorbed on an insoluble support material. Preferably the homopolyamino acids have a chain length of 5 to 100 amino acids, more preferably 7 to 50. Homopolyamino acids from the group polyneopentylglycine, polyleucine, polyisoleucine, polyvaline, polyphenylalanine and polyalanine are preferred. In one preferred embodiment, the homopolyamino acids are crosslinked together or are enlarged by organic polymers. Preferred as support material for the homopolyamino acids are compounds containing silicon oxide, nitrocellulose, cellulose or activated carbon. The ratio of homopolyamino acid to support material is preferably between 1:7 and 2:1 parts by weight, more preferably between 1:1 and 1:4 parts by weight.
Because diastereomer-enriched and enantiomer-enriched homopolyamino acid is adsorbed on an insoluble support material, catalysts for enantioselective epoxidation are obtained which are extremely simple and thus low in cost to produce and furthermore, utterly surprisingly, are capable of considerably raising the rates of reaction in this reaction in comparison with prior art catalysts. Increased yield and enantiomer excesses in the epoxide products are simultaneously unexpectedly achieved. Furthermore, the supported homopolyamino acids according to the invention may be recycled very effectively and, by virtue of the enlargement and heterogenization thereof, such catalysts have very good handling characteristics on the industrial scale.
The supported catalysts may be produced using various diastereomer- and enantiomer-enriched homopolyamino acids. Preferably, however, homopolyamino acids from the group comprising polyneopentylglycine, polyleucine, polyisoleucine, polyvaline, polyalanine and polyphenylalanine are used. Of this group, polyneopentylglycine is the most highly preferred.
The chain length of the polyamino acids should be selected such that, on the one hand, chiral induction in the reaction is not impaired and, on the other, the costs for synthesizing the polyamino acids do not rise excessively. The chain length of the homopolyamino acids is preferably between 5 and 100, preferably 7 to 50, amino acids. A chain length of 10 to 40 amino acids is very particularly preferred.
A further preferred embodiment is that in which the homopolyamino acids are crosslinked with polyfunctional amines or are enlarged by other organic polymers. Crosslinking agents which are advantageously used are amines, such as for example 1,3-diaminopropane, 1st generation propyleneiminetetraamine dendrimers or crosslinked hydroxy- or aminopolystyrene. Polyethylene glycol/polystyrene based nucleophiles are preferably considered as polymer enlargers. Polyamino acids modified in this manner are described in
Chem. Commun
. 1998, 841 et seq., 1159 et seq. and
Tetrahedron Asymmetry
1997, 8, pages 3165 et seq.
The insoluble support materials are those preferably synthesized on the basis of silicon oxide, such as for example molecular sieve, silica gel or zeolites together with Celite 521® or Celite Hyflo Super Cell®, Wessalith® Day P. Silica gels having defined pore sizes, such as for example CPC I or CPC II are also advantageous. Sugar derivatives such as nitrocellulose, cellulose or activated carbon are also preferred as support material.
The ratio of support material to polyamino acid is determined by two limits. On the one hand, only a certain quantity of polyamino acid may be adsorbed on the insoluble support, while on the other, chiral induction diminishes at a ratio of below 10 wt. % of polyamino acid to support. The ratio of homopolyamino acid to support material is preferably between 1:7 and 2:1 parts by weight, particularly preferably between 1:1 and 1:4 parts by weight.
The present invention also provides a simple but extremely advantageous process for the production of the homopolyamino acids, which is distinguished in that a mixture of homopolyamino acid and support material is suspended in an organic solvent and, after filtration, the residue is dried.
Another aspect of the present invention is the use of the
Dhanda Anupma
Drauz Karlheinz
Geller Thomas
Roberts Stan M.
Degussa - AG
Low Christopher S. F.
Lukton David
Pillsbury & Winthrop LLP
LandOfFree
Catalysts for the enantioselective epoxidation of C═C... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Catalysts for the enantioselective epoxidation of C═C..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Catalysts for the enantioselective epoxidation of C═C... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3041056