KR20100114483A - Chiral salicyl aldehydes and chiral naphthol aldehydes for l/d optical conversion of amino acids and optical resolution of amino acids and amino alcohols - Google Patents
Chiral salicyl aldehydes and chiral naphthol aldehydes for l/d optical conversion of amino acids and optical resolution of amino acids and amino alcohols Download PDFInfo
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- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
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- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/38—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by doubly-bound oxygen atoms
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- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/40—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
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Abstract
Description
The present invention relates to chiral salicyl aldehyde and chiral naphthol aldehyde compounds that can optically convert amino acids or optically split amino acids and aminoalcohols.
Optically pure amino acids are of great industrial importance because they are widely used as ligands for asymmetric catalysts or as starting materials or intermediates for the synthesis of various pharmaceuticals and bioactive substances ((a) Coppola, GM; Schuster, HF Asymmetric Synthesis.Construction of Chiral Molecules Using Amino Acids; Wiley: New York, 1987; (b) Bergmeier, SC Tetrahedron 2000, 56 , 2561-2576; (c) Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley & Sons: New York, 1994; (d) Helmchen, G .; Pfaltz, A. Acc. Chem. Res . 2000, 33 , 336-345. (E) Ager, DJ; Prakash, I .; Schaad, DR Chem. Rev. 1996, 96 , 835-876).
Fermentation is a method of obtaining amino acids inexpensively and economically. However, the amino acids obtainable by fermentation are limited to L-amino acids among natural amino acids. Although optically pure D-amino acids and non-natural amino acids are produced through enzymatic and optical splitting methods, the production cost is high, and the unit price is 5-10 times higher than that of natural L-amino acids produced by fermentation. Are going through. Therefore, there is still an active effort to economically mass-produce amino acids ((a) Williams, RM In Synthesis of Optically Active a-Amino Acids ; Baldwin, JE, Ed .; Organic Chemistry Series; Pergamon Press: Oxford, (1989) (b) Williams, RM; Hendrix, JA Chem. Rev. 1992, 92 , 889. (c) Duthaler, RO Tetrahedron 1994, 50 , 1539. (d) Seebach, D .; Sting, AR; Hoffman, M. Angew.Chem . , Int.Ed. Engl. 1996, 35 , 2708. (e) Maruoka, K .; Ooi, T. Chem. Rev. 2003, 103 , 3013.).
Therefore, the present inventors have developed a method for converting L-amino acid to D-amino acid by recognizing chirality of chiral amino alcohol and amino acid through imine bond using a binaphthol derivative (compound of Formula a) having an aldehyde group. ((a) Park, H .; Kim, KM; Lee, A .; Ham, S .; Nam, W .; Chin, J. J. Am. Chem. Soc. 2007, 129, 1518-1519; (b ) Kim, KM; Park, H .; Kim, H .; Chin, J .; Nam, W. Org. Lett. 2005, 7 , 3525-3527.).
(A)
The binaphthol derivative (compound of formula a) is a PLP compound ((a) Shaw, JP; Petsko, GA Ringe, D. Biochemistry, 1997, which plays a central role in the activity of an enzyme called amino acid lasmaze). 36 , 1329-1342; (b) Walsh, CTJ Biol. Chem. 1989, 264 , 2393-2396) was developed in the light of the mechanism of action. The pure acquisition of optical isomers of amino acids or aminoalcohols using such compounds is expected to be a new alternative to obtain amino acids and aminoalcohol optical isomers due to the wider range of application and lower cost than conventional enzymatic or conventional optical splitting methods. .
On the other hand, the binaphthol derivatives are about 3-4 times larger in molecular weight than amino acids and aminoalcohols, so reducing the working volume is expected to be more effective in optical conversion and optical splitting of amino acids and aminoalcohols.
The present invention is to provide a compound that can be used more effectively in the optical conversion and optical splitting of amino acids and aminoalcohols that require optical conversion and optical splitting so that the difference in molecular weight and amino acids and aminoalcohols can be produced more economically. The purpose.
It is also an object of the present invention to provide a method for optically converting amino acids or optically splitting amino acids and amino alcohols using the above compounds.
The present invention,
It provides a chiral salicyl aldehyde compound represented by the formula (1):
In the above formula
R 1 is substituted or substituted with alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH unsubstituted or substituted with straight or branched chain alkyl, halogen or OH unsubstituted or substituted with hydrogen, halogen or OH or Unsubstituted alkynyl or aryl unsubstituted or substituted with halogen or OH;
R2 is unsubstituted or substituted with linear or branched alkyl, unsubstituted or substituted with halogen or OH, alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH, substituted or unsubstituted. Alkynyl or aryl unsubstituted or substituted with halogen or OH;
R3 is -NHCXR4, -NHS (= O) a R4, -NHPO (OH) R4 or -NHC (NHR5) (NHR6) + , X is oxygen or sulfur, a is 1 or 2, and R4 is halogen Substituted or unsubstituted straight or branched chain alkyl, NR 7 R 8, or OR 9, and R 5 to R 9 are each independently hydrogen; Straight or branched chain alkyl substituted or unsubstituted with halogen; Or aryl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, nitro, alkyl, alkoxy and perfluoroalkyl groups, R5 and R6 may combine to form a ring, wherein R3 is -NHC (NH 2 ) when NH 2 + , the counterion is a halogen ion or R 10 CO 0 — , wherein R 10 is alkyl or aryl unsubstituted or substituted with alkyl;
The alkyl group has 1 to 10 carbon atoms, the alkenyl and alkynyl have 2 to 10 carbon atoms, and the aryl group has 5 to 12 carbon atoms.
The present invention also provides
It provides a chiral naphthol aldehyde compound represented by the formula (2).
In the above formula
R 1 is substituted or substituted with alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH unsubstituted or substituted with straight or branched chain alkyl, halogen or OH unsubstituted or substituted with hydrogen, halogen or OH or Unsubstituted alkynyl or aryl unsubstituted or substituted with halogen or OH;
R2 is unsubstituted or substituted with linear or branched alkyl, unsubstituted or substituted with halogen or OH, alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH, substituted or unsubstituted. Alkynyl or aryl unsubstituted or substituted with halogen or OH;
R3 is -NHCXR4, -NHS (= O) a R4, -NHPO (OH) R4 or -NHC (NHR5) (NHR6) + , X is oxygen or sulfur, a is 1 or 2, and R4 is halogen Substituted or unsubstituted straight or branched chain alkyl, NR 7 R 8, or OR 9, and R 5 to R 9 are each independently hydrogen; Straight or branched chain alkyl substituted or unsubstituted with halogen; Or aryl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, nitro, alkyl, alkoxy and perfluoroalkyl groups, R5 and R6 may combine to form a ring, wherein R3 is -NHC (NH 2 ) when NH 2 + , the counterion is a halogen ion or R 10 CO 0 — , wherein R 10 is alkyl or aryl unsubstituted or substituted with alkyl;
The alkyl group has 1 to 10 carbon atoms, the alkenyl and alkynyl have 2 to 10 carbon atoms, and the aryl group has 5 to 12 carbon atoms.
The present invention also provides
Provided is a method of optically converting amino acids or optically splitting amino acids and aminoalcohols using the compound of Formula 1 or Formula 2 above.
Compounds of formulas (1) and (2) of the present invention are more suitable for optical conversion and optical splitting of amino acids and aminoalcohols because the difference in molecular weight is not large with amino acids and aminoalcohols requiring optical conversion and optical splitting. Effectively used.
In addition, because it can be manufactured economically, it provides an effect of reducing the cost of optical conversion of amino acids and optical splitting of amino acids and amino alcohols.
The present invention relates to a chiral salicyl aldehyde compound (Formula 1) and a chiral naphthol aldehyde compound (Formula 2). Both compounds have an —OH group and a carbonyl group located next to each other in the benzene ring, contain one asymmetric carbon, and both compounds have a relatively small molecular weight when compared to the pore-opened binaphthol derivatives.
[Formula 1]
[Formula 2]
In Chemical Formulas 1 and 2
R 1 is substituted or substituted with alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH unsubstituted or substituted with straight or branched chain alkyl, halogen or OH unsubstituted or substituted with hydrogen, halogen or OH or Unsubstituted alkynyl or aryl unsubstituted or substituted with halogen or OH;
R2 is unsubstituted or substituted with linear or branched alkyl, unsubstituted or substituted with halogen or OH, alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH, substituted or unsubstituted. Alkynyl or aryl unsubstituted or substituted with halogen or OH;
R3 is -NHCXR4, -NHS (= O) a R4, -NHPO (OH) R4 or -NHC (NHR5) (NHR6) + , X is oxygen or sulfur, a is 1 or 2, and R4 is halogen Substituted or unsubstituted straight or branched chain alkyl, NR 7 R 8, or OR 9, and R 5 to R 9 are each independently hydrogen; Straight or branched chain alkyl substituted or unsubstituted with halogen; Or aryl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, nitro, alkyl, alkoxy and perfluoroalkyl groups, R5 and R6 may combine to form a ring, wherein R3 is -NHC (NH 2 ) when NH 2 + , the counterion is a halogen ion or R 10 CO 0 — , wherein R 10 is alkyl or aryl unsubstituted or substituted with alkyl;
The alkyl group has 1 to 10 carbon atoms, the alkenyl and alkynyl have 2 to 10 carbon atoms, and the aryl group has 5 to 12 carbon atoms.
All compounds represented by Chemical Formulas 1 and 2 are divided into R-optical isomers and S-optical isomers according to the steric nature of the carbon to which R 2 is bonded. Synthesizing the compounds represented by Formulas 1 and 2 by a general method is obtained as a racemic mixture, the R- and the S- optical isomer is a pure compound, respectively, separated from the race mixture by the conventional optical splitting method in the form of a pure compound You can get it.
Specific examples of the compounds of Formulas 1 and 2 of the present invention include compounds illustrated in Table 1 below.
Hereinafter, a method for preparing the compound will be described.
Any method for synthesizing the compound of Chemical Formula 1 may be used, but it can generally be synthesized by the method of Scheme 1 below.
Scheme 1
Protect both hydroxy groups with methoxymethyl (MOM) chloride in 1,3-dihydroxybenzene (resorcinol), which is readily available on reagents (Compound 12), and formylation in 2-position with DMF / BuLi. (Compound 13), and deprotection under acidic conditions results in only one MOM group falling (compound 14). Compound 15, obtained by reacting acylaminobenzylhalide or phenylurylbenzylhalide compound with compound 14 in the presence of a base, is deprotected under acidic conditions to obtain compound 1-4 as a desired racemic mixture.
The reaction of Scheme 1 may be carried out under conventional solvent and acid or base conditions. MOM protection reaction and deprotection reaction are carried out in a general manner, and the solvent in the reaction of acylaminobenzylhalide or phenylurylbenzylhalide-based compound with compound 14 is N, N-dimethylformamide ( N, N-dimethylformamide, DMF), tetrahydrofuran (THF), CH 2 Cl 2 and the like can be used, with DMF being preferred. Examples of the base may be an organic or inorganic base such as Et 3 N, NaH, NaOH, is Et 3 N, or NaH being preferred. The reaction temperature of acylaminobenzylhalide-based or phenylurylbenzylhalide-based compound with compound 14 can be from -20 to boiling temperature, but usually at room temperature.
Compound 1-4, the racemic mixture obtained above, may be treated according to Scheme 2 to obtain optically pure compound 1-4.
Scheme 2
Compound 1-4, a racemic mixture, is reacted with optically pure (R) -aminopropanol to form an imine compound. In the imine compound, diastereomers of (R, R) and (R, S) exist, and these two isomers can be separated by a general silica column. By treating the two isomers separated with an acid (H + ), the R and S forms of Compound 1-1 can be obtained in the pure form, respectively. Other compounds represented by the formula (1) can also be synthesized by the same method as the synthesis of compound 1-4.
Any method for synthesizing the compound of Chemical Formula 2 may be used, but can be generally synthesized by the method of Scheme 3 below.
Scheme 3
In addition, the present invention,
Method for optically splitting racemic amino alcohol or racemic amino acid using the compound of Formula 1 or Formula 2 and D-form amino acid to L-form amino acid or L-form using compound of Formula 1 or 2 The present invention relates to a method for optically converting an amino acid into a D-form amino acid.
The compounds of formula 1 or formula 2 of the present invention are useful for the optical splitting of racemic amino alcohols or racemic amino acids. Compounds of Formula 1 or Formula 2 of the present invention have an aldehyde group capable of reacting with various amine groups to form imine, and the principle of optical splitting is the same as the optical splitting principle of baanaphthol derivative (compound of compound a). It may be attributed to the difference in stability of the compound.
Examples of the amino alcohol that can be optically divided by the compound of Formula 1 or Formula 2 include, but are not limited to, b- or g-amino alcohols having a monovalent amine group. Representative examples of the b- or g-aminoalcohol having a monovalent amine group include compounds represented by the following general formula (3), which include optical isomers of R-form or S-form due to the carbon in the molecule.
(3)
NH 2 CHRaCRbRcOH
Ra in Chemical Formula 3 is a monovalent organic group or halogen except hydrogen, preferably substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic alkyl, or substituted Or unsubstituted aryl, Rb and Rc are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic alkyl, or substituted or unsubstituted aryl.
Examples of amino acids that may be optically divided by the compound of Formula 1 or Formula 2 include a- or b-amino acids, but are not limited thereto. Representative examples of the a- or b-amino acids include amino acids of the following formula (4) or (5).
[Formula 4]
NH 2 CHRdCOOH
[Chemical Formula 5]
H 2 NCHRdCHReCOOH
Rd in Formulas 4 and 5 is a monovalent organic group or halogen except hydrogen, preferably substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic alkyl, or substituted or unsubstituted Substituted aryl, and Re is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cyclic alkyl, or substituted or unsubstituted aryl.
As a process for optically splitting racemic amino alcohols or racemic amino acids using the compounds of the formula (1) or (2) of the present invention, the racemic amino alcohols or racemic amino acids may be optically synthesized using compounds having the same or similar functions as those of the present invention. It is possible to use any method known in the art as the partitioning process. That is, it can be used in a batch method using a solvent, a column method used to fill the column. If necessary, the primary optically divided amino alcohol or amino acid may be repeatedly optically divided to obtain an amino alcohol or amino acid having higher optical purity.
In addition, the compound of Formula 1 or 2 of the present invention may convert the D-form and L-form of the amino acids of Formulas 4 and 5. For example, in the case of the R-type optical isomer (( R ) -2) of the compound of formula 2 of the present invention, the L-form amino acid can be converted into a D-form amino acid, and the S-type optical isomer (( S ) -2) In the case of D-form amino acid can be converted to L-form amino acid. Such a phenomenon is a result of chiral recognition of chiral compounds.
As a process of optically converting amino acids using the compound of Formula 1 or 2 of the present invention, it is possible to use all methods known in the art as a process of optically converting amino acids using compounds having the same or similar functions as those of the present invention. It is possible.
Representative examples of the process of optically dividing racemic amino alcohol or racemic amino acid and the process of optically converting amino acid by using a compound similar to the compound of Formula 1 or Formula 2 in the present invention, Korean Patent No. 10-0661280, Korea Patent Application No. 10-2010-0030373, PCT Application No. PCT / KR2010 / 001707, Korea Patent Application No. 10-2010-0024590, etc. are mentioned. The entire contents of the patent documents are incorporated into the contents of the present invention by such citation.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, the following examples are intended to illustrate the present invention more specifically, but the scope of the present invention is not limited by the following examples. The following examples may be appropriately modified and changed by those skilled in the art within the scope of the present invention.
Example 1 Preparation of Compound 12
1, 3-dihydroxybenzene (resorcinol) was reacted with NaH in -20 ℃, DMF solvent for about 1 hour. Methoxymethyl (MOM) chloride was added to the reaction and reacted at -20 ° C for about 1 hour. The reaction product was extracted with water and ethyl acetate, and the organic layer was recovered, and then Compound 12 was separated by column chromatography.
1 H NMR (CDCl 3 ) d 7.20 (t, 1H), 6.70 (m, 3H), 5.16 (s, 4H), 3.47 (s, 6H)
Example 2. Preparation of Compound 13
Compound 12 obtained in Example 1 was dissolved in a dry THF solvent, tetramethylethylenediamine (TMEDA) was added, cooled to 0 ° C., and then reacted dropwise with BuLi / hexane for 2 hours. The temperature of the reaction was raised to room temperature and allowed to react for 30 minutes by adding dry DMF. After removing the solvent of the reaction product, the mixture was extracted with water and diethyl ether, and the organic layer was recovered, and then Compound 13 was separated by column chromatography.
1 H NMR (CDCl 3 ) d 10.54 (s, 1H) 7.40 (t, 1H), 6.85 (d, 2H), 5.27 (s, 4H), 3.50 (s, 6H)
Example 3. Preparation of Compound 14
Compound 13 obtained in Example 2 was reacted with HCl and water in an ethanol solvent for about 2 hours. The solvent in the reaction product was removed and compound 14 was separated by column chromatography.
1 H NMR (CDCl 3 ) d 12.24 (s, 1H), 10.42 (s, 1H), 7.40 (t, 1H), 6.59 ~ 6.50 (m, 2H), 5.27 (s, 2H), 3.49 (s, 3H )
Example 4. Preparation of Compound 15
Compound 14 obtained in Example 3 was reacted with NaH in 0 ° C. in a DMF solvent for about 2 hours. 1- (3- (1-bromoethyl) phenyl) -3-phenylurea was added to the reaction and reacted for about 12 hours. The reaction product was extracted with water and ethyl acetate, the organic layer was recovered, and compound 15 was separated by column chromatography.
1 H NMR (CDCl 3 ) d 10.38 (s, 1H), 7.46-7.05 (m, 12H), 6.41 (br, 1H), 6.22 (br, 1H), 5.47 (s, 2H), 5.15 (q, 1H ), 3.49 (s, 3H), 1.22 (d, 3H).
Example 5. Preparation of Compound 1-4
Compound 15 obtained in Example 4 was refluxed with HCl for 12 hours at 70 ℃, water and THF mixed solvent. After removing the solvent of the reaction product, the mixture was extracted with water and ethyl acetate and the organic layer was recovered, and then Compound 1-4 was separated by column chromatography.
1 H NMR (CDCl 3 ) d 11.92 (s, 1H), 10.45 (s, 1H), 7.7-7.0 (m, 12H), 6.47 (br, 1H), 6.20 (br, 1H), 5.30 (q, 1H ), 1.60 (d, 3 H)
Example 6. Optical Fractionation of Compounds 1-4
Compound 1-4 obtained in Example 5 was reacted with L-Leucinol of 1.1eq in a chloroform solvent for about 12 hours. The solvent of the reaction product was removed, and Compound 1-4 of R-form and S-form was separated by column chromatography. Each isomer was reacted for about one day in 2eq HCl and ethanol solvent. The solvent of the reaction product was removed, extracted with water and ethyl acetate solvent, and the organic layer was recovered.
Example 7. Preparation of Compound 16
Methyl 3-Hydroxy-2-naphthoate dissolved in Yb (OTf) 3 and nitromethane solvent 3- (1-hydroxyethyl) -1-phenylureyl- Reflux with benzene for 12 hours. The solvent in the reaction product was removed, extracted with water and ethyl acetate solvent, and the organic layer was recovered. Silica column chromatography separated compound 16 cleanly.
1 H NMR (CDCl 3 ) d 10.85 (br, 1H), 8.8-6.8 (m, 16H), 5.32 (q, 1H) 4.02 (s, 3H), 1.86 (d, 3H)
Example 8. Preparation of Compound 17
Compound 17 obtained in Example 7 was reacted with NaBH 4 in 65 ° C., THF solvent for about 6 hours. The reaction product was quenched with HCl and water, the THF solvent was removed, extracted with MC solvent, and column chromatography was performed to separate compound 17.
1 H NMR (CDCl 3 ) d 7.86 (d, 1H), 7.66 (d, 1H), 7.4-7.04 (m, 15H), 5.20 (q, 1H), 4.87 (d, 2H), 3.32 (br, 1H ), 1.80 (d, 3 H)
Example 9. Preparation of Compound 2-4
Compound 17 obtained in Example 8 was reacted with Pyridinium Dichlorochromate (PDC) in MC solvent for about 12 hours. The reaction product was filtered to remove PDC and then the solvent was removed. After extraction with HCl and ethyl acetate solvent, Compound 2-4 was isolated by column chromatography.
1 H NMR (CDCl 3 ) d 10.72 (s, 1H), 9.96 (s, 1H), 7.99 (s, 1H), 7.82 ~ 6.90 (m, 16H), 5.20 (q, 1H), 1.78 (d, 3H ).
Example 10: Chiral Selectivity Identification of Amino Alcohols of Compound 1-4
Compound 1-4 Forms imine with aminoalcohol. K R / K S becomes chiral selectivity when the constant of the imine-forming reaction with R -amino alcohol is K R , and the constant of the imine-forming reaction with S-amino alcohol is K S. Chiral selectivity is the same as that of the published article (Kim, KM; Park, H .; Kim, H .; Chin, J .; Nam, W. Org. Lett. 2005, 7 , 3525-3527.) Various amino alcohols were reacted with Compound (S) -1-4 to form imine, and confirmed through 1 H NMR analysis. The results are shown in Table 2 below.
Example 11: Confirmation of Amino Acid Chiral Conversion by Compound 1-4
Compound ( S ) -1-4 forms an imine with an amino acid in a solvent of DMSO, and the amino acid bound to the imine in the presence of ET 3 N, which is a base, changes L form to D form. When equilibrium is reached, the D / L ratio of amino acids bound to imines becomes chiral selectivity. The measurements are published in published papers (Park, H .; Kim, KM; Lee, A .; Ham, S .; Nam, W .; Chin, J. Am. Chem. Soc. 2007, 129, 1518-1519 It was carried out by the 1 H NMR method in the same manner as in). As a result, the optical conversion of the imine compound prepared by reacting Compound ( S ) -1-4 with amino acid, the D / L ratio of amino acid in the equilibrium state is shown in Table 3. If, the compound (S) The use of a compound (R) -1-4 -1-4 instead, so that it is that L / D ratio when the obtained in the same manner as in Table 3 in the experimental error apparent theoretically compound (R The experiment to confirm chiral selectivity using) -1-4 was not carried out.
Claims (12)
[Formula 1]
In the above formula
R 1 is substituted or substituted with alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH unsubstituted or substituted with straight or branched chain alkyl, halogen or OH unsubstituted or substituted with hydrogen, halogen or OH or Unsubstituted alkynyl or aryl unsubstituted or substituted with halogen or OH;
R2 is unsubstituted or substituted with linear or branched alkyl, unsubstituted or substituted with halogen or OH, alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH, substituted or unsubstituted. Alkynyl or aryl unsubstituted or substituted with halogen or OH;
R3 is -NHCXR4, -NHS (= O) a R4, -NHPO (OH) R4 or -NHC (NHR5) (NHR6) + , X is oxygen or sulfur, a is 1 or 2, and R4 is halogen Substituted or unsubstituted straight or branched chain alkyl, NR 7 R 8, or OR 9, and R 5 to R 9 are each independently hydrogen; Straight or branched chain alkyl substituted or unsubstituted with halogen; Or aryl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, nitro, alkyl, alkoxy and perfluoroalkyl groups, R5 and R6 may combine to form a ring, wherein R3 is -NHC (NH 2 ) when NH 2 + , the counterion is a halogen ion or R 10 CO 0 — , wherein R 10 is alkyl or aryl unsubstituted or substituted with alkyl;
The alkyl group has 1 to 10 carbon atoms, the alkenyl and alkynyl have 2 to 10 carbon atoms, and the aryl group has 5 to 12 carbon atoms.
R 1 is hydrogen,
R2 is a chiral salicyl aldehyde compound, characterized in that straight or branched chain alkyl substituted or unsubstituted with halogen or OH.
[Formula 2]
In the above formula
R 1 is substituted or substituted with alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH unsubstituted or substituted with straight or branched chain alkyl, halogen or OH unsubstituted or substituted with hydrogen, halogen or OH or Unsubstituted alkynyl or aryl unsubstituted or substituted with halogen or OH;
R2 is unsubstituted or substituted with linear or branched alkyl, unsubstituted or substituted with halogen or OH, alkenyl, halogen or OH unsubstituted or substituted with cyclic alkyl, halogen or OH, substituted or unsubstituted. Alkynyl or aryl unsubstituted or substituted with halogen or OH;
R3 is -NHCXR4, -NHS (= O) a R4, -NHPO (OH) R4 or -NHC (NHR5) (NHR6) + , X is oxygen or sulfur, a is 1 or 2, and R4 is halogen Substituted or unsubstituted straight or branched chain alkyl, NR 7 R 8, or OR 9, and R 5 to R 9 are each independently hydrogen; Straight or branched chain alkyl substituted or unsubstituted with halogen; Or aryl unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, nitro, alkyl, alkoxy and perfluoroalkyl groups, R5 and R6 may combine to form a ring, wherein R3 is -NHC (NH 2 ) when NH 2 + , the counterion is a halogen ion or R 10 CO 0 — , wherein R 10 is alkyl or aryl unsubstituted or substituted with alkyl;
The alkyl group has 1 to 10 carbon atoms, the alkenyl and alkynyl have 2 to 10 carbon atoms, and the aryl group has 5 to 12 carbon atoms.
R 1 is hydrogen,
R2 is a chiral naphthol aldehyde compound, characterized in that linear or branched alkyl unsubstituted or substituted with halogen or OH.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020090032956 | 2009-04-15 | ||
| KR20090032956 | 2009-04-15 |
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| KR20100114483A true KR20100114483A (en) | 2010-10-25 |
| KR101641386B1 KR101641386B1 (en) | 2016-07-20 |
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| WO2022035228A1 (en) * | 2020-08-13 | 2022-02-17 | 이화여자대학교 산학협력단 | Amino acid extraction process using t-butyl ketone binaphthol derivative or t-butyl ketone derivative, and continuous reactor for performing same |
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| KR20060088489A (en) * | 2005-02-01 | 2006-08-04 | 이화여자대학교 산학협력단 | Binaphthol derivatives and their use for optical resolution or optical transformation |
| KR100870227B1 (en) * | 2007-07-20 | 2008-11-24 | (주)그린포뮬라 | Alanine racemase chiral binaphthol analogue with powerful hydrogen bonding donor, and the methods for optical resolution and optical transformation |
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| KR20060088489A (en) * | 2005-02-01 | 2006-08-04 | 이화여자대학교 산학협력단 | Binaphthol derivatives and their use for optical resolution or optical transformation |
| KR100870227B1 (en) * | 2007-07-20 | 2008-11-24 | (주)그린포뮬라 | Alanine racemase chiral binaphthol analogue with powerful hydrogen bonding donor, and the methods for optical resolution and optical transformation |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2022035228A1 (en) * | 2020-08-13 | 2022-02-17 | 이화여자대학교 산학협력단 | Amino acid extraction process using t-butyl ketone binaphthol derivative or t-butyl ketone derivative, and continuous reactor for performing same |
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| WO2010120138A3 (en) | 2011-01-20 |
| KR101641386B1 (en) | 2016-07-20 |
| WO2010120138A2 (en) | 2010-10-21 |
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