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dc.description.abstract유기체에 존재하는 D-amino acid는 매우 중요한 역할을 하고 있다. D-alanine은 세포벽 형성에 관여하고,¹ D-serine과 D-aspartic acid는 뇌의 기능에 영향을 미치는 것으로 알려져 있다.^(2-4) 살아있는 유기체는 L-amino acid를 racemization하여 racemic 상태로 만든 후, 생존에 필요한 D-amino acid를 얻는다. Alanine racemase는 vitamine B6인 pyridoxal 5’-posphate (PLP)단위가 활성자리에 존재한다. Achiral PLP는 amino acid와 결합하여 imine을 형성하고, amino acid의 α-proton의 산성을 증가시켜^(6-8) alanine racemize를 유도하게 된다.^(9-14) 이 형태를 schiff base 형태라 하는데 imine결합에 resonance assisted hydrogen bond가 있는 것이다(figure 1). 이 Schiff base형태를 모방하여 amino acid와 상호 작용하며 키랄성을 가진 그룹이 있으면, 역으로 deracemize가 형성될 수 있다고 예상하여 이를 만족하는 화합물 (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-phenylurylbenzyl-3-carboxaldehyde (화합물 1)를 합성하였다.^(15) 화합물 1은 amino acid와 결합하여 입체 선택적인 imine form을 형성하였고, amino acid의 carboxylate group과 화합물 1의 uryl group이 강한 수소결합으로 상호작용하여, amino acid의 전체적인 위치를 고정시키고 binol의 키랄성 때문에 amino acid의 D-form과 L-form 사이에 에너지 안정성의 차이가 나타나게 되었다. 이로써, L-amino acid를 D-amino acid로 직접 전환시킬 수 있었다.^(16) 이는 컴퓨터 계산에 의해서 예측할 수 있었으며, 화합물 1과 L-alanine을 dmso-d6에서 결합시켜 imine을 형성한 후 triethylamine을 base로 썼을 때 시간에 따라 변화하는 형태를 1H NMR로 관찰하였다. triethyamine을 넣자마자 L-Alanine과 결합한 imine의 siganal은 사라지며, L-alanine은 D-alanine으로 시간이 변화함에 따라 변화하였다. 이후, 48시간 후에 용액은 평형에 도달하게 되고, 그 때에 D-alanine과 결합한 imine은 L-alanine에 비해 양이 절대적으로 변하며, D/L 의 비율은 약 7 : 1이다. L-형태에서 D-형태로의 직접적인 전환은 다른 amino acid에서도 확인할 수 있었다. 이 결과를 좀더 개선하기 위해 전자 끌개를 도입한 물질인 (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-(3-nitro-phenylurylbenzyl)-3-carboxaldehyde (화합물 2)와 (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-[3,5-bis(trifluoromethane)-phenylurylbenzyl]-3-carboxaldehyde (화합물 3)을 합성하였다. 화합물 2와 3을 L-alanine과 dmso-d6에서 결합시켜 imine을 형성한 후 화합물 1과 동일한 조건에서 관찰하였다. 화합물 2와 3은 화합물 1보다 더 좋은 결과를 보였으며 D/L 의 비율은 alanine의 경우 각각 7.8 : 1, 13.6 : 1이다.;Chiral amino acids are useful as intermediates for making a variety of biologically active molecules and also as ligands for stereoselective catalysts. Over the years there have been numerous publications on developing receptors for amino acids. In most of the studies, molecular recognition is based on noncovalent interactions such as hydrogen bonding, metal coordination, and hydrophobic interactions. Reversible imine formation has rarely been explored for the recognition studies. When compared to noncovalent interactions, imins bonds are slower to form, but have the advantage of being much stronger and structurallywell defined. These are features that are particularly desirable for developing stereoselective receptors. In nature, alanine racemase is being in pyridoxal 5'-posphate (PLP) of vitamine B6. Achiral PLP can attach with amino acid and make imine. It also improves acidity of amino acid's α-proton and induces alanine racemize. The PLP unit is achiral, so it produces only racemic mixture of 50 : 50% in L-and D-. One of the important deatures found in alanine racemise is resonance-assisted hydrogen bond (RAHB), which fixes the orientation of imine nitrogen and greatly contributes to increase the acidity of the α-proton. It may be imagined that amino acids would be deracemized by introducing chiral environment around PLP-like unit. In order to realize deracemization, combination of chirality, RAHB and another interaction are required. So we synthesized (S)-[1,1'-Binaphthalene]-2-Hydroxy-2'-phenylurylbenzyl-3-carboxaldehyde (compound 1). Compound 1 can make aldimine with RAHB, which fixes imime nitrogen toward phenol -OH. RAHB and the hydrogen bonds between carboxaylate and uryl -NH groups will fix the whole orientation of the amino acids. This provokes energy difference between the imine of D-alanine and L-alanine bound imines. Compounf 1 shows selectivity of amino acids, and it can invert L-amino acids to D- amino acids. A striling result is that L-form is changed to D-form as time passes, that is absolute configuration of alanine in the imine is inverted. In case of attach with Alanine, the D/L ratio is 7/1. To improve this result, we developed new receptor (S)-[1,1'-Binaphthalene]-2-Hydroxy-2'-(3-nitro-phenylurylbenzyl)-3-carboxaldehyde (compound 2) and (S)-[1,1'-Binaphthalene]-2-Hydroxy-2'-[3,5-bis(trifluoromethane)-phenylurylbenzyl]-3-carboxaldehyde (compound 3). We expected that they can make stronger hydrogen bond between carboxylate and uryl -NH because of their electronwithdrawing groups Compound 2 and 3 shows more good result than compound 1. The D/L retion is 7.8:1, 13.6:1 each. (Table 1, 2)-
dc.description.tableofcontents서론 = 1 Ⅱ. 실험 방법 = 6 Ⅱ-1. 시약 = 6 Ⅱ-1-1. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-phenylurylbenzyl-3-carboxaldehyde (1)의 준비 = 6 Ⅱ-1-1-1. (S)-[1,1’-Binaphthalene]-2,2’-dimethyl methyl ether (4)의 합성 = 6 Ⅱ-1-1-2. (S)-[1,1’-Binaphthalene] -2,2’-dimethyl methyl ether -3-carboxaldehyde (5)의 합성 = 7 Ⅱ-1-1-3. (S)-[1,1’-Binaphthalene] -2,2’-dihydroxy-3-carboxaldehyde (6)의 합성 = 8 Ⅱ-1-1-4. 3-Phenylurylbenzyl alcohol (7)의 합성 = 8 Ⅱ-1-1-5. 3-Phenylurylbenzyl bromide (8)의 합성 = 9 Ⅱ-1-1-6. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-phenylurylbenzyl-3-carboxaldehyde (1)의 합성 = 9 Ⅱ-1-2. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-(3-nitro-phenylurylbenzyl)-3-carboxaldehyde (2)의 준비 = 10 Ⅱ-1-2-1. (S)-[1,1’-Binaphthalene] -2-methyl methyl ether -3-carboxaldehyde (9)의 합성 = 10 Ⅱ-1-2-2. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-Nitrobenzyl-3-carboxaldehyde (10)의 합성 = 11 Ⅱ-1-2-3. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-Nitrobenzyl-3-methylalcohol (11)의 합성 = 12 Ⅱ-1-2-4. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-Aminobenzyl-3-methylalcohol (12) 의 합성 = 12 Ⅱ-1-2-5. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-(3-nitrophenylurylbenzyl)-3-methylalcohol(13) 의 합성 = 13 Ⅱ-1-2-6. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-(3-nitrophenylurylbenzyl)-3- carboxaldehyde (14) 의 합성 = 14 Ⅱ-1-2-7. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-(3-nitro-phenylurylbenzyl)-3-carboxaldehyde (2) 의 합성 = 15 Ⅱ-1-3. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-[(3,5-bis(trifluoromethane)-phenylurylbenzyl]-3- carboxaldehyde (3) = 15 Ⅱ-1-3-1. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-Aminobenzyl-3-methylalcohol (12) 의 합성 = 16 Ⅱ-1-3-2. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-[(3-5-bis(trifluoromethane)-phenylurylbenzyl]-3-methylalcohol (15) 의 합성 = 16 Ⅱ-1-3-3. (S)-[1,1’-Binaphthalene]-2-methyl methyl ether-2’-(3-5-bis(trifluoromethane)-3- carboxaldehyde (16) 의 합성 = 17 Ⅱ-1-3-4. (S)-[1,1’-Binaphthalene]-2-Hydroxy-2’-[(3-5-bis(trifluoromethane)-phenylurylbenzyl]-3- carboxaldehyde (3) 의 합성 = 17 Ⅱ-1-4.Amino acid의 준비 = 18 Ⅱ-1-5.Amino alcohol의 준비 = 19 Ⅱ-2. 기기 = 19 Ⅱ-3. 반응 조건 = 19 Ⅱ-3-1.L-amino acids 의 D-amino acids 로의 전환 반응 = 19 Ⅱ-3-2.Amino alcohol 과의 입체 선택성에 관한 반응 = 20 Ⅲ. 실험 결과 및 토의 = 21 Ⅲ-1.L-amino acids 의 D-amino acids 로의 전환 반응 = 21 Ⅲ-2.Amino alcohol 과의 입체 선택성에 관한 반응 = 29 Ⅳ 결론 = 36 Ⅴ 참고 문헌 = 38 영문초록 = 43 Appendix = 45 감사의 글 = 58-
dc.format.extent6007515 bytes-
dc.publisher이화여자대학교 대학원-
dc.titleDirect Inversion of L-Amino Acids to D-Amino Acids with Chiral BINOL Receptor and Effect of Electron Withdrawing Groups-
dc.typeMaster's Thesis-
dc.creator.othernameRyu, Ja Young-
dc.format.pagexiv, 59 p.-
dc.identifier.major대학원 나노과학부- 8-
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