Resolução cinética enzimática do análogo da ketamina (rac-8)

Em um erlenmeyer de 5mL, dissolveu-se 1 eq. do (rac-8) em 20% de THF ou e 80% de tampão fosfato (PO42-), 0,1 M, pH 7, e por último, foi adicionado 2 eq. de lipase. A

reação foi processada em temperatura de 35°C e tempo reacional de 24h, com rotação 250 rpm. Em seguida, realizou-se uma extração do produto com AcOEt (3 x 5mL), sendo a fase orgânica tratada com Na2SO4 anidro. O AcOEt foi evaporado a pressão reduzida.

Posteriormente, o produto foi purificado em uma coluna cromatográfica, utilizando gel de sílica como fase estacionária, e hexano/acetato de etila (70/30) como fase móvel.

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ANEXO A – DADOS EXPERIMENTAIS DO RAC-2A-FENILETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,49 (d, 3Ha, J= 6,5 Hz); δ: 4,88 (q, 1Hb, J= 6,5 Hz); δ: 7,25-} 7,40 (m, 5Hdefgh). RMN13_{C (75 MHz, CDCl3) δ: 25,11 (Ca); δ: 70,15 (Cb); δ:125,08 (Cd, Ch); δ:127,20 (Cf);} δ:128,17 (Ce, Cg); δ:145,52 (Cc). Espectro de RMN 1_{H (300 MHz, CDCl} 3)

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO B – DADOS EXPERIMENTAIS DO RAC-2B-(3-METILFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,49 (d, 3Ha, J= 6,5Hz); δ: 2,37 (s, 3Hi); δ: 4,86 (q, 1Hb, J=} 6,4 Hz); δ: 7,04-7,30 (m, 4Hdefh). RMN13_{C (75 MHz, CDCl3) δ: 21,55 (Ci); δ:25,20 (Ca); δ:70,53 (Cb); δ:122,55 (Cd); δ:126,22} (Cf); δ:128,32 (Ce); δ:128,53 (Ch); δ:138,26 (Cg); δ:145,93 (Cc). Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO C – DADOS EXPERIMENTAIS DO RAC-2C-(3-FLUOROFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,48 (d, 3Ha, J= 6,5 Hz); δ: 4,89 (q, 1Hb, J= 6,4 Hz); δ: 6,95} (td, J = 8,4, 1,7 Hz 1Hh); δ: 7,04-7,21 (m, 2Hdf); δ: 7,24-735 (m, 1He). RMN13_{C (75 MHz, CDCl3) δ: 25,05 (Ca); δ: 69,65 (Cb); δ: 112,15 (Ch); δ: 114,05 (Cf); δ:} 120,77 (Cd); δ: 129,82 (Ce); δ: 148,37 (Cc); δ: 164,26 (Cg). Espectro de RMN 1_{H (300 MHz, CDCl} 3)

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO D – DADOS EXPERIMENTAIS DO RAC-2D-(3-METÓXIFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,48 (d, 3Ha, J= 6,50 Hz); δ: 3,82 (s, 3Hi); δ: 4,87 (q, 1Hb, J=} 6,50 Hz); δ: 6,80-6,83 (m, 1Hf); δ: 6,94-6,95 (m, 2Hhd) δ: 7,27 (t, 1He, J= 8Hz). RMN13_{C (75 MHz, CDCl3) δ: 25,32 (Ca); δ: 55,42 (Ci); δ: 70,52 (Cb); δ: 111,13 (Ch); δ:} 113,09 (Cf); δ: 117,88 (Cd); δ: 129,72 (Ce); δ: 147,80 (Cc); δ: 160,00 (Cg). Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO E – DADOS EXPERIMENTAIS DO RAC-2E-(4-METILFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,49 (d, 3Ha, J= 6,4 Hz); δ: 2,36 (s, 3Hi); δ: 4,86 (q, 1Hb, J=} 6,4 Hz); δ: 7,17 (d, 2Heg, J= 7,8 Hz); δ: 7,27 (d, 2Hdh, J= 7,8 Hz). RMN13_{C (300 MHz, CDCl3) δ: 21,18 (Ci); δ: 25,16(Ca); δ: 70,32(Cb); δ: 125,57(Cd,Ch); δ:} 129,26(Ce, Cg); δ: 137,22(Cf); δ: 143,01(Cc) Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO F – DADOS EXPERIMENTAIS DO RAC-2F(3-BROMOFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,46 (d, 3Ha, J= 6,5 Hz); δ: 4,84 (q, 1Hb, J= 6,4 Hz); δ: 7,13-} 7,29 (m, 2Hdf); δ: 7,39 (d, 1He, J= 7,7 Hz); δ: 7,52 (s, 1Hh). RMN13_{C (75 MHz, CDCl3) δ: 25,35 (Ca); δ: 69,85 (Cb); δ: 122,73 (Cg); δ: 124,14 (Cd); δ:} 128,70 (Ce); δ: 130,21 (Cf); δ: 130,59 (Ch); δ: 148,27 (Cc). Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO G – DADOS EXPERIMENTAIS DO RAC-2G-(2-METILFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,46 (d, 3Ha, J= 6,4 Hz); δ: 2,35 (s, 3Hi); δ: 5,11 (q, 1Hb, J=} 6,4 Hz); δ: 7,07-7,30 (m, 3Hdfg); δ: 7,50 (d, 1He, J= 7,3 Hz). RMN13_{C (75 MHz, CDCl3) δ: 18,96 (Ci); δ: 23,98 (Ca); δ: 66,86 (Cb); δ: 124,59 (Cd); δ:} 126,44 (Ce); δ: 127,22 (Cg); δ: 130,44 (Cf); δ: 134,30 (Ch); δ: 143,94 (Cc). Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl} 3)

Cromatograma obtido por CG-FID

ANEXO H – DADOS EXPERIMENTAIS DO RAC-2H-(4-BROMOFENIL)ETANOL RMN1_{H (300 MHz, CDCl3) δ: 1,47 (d, 3Ha, J= 6,5 Hz); δ: 4,86 (q, 1Hb, J= 6,4 Hz); δ: 7,25} (d, 2Heg, J= 8,4Hz); δ: 7,47 (d, 2Hdh, J= 8,4Hz). RMN13_{C (300 MHz, CDCl3) δ: 25,35 (Ca); δ: 69,91(Cb); δ: 121,30(Cf); δ: 127,29(Cd, Ch); δ:} 131,70(Ce, Cg); δ: 144,93(Cc). Espectro de RMN 1_{H (300 MHz, CDCl3)}

Espectro de RMN 13_{C-BB (75 MHz, CDCl3)}

Cromatograma obtido por CG-FID

ANEXO I – DADOS EXPERIMENTAIS DO RAC-2I-(2-METÓXIFENIL)ETANOL