Biocatalytic Preparation of Optically Active 4-( N , N - - - PowerPoint PPT Presentation

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Biocatalytic Preparation of Optically Active 4-( N , N - - - PowerPoint PPT Presentation

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Departamento de Qumica Orgnica e Inorgnica Instituto Universitario de Biotecnologa de Asturias Universidad de Oviedo Biocatalytic Preparation of Optically Active 4-( N , N - Dimethylamino)pyridine Analogues Using Lipases and

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SLIDE 1

Departamento de Química Orgánica e Inorgánica Instituto Universitario de Biotecnología de Asturias Universidad de Oviedo

Biocatalytic Preparation of Optically Active 4-(N,N- Dimethylamino)pyridine Analogues Using Lipases and Oxidoreductases

  • Dr. Vicente Gotor Fernández

Graz, 18th April 2006

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SLIDE 2

♦ Enzymatic aminolysis and ammonolysis ♦ Natural Products ♦ Applied biocatalysis ♦ Microorganisms

Bioorganic Research Group University of Oviedo

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SLIDE 3

♦ Enzymatic aminolysis and ammonolysis ♦ Natural Products ♦ Applied biocatalysis ♦ Microorganisms

Bioorganic Research Group University of Oviedo

♦ Synthesis of nucleophilic catalysts ♦ Preparation of pharmaceuticals ♦ Development of non-conventional processes

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SLIDE 4

♦ Enzymatic aminolysis and ammonolysis ♦ Natural Products ♦ Applied biocatalysis ♦ Microorganisms

Bioorganic Research Group University of Oviedo

♦ Synthesis of nucleophilic catalysts (Chiral DMAP derivatives) ♦ Preparation of pharmaceuticals ♦ Development of non-conventional processes

N NMe2

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SLIDE 5

♦ Introduction:

  • Importance of DMAP
  • Chiral DMAP derivatives

♦ Objectives ♦ Results and Discussion:

  • Synthesis of 2- and 3-substituted DMAP derivatives using lipases
  • Synthesis of 2- and 3-substituted DMAP derivatives using oxidoreductases
  • Applicactions in asymmetric catalysis

♦ Conclusions and future aims

Biocatalytic Preparation of Optically Active 4-(N,N-Dimethylamino)pyridine Analogues Using Lipases and Oxidoreductases

N NMe2

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SLIDE 6

Introduction Chemical reactions: catalyst of different processes like acylation, Baylis-Hillman, carbonylation... Uses in industrial sector: pharmaceuticals, agrochemicals... Application areas: alcohols, amino acids, stereoids...

N NMe2

Some representative examples in “difficult” processes:

OH OAc Ph OH OH Ph OTBDMS OH Ph OTBDMS OTBDMS O OMe O ROH, DMAP O OR O MeOH Ac2O, NEt3 DMAP, CH2Cl2 TBDMSCl, CH2Cl2 DMAP + Cyclohexane +

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SLIDE 7

Introduction Application in catalytic processes

N NMe2 N NMe2

Introduction of some type of chirality Chiral DMAP derivatives for the development

  • f asymmetric catalytic processes

BIOCATALYSIS Transesterifications: lipases Bioreductions: oxidoreductases

N NMe2 R OH N Me2N OH

* *

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SLIDE 8

Objectives ♦ Preparation of enantiomerically pure DMAP derivatives:

  • Chemical synthesis and kinetic resolution of 2- and 3-substituted DMAP

analogues using lipases

  • Chemoenzymatic synthesis of 2- and 3-substituted DMAP analogues using
  • xidoreductases

♦ Modification of DMAP derivatives and application in asymmetric catalysis

N Cl Acyl donor Lipase Solvent T, 250 rpm N Cl N Cl + OH OAc OH N Cl Oxidoreductase Solvent T, 250 rpm N Cl O OH

*

N Cl OH

*

N Me2N OR

*

Alkoxycarbonylation reactions Rearrangements processes Use as chiral ligands

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SLIDE 9

Results and Discussion

Chemical synthesis of racemic DMAP derivatives Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases Kinetic resolution of racemic 2-(1-hydroxyalkyl)-4-(substituted)pyridines

N X Acyl donor Lipase Solvent T, 250 rpm N X N X + R R R OH OAc OH R=Me, Et, Pr, Bu, Ph N Cl O + N Cl R OH N NMe2 OH R

_

R=Me, Et, Pr, Bu, Ph

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SLIDE 10

Results and Discussion

Chemical synthesis of racemic 2-(1-hydroxyalkyl)-4-(substituted)pyridines

Table 1. Transformation of 4-chloro- 2-cyanopyridine in alcohols 3a-e

73 I Me 3a 73 Br Ph 3e 74 Cl Bu 3d 76 Br Pr 3c 76 Br Et 3b Isolated Yield (%) X R Reaction product

Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases Next: enzymatic kinetic resolution, optimisation with compound 3a and 4a (R=Me)

N Cl O + N Cl CN N Cl R OH N NMe2 OH R Me2NH 1 2 3a-e 4a-e Me3SiCN Me2NOCl CH2Cl2, rt (77%) 1) RMgX, Et2O NH4Cl, HCl 0 ºC to rt 2) NaBH4, MeOH 0 ºC to rt 100 ºC quantitative

_

R=Me, Et, Pr, Bu, Ph

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SLIDE 11

NMe2 Cl Cl Cl Cl X >200 34 >99 52 38 PSL-C 5 >200 50 >99 (85)d >99 (88)d 14.5 PSL-C 4 >200 41 >99 70 70 CAL-B (Chirazyme) 3 >200 42 >99 82 48 CAL-B (Novozyme) 2

  • 38

CAL-A 1 Ec c (%)b eeP (%)a eeS (%)a t (h) Enzyme Entry

Table 2. Enzymatic acylation of 3a using 3 equivalents of 5 like acyl donor and THF as solvent

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)], d Isolated yields in brackets

Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases

Results and Discussion

N Me OH X N Me OAc X N Me OH X O O (±)-3a, X=Cl (±)-4a, X=NMe2 + + (-)-3a, X=Cl (-)-4a, X=NMe2 5 Enzyme THF 30 ºC, 250 rpm (+)-6a, X=Cl (+)-7a, X=NMe2

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SLIDE 12

NMe2 Cl Cl Cl Cl X >200 34 >99 52 38 PSL-C 5 >200 50 >99 (85)d >99 (88)d 14.5 PSL-C 4 >200 41 >99 70 70 CAL-B (Chirazyme) 3 >200 42 >99 82 48 CAL-B (Novozyme) 2

  • 38

CAL-A 1 Ec c (%)b eeP (%)a eeS (%)a t (h) Enzyme Entry

Table 2. Enzymatic acylation of 3a using 3 equivalents of 5 like acyl donor and THF as solvent

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)], d Isolated yields in brackets

Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases

Results and Discussion

N Me OH X N Me OAc X N Me OH X O O (±)-3a, X=Cl (±)-4a, X=NMe2 + + (-)-3a, X=Cl (-)-4a, X=NMe2 5 Enzyme THF 30 ºC, 250 rpm (+)-6a, X=Cl (+)-7a, X=NMe2

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SLIDE 13

Enzymatic resolution of racemic 4-chloro-2-(1-hydroxyalkyl)pyridine derivatives

>200 50 >99 (88)d >99 (89)d 60 Bu 6

  • 96

Ph 7 >200 33 >99 49 14.5 Bu 5 >200 50 99 (97)d >99 (89)d 38 Pr 4 >200 47 >99 88 14.5 Pr 3 >200 50 >99 (77)d >99 (88)d 14.5 Et 2 >200 50 >99 (85)d >99 (88)d 14.5 Me 1 Ec c (%)b eeP (%)a eeS (%)a t (h) R Entry

Table 3. Enzymatic acylation of 3a-e using 3 equivalents of 5 like acyl donor, THF as solvent and PSL-C as biocatalyst

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)], d Isolated yields in brackets

Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases

Results and Discussion

N R OH Cl N R OAc Cl N R OH Cl O O (±)-3a-e + (+)-6a-e + (-)-3a-e 5 PSL-C THF 30 ºC, 250 rpm

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SLIDE 14

Enzymatic resolution of racemic 4-chloro-2-(1-hydroxyalkyl)pyridine derivatives

>200 50 >99 (88)d >99 (89)d 60 Bu 6

  • 96

Ph 7 >200 33 >99 49 14.5 Bu 5 >200 50 99 (97)d >99 (89)d 38 Pr 4 >200 47 >99 88 14.5 Pr 3 >200 50 >99 (77)d >99 (88)d 14.5 Et 2 >200 50 >99 (85)d >99 (88)d 14.5 Me 1 Ec c (%)b eeP (%)a eeS (%)a t (h) R Entry

Table 3. Enzymatic acylation of 3a-e using 3 equivalents of 5 like acyl donor, THF as solvent and PSL-C as biocatalyst

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)], d Isolated yields in brackets

Chemical synthesis and kinetic resolution of 2-substituted DMAP analogues using lipases

Results and Discussion

N R OH Cl N R OAc Cl N R OH Cl O O (±)-3a-e + (+)-6a-e + (-)-3a-e 5 PSL-C THF 30 ºC, 250 rpm

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SLIDE 15

Results and Discussion

Chemical synthesis of racemic DMAP derivatives Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases Kinetic resolution of racemic 3-(1-hydroxyalkyl)-4-(substituted)pyridines

N Cl Acyl donor Lipase Solvent T, 250 rpm N Cl N Cl + R=Me, Et, Pr, Bu, Ph R OH R R OAc OH N Cl R OH N N Cl + Cl

_

N Me2N R OH

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SLIDE 16

Table 4. Synthesis of 4-chloro-3-(1-hydroxyalkyl)pyridines and 4-chloro-3-(1-hydroxybenzyl)pyridine

82 1 Ph 5 65 2 Bu 4 63 2 Pr 3 61 2 Et 2 68 2 Me 1 Isolated Yield (%) LDA (eq) R Entry

Chemical synthesis of 4-chloro-3-(1-hydroxyalkyl)pyridine derivatives Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases

Results and Discussion

N Cl N Cl R OH N N Cl + Cl NaOH 1) LDA, Et2O 2) R-CHO 7 8 (±)-9a-e

_

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SLIDE 17

>200 49 >99 96 91 CAL-B 60 10 THF 6

  • 10

3 3 3 3 5 (eq) 7 5 4 3 2 1 Entry VA THF THF THF THF THF Solvent 60 60 45 45 30 30 T (ºC) >200 50 >99 >99 14 CAL-B >200 29 >99 40 62 PSL-C >200 37 >99 58 38 CAL-B >200 23 >99 31 62 PSL-C >200 31 >99 45 38 CAL-B >200 17 >99 20 62 PSL-C Ec c (%)b eeP (%)a eeS (%)a t (h) Enzyme

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)]

Table 5. Enzymatic kinetic resolution of 4-chloro-3-(1-hydroxyethyl)pyridine through transesterification

Results and Discussion

Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases

N Cl OH N Cl OAc N Cl OH O O (±)-9a + Enzyme (+)-10a + (-)-9a (5, VA) Solvent T, 250 rpm

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SLIDE 18

>200 49 >99 96 91 CAL-B 60 10 THF 6

  • 10

3 3 3 3 5 (eq) 7 5 4 3 2 1 Entry VA THF THF THF THF THF Solvent 60 60 45 45 30 30 T (ºC) >200 50 >99 >99 14 CAL-B >200 29 >99 40 62 PSL-C >200 37 >99 58 38 CAL-B >200 23 >99 31 62 PSL-C >200 31 >99 45 38 CAL-B >200 17 >99 20 62 PSL-C Ec c (%)b eeP (%)a eeS (%)a t (h) Enzyme

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)]

Table 5. Enzymatic kinetic resolution of 4-chloro-3-(1-hydroxyethyl)pyridine through transesterification

Results and Discussion

Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases

N Cl OH N Cl OAc N Cl OH O O (±)-9a + Enzyme (+)-10a + (-)-9a (5, VA) Solvent T, 250 rpm

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SLIDE 19

Tabla 6. Enzymatic kinetic resolution of 9a-e through transesterification

2 15 34 6 88 CAL-A Et 10 25 39 87 55 48 CAL-A Ph 11 2 12 37 5 24 CAL-A Et 9 8 13 76 12 24 CAL-A Pr 7 6 25 65 21 88 CAL-A Pr 8 >200 14 >99 16 136 CAL-A Bu 6

  • 231

CAL-B Ph 5

  • 231

CAL-B Bu 4

  • 62

CAL-B Pr 3 195 49 97 (89)d 93 (88)d 62 CAL-B Et 2 >200 50 >99 (83)d >99 (86)d 14 CAL-B Me 1 Ec c (%)b eep (%)a ees (%)a t (h) Enzyme R Entry

Results and Discussion

Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)] , d

Isolated yields in brackets N Cl R OH O O N Cl R OH N R OAc Cl (±)-9a-e + Enzyme (+)-10a-e + (-)-9a-e 5 60 ºC

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SLIDE 20

Table 6. Enzymatic kinetic resolution of 9a-e through transesterification

2 15 34 6 88 CAL-A Et 10 25 39 87 55 48 CAL-A Ph 11 2 12 37 5 24 CAL-A Et 9 8 13 76 12 24 CAL-A Pr 7 6 25 65 21 88 CAL-A Pr 8 >200 14 >99 16 136 CAL-A Bu 6

  • 231

CAL-B Ph 5

  • 231

CAL-B Bu 4

  • 62

CAL-B Pr 3 195 49 97 (89)d 93 (88)d 62 CAL-B Et 2 >200 50 >99 (83)d >99 (86)d 14 CAL-B Me 1 Ec c (%)b eep (%)a ees (%)a t (h) Enzyme R Entry

Results and Discussion

Chemical synthesis and kinetic resolution of 3-substituted DMAP analogues using lipases

a Calculated by HPLC, b c = ees/ (ees + eep), c E = ln [(1 - c) × (1 - eep)]/ ln [(1 - c) × (1 + eep)] , d

Isolated yields in brackets N Cl R OH O O N Cl R OH N R OAc Cl (±)-9a-e + Enzyme (+)-10a-e + (-)-9a-e 5 60 ºC

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SLIDE 21

Results and Discussion

Chemical synthesis of ketone DMAP derivatives Chemoenzymatic synthesis of 2- and 3-substituted DMAP analogues using oxidoreductases Bioreduction of ketones using oxidoreductases

N Cl Oxidoreductase Solvent T, 250 rpm N Cl O OH

*

N Cl R O N Cl R O

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SLIDE 22

Results and Discussion

Chemical synthesis of racemic DMAP ketone derivatives Chemoenzymatic synthesis of 2-substituted DMAP analogues using oxidoreductases

N Cl O + N Cl CN N Cl R OH N NMe2 OH R Me2NH 1 2 3a-e 4a-e Me3SiCN Me2NOCl CH2Cl2, rt (77%) 1) RMgX, Et2O NH4Cl, HCl 0 ºC to rt 2) NaBH4, MeOH 0 ºC to rt 100 ºC quantitative

_

R=Me, Et, Pr, Bu, Ph ISOLATION OF THE CORRESPONDING KETONES (PRECAUTIONS BECAUSE OF THEIR VOLATILITY) N Cl R O 11a-e

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SLIDE 23

Results and Discussion

Chemoenzymatic synthesis of 2-substituted DMAP analogues using oxidoreductases

Me Ph Bu Pr Et Me R2 79 (73) 81 60 Cl 3 88 (84) 97 60 Cl 5 84 (72) 80 60 Cl 4 58 (40) 98 168 NMe2 6 90 (71) 91 60 Cl 2 100 (72) 98 60 Cl 1 c (%)b eeP (%)a t (h) R1 Entry

Table 7. Bioreduction with Baker’s Yeast of ketones 11a-f

a Calculated by HPLC, b Conversion calculated by 1H NMR of the

reaction crude and isolated yields in brackets

Bioreduction of ketone DMAP derivatives using Baker’s Yeast

H2O N R1 R2 OH N R1 R2 O Baker's Yeast (S)-3a-d (R)-3e (S)-4a * 11a: R1= Cl, R2= Me 11b: R1= Cl, R2= Et 11c: R1= Cl, R2= Pr 11d: R1= Cl, R2= Bu 11e: R1= Cl, R2= Ph 11f: R1= NMe2, R2= Me

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SLIDE 24

Results and Discussion

Chemoenzymatic synthesis of 2-substituted DMAP analogues using oxidoreductases

Me Ph Bu Pr Et Me R2 79 (73) 81 60 Cl 3 88 (84) 97 60 Cl 5 84 (72) 80 60 Cl 4 58 (40) 98 168 NMe2 6 90 (71) 91 60 Cl 2 100 (72) 98 60 Cl 1 c (%)b eeP (%)a t (h) R1 Entry

Table 7. Bioreduction with Baker’s Yeast of ketones 11a-f

a Calculated by HPLC, b Conversion calculated by 1H NMR of the

reaction crude and isolated yields in brackets

Bioreduction of ketone DMAP derivatives using Baker’s Yeast

H2O N R1 R2 OH N R1 R2 O Baker's Yeast (S)-3a-d (R)-3e (S)-4a * 11a: R1= Cl, R2= Me 11b: R1= Cl, R2= Et 11c: R1= Cl, R2= Pr 11d: R1= Cl, R2= Bu 11e: R1= Cl, R2= Ph 11f: R1= NMe2, R2= Me

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SLIDE 25
  • 168
  • Lacto. brevis

Ph 10

  • 168
  • Thermo. species

Ph 9

  • 168
  • Lacto. brevis

Bu 8

  • 168
  • Thermo. species

Bu 7

  • 168
  • Lacto. brevis

Pr 6

  • 168
  • Thermo. species

Pr 5 R 100 (91) >99 47

  • Lacto. brevis

Et 4 S 100 (94) >99 47

  • Thermo. species

Et 3 R 100 (87) >99 38

  • Lacto. brevis

Me 2 S 100 (89) >99 38

  • Thermo. species

Me 1 Config. c (%)b eep (%)a t (h) ADH R Entry

Table 8. Bioreduction of ketones 11a-e with alcohol dehydrogenases

Results and Discussion

Chemoenzymatic synthesis of 2-substituted DMAP analogues using oxidoreductases Bioreduction of ketone DMAP derivatives using other ADH’s

a Calculated by HPLC, b Conversion calculated by 1H NMR of the reaction crude and isolated yields in brackets

N Cl R O TRIS pH= 7/IPA N Cl R OH NADP * 11a-e 3a-e ADH's

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SLIDE 26

Chemoenzymatic synthesis of 3-substituted DMAP analogues using oxidoreductases

Results and Discussion

Oxidation reactions were carried out in different systems obtaining the best results with CrO3 in acetone These ketone derivatives resulted very unstables so we decided to carried out inmediately the sequence chemical oxidation-enzymatic reduction

Acetone N Cl R O N Cl R OH CrO3 quantitative 12a-e (±)-9a-e

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SLIDE 27

Chemoenzymatic synthesis of 3-substituted DMAP analogues using oxidoreductases

Results and Discussion

100 (75) >99 43 30 Ph 7c

  • 24

45 Ph 6 82 >99 115 30 Ph 5 100 (74) >99 14 30 Bu 4 100 (73) 98 14 30 Pr 3 100 (76) >99 14 30 Et 2 100 (79) >99 14 30 Me 1 c (%)b eep (%)a t (h) T (ºC) R Entry

a Calculated HPLC, b Calculated by 1H NMR and isolated yield in

brackets, c Using double amount of enzyme

Table 9. Chemoenzymatic synthesis of optically active 10a-e through chemical oxidation and bioreduction sequence with Baker’s Yeast

N Cl R OH CrO3 Acetone N Cl R O N Cl R OH (±)-9a-e 12a-e (S)-9a-e Baker's yeast glucose solution

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SLIDE 28

Chemoenzymatic synthesis of 3-substituted DMAP analogues using oxidoreductases

Results and Discussion

Table 10. Chemoenzymatic synthesis of optically active 9a-e through chemical oxidation and bioreduction sequence with ADH’s

  • 92
  • Lacto. brevis

Ph 10

  • 92
  • Thermo. species

Ph 9

  • 62
  • Lacto. brevis

Bu 8

  • 62
  • Thermo. species

Bu 7

  • 90
  • Lacto. brevis

Pr 6

  • 90
  • Thermo. species

Pr 5

  • traces
  • n. m.

88

  • Lacto. brevis

Et 4 S 43 93 88

  • Thermo. species

Et 3 R 100 (91) 98 69

  • Lacto. brevis

Me 2 S 100 (89) >99 45

  • Thermo. species

Me 1 Config. c (%)b eep (%)a t (h) ADH R Entry

a Calculated by HPLC, b Calculated by 1H NMR and isolated yield in brackets

N Cl R OH CrO

3

Acetone N Cl R O N Cl R OH (±)-9a-e 12a-e 9a-e TRIS pH= 7/IPA NADP ADH's

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SLIDE 29

Synthesis of 2- and 3-substituted DMAP analogues

Results and Discussion

N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH N Me2N OH

  • E. Busto, V. Gotor-Fernández, V. Gotor, Tetrahedron:

Asymmetry 2005, 16, 3427-3435

  • E. Busto, V. Gotor-Fernández, V. Gotor, accepted in

Tetrahedron: Asymmetry

  • E. Busto, V. Gotor-Fernández, V. Gotor, manuscript in

preparation

Me2NH N Cl 100 ºC N NMe2 3a-e 4a-e OH

* *

OH Me2NH N Cl R OH 100 ºC N Me2N R OH 9a-e 13a-e

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SLIDE 30

Applicactions in asymmetric catalysis

Results and Discussion

H O N X R OH Toluene + * OH ZnEt2

♦ Non-enzymatic kinetic resolution of 1-phenylethanol ♦ Enantioselective rearrangement of O-acylated azlactones ♦ Enantioselective addition of diethyl zinc to benzaldehyde

N NMe2 R1 OR2 Cl3C O Cl O CH2Cl2 O O N NMe2 R1 OR2 Cl3C + O O CCl3 O OH ZnCl2 Et3N * * *

+

OH * O N MeO Me O O Ph O Ph O N MeO O O O N Me2N R

1

OR

2

t-amyl alcohol, T + Me

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SLIDE 31

Conclusions

♦ Enantiomerically pure 2- and 3-substituted DMAP have been obtained through chemoenzymatic methods using lipases and oxidoreductases ♦ 4-Chloro compounds have shown better enantiopreferences than the corresponding 4-(N,N-dimethylamino) derivatives ♦ Pseudomonas cepacia lipase has been very efficient in the preparation

  • f optically active 2-substituted DMAP

♦ Baker’s yeast have enantioselectively reduced 2- and 3-substituted ketone analogues ♦ DMAP derivatives have shown interesting properties in asymmetric catalytic processes, and different processes are currently under investigation ♦ Other chiral DMAP catalysts like amino functionalized compounds are being synthesized to later explore their catalytic properties

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SLIDE 32

Acknowledgements

♦ Professor Dr. Vicente Gotor ♦ Ph. D. Student Eduardo Busto ♦ Members of the Bioorganic research group of the University of Oviedo ♦ Ministerio de Educación y Ciencia (Juan de la Cierva Program)

Preparation of Chiral 4-(N,N-Dimethylamino)pyridine Derivatives by Bioreduction Processes. E. Busto, V. Gotor-Fernández and V. Gotor (P06) Biocatalytic Preparation of Optically Active 4-(N,N- Dimethylamino)pyridine Analogues Using Lipases in Organic Solvents. E. Busto, V. Gotor-Fernández and

  • V. Gotor (P18)

Preparation of enantiopure N-substituted aziridine-2- carboxamides by bacterial hydrolysis of their corresponding racemic nitriles or amides. R. Morán- Ramallal, R. Liz and V. Gotor (P41) www.uniovi/bioorganica.es

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SLIDE 33

Departamento de Química Orgánica e Inorgánica Instituto Universitario de Biotecnología de Asturias Universidad de Oviedo

Biocatalytic Preparation of Optically Active 4-(N,N- Dimethylamino)pyridine Analogues Using Lipases and Oxidoreductases

  • Dr. Vicente Gotor Fernández

Graz, 18th April 2006