Download α-alkyl-β-keto esters – bioreduction 315 – dynamic kinetic resolution

j375
Index
a
a-alkyl-b-keto esters
– bioreduction 315
– dynamic kinetic resolution 315, 319
a-aminobutyric acid 199
acetoacetyl-CoA reductase 154
acetophenone 154, 164, 247, 251
2-acetylbenzonitriles 106
Acinetobacter sp., cyclohexanol dehydrogenase
(ACDH) 154
active pharmaceutical ingredient (API)
syntheses 71, 74, 75, 329, 363
acutiphycins 96
a-acylaminoacrylic acid 49
(S)-acyloins 62
Aeropyrum camini 215
AG7088 (rupintrivir) 358
b-3 agonist precursors, synthesis using
enzymatic reductions 92
alanine dehydrogenase (AlaDH) 226, 301, 302
Alcaligenes eutropha 214
Alcaligenes faecalis 288
– enantioselective biooxidation reaction 288
alcohol dehydrogenase (ADH) 2, 4, 6, 7, 31, 86,
99, 210, 240, 242, 265, 288, 308, 329
– anti-Prelog 290
– cascade, for in situ regeneration of
NADH 220
– catalyzed reduction of
phenylacetaldoxime 42
– Clostridium acetobutylicum (CaADH) 320
– enantioselectivity 257
– Lactobacillus brevis (LB-ADH) 90, 248, 290,
319, 339
– Lactobacillus kefir ADH (ADH-LK) 294
– oxidation reaction 288
– Prelog 290
– Ralstonia sp. (RasADH) 321
– reduction reaction 288
– Rhodococcus ruber ADH (ADH-A) 290
– Sphingobium yanoikuyae (SyADH) 321
– stability 248
– stereochemistry 150
– strategies to synthesis biologically active
compounds involving 99
– T. ethanolicus (TESADH) 322
– Thermoanaerobacter ADH (ADH-T) 294
alcohols as stoichiometric reductants
218–220, 223
aldehyde dehydrogenase (AldDH) 97
– cascade, for in situ regeneration of
NADH 220
aldehyde oxidoreductases 43
aldimine 189
aldo-keto reductase (AKR) 172
aldol-catalyzed reaction 104
alkene reductases 245
a-alkoxycyclohexenones 62
a-alkyl-b-arylketones 61
sec-alkyl 2-methyl-3-oxobutyrate
– reduction of 313
allylic alcohols 103, 227
– biocatalytic redox isomerization 227
amine dehydrogenase 35, 329
amino acid dehydrogenase 34, 227
– catalyzed processes
– – AG7088 (rupintrivir) 358
– – applications 333
– – corticotropin-releasing factor-1 (CRF-1)
receptor antagonist 357–358
– – inogatran 357
– – omapatrilat 356–357
– – saxagliptin 355–356
amino acid dehydrogenases (AADHs)
295–297
– L-amino acid dehydrogenase (L-AADH) 297
amino acid dehydrogenases (AaDHs) 86
D-amino acid oxidase (D-AAO) 356
Synthetic Methods for Biologically Active Molecules: Exploring the Potential of Bioreductions, First Edition.
Edited by Elisabetta Brenna.
Ó 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA.
376
j Index
b2-amino acids 353
c-aminobutanoic acid (GABA) derivatives 353
– microbial reduction of 354
(S)-3-(1-aminoethyl)phenyl ethyl(methyl)
carbamate 363
2-amino-1-phenylpropane-1,3-diol 197
aminotransferases 188
– asymmetric synthesis, and resolution
mode 188
– future research need 203
– improving reaction yield 197–200
– modified 191
– process scale-up 200–203
– (R)-aminotransferases 188, 197
– (S)-aminotransferases 188, 197
– shifted enantioselectivity 192
– stereoselectivity 189–192
– substrate specificity 197
– variant Trp60Cys 191
– v-aminotransferases 197
– wild-type, stereoselectivity 190
AMMOENGTM 101, 248
amprenavir precursors, through ADHcatalyzed bioreductions 93
30 - and 40 -halogenated acetophenones 154
anti-Alzheimer’s disease drug
(S)-rivastigmine 300, 301
anti-(4S,5R)-5-hydroxy-c-decalactone 313
antistereochemistry 30
AOT-based microemulsions 255
AOT/isooctane reverse micelles 255
API synthesis
– amino acid dehydrogenase-catalyzed
reactions, applications 333
– ene reductase-catalyzed reactions,
applications 335
– ketoreductase-catalyzed reactions,
applications 330
aqueous–hexane (1:1) biphasic system 244
aqueous systems, bioreduction in 240, 241
armentomycin 70
Artemisia annua 60
artemisinin 60
Arthrobacter citreus 195, 197
aryl ketones 154
2-aryl-1-nitro-1-propenes 66
3-aryl-2-oxopropanoic acids 6
Aspergillus nidulans glycerol
dehydrogenase 172
atazanavir synthesis 343
atomoxetine 97
atorvastatin calcium 105
avermectins 96
b
Bacillus megaterium 197
Bacillus pumilus 89
Bacillus stearothermophilus 299
Bacillus subtilis 7, 129
Baeyer–Villiger monooxygenase (BVMO) 226
Baeyer–Villiger oxidation 226
baker’s yeast-mediated reduction 294
Beauveria bassiana 61
2-benzenesulfonylcycloalkanones 310
benzoyl coenzyme A reductases 14
(2S,3S)-N-benzoyl-3-phenylisoserine ethyl
ester 346
benzylacetone 167, 169
benzylic amines [a-methylbenzylamine
(a-MBA)] 35
5-benzylidenethiazolidine-2,4-dione 74
(S)-BHBM production system, with KER and
glucose dehydrogenase (GDH) 173
BINAP-Rh complex 59
BINAP-Ru catalyst 139
biocatalysis 44, 263
– gas/solid phase 252–254
biocatalyst format 269–273
– isolated enzyme processes 272, 273
– – bioreductions 273
– – enzyme-coupled cofactor
regeneration 272, 273
– – enzymes dehydrogenases 272
– – substrate-coupled cofactor
regeneration 272, 273
– whole-cell processes 271, 272
– – cofactor regeneration 271
– – ketone reduction 271
– – metal-catalyzed hydrogenation 271
– – n-butyl acetate-buffer biphasic system 271
– – Ru-based asymmetric hydrogenation 272
– – substrate-coupled regeneration 271
biocatalysts 2, 286–289, 293, 296, 298,
299, 302
biocatalytic
– approach to montelukast key
intermediate 340
– deoxygenation reactions 12–14
– hydrogenation reaction 214
– reductive processes approaches 28
biocatalytic (whole-cell) acid reduction
scheme 215
biocatalytic reduction processes
– C¼C double bonds 8–10
– C¼O double bonds 3
– – aldehydes to alcohols 6–8
– – carboxylic acids to alcohols 8
Index
– – carboxylic acids to aldehydes 8
– – ketones to alcohols 3–6
– imines to amines 10–12
– nitriles to amines 12
– and optimization of redox state changes 1
– reaction engineering for 16, 17
biocatalytic reduction reactions, environmental
issues 211
biocatalyzed
– reduction 286
– – whole cell 308
– reductive amination
– – in situ generation 296, 297, 299, 302
– synthesis 289
biodiesel 243
biologically active compounds through C¼O
bioreduction
– “bulky–bulky” ketones 96, 97
– dihydroisocoumarins 99
– diketones 90, 91
– ethyl 5-hydroxyhept-6-enoate 89, 90
– a-halo ketones 91–93
– (hetero)cyclic ketones 94–96
– b-hydroxy nitriles 98
– a-keto esters 87–89
– b-keto esters 89
– lisofylline 98
– (S)-1-[3,5-Bis(trifluoromethyl)phenyl]
ethanol 98
– tetrahydroisoquinolines 99
bioreduction 31
– process engineering 265–267
– – carbon-oxygen double bond reduction 265
– – cofactor regeneration 266
– – whole-cell biocatalyst (See whole-cell
biocatalyst)
– supported processes 361–363
– a,b-unsaturated carboxylic compounds 32
biotransformation 30, 294
biphasic aqueous–organic systems,
bioreduction in 243–245
Birch reduction mechanism 15
bisabolene sesquiterpenes 57
(S)-1-(3,5-bistrifluoromethylphenyl)ethanol 98
boronic acid 102
BRENDA database 2
(S)-2-bromobutanoic acid 71
a-bromoesters 71
buspirone 345
2-butanone 254
butyl acetate–water biphasic system 244
3-butyn-2-one 247
c-butyrolactones 64
BY-catalyzed reduction
– a-(chloromethyl)cinnamaldehyde 56
BY-catalyzed reduction of (Z)alkoxycinnamaldehydes 55
c
Candida boidinii 217, 245
Candida magnoliae 139, 338
Candida parapsilosis 11, 29, 139, 246, 312
capromorelin 96
b-carbolines
– pharmacological activities 359–360
– yeast-mediated imine-reduction 360
carbonyl reductase 29, 105, 244
– Sporobolomyces salmonicolor (SSCR) 178
carbonyl reductases (CRs) 2, 85
carboxylic acid reductases (CARs) 8
carboxylic acids 43, 73
carvone 63
(5R)-carvone
– diastereoselective reduction 348
cascade system
– ADH-catalyzed reactions 291, 292
– ADH/ER system 291
– biocatalyzed reductive amination 296–302
– bioreduction, prochiral unstaturated
aldehydes 295
– deracemization of racemic amino acids
– – DAAO’s-catalyzed reactions 298
– enantiopure amino acids synthesis,
AADH 296, 297
– enantiopure (S)- or (R)-alcohols 288, 289
– enantioselective reduction, prochiral
unsaturated aldehydes 195
– ER–ADH cascade system 294–296
– ER-catalyzed reductions 291, 292
– parallel interconnected kinetic asymmetric
transformations (PIKAT ) 289, 290
– redox neutral 296
– redox neutral (or self-sufficient) cascade 289
CASTing 129
catalytic hydrogenations 1
CDOCKER energy 151
chemoselectivity 32
chiral alcohol 6, 139, 140
– asymmetric bioreduction 341
– optical purity 181
– oxidoreductases/microorganisms, for
preparation of 139
– production level 168
– from various ketones by E. coli
biocatalysts 166
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j Index
chiral azetidone 64
chiral chlofibrate 317
chiral Co (II) salen complex 139
chiral cyclic pentanones 62
chiral 1, 3-diols 104
chirality generating tools 361
chiral lactones 64
chiral metal catalysts 139
chlofibrate 317
chlofibrate [ethyl 2-(4-chlorophenoxy)-2methylpropanoate] 317
20 -chloroacetophenone 164, 166, 168, 243
2-chloroacetophenone (phenacyl chloride) 155
40 -chloroacetophenone 245, 250
a-chloroalkenoates 70
4-chlorobenzophenone 241
3-chloro-4-(4-chlorophenyl)-2-butanone 322
a-chloroesters 71
achloro ketones 220, 289, 290
2-chloro-1-(3,4-methylenedioxyphenyl)
ethanone 167
chloromethyl 3,4-methylenedioxyphenyl
ketone 164, 165
(R)-1-chloro-2-propanol 180
(S)-4-chlroro-3-hydroxybutyrate (CHBE) 172
Chromobacterium violaceum 190, 191, 192
cinnamaldehydes 61
cinnamyl alcohol 363
cinnamyl aldehyde 6
cinnamylamine 363, 364
cis-diastereomer (1R,2S)-2-(3,4dimethoxyphenethoxy)
cyclohexanamine 191
citraconic anhydride 74
citral 60
Citrobacter braakii 13
citronellal 59
citronellal cyclases 16
Clostridium acetobutylicum (CaADH) 100
Clostridium kluyveri 73
Clostridium ljungdahlii 8
Clostridium ragsdalei 8
Clostridium sporogenes 67
Clostridium tyrobutyricum 73
codeinone 32
cofactor-dependent enzyme 286
cofactor regeneration systems, for
dehydrogenases 27
corticotropin-releasing factor-1 (CRF-1)
receptor 357
Corynebacterium aquaticum 63
“coupled-enzyme” approach 86
coupled oxidation, reduction reactions 287–292
Curvularia falcata 3
a-cyano-a,b-unsaturated esters 75
b-cyano-a,b-unsaturated esters 10, 75
cyclic b-keto esters 309
cyclohexa-1,5-diene-1-carboxyl CoA 15
cyclohexane 246, 254
cyclohexenone 66
D-cyclohexylalanine 357
cyclopentenone 62
(S)-cyclopropylglycine
– cyclopropylglyoxylic acid, conversion 358
d
D-amino
acid oxidases (DAAOs) 297, 298
2-dehydrogenase 154
d-decanolide 68
a,b-dehydroamino acid derivatives 354
dehydrocholic acid (DHCA) 16
dehydrogenase-catalyzed oxidation 296–298
dehydrogenases 28, 29
density 248
deracemization 101, 288
– preparation of propargylic alcohols 101
– propargylic alcohols 101
– (R)-chlorohydrins 104
– secondary alcohols, biocatalytic cascade 288
(see Alcaligenes faecalis)
– using Pichia glucozyma in water/organic
solvent biphasic systems 256
deracemizations 87
designer solvents 248
detoxification 30
dextroamphetamine 154, 195, 200
diastereomers 293, 315, 320, 346
dicarbonyl reductases 6
2,30 -dichloroacetophenone 164, 166
2,40 -dichloroacetophenone 164, 165, 166
diethyl-2-alkyl-3-ketoglutarates 317
diethyl ether 250
a,a-difluoro hydroxylated compounds 93
(11S)-dihydroartemisinic aldehyde 60
4,9-dihydro-1H-carbazol-3 (2H)-one 340
dihydrocarvone 63
dihydrofolate reductase (DHFR) 329, 359
– (6S)-tetrahydrofolic acid 359
4,9-dihydro-1H-carbazol-3(2H)-one 340
dihydroisocoumarins 99
2,3-dihydroxy-isovalerate (DHIV) 177
1,3-dihydroxy-1-phenylpropan-2-one 197
diisopropyl ether 246
diketone
– corresponding 1,3 diols through dynamic
kinetic resolution 318
D-arabinitol
Index
– dynamic kinetic resolution 318
– through ADH-mediated processes 90
6,7-dimethoxy-1-methyl-3,4dihydroisoquinoline 11
2-(3,4-dimethoxyphenethoxy)
cyclohexanone 191, 193
4,4-dimethoxytetrahydro-2H-pyran-3-one,
asymmetric reduction 344
dimethyl(1-chloro-2-oxopropyl)
phosphonate 100
dimethyl citraconate 74
dimethyl (S)-2-methylsuccinate 71
a,b-dimethyl nitrostyrenes 67
dispirotetraoxane 63
DKR methodology 101
D-Lactate dehydrogenase (D-Lactate DH) 358
DMSO reductase 12
DNA
– sequencing 337
– shuffling 115
Docetaxel 100
dolastatin 97
L-DOPA 49
dynamic kinetic resolution (DKR)
– approach 99, 100
– process 307
– – acyclic a-substituted b-keto esters
313–321
– – acyclic ketones 322, 323
– – of aldehyde 323
– – aldehydes 322, 323
– – 2-benzenesulfonylcyclopentanone and
cyclohexanone 310
– – carboxamides, microbial reduction of 310
– – cyclic compounds 309–312
– – cycloalkanecarbonitriles 310
– – diketo ester 320
– – ketoreductases (KREDs) 311
– – 3-oxo-4-phenyl-b-lactam 311
– – of 2-phenylpropanal 322
– – 2-substituted-3-carbonyl butanoates
313–321
– – a-substituted carbonyl compounds 309
e
(E)-2-ethoxy-3-(p-methoxyphenyl)
prop-2-ene-1-al 10
electrochemical regeneration, of
NAD(P)H 212
electroenzymatic reduction system 212, 213
electron-withdrawing groups (EWGs) 113
emerging reductive biocatalytic
reactions 14–16
enantiomeric 3-hydroxy-2-methylpropionate,
see Roche ester
enantiomeric purity 296
enantiopure 2hydroxycyclopentanecarboxamides 310
enantiopure (S)-phenylglycine 226
enantioselective
– biocatalytic reduction 29
– organic synthesis 139
enantioselectivity 31, 126, 132
ene reductase (ERs) 30, 50, 64, 66, 294, 353
– amino acid derivatives, asymmetric
synthesis 353–355
– amphidinolides 348, 349
– butyrolactone – jasplakinolide 348, 349
– catalyzed reduction 10
– (þ)-dihydrocarvone 348
– ethyl (S)-2-ethoxy-3-(4-methoxyphenyl)
propanoate (EEHP) 350
– (R)-flurbiprofen 349, 350
– human neurokinin-1 receptor
antagonists 352
– levodione 347, 348
– methyl (z)-2-bromocrotonate – antidiabetic
drug candidates 350, 351
– OYE1
– – reduction, mediated 294
– – Saccharomyces pastorianus 294
– OYE2 294, 295
– OYE3 294, 295
– Roche ester 351, 352
engineering database 179, 180
engineering of b-keto ester reductase
(KER) 172–174
– and characterization of mutant
enzymes 175–177
– for raising thermal stability and
stereoselectivity 172
engineering of PAR
– in 2-propanol/water medium
– – characterization of Sar268 and HAR1
161–165
– – construction of HAR1 mutant 160, 161
– – construction of Sar268 mutant 157–159
engineering substrate- and stereospecificity of
reductases 178, 179
E-nitroolefins 126
enoate 30
enoate reductase (ER) 31, 34, 50, 51, 227, 228
– catalytic mechanism 30, 229
– NAD(P)H independent regeneration
approaches 230
enzymatic methods 86
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j Index
enzyme
– modification 200
– selectivity, solvent control of 255–257
epimerization 66
epoxide hydrolase 129
epoxides 139
error-prone polymerase chain reaction
(epPCR) 115
Escherichia coli 3, 4, 12, 140, 311
– biocatalysts possessing 140
ethyl benzoylformate 180
ethyl 1-benzyl-3-oxo-piperidine-4-carboxylate
– microbial reduction of 312
ethyl benzylpyruvate 164, 166
ethyl b-nitroacrylates 67
ethyl 4-chloroacetoacetate (CAE) 172
ethyl 4-chloro-3-hydroxybutanoate
(CHBE) 244, 338
ethyl (S)-4-chloro-3-hydroxybutyrate 106
ethyl 4-chloro-3-oxobutanoate (COBE) 164,
166, 244, 337
ethyl (S)-2-ethoxy-3-(4-methoxyphenyl)
propanoate (EEHP)
– OYE-mediated gram-scale synthesis 350
ethyl (S)-2-ethoxy-3-(4-methoxyphenyl)
propanoate
– gram-scale enzymatic production 350
ethyl 5-hydroxyhept-6-enoate, synthesis
employing isolated ADHs 90
(R)-ethyl mandelate 180
ethyl (E)-2-methyl-4-oxopent-2-enoate 348
ethyl 3-oxobutanoate 166
ethyl 3-oxobutanotate 164
ethyl pyruvate 164, 166
ezetimibe 96, 341
– promoted bioreduction reactions 216, 217
– regeneration system 217
formates, as reducing agents 215, 217, 218
fosfomycin 101
(–)-fosfomycin 101
furfural 6
g
gas/solid continuous reactor 254
Geobacillus kaustophilus 12, 13, 41
Geobacter metallireducens 15
Geotrichum candidum 3, 251
Geotrichum sp. 313
Gibberella zeae reductase 172
gluconate 5-dehydrogenase 154
gluconic acid 224
Gluconobacter oxydans 6, 7
1,5-gluconolactone 223
glucose as stoichiometric reductant 223, 224
glucose dehydrogenase 6, 210, 223, 224, 244
glucose 1-dehydrogenase 154
glucose dehydrogenase (GDH) 86, 176, 223,
224, 240, 265, 271, 272, 321, 337
– mediated regeneration of NAD(P)H by
means of glucose oxidation 223
– promoted reduction reactions 224
glucose-6-phosphate dehydrogenase
(G6PDH) 271, 345
glutamate dehydrogenase (GluDH) 356
– L-6-hydroxynorleucine 356
glutaraldehyde (GA) 169
glycerol 242
good manufacturing practices (cGMPs) 200
green chemistry 85, 225
h
f
fenpropidine 54
ferredoxins 51
flavin mononucleotide (FMN) 30, 113
flavoprotein 49
a-fluorocinnamyl alcohol 55
(R)-3-(4-fluorophenyl)-2-hydroxypropionic
acid 358
(1R,2R)-2-(4-fluorophenyl)-3oxocyclopentanecarboxylate 352
3-fluoropyruvate 190
fluoxetine 97
flurbiprofen, anti-inflammatory drug 349
FMN oxidation 30
formate dehydrogenase (FDH) 86, 210, 245,
271, 312
– catalyzed regeneration of NAD(P)H 215
a-halogenated cinnamic esters 354
halohydrin dehalogenase (HHDH) 105,
106, 338
halohydrins 92
a-haloketones 225
Hansenula sp. 346
Hase 210
Hase-driven NAD(P)H-dependent carbonyl
reduction reactions 214
H2 as reducing agent 213–215
Heck reaction 103
Helional 58
2-heptanone 254
(hetero)cyclic alcohols 95
hexane 246
hexane–buffer system 251
hexanones 62
Index
HIV-1 protease inhibitors 55
HLADH-catalyzed reduction 6
horse liver alcohol dehydrogenase
(HLADH) 59, 226, 294, 295, 322
human neurokinin-1 (hNK-1) 65
hydride–Meisenheimer complex 34
hydrocodone 32
hydrogenases (Hases) 43, 214
hydrogenation 105, 256
Hydrogenovibrio marinus 215
hydromorphinone 32
hydrophobicity 248
hydrophobic solvents 243, 246
(S)-3-hydroxyadamantylglycine 356
6-hydroxybuspirone 345
6-hydroxybuspirone (6-hydroxy-8–8-azaspiro
[4.5]decane-7,9-dione) 345
(2S,3S)-hydroxyester 64
(2R,3S,1’R)-hydroxy ester 314
cis-(3R,4R)-Hydroxy ester 312
hydroxyesters 64
a-hydroxy esters, synthesis using alcohol
dehydrogenases 88
b-hydroxy esters, synthesized by means of
enzymatic bioreductions 89
hydroxy keto ester 313
2-hydroxy-methylacrylic acid methylester 10
3-hydroxy-3-methyl-glutaryl-CoA (HMGCoA)
reductase inhibitors 337
L-6-hydroxynorleucine
– enzymatic route 356
– 2-keto-6-hydroxyhexanoic acid 356
3a-hydroxysteroiddehydrogenase (HSDH) 255
i
IlvC gene 177
imine complex 188
imine reductases 36–38
in situ product removal (ISPR)
technologies 263, 267–269, 346
– biocatalytic processes 267
– capacity 269
– couple scheme, systematic evalutaion 277
– fermentation 267
– flow sheet options 270
– indutrial scale implementation 268
– ISPR with crystallization 274, 275
– – asymmetric reduction 4oxoisophorone 275
– – in situ product crystallization (ISPC)
– – systematic evaluation, ISPR 275
– ISPR with resins 273, 274
– – Amberlite XAD-7HP 274
– – AmberliteÒ XAD-2 resin 273
– – fed-batch strategy 274
– – large-scale stereoselective enzymatic
reduction 273
– – o-chloroacetophenone, bioreduction 274
– – in situ substrate supply 274
– ISPR with solvent extraction 274
– – two-phase system, ISPR 274
– membrane technology 269
– methods, and choice 268, 269, 276–278
– – cost-benefit analysis 278
– – ISPR benefits 277
– – ISPR technologies qualitative comparison,
alcohol removal 278
– – qualitative comparison of ISPR
technologies, alcohol removal 278
– – removal of alcohol methods
comparison 278
– potential benefits 268
– process integration 278, 279
– – simulated moving bed (SMB) technology 289
– rate of removal 679
– removal of acetone 275
– – coupled-substrate, cofactor
regeneration 275
– in situ coproduct removal (IScPR) 267, 268
in situ redox cofactor regeneration system 286,
288
– enzyme coupled 286
– formate/formate dehydrogenase
(FDH) 296, 298
– glucose/glucose dehydrogenase (GDH)
system 293
in situ SFPR technology 59
ionic liquids (ILs) 247–250
– combining with supercritical fluids 251, 252
– continuous biocatalytic synthesis
of (R)-2-octanol in 252
– water-miscible 248
IPA–aqueous solution system 140
irreversible morphinone reductase reaction
isonitramine 96
isopropanol 242, 247
isopropylamine 190, 198
isopulegol 59
isoxazoles 66
isoxazolines 66
iterative saturation mutagenesis (ISM) 116
k
ker gene 177
KER mutants 175
ketamine 189
j381
382
j Index
a-keto acid 34, 199
2-keto-3-(N-benzoylamino)-3-phenylpropionic
acid ethyl ester
– diastereoselective reduction 347
keto ester 65
– enzymatic reduction of 314
b-keto ester 164
– diastereoselective reductions 316
– dynamic kinetic resolution 321
– reduction 314
b-keto ester reductase (KER) 140, 149
a-keto esters 164
a-ketoglutarate
– L-GluDH/NADH oxidase, coupled-enzyme
system 361
2-keto-6-hydroxyhexanoic acid 356
ketoisophorone 63
– microbial reduction 347
ketol-acid reductoisomerase (KARI) 177
ketones 113
ketoreductase 2, 5, 7, 329
– atazanavir 343
– atorvastatin 338, 339
– chemokine receptor inhibitor 343, 344
– chiral precursor, stereoselective
synthesis 344
– duloxetin 344
– ethyl 4-chloro-3-hydroxybutanoate
(CHBE) 338
– ezetimibe 341, 342
– 6-hydroxybuspirone 345, 346
– LY 300164 346
– montelukast 339, 340
– paclitaxel 346, 347
– profens 342, 343
– ramatroban 340, 341
ketoreductases (KREDs) 85, 311
12-keto-ursodeoxycholic acid 16
kinetic
– oxidative resolution 289, 290
– resolutions (KRs) 100, 307
Klebsiella oxytoca 215
Kluyveromyces marxianus 100, 317
Kluyveromyces thermotolerans 4
KRED kit 312
l
lactate dehydrogenase (LDH) 299, 301, 361
Lactobacillus brevis 248, 319
Lactobacillus kefir 3, 7, 139
Lactobacillus kefir ADH (LKADH) 96
Lactobacillus kefiri 91
Lactobacillus leichmannii 13
lactones 64
LbADH-catalyzed reduction of aliphatic
ketones 248
Leifsonia alcohol dehydrogenase (LSADH) 140
– amino acid sequence alignment 154
– enzymatic properties 153–155, 157
– physicochemical properties 153
– properties 149
– purified, substrate specificity of 164
– screening, from styrene-assimilating soil
microorganisms 151, 152
– stereochemistry 150
– substrate and stereospecificity 145–147
leucine dehydrogenase (LeuDH) 357
Leuckart–Wallach reaction 35
(S)-leucovorin [(6S)-5-formyl-5,6,7,
8-tetrahydrofolate]
– cancer chemotherapy 359
leukotriene B4 12-hydroxydehydrogenase 57
(6R)-levodione 347
levodione reductase (LVR) 63
light-driven system 265
lipases 308
lisofylline 98
lithium aluminum hydride 1
m
mandelate dehydrogenase 227
mandelate racemase (MR) 226
marine microalgae 314
Meerwein–Ponndorf–Verley (MPV)
reduction 85, 219, 220
melilotol 68
menthol 59
metagenomics 180, 181
metal-catalyzed hydrogenation 85
methoxyacetone 190, 191
40 -methoxyacetophenone 249
– biocatalytic anti-prelog stereoselective
reduction 249
5-methoxy-2-aminotetralin 201
(R)-1-(40 -methoxyphenyl)-ethanol 179
methyl acrylate 68
2-methyl-3-aryl-propanols 10
4-methylbenzophenone 241
methyl benzoylformate 242
methylbenzylamine 199
methyl (S)-BHBM 172
methyl 4-bromo-3-hydroxybutanoate 174
methyl (S)-4-bromo-3-hydroxybutyrate
(BHBM) 172
methyl 4-bromo-3-oxobutyrate (BAM) 172
methyl (S)-2-bromopropionate 351
Index
methyl (Z)-2-chloro-3-(4-fluorophenyl)
acrylate 355
methyl (S)-4-chloro-3-hydroxybutanoate
(CHBE) 174
methyl cinnamate 68
methyl crotonate 68
3-methyl-2-cyclohexenone 130
a-methylcyclohexenone 50
3-methyl-3,4-dihydroisocoumarins 98
3,4-methylenedioxyphenylacetone
– biocatalytic reduction 346
3,4-methylene-dioxyphenyl acetone 16
methylenic methylesters 69
methylesters 70
methyl 2-(3-fluoro-4-hydroxyphenyl) acrylate 349
methyl (R)-4-fluorophenylalanine
hydrochloride 355
methyl 2-hydroxymethylacrylate 69
methyl isobutyl ketone 365
methyl methacrylate 68
2-methylpent-2-enal 129
methyl tert-butyl ether (MTBE) 96
3-methyl-1,2,3,4-tetrahydroisoquinolines 98
Metrosideros polymorpha 316
rac-mexiletine 362
mexiletine (R)/(S)-enantiomers 361
miconazole, synthesis using enzymatic
reductions 92
micro- or nonaqueous systems, bioreduction
in 245–247
Mitsunobu reaction 227
monophasic aqueous–organic systems,
bioreduction in 241–243
morphine dehydrogenase 33
morphinone reductase 32
Mucor javanicus 3
Mucor rouxii 315
multienzymatic processes 285
– cascades
– – bioreductive reactions 302–304
– one-pot processes 285, 286 (See one-pot
processes)
– representation 286
– synthesis 285
– – in vitro 285
– – in vivo 285
mutations 115
mutator strain 115
Mycobacterium marinum 8
n
NADH 288
– NADH-dependent ene reductase (ER) 291
– NADH-dependent enzymes 35
– NADH-dependent phenylacetaldehyde
reductase (PAR) 140
– – characterization 140
– – docking model construction 151
– – 3D structural models 148, 151
– – enzymatic properties 147, 149–151
– – kinetic parameters 162
– – location in styrene metabolic pathway
140–142
– – metabolic pathway of styrene by
Rhodococcus sp. 141
– – physicochemical properties 142, 147
– – stereochemistry 150
– – substrate and stereospecificity 143, 144
– – substrate specificity
– – for oxidative reaction 156
– – purified 164
– NADH regeneration system 217
NAD(P)H 288
– dependent b-keto ester reductase 173
– dependent 2-cyclohexen-1-one reductase
(NCR) 32
– dependent dehydrogenases 361
– dependent ketoreductases (KRED) 292,
293, 317
– dependent oxidoreductases
– – one-spot processes 287
– oxidation 30
– substrate-coupled regeneration of 219
NAD(P)þ-linked biocatalytic redox
processes 225
Na2HPO3/phosphite dehydrogenase (PDH)
recycling system 352
Nannochloropsis sp. 314
naproxen precursor 343
N-based enzymatic reductions 41, 42
1-N-Boc-3-pyrrolidinone 164, 167, 168
Nef pathway 42
N-gluconyl glutamic acid didecyl ester 255
Nicotiana tabacum 31
nicotinamide cofactor 209, 228
– chemical structure 209
– electrochemical regeneration 212
– electrochemistry 210
– regeneration methods 210
nicotinamide-dependent 2-cyclohexenone
reductase 129
nicotin-amide-independent system 265
nicotinamide recycling system 344
nitrile reductases 38–41
– postulated mechanism 40
nitroalkenes 41, 65
j383
384
j Index
1-nitro-1-alkenes 30
nitrocyclohexene 66
nitroolefin reduction, catalyzed by PETN
reductase 126
nitroolefins 65, 66, 113
– bioreduction of 65–67
N-nitramines 33
nonconventional media, bioreduction in 247
– combining ILs and SFs 251, 252
– gas-phase media 252–254
– ionic liquids 247–250
– reverse micelles 254, 255
– supercritical fluids 250, 251
c-2-nonenolide 68
nonflavin-dependent ene reductases 50
nonflavo ene reductases 51
nonselective reductions 1
nonsteroidal anti-inflammatory drugs
(NSAIDs) 69
N-substituted-2-methylmaleimide 74
o
2-octanone 250
old yellow enzyme (OYE) 117, 265
– enhancement of selectivity 133
– evolving, in stereoselective reduction 117,
119
– – NCR for a,b-unsaturated ketones 129
– – OYE1 for 3-alkyl-2-cyclohexenone
derivatives 119–122
– – PETN reductase for a,b-unsaturated
carbonyl compounds and
E-nitroolefins 123, 126
– – YqjM for a,b-unsaturated ketones 129–133
– mutants, excellent catalysts in reduction 133
– rational design 117
– structural overview 118
old yellow enzymes (OYEs) 10, 17, 30–34, 50,
51, 53, 58, 59, 61, 63, 67, 73, 114, 117, 119,
134, 295, 302, 315, 317, 318, 320, 322
oligomerizations 30
omapatrilat synthesis 356
one-pot chemo/biocatalyzed cascade reactions,
in biphasic system 249
one-pot processes 285–287
– cascade reductions 292–296 (see cascade
system)
– consecutive reductions 292–296
– linear (or sequential) reactions 285, 286
– mixed-type reactions 286
– multienzymatic synthesis
– – 12-ketoursodeoxycholic acid 289
– – optically pure b-hydroxy carboxylic acids 302
– orthogonal (or parallel) reactions 286
– stereoselective synthesis 292 (see also
NAD(P)H)
– – 2-alkyl-1,3-diols, KRED 292, 293
– – tert-butyl 3,5-dihydroxyhexanoate
stereoisomers 293
– synthesis
– – enantiopure bazidoalcohols and
b-hydroxynitriles 303, 304
– – enantiopure b-hydroxytriazoles 303, 304
– two step synthesis, enantiopure
2,4-dimethylbutyrolactones 294
– in vitro chemoenzymatic synthesis 294
– vs. cascade processes 286
OPR1 (12-oxophytodienoate reductase 1) 58
optically active hydroxyl ester (CHBE) 244
organoboranes 1
oscillatoxins 96
oxazete formation 42
oxcarbazepine 95
– transformation 95
oxidized NADþ cofactor 302
oxidoreductases 3, 6, 10, 28, 29, 39, 85, 86, 102,
113, 183, 337
oximes 41
3-oxoacyl-[acylcarrier-protein] reductase
– amino acid sequence alignment 154
2-oxocycloalkanecarbonitriles
– enantio- and diastereoselective bioreduction
of 310
b-oxoesters 309
2-oxotetralin 191
OYE-catalyzed reduction 30
OYE3-catalyzed reduction 10
OYE-catalyzed reduction reaction 30
– of alkene 114
OYE homologs PETN reductase 34
OYE-like ene reductases 51
OYE-like flavoproteins 71
OYE1 mutants 69
p
par gene 142
Pd catalyst 250
Pd(II)-catalyzed Wacker-type oxidation 102
Penicillium citrinum 139, 140
– substrate specificity of recombinant
KER 174
pentaerythritol tetranitrate (PETN)
reductase 33
PETNR (pentaerythritol tetranitrate
reductase) 60
PETN reductase mutants 126
Index
pharmaceutical intermediate
4-phenylpyrrolidin-2- one 300, 301
phenylacetic acid (PAA) 142
phenylacetone, asymmetric reduction 247
2-phenylacrylonitrile 74
phenylalanine dehydrogenase (PheDH) 355
(S)-1-phenyl-1-butanol 257
1-phenyl-1-butanone 155
1-phenyl-3-butanone 155
1-phenylethanol 154
phenyl n-propyl ketone 257
1-phenyl-2-propyn-3-trimethylsilyl-1-on 16
phenyl trifluoromethyl ketone (PTK) 151
phosphite dehydrogenase 210, 218
phosphites, as stoichiometric reductants 218
Pichia glucozyma 255, 256
Pichia stipitis 61
piperidin-3-ols 95
piperonylacetone 167
piperonyl methyl ketone 164
Plasmodium falciparum 60
polar organic solvents 248
polyethyleneimine (PEI) 169
Prelog’s rule 3, 4, 316
profens 342, 343
(S)-proline 359
2-propanol [isopropyl alcohol (IPA)] 140
propionoic acid class, see profens
protection–deprotection steps 1
protein engineering 10, 31, 114, 218, 276
– B-FIT method, for improving
thermostability/robustness 116
– combinatorial active-site saturation test
(CAST) 116
– combinatorial space 115
– examples 276
– generation of high-quality (“smart”)
libraries 115
– mutations 115, 116
– reductase enzymes 276
– screening effort 115
– in situ product removal 276
– synthetic chemistry 276
protein–inhibitor complexes 50
Proteus mirabilis 13
Pseudomonas aeruginosa 12
Pseudomonas fluorescens 288
Pseudomonas testosteroni 255
Pseudotriton ruber 321
pyridoxamine 5-phosphate (PMP) 188, 189
Pyrococcus furiosus 8, 43, 214, 255
pyrrolidin-3-ols 95
pyrrolo[2,1-c][1,4]benzodiazepines
– biocatalytic azide reduction–cyclization
sequence 359
pyrrolo[2,1-c][1,4]benzodiazepines (antitumor
agents) 358, 359
pyrrolo[2,1-c][1,4]benzodiazepines (PDB) 359
q
quick quality control (QQC) 115
3-quinuclidinone 164, 167, 168
r
racemic ketone 311
racemization 67
Rac-2-hydroxycyclohexanone 312
Ralstonia eutropha 215
(R)-aminotetralin 191
(R)-2-aminotetralin 190
(R)-ramatroban, synthesis 340
random mutagenesis 115
Raney Ni-catalyzed hydrogenation 353
(R)-1-cyclopropylethylamine 197
(R)-4,4-dimethoxytetrahydro-2H-pyran3-ol 96
reaction engineering for biocatalytic reduction
processes 16, 17
recombinant enoate reductase (ER) 105
redox economy 1
redox isomerizations 227
reductases 27
reductive amination 35
reductive denitration 33
reverse micelles 254, 255
– water-to-surfactant ratio 254
(R)-3-fluoroalanine 190, 195
Rhizopus arrhizus 309
rhodium complexes 217
Rhodobacter capsulatus 12
Rhodoccocus ruber 341
Rhodococcus erythropolis 141, 254
Rhodococcus opacus 142
Rhodococcus ruber 246
Rhodococcus sp. 320
Rhodotorula rubra 61
(S)-rivastigmine synthesis 363
(R)-1-methoxy2-propanamine 197
(R)-2-methylpyrrolidine 11
robalzotan 59
Roche ester 69, 351, 352
– stereocomplementary strategies 352
rotigotine 59
(R)-4-phenyl-2-butanamine 197
(R)-4-phenyl-2-butanol 168, 169
(R)-(–)-3-quinuclidinol production system 171
j385
386
j Index
(1R,2R)-2-(3,4-dimethoxyphenethoxy)
cyclohexanamine 190, 193
(R)-rhododendrol 103
(R)-sec-butylamine 197
(R)-tamsulosin 98
(R)-tetrahydrothiophene-3-ol 96
ruthenium complexes 217
s
Saccharomyces cerevisiae 3, 49, 56, 320
– D-arabinose dehydrogenase 172
Saccharomyces montanus 310
(S)-(a)-methylbenzylamine 190
(S)-a-methylbenzylamine 197
(S)-2-aminotetralin 191
saturation mutagenesis 115
saxagliptin 355
(S)-2-bromo-2-cyclohexen-1-ol 16
(S)-2-butanamine 197
scale-up processes, requirement 263–265
– biocatalyst yield 264
– biocatalytic processes 263–265
– product concentration 264
– reaction yield 264
– space-time yield (STY) 264
scCO2–buffer biphasic system 251
Schiff’s base 188
serotonin (5-hydroxytryptamine 5-HT)
transporter 344
(S)-2-ethoxy-3-(p-methoxyphenyl)propion-1aldehyde 10
Sheldon’s E-factor 211
sibirine 96
sitagliptin 35, 36, 156
site-specific mutagenesis 114, 115
sitophilate 319
Sitophilus granarius 318
(S)-licarbazepine 95
(S)-7-methoxy-2-aminotetralin 198, 201
(S)-methoxyisopropylamine 190,
191, 198
– synthesis, from methoxyacetone 191
(S)-1-methoxy-2-propanamine 197
(S)-3,4-methylene-dioxyphenyl
isopropanol 16
(S)-methyl p-tolyl sulfoxide 12
(S)-2-methylpyrrolidine 10
sodium bicarbonate 251
sodium borohydride 1
sodium dioctyl sulfosuccinate 255
solid-phase extraction (SPE) 252
solvent control, of enzyme selectivity
255–257
solvent systems, for biocatalytic
reductions 239
(S)-phenylethylamine 190
(S)-1-phenylethylamine 189
(S)-1-phenyltrifluoroethanol (PTE) 151
Sphingomonas pausimobilis 2,5dichloro-2,5-cyclodiene-1,4-diol
dehydrogenase (SDCDDH) 154
(S)-phthalides 106
spiro nitrile 74
Sporidiobolus salmonicolor
– aldehyde reductase 172
Sporobolomyces salmonicolor 92, 139
squalene–hopene cyclase 16
stegobinone 319
stegobiol 319
stenusine 61
stereocontrol strategies, for bioreduction 52
stereoisomeric products, asymmetric
reduction 308
stereoisomers 292, 293
– tert-butyl 3,5-dihydroxyhexanoate 293
stereoselective reduction 289, 290
Streptomyces coelicolor (ScCR) 244
Streptomyces fradiae 100
Streptomyces virginiae 35
Streptosporangium roseum 11
structure–function relationships 2
styAB gene 142
styCD gene 142
a-substituted b-keto esters
– ruthenium-catalyzed hydrogenation 308
2-substituted-3-carbonyl butanoate 313
substrate-coupled biocatalytic reduction
reactions 221, 222
substrate feeding product removal (SFPR)
concept 350
Sulfolobus solfataricus 323
supercritical carbon dioxide (scCO2) 251,
252
supercritical fluids (SFs) 250
Suzuki cross-coupling 102
Suzuki–Miyaura coupling 349
syn-hydrogenation 31
– N. tabacum OYE-catalyzed, for enones 31
syn-(1R,2S) halohydrin 101
synthetic mNADs 228
t
talaromycins 96
taxoid anticancer drugs 321
taxotere 100, 321
4-tert-butylcyclohexanone 96
Index
tetrahydroisoquinolines 99
Thermoactinomyces intermedius 355
Thermoanaerobacter species 348
Thermoanaerobium brockii 3, 139
thermophilic microorganism 299
Thermoplasma acidophilum 6
thiazolidine-2,4-diones 74
three-enzyme system
– biotransformation of morphine to
hydromorphone 287, 288
– irreversible morphinone reductase
reaction 288
toluene 244, 246
toluene–buffer biphasic system 244
total turnover number (TTN)
211, 212
a-transaminases
– application 299, 300
– D-amino acids synthesis 300
– the herbicide L-phosphothricin
synthesis 300
v-transaminase (v-TA)-catalyzed
processes 35, 299–301, 361
– application 300, 301
– catalyzed transamination 302
– multienzymatic cascade 301
– optically pure amines synthesis 299
– redox-neutral cascade 301, 302
transamination reaction 188, 189
– mechanism 189
transition metal catalysis 113
transition metal complexes 217
trans-stereospecificity 8
2,2,2-trifluoroacetophenone 164, 165, 167
Trigonopsis variabilis 249
trinitrotoluene (TNT) 34
triphenylphosphane 102
Triton X-100 199, 255
tyrosine 113
u
a,b-unsaturated aldehydes 30, 113
– chemical pathway of bioreduction 53
a,b-unsaturated carbonyl compounds,
bioreduction 53
– aldehydes 54–60
– ketones 61–65
a,b-unsaturated carboxylic acids and
derivatives, bioreduction 68
– anhydrides 73, 74
– carboxylic acids 73
– diesters 71–73
– imides 73, 74
– lactones 68–71
– monoesters 68–71
a,b-unsaturated nitriles, bioreduction 74–76
v
viscosity 248, 252, 274
w
Wacker–Tsuji oxidation 103
water-miscible ionic liquids 248
whole-cell biocatalysts
– limited substrate 266
– possessing mutant PARs and LSADH,
applications
– – continuous production of chiral
alcohol 166, 168–171
– – immobilized E. coli whole-cell catalysts
mutants 165, 168, 170
– – for regenerating NADH with IPA 171, 172
– product transport into and out 266
– slide reaction 266
– toxic substrates, products 266, 267
Wittig reaction 32, 103
WT PETN reductase 126
– catalytic performance 127, 128
x
xylitol 225
xylose 225
y
yeast alcohol dehydrogenase (YADH) 255
Yersinia enterocolitica 12
YqjM mutants 131–133
– evaluation 131
– pathways leading maximum
enantioselectivity 132
– from saturation mutagenesis 133
z
zeaxanthin 63
zinc-containing ADHs 142
Zn2þ–cyclen complexes 105
Zn2þ ion cofactor 257
Zygosaccharomyces rouxii 16, 346
– glycerol dehydrogenase 172
Zymomonas mobilis 16, 129
j387