Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOC1.Br[CH2:57]/[CH:58]=[CH:59]\[C:60]([CH3:70])([O:62][Si:63]([CH2:68][CH3:69])([CH2:66][CH3:67])[CH2:64][CH3:65])[CH3:61]>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:57]/[CH:58]=[CH:59]\[C:60]([CH3:70])([O:62][Si:63]([CH2:66][CH3:67])([CH2:68][CH3:69])[CH2:64][CH3:65])[CH3:61])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC[Si](CC)(CC)OC(C)(C)/C=C\CBr
Reactant: C[C@@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC[Si](CC)(CC)OC(C)(C)/C=C\CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Yield: 85.2 %

Procedure:
Under the same conditions as in Example 83, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-hydroxypregna-5,7,16-triene (60.0 mg, 0.107 mmol), sodium hydride (60%, 17.1 mg, 0.428 mmol), 15-crown-5 (10 μl) and (Z)-1-bromo-4-methyl-4-triethylsilyloxy-2-pentene (125 mg, 0.428 mmol) were reacted in tetrahydrofuran (1 ml) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, hexane:ethyl acetate=30:1, developed once) to give the title compound as a colorless oil (70.3 mg, 85%).
Reaction SMILES: [CH2:1]([CH:3]1[O:5][CH2:4]1)[Br:2].[F:6][C:7]([F:15])([F:14])[C:8]([C:10]([F:13])([F:12])[F:11])=[O:9]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[F:6][C:7]([F:15])([F:14])[C:8]1([C:10]([F:13])([F:12])[F:11])[O:5][CH:3]([CH2:1][Br:2])[CH2:4][O:9]1
Reactant: O=C(C(F)(F)F)C(F)(F)F
Reactant: BrCC1CO1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Solvent: O
Product: FC(F)(F)C1(C(F)(F)F)OCC(CBr)O1

Procedure:
This compound was prepared from epibromohydrin and hexafluoroacetone (HFA) (1:1 mole ratio) in the presence of catalytic amounts of tetrabutylammonium bromide and water at 125° C. in 95% isolated yield. Compound 7 has a boiling point 56° C./2 mm. 1H NMR (neat): δ4.88 (m, IH), 4.73 (t, J =7.5 Hz, IH), 4.22 (t, J=7.5 Hz, lH), 3.60 (m, 2H); 19F NMR (neat): -80.5 (q, J=8.5 Hz, 3F), -81.0 (q, J=8.5 Hz, 3F). Anal. Calc. for C6H5BrF6O2 : C: 23.78, H: 1.66, Br: 26.37, F: 37.62; Found: C: 23.91, H: 1.64, Br: 26.87, F: 37.84.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][C:12]#[N:13].[C:14](=O)([O:22]C1C=CC=CC=1)[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>O1CCCC1>[C:12]([CH:11]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[O:4][CH3:3])[C:14]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:22])#[N:13]
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Reactant: COc1ccccc1CC#N
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccccc1C(C#N)C(=O)Oc1ccccc1
Reaction time: 0.5 h
Yield: 78.8 %

Procedure:
To a slurry of sodium hydride (3.39 g of 60% in mineral oil, 84.9 mmol) in tetrahydrofuran (200 mL) at room temperature was added 2-(2-methoxyphenyl)acetonitrile (10.0 g, 67.9 mmol) dropwise. The reaction mixture was then heated to reflux and the gray suspension turned dark red over 30 min. Diphenyl carbonate (18.2 g, 84.9 mmol) was added portionwise, and the reaction suspension was heated at reflux for an additional 18 h. The reaction mixture was cooled, poured into 1 N HCl (200 mL) and extracted with ethyl acetate (3×200 mL). The organic phases were combined, dried over magnesium sulfate, filtered and concentrated onto Celite® under reduced pressure. The resultant residue was purified by chromatography on silica gel using 10-90% ethyl acetate/hexane as eluant to give the title compound as a light yellow solid (14.3 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[N:6][CH:5]=1.[CH3:12][C:13]1[O:17][N:16]=[C:15]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:14]=1[CH2:24]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:24][C:14]2[C:15]([CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[N:16][O:17][C:13]=2[CH3:12])=[N:6][CH:5]=1
Reactant: Cc1onc(C2CCOCC2)c1CO
Reactant: COC(=O)c1ccc(O)nc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(OCc2c(C3CCOCC3)noc2C)nc1
Temperature: 25 °C
Yield: 36.2 %

Procedure:
To a stirred solution of 6-hydroxy-nicotinic acid methyl ester (1.67 g, 10.9 mmol) and [5-methyl-3-(tetrahydro-pyran-4-yl)-isoxazol-4-yl]-methanol (2.15 g, 10.9 mmol) in THF (55 mL) at 5° C. under argon was added triphenylphosphine (10.6 g, 39 mmol), then diisopropyl azodicarboxylate (40%, 6.5 mL, 14.2 mmol) was added dropwise. The reaction mixture was warmed to room temperature for 2 h. The reaction mixture was then extracted with tert-butyl methyl ether, and washed with aqueous HCl (2 N) and the organic extract washed with water, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, heptane:ethyl acetate=1:0 to 1:1) afforded the title compound (1.31 g, 36%) as a white solid. MS: m/e=333.2 [M+H]+.
Reaction SMILES: [CH:1]([C:3]1[C:19]2[CH:18]=[C:17](C(OCC)=O)[O:16][C:15]=2[C:14]2[CH:13]=[CH:12][C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]=2[CH:4]=1)=[O:2].[OH-].[Na+].C1COCC1.Cl>O>[CH:18]1[C:19]2[C:3]([CH:1]=[O:2])=[CH:4][C:5]3[C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=4[CH:12]=[CH:13][C:14]=3[C:15]=2[O:16][CH:17]=1
Reactant: CCOC(=O)c1cc2c(C=O)cc3c4ccccc4ccc3c2o1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=Cc1cc2c3ccccc3ccc2c2occc12
Yield: 37 %

Procedure:
To a RB flask equipped with magnetic stirring bar, condenser, and N2 inlet line with bubbler was added ethyl 11-formyl-phenanthro[1,2-b]furan-2-carboxylate (15A, 2.5 g. 7.8 mmol), 1N NaOH solution (25 mL), THF (50 mL) and H2O (25 mL). The mixture was refluxed for 2 h until it became homogeneous. The mixture was acidified with 1N HCl and the solvent removed by rotary evaporation. The crude solid was then heated to 150° with copper powder (0.9 g) and quinoline (Aldrich, 25 mL) for 1 h. The reaction mixture was cooled and the quinoline removed under vacuum to give a crude dark green solid. After chromatography and crystallization (CH2Cl2 /hexane) 0.71 g (37% yield) of phenanthro[1,2-b]furan-11-carbaldehyde, mp 145°-150°, (C,H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:13][CH2:14][O:15][CH3:16])/[C:9](/[F:12])=[CH:10]\[F:11])=[CH:4][CH:3]=1.C([Li])CCC.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:25]=1>O1CCCC1.CCCCCC.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH2:13][CH2:14][O:15][CH3:16])/[C:9](/[F:12])=[C:10](\[F:11])/[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:25]=2)=[CH:6][CH:7]=1
Reactant: COCCC(/C(F)=C\F)c1ccc(Cl)cc1
Reactant: BrCc1cccc(Oc2ccccc2)c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COCCC(/C(F)=C(\F)Cc1cccc(Oc2ccccc2)c1)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.5 %

Procedure:
To a stirred solution of 1-chloro-4-[(2E)-2,3-difluoro-1-(2-methoxyethyl)-2-propenyl]benzene (0.87 g, 3.52 mmol) in tetrahydrofuran (10 ml) under nitrogen at −65° C. was added n-butyllithium (1.1 ml of a 2.5 M solution in hexane, 2.75 mmol). To this mixture was added zinc chloride (5.3 ml of 0.5 M in tetrahydrofuran, 2.65 mmol) and the resulting mixture was stirred for one hour. Tetrakis(triphenyl-phosphine)palladium (0.066 g, 0.057 mmol) in tetrahydrofuran (1 ml) was added, followed by α-bromo-3-phenoxytoluene (0.70 g, 2.66 mmol) in tetrahydrofuran (2 ml), and the resulting mixture was stirred and allowed to warm to room temperature over four hours and was then stirred for another sixteen hours. The reaction mixture was then quenched with water, diluted with 10% hydrochloric acid and thoroughly extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to a brown oil (1.378 g). Chromatography of this oil on silica gel eluting with ethyl acetate:hexane (5:95) afforded the title compound as a yellow syrup (0.359 g) which was characterized by IR, 1HNMR, 19FNMR and mass spectral analysis.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[N:15]1([CH2:21][CH2:22][CH2:23][NH2:24])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[O:18]1[CH2:19][CH2:20][N:15]([CH2:21][CH2:22][CH2:23][NH:24][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=2[N+:12]([O-:14])=[O:13])[CH2:16][CH2:17]1
Reactant: NS(=O)(=O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: NCCCN1CCOCC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccc(NCCCN2CCOCC2)c([N+](=O)[O-])c1

Procedure:
4-Fluoro-3-nitrobenzenesulfonamide (550 mg), 3-(N-morpholinyl)-1-propylamine (1.00 g), and triethylamine (1 g) were stirred in THF (30 mL) for 24 hours. The mixture was diluted with ethyl acetate, washed with NaH2PO4 solution and brine, and dried (Na2SO4), filtered and concentrated. The product was triturated from ethyl acetate.
Reaction SMILES: Cl.O1CCOCC1.C(OC([N:15]1[CH2:19][CH2:18][CH2:17][C@@H:16]1[CH2:20][N:21]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH2:25][O:24][C:23]2[CH:32]=[CH:33][CH:34]=[CH:35][C:22]1=2)=O)(C)(C)C.C(N(CC)CC)C>O1CCOCC1>[NH:15]1[CH2:19][CH2:18][CH2:17][C@@H:16]1[CH2:20][N:21]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH2:25][O:24][C:23]2[CH:32]=[CH:33][CH:34]=[CH:35][C:22]1=2
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CN1c2ccccc2COc2ccccc21
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: c1ccc2c(c1)COc1ccccc1N2C[C@H]1CCCN1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
4 M hydrochloride/dioxane solution (1.5 ml) was added to a solution of 400 mg of (R)-5,11-dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine in dioxane (1.5 ml)), and the mixture was stirred at room temperature for one hour. The solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane (20 ml). Triethylamine (0.16 ml, 1.1 mmol) was added to the obtained solution, and the solution was stirred at room temperature for 30 minutes and then washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over magnesium sulfate. The solvent was evaporated under reduced pressure to obtain the title compound, i.e. (R)-5,11-dihydro-5-(2-pyrrolidinylmethyl)dibenzo [b,e][1,4]oxazepine, in the form of a light yellow oil(280 mg, 96%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]([CH3:27])([CH2:22][C:23]#[C:24][CH2:25][CH3:26])[CH:20]=O>>[CH3:18][C:19]([CH3:27])([CH2:22][C:23]#[C:24][CH2:25][CH3:26])/[CH:20]=[CH:17]/[S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:9][CH2:10]1)(=[O:15])=[O:16]
Reactant: CS(=O)(=O)N1CCN(c2ccc(F)cc2)CC1
Reactant: CCC#CCC(C)(C)C=O
Product: CCC#CCC(C)(C)/C=C/S(=O)(=O)N1CCN(c2ccc(F)cc2)CC1

Procedure:
The title compound was prepared, following procedure described in Example 1, step a), but starting from 1-(4-fluorophenyl)-4-(methylsulfonyl)piperazine (Intermediate B1, 855 mg; 3.31 mmol) and of 2,2-dimethyl-hept-4-ynal, 457 mg; 3.31 mmol), as a white powder (764 mg, 61% yield). HPLC, Rt: 4.75 min (purity: 97.7%). LC/MS, M+(ESI): 379.4, 1H NMR (DMSO-d6) δ: 6.97-6.82 (m, 4H), 6.74 (d, J=15.4 Hz, 1H), 6.07 (d, J=14.9 Hz, 3.26 (m, 4H), 3.15 (m, 4H), 2.21 (m, 2H), 2.01-2.16 (m, 2H), 1.15 (s, 6H), 1.06 (t, J=7.4 Hz, 3H).
Reaction SMILES: CSC1N=CC(O)=CC=1.CS[C:12]1[N:17]=[CH:16][C:15]([O:18][C:19]2[CH2:23][CH2:22][O:21][N:20]=2)=[CH:14][CH:13]=1.ClC1C=CC=C(C(OO)=O)C=1>C(Cl)Cl>[N:17]1[CH:12]=[CH:13][CH:14]=[C:15]([O:18][C:19]2[CH2:23][CH2:22][O:21][N:20]=2)[CH:16]=1
Reactant: CSc1ccc(OC2=NOCC2)cn1
Agent: CSc1ccc(O)cn1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: c1cncc(OC2=NOCC2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3-(pyridin-3-yloxy)-4,5-dihydroisoxazole II-28a and II-28b were prepared in 2 steps from racemic compound II-6 by first reacting II-6 with 6-(methylthio)pyridin-3-ol (prepared from 6-(methylthio)pyridin-3-ylboronic acid using Method 11) using Method 5 followed by oxidation according to the following procedure: racemic 3-(6-(methylthio)pyridin-3-yloxy)-4,5-dihydroisoxazole was dissolved in methylene chloride (0.5 M with respect to isoxazole) after which point m-chloroperbenzoic acid (2.0 equiv) was added in 1 portion and the reaction was allowed to stir at room temperature for 1 h. After the reaction was determined to be complete by LC/MS, the solvent was evaporated. The crude mixture was then redissolved in tert-butylmethyl ether (0.5 M) after which hexane was slowly added until a solid precipitated. The solid was then collected via vacuum filtration and washed with 1:1 hexanes/MTBE to provide the desired 3-(pyridin-3-yloxy)-4,5-dihydroisoxazole II-29a and II-29b as a white solid. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=404.1 m/z. Activity: A
Reaction SMILES: [CH2:1]([C:5]1([CH2:24][CH2:25][CH2:26][CH3:27])[C:17]2[CH:16]=[C:15]([C:18](=O)[CH3:19])[CH:14]=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][C:8]([N+:21]([O-:23])=[O:22])=[CH:9][CH:10]=2)[CH2:2][CH2:3][CH3:4].Cl.[NH2:29][OH:30].C([O-])(=O)C.[Na+].O>C(O)C>[CH2:1]([C:5]1([CH2:24][CH2:25][CH2:26][CH3:27])[C:17]2[CH:16]=[C:15]([C:18](=[N:29][OH:30])[CH3:19])[CH:14]=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][C:8]([N+:21]([O-:23])=[O:22])=[CH:9][CH:10]=2)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC1(CCCC)c2cc(C(C)=O)ccc2-c2ccc([N+](=O)[O-])cc21
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCC1(CCCC)c2cc(C(C)=NO)ccc2-c2ccc([N+](=O)[O-])cc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 93.8 %

Procedure:
After 5.0 g of 1-(9,9-di-n-butyl-7-nitrofluorene-2-yl)-ethanone (6) (13.7 mmol) was dispersed in 150 ml of ethanol and 1.04 g of hydroxylamine hydrochloride (15.1 mmol) and 1.24 g of sodium acetate (15.1 mmol) were added thereto, the reaction mixture was slowly heated and refluxed for 1 hour. The reaction mixture was cooled to room temperature and 100 ml of distilled water was added thereto. Then, a solid product obtained by stirring the reaction mixture for about 30 minutes was filtered and washed with distilled water several times, followed by drying, thereby obtaining 4.89 g of 1-(9,9-di-n-butyl-7-nitrofluorene-2-yl)-ethanone oxime (7) (93.9%) as a light yellow product.
Reaction SMILES: [C:1]([OH:20])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]CCCCCCC.[SH:21]C(O)CCCCCCCCCC.C(O)C>C(Cl)(Cl)Cl>[SH:21][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][OH:20]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: CCCCCCCCCCC(O)S
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: OCCCCCCCCCCCS

Procedure:
Five (5) mg of the oleic acid-stabilized CdSe quantum dots and 50 mg of 1-mercapto-1-undecanol were mixed with 5 ml of chloroform and 5 ml of ethanol. The mixture was then sonicated for 3 hours. Then, 40 ml of chloroform was added to the mixture to obtain a precipitate of 11-mercapto-1-undecanol capped CdSe quantum dots. The precipitate was dissolved in ethanol and dimethyl sulfoxide (“DMSO”).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3OP(O)(O)=O)C=2N=1.P([O-])([O-])([O-])=O.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O>>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)C1CCCCC1=O
Agent: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=P([O-])([O-])[O-]
Product: CCOC(=O)C1CCCCC1O
Reaction time: 4 h
Yield: 99 %

Procedure:
The asymmetric reduction of ethyl 2-oxocyclohexanecarboxylate was carried out by using this reductase (2). Namely, 4 ml of the reaction mixture containing the reductase (2) (2U), NADPH (0.8 μmol), ethyl 2-oxocyclohexanecarboxylate (100 μmol, 17 mg), phosphate buffer solution (pH 7.0, 400 μmol), glucose dehydrogenase (the same enzyme as that used in Example 4; 2U) and glucose (100,μmol) was incubated at 30° C. with gentle shaking to promote the reaction. After 4 hour-incubation, the reaction mixture was extracted according to the same manner as in Example 3. The extract was analyzed by gas chromatography described in Example 1. As a result, the yield of the cis isomer was 17.0 mg (reduction yield >99%), and neither the remaining substrate nor the trans isomer was detected. On the other hand, the extract above was distilled off according to the the same manner as in Example 3 to obtain the reduction product, ethyl 2-hydroxycyclohexanecarboxylate. The resulting reduction product was analyzed by high performance liquid chromatography described in Example 1. As a result, only the cis 2 isomer was detected and no other isomers were detected.
Reaction SMILES: [CH3:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:9][C:10]3[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=3)[CH:7]=[N:8][C:4]=2[C:3]=1[N+:18]([O-:20])=[O:19].Cl.Cl[CH2:23][C:24]1C2C(=CC=CC=2)N=[CH:26][CH:25]=1>>[CH3:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:9][C:10]3[C:11]4[C:12](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:13]=[CH:14][CH:15]=3)[CH:7]=[N:8][C:4]=2[C:3]=1[N+:18]([O-:20])=[O:19]
Reactant: Cc1ccc2c(ncn2Cc2ccncc2)c1[N+](=O)[O-]
Reactant: ClCc1ccnc2ccccc12
Agent: Cl
Product: Cc1ccc2c(ncn2Cc2ccnc3ccccc23)c1[N+](=O)[O-]

Procedure:
Compound 5a was synthesized in the same manner as compound 2c using 4-chloromethylquinoline hydrochloride instead of 4-chloromethylpyridine hydrochloride.
Reaction SMILES: [OH:1][CH:2]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]([OH:6])=[O:5].[CH2:38](Br)[C:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:40].C(N(CC)CC)C>O1CCCC1>[OH:1][CH:2]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH:28]=[CH:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:4]([O:6][CH2:38][C:39]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:40])=[O:5]
Reactant: CCCCCCCCC=CCCCCCCCC(O)C(CCCCCCCCCCCCCC)C(=O)O
Reactant: O=C(CBr)c1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCCCC=CCCCCCCCC(O)C(CCCCCCCCCCCCCC)C(=O)OCC(=O)c1ccccc1
Temperature: 25 °C
Yield: 22.1 %

Procedure:
3-Hydroxy-2-n-tetradecyl-11-icosenoic acid (II)(3.68 g, 7.04 millimole) was dissolved in dry tetrahydrofuran (100 ml), and phenacyl bromide (2.10 g, 10.56 millimole) and triethyl amine (1.47 ml, 10.56 millimole) were successively added thereto with ice cooling. The reaction mixture was allowed to warm to room temperature, and to react for 13.5 hours. The insoluble matter in the reaction mixture was filtered off with suction and the solvent was distilled off from the filtrate. The residue was dissolved in methylene chloride and the obtained solution was successively washed with water and saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. The inorganic salt was filtered off and the solvent was distilled off from the filtrate. The obtained residue was purified over a silicagel column (benzene -→ benzene:ethyl acetate=8:2) to give phenacyl 3-hydroxy-2-n-tetradecyl-11-icosenoate (IV)(998.6 mg, yield 22.1%) in the form of white viscous solid. IR(νmaxKBr, cm-1); 3340, 2900, 2850, 1740, 1705
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([Cl:15])=[CH:10][C:9]=1[NH2:16])(C)(C)C.C(O[C:23](=[O:41])[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]2[CH:38]=[C:37]([CH3:39])[N:36]=[C:35]([NH2:40])[N:34]=2)[CH:28]=1)=O)(C)(C)C>>[NH2:40][C:35]1[N:34]=[C:33]([C:29]2[CH:28]=[C:27]([C:25]3[CH2:24][C:23](=[O:41])[NH:16][C:9]4[CH:10]=[C:11]([Cl:15])[C:12]([CH3:14])=[CH:13][C:8]=4[N:7]=3)[CH:32]=[CH:31][CH:30]=2)[CH:38]=[C:37]([CH3:39])[N:36]=1
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)nc(N)n1
Product: Cc1cc(-c2cccc(C3=Nc4cc(C)c(Cl)cc4NC(=O)C3)c2)nc(N)n1

Procedure:
The title compound was prepared from (2-amino-4-chloro-5-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (128 mg, 0.5 mmol) and 3-[3-(2-amino-6-methyl-pyrimidin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K45) (180 mg, 0.55 mmol) according to the general procedure M and subsequent treatment of the crude product according to the general procedure N. Obtained as a light yellow solid (108 mg).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][S:8]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)(=[O:10])=[O:9])([CH3:4])([CH3:3])[CH3:2].Br[CH2:20][C:21]#[C:22][CH3:23]>>[C:1]([O:5][C:6](=[O:18])[C:7]([S:8]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)(=[O:10])=[O:9])([CH2:16][C:11]#[C:12][CH3:13])[CH2:20][C:21]#[C:22][CH3:23])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC#CCBr
Reactant: CC(C)(C)OC(=O)CS(=O)(=O)c1ccc(F)cc1
Product: CC#CCC(CC#CC)(C(=O)OC(C)(C)C)S(=O)(=O)c1ccc(F)cc1
Yield: 77 %

Procedure:
2-(4-Fluoro-benzenesulfonyl)-2-but-2-ynyl-hex-4-ynoic acid tert-butyl ester was prepared according to the procedure as outlined in Example 9. Starting from 2-(4-fluoro-benzenesulfonyl)-acetic acid tert-butyl ester (4.87 g, 20 mmol) and 1-bromo-2-butyne (5.36 g, 40 mmol), 6.0 g of the product was isolated. Yield 77%; white solid; mp 85° C.; MS: 379.1 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:17])=[CH:12][N:11]=2)=[CH:5][C:4]([C:24]2[C:29]([CH:30]=[O:31])=[C:28]([N:32]3[CH2:44][CH2:43][N:35]4[C:36]5[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=5[CH:42]=[C:34]4[C:33]3=[O:45])[N:27]=[CH:26][CH:25]=2)=[CH:3]1.[BH4-].[Na+]>CO>[OH:31][CH2:30][C:29]1[C:28]([N:32]2[CH2:44][CH2:43][N:35]3[C:36]4[CH2:37][CH2:38][CH2:39][CH2:40][C:41]=4[CH:42]=[C:34]3[C:33]2=[O:45])=[N:27][CH:26]=[CH:25][C:24]=1[C:4]1[CH:5]=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:17])=[CH:12][N:11]=2)[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1
Reactant: Cn1cc(-c2ccnc(N3CCn4c(cc5c4CCCC5)C3=O)c2C=O)cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cn1cc(-c2ccnc(N3CCn4c(cc5c4CCCC5)C3=O)c2CO)cc(Nc2ccc(C(=O)N3CCOCC3)cn2)c1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 88.6 %

Procedure:
A mixture of 111d (60 mg, 0.05 mmol), NaBH4 (6.4 mg, 0.1 mmol) and MeOH (5 mL) was stirred at 0° C. for 30 mins. The mixture was evaporated in vacuo and the residue was extracted with EtOAc (10 mL×2). The combined EtOAc extract was concentrated under reduced pressure and the residue was purified with reverse-phase prep-HPLC to give 111 (27 mg, 44%). LCMS: [M+H]+ 610. 1H NMR (500 MHz, DMSO) δ 9.00 (s, 1H), 8.78 (d, J=2.0, 1H), 8.49 (d, J=5, 1H), 8.26 (d, J=2.0, 1H), 7.65-7.67 (m, 2H), 7.60 (d, J=2.5, 1H), 6.58 (s, 1H), 4.96 (t, J=5, 1H), 4.40-4.46 (m, 2H), 4.11-4.24 (m, 3H), 3.86-3.88 (m, 1H), 3.56-3.62 (m, 8H), 3.50 (s, 4H), 2.62-2.63 (m, 2H), 2.46-2.47 (m, 2H), 1.67-1.80 (m, 4H)