l4777 , specification:5000  u  g ) was purchased from sigma  aldrich ; lipase ak ( pseudomonas fruorescens ) was from amano pharmaceuticals . lipase psim ( burkholderia cepacia immobilized on diatomaceous earth ) was from amano enzyme europe ltd . reactions in the continuousflow system were carried out in the hcube from thalesnano inc ( budapest , hungary ) . the stainlesssteel cartridges used ( 70  mm in length , 4  mm in internal diameter and 0.75  ml in volume ) , were also from thalesnano inc . with calb ( 230  mg ) as enzyme charge and a flow rate of 0.1  ml  min ( toluene ) , the experimentally determined ( staining procedure ) residence time within the packed bed of the reactor was 7  min and 40  s. the hcube was used in  no h2  mode . the h  nmr and c  nmr spectra were recorded with a bruker avance drx 400 instrument ( billerica , ma , usa ) . elemental analyses were performed with a perkinelmer chns2400 ser ii elemental analyzer ( waltham , ma , usa ) . microwave ( mw ) reactions were performed in a cem discover mw reactor ( matthews , nc , usa ) . the ee values of the nbocprotected amino alcohols [ ( r)7(r)9 ) and ( s)7(s)9 ] and amino esters [ ( s)10(s)12 ) ] were determined directly , while those of the deprotected enantiomers [ ( r)4(r)6 and ( s)4(s)6 ] were determined after derivatization with boc2o by using highperformance liquid chromatography ( hplc ) with a chiralpak odh column ( 4.6  mm250  mm ) , eluent : nhexane : isopropyl alcohol ( 93:7 ) , flow rate : 0.5  ml  min , detection at 260  nm , at rt . retention times ( min ) : for ( r)7 : 27.7 , ( s)7 : 16.6 , ( r)8 : 38.6 , ( s)8 : 21.9 , ( r)9 : 28.8 , ( s)9 : 15.6 , ( s)10 : 13.8 , ( r)10 : 18.8 , ( s)11 : 17.0 , ( r)11 : 25.3 , ( s)12 : 12.6 , and ( r)12 : 19.9 . the ee value of nacetyl amino alcohol ( r)13 was determined with a chiralpak ia column ( 4.6  mm250  mm ) , eluent : nhexane : isopropyl alcohol ( 95:5 ) , flow rate : 0.5  ml  min , detection at 210  nm , at rt . retention times ( min ) : for ( r)13 : 92.8 and ( s)13 : 88.2 . smallscale experiments in the continuousflow system : the racemic substrate [ ( )7 , 0.0125  mmol ] and the acyl donor ( 1.1  equiv ) were dissolved in the solvent ( 1  ml ) , and the mixtures were pumped with an hplc pump through the heated ( 45  c , 60  c , 70  c , and 80  c ) and compressed ( 1  bar , 20  bar , 40  bar , 60  bar , 80  bar , and 100  bar ) cartridge filled with enzyme ( flow rate : 0.1  ml  min ) . smallscale experiments in batch mode : the racemic compound [ ( )7 , ( )8 , or ( )9 , 0.0125  mmol ] was dissolved in the solvent ( 1  ml ) , and the enzyme ( 30  mg  ml ) and acyl donor ( 2 , 6 , or 8  equiv of acetic anhydride ) were then added . tryptamine hydrochloride ( 1 , 5.9  g , 0.03 mol ) was dissolved in a mixture of water and 2  n hcl ( 15  ml ) . the solution was cooled to 0  c , and a solution of glycolaldehyde dimer ( 2.3  g , 0.02 mol , dissolved in 5  ml water ) was added . the reaction mixture was stirred at 90  c for 4  h. the cooled solution was treated with activated carbon , and then extracted with diethyl ether . to the aqueous layer , 20  % naoh was added until ph  10 , and the mixture was then extracted with etoac ( 330  ml ) . the product ( )4 was purified by column chromatography ( 5.2  g , yield : 87  % , m.p.=146147  c , lightyellow crystals , r 
 f=0.27 , eluent : meoh ) . alcohol ( )4 ( 3.0  g , 0.015 mol ) was dissolved in 80  ml 1,4dioxane and cooled to 0  c , and a solution of naoh ( 0.62  g , 0.016 mol , in 5  ml water ) and then a solution of ditertbutyl dicarbonate ( 3.56  g , 0.016 mol , in 10  ml 1,4dioxane ) were added . the reaction was carried out at 1  h under icecooling , and then at room temperature for 24  h. the reaction mixture was extracted with dichloromethane ( 330  ml ) and the extract was dried on anhydrous na2so4 and evaporated . the resulting nbocprotected amino alcohol ( )7 ( 3.6  g , yield : 81  % , m.p.=115117  c , lightyellow crystals from with diethyl ether . ) was purified by column chromatography [ r 
 f=0.23 , eluent : nhexane : etoac ( 2:1 ) ] . h  nmr ( 400  mhz , cdcl3 ) for ( )4 : =8.128.26 ( br s , 1  h , nh ) , 7.497.56 ( d , j=7.69  hz , 1  h , ar h ) , 7.327.39 ( d , j=8.14  hz , 1  h , ar  h ) , 7.107.23 ( m , 2  h , ar h ) , 4.184.26 ( t , j=2.30  hz , 1  h , ch ) , 3.773.96 ( m , 2  h , ch2 ) , 3.113.36 ( m , 2  h , ch2 ) , 2.712.87  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )4 : =135.35 , 131.43 , 125.98 , 119.67 , 117.22 , 116.13 , 109.46 , 107.18 , 62.11 , 53.19 , 40.17 , 20.35  ppm ; anal . calcd . for c12h14n2o : c 71.26 , h 6.98 , n 13.85 , found : c 71.21 , h 6.93 , n 13.79 . h  nmr ( 400  mhz , dmso ) for ( )7 : =10.6610.87 ( br s , 1  h , nh ) , 7.357.43 ( d , j=7.6  hz , 1  h , ar h ) , 7.287.35 ( d , j=8.0  hz , 1  h , ar  h ) , 7.017.09 ( t , h ) , 6.916.99 ( t , j=7.2  hz , 1  h , ar h ) , ) , 4.885.24 ( m , 2  h , ch2 ) , 4.104.43 ( m , 1  h , ch ) , 3.693.84 ( m , 2  h , ch2 ) , 2.572.74 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )7 : =136.68 , 132.30 , 127.01 , 122.24 , 119.76 , 118.50 , 111.56 , 81.10 , 64.62 , 53.32 , 28.94 , 21.91  ppm ; anal . calcd . for c17h22n2o3 : c 67.53 , h 7.33 , n 9.26 , found : c 67.43 , h 7.39 , n 9.22 . with the procedure described above [ 5methoxytryptamine hydrochloride ( 2 , 1.0  g , 4.4  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.8  ml ) , glycolaldehyde dimer ( 0.52  g , 4.3  mmol ) ] , the reaction resulted in ( )5 [ 0.52  g , yield : 51  % , m.p.=152153  c , r 
 f=0.25 , eluent : meoh ] as yellow crystals . to a solution of ( )5 ( 0.52  g , 2.26  mmol ) in 1,4dioxane ( 35  ml ) , naoh ( 0.09  g , 2.25  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.54  g , 2.47  mmol ) in 1,4dioxane ( 5  ml ) ( )8 [ 0.65  g , yield : 87  % , m.p.=155156  c from nhexane , r 
 f=0.34 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , cdcl3 ) for ( )5 : =8.088.24 ( br s , 1  h , nh ) , 7.227.24 ( d , 1  h , j=8.80  hz , ar h ) , 6.786.88 ( d , j=8  hz , 1  h , ar h ) , 4.134.26 ( m , 1  h , ch ) , 3.753.97 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 3.043.37 ( m , 2  h , ch2 ) , 2.632.88  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )5 : =152.55 , 132.38 , 130.56 , 126.30 , 110.07 , 109.48 , 107.05 , 98.70 , 62.12 , 53.90 , 53.27 , 40.23 , 20.42  ppm ; anal . c 67.22 , h 6.94 , n 12.06 , found : c 67.20 , h 6.88 , n 12.14 . h  nmr ( 400  mhz , dmso ) for ( )8 : =10.4910.72 ( br s , 1  h , nh ) , 7.167.31 ( d , 1  h , j=8.48  hz , ar h ) , 6.88 ( s , 1  h , arh ) , 6.616.77 ( dd , h ) , 4.905.23 ( m , 2  h , ch2 ) , 4.084.43 ( m , 1  h , ch ) , 3.703.85 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 2.512.61 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )8 : =154.45 , 133.12 , 131.80 , 127.37 , 112.18 , 100.91 , 81.05 , 64.68 , 56.42 , 53.32 , 28.90 , 21.92  ppm ; anal . : c 65.04 , h 7.28 , n 8.43 , found : c 65.07 , h 7.19 , n 8.49 . with the procedure described above [ 5fluorotryptamine hydrochloride ( 3 , 1.0  g , 4.6  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.5  ml ) , glycolaldehyde dimer ( 0.55  g , 4.6  mmol ) ] , the reaction resulted in ( )6 [ 0.93  g , yield : 91  % , m.p.=138141  c , r 
 f=0.15 , eluent : toluene : meoh ( 1:1 ) ] as yellow crystals . to a solution of ( )6 ( 0.83  g , 3.77  mmol ) in 1,4dioxane ( 30  ml ) , naoh ( 0.15  g , 3.75  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.91  g , 4.17  mmol ) in 1,4dioxane ( 5  ml ) the product ( )9 [ 0.88  g , yield : 73  % , m.p.=124125  c from nhexane , r 
 f=0.26 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , [ d4]meoh ) for ( )6 : =7.167.28 ( q , j=4.44  hz , 1  h , ar h ) , 7.007.08 ( dd , j=2.48  hz , 9.68  hz , 1  h , ar  h ) , 6.726.85 ( dt , h ) , 4.034.15 ( m , 1  h , ch ) , 3.783.92 ( m , 1  h , ch2 ) , 3.563.66 ( m , 1  h , ch2 ) , 3.253.32 ( m , 1  h , ch2 ) , 2.933.03 ( m , 1  h , ch2 ) , 2.622.78  ppm ( m , 2  h , ch2 ) ; c  nmr : ( 400  mhz , [ d4]meoh ) for ( )6 : =157.62 , 155.31 , 133.72 , 131.84 , 126.26 , 110.07 , 107.34 , 100.86 , 62.02 , 47.39 , 40.16 , 20.28  ppm ; anal . calcd . for c12h13fn2o : c 65.44 , h 5.95 , n 12.72 , found : c 65.27 , h 5.99 , n 12.85 . h  nmr ( 400  mhz , dmso ) for ( )9 : =10.7810.92 ( br s , 1  h , nh ) , 7.257.34 ( q , h ) , 4.955.19 ( m , 2  h , ch2 ) , 4.114.39 ( m , 1  h , ch ) , 3.693.81 ( m , 2  h , ch2 ) , 2.562.69 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( )9 : =159.37 , 157.04 , 134.25 , 133.13 , 127.32 , 112.03 110.33 , 103.54 , 81.22 , 64.49 , 53.24 , 40.36 , 28.89 , 21.85  ppm ; anal . c 63.74 , h 6.61 , n 8.74 , found : c 63.70 , h 6.71 , n 8.68 . to ( )7 ( 0.5  g , 1.66  mmol ) in toluene ( 30  ml ) , lipase calb ( 900  mg ) and acetic anhydride ( 2  equiv , 310  l ) were added , and the reaction mixture was shaken in an incubator shaker at 60  c for 1.5  h. the reaction was stopped at 50  % conversion ( ee=98  % ) by filtering off the enzyme , and the solvent was then evaporated off . the products were separated by column chromatography on silica [ eluent : nhexane : etoac ( 2:1 ) ] , resulting in the unreacted amino alcohol ( r)7 as lightyellow crystals [ 235  mg , yield : 47  % , [ ]d 
 = + 107.5 ( c=0.34 in etoh ) , m.p.=136137  c , r 
 f=0.24 ] and the product amino ester ( s)10 as white crystals [ 263  mg , yield : 46  % , [ ]d 
 = 102.2 ( c=0.32 in etoh ) , m.p.=124125  c , r 
 f=0.76 ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)7 were similar to those for ( )7 . h  nmr ( 400  mhz , cdcl3 ) for ( s)10 : =7.988.15 ( br s , 1  h , nh ) , 7.527.54 ( d , 1  h , j=8.0  hz , ar h ) , 7.377.39 ( d , 1  h , j=7.6  hz , ar  h ) , 7.27.26 ( t , h ) , 5.315.69 ( m , 1  h , ch ) , 4.294.47 ( m , 1  h , ch2 overlapping with m , 2  h , ch2 ) , 3.473.56 ( m , 1  h , ch2 ) , 2.712.96 ( m , 2  h , ch2 ) , 2.15 ( s , 3  h , ch3 ) , 1.46  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)10 : =171.30 , 136.70 , 130.76 , 127.06 , 122.57 , 120.00 , 118.66 , 111.47 , 80.81 , 65.16 , 50.09 , 39.90 28.87 , 21.90 , 21.37  ppm ; anal . c 66.26 , h 7.02 , n 8.13 , found : c 66.29 , h 7.12 , n 8.04 . with the procedure described above , the reaction of ( )8 ( 200  mg , 0.6  mmol ) , in toluene ( 25  ml ) , calb ( 750  mg ) and acetic anhydride ( 8  equiv , 466  l ) after 2.5  h resulted in ( r)8 as white crystals [ 93  mg , yield : 47  % , [ ]d 
 = + 82 ( c=0.23 in etoh ) , m.p.=196198  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 2:1 ) ] and ( s)11 as a yellow oil [ 98  mg , yield : 43  % , [ ]d 
 = 92.3 ( c=0.61 in etoh ) , ee=98  % , r 
 f=0.63 , eluent : nhexane : etoac ( 2:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)8 were similar to those for ( )8 . h  nmr ( 400  mhz , dmso ) for ( s)11 : =10.7210.88 ( d , 1h j=14.04  hz , nh ) , 7.187.25 ( d , 1  h , j=8.4  hz , ar h ) , 6.896.94 ( d , 1  h , j=2.12  hz , ar h ) , 6.696.75 ( dd , 1  h , j=2.34  hz , 8.84  hz , ar h ) , 5.285.47 ( m , 1  h , ch ) , 4.104.50 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 3.75 ( s , 3  h , ch3 ) , 2.552.73 ( m , 2  h , ch2 ) , 1.952.10 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)11 : =171.36 , 154.56 , 131.84 , 127.45 , 112.19 , 100.96 , 80.78 , 65.07 , 56.39 , 50.17 , 28.87 , 21.93 , 21.35  ppm ; anal . c 64.15 , h 7.00 , n 7.48 , found : c 64.26 , h 7.02 , n 7.39 . similarly , the preparativescale reaction of ( )9 ( 500  mg , 1.56  mmol ) in toluene ( 50  ml ) , calb ( 1500  mg ) and acetic anhydride ( 6  equiv , 885  l ) resulted after 2  h in ( r)9 as lightyellow crystals [ 234  mg , isolated yield : 47  % , [ ]d 
 = + 97 ( c=0.21 in etoh ) , m.p.=99100  c , ee=96  % , r 
 f=0.12 , eluent : nhexane : etoac ( 3:1 ) ] and ( s)12 as white crystals [ 255  mg , isolated yield : 45  % , [ ]d 
 = 131.8 ( c=0.38 in etoh ) , m.p.=143145  c , ee=98  % , r 
 f=0.49 , eluent : nhexane : etoac ( 3:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)9 were similar to those for ( )9 . h  nmr ( 400  mhz , dmso ) for ( s)12 : =10.9911.21 ( d , 1  h , j=16  hz , nh ) , 7.277.35 ( 2d , h ) , 7.157.21 ( dd , 1  h , j=2.4  hz , 9.82  hz , ar h ) , 5.315.53 ( d , 1  h , j=27.4  hz , ch ) , 4.104.59 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 2.552.70 ( m , 2  h , ch2 ) , 1.942.12 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)12 : =171.31 , 159.46 , 157.12 , 133.17 , 132.64 , 127.45 , 111.98 , 110.79 , 103.73 , 80.94 , 65.07 , 50.13 , 28.85 , 21.82 , 21.35  ppm ; anal . c 62.97 , h 6.40 , n 7.73 , found : c 62.89 , h 6.44 , n 7.78 . enantiomeric ( s)10 ( 30  mg , 0.09  mmol ) , ( s)11 ( 40  mg , 0.11  mmol ) , or ( s)12 ( 50  mg , 0.14  mmol ) was dissolved in meoh ( 10  ml ) . k2co3 ( 50  mg , 0.36  mmol ) was added , and the reaction mixture was shaken at 60  c for 10  min . the following products were obtained as white crystals : ( s)7 [ 24  mg , yield : 90  % , [ ]d 
 = 108.8 ( c=0.33 in etoh ) , m.p.=135137  c , ee=98  % , r 
 f=0.48 , eluent : nhexane : etoac ( 1:1 ) ] , ( s)8 [ 31  mg , yield : 88  % , [ ]d 
 = 81 ( c=0.12 in etoh ) , m.p.=195197  c , ee=98  % , r 
 f=0.47 , eluent : nhexane : etoac ( 1:1 ) ] , or ( s)9 [ 33  mg , yield : 75  % , [ ]d 
 = 105 ( c=0.195 in etoh ) , m.p.=98100  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 3:1 ) ] . ( r)7 ( 50  mg , 0.16  mmol ) , ( r)8 ( 30  mg , 0.09  mmol ) , ( r)9 ( 30  mg , 0.09  mmol ) , ( s)10 ( 50  mg , 0.15  mmol ) , ( s)11 ( 40  mg , 0.1  mmol ) , or ( s)12 ( 30  mg , 0.08  mmol ) was suspended in water ( 5  ml ) in a tube , and stirred at 100  c for 1  h under maximum mw irradiation of 150  w. the solvent was evaporated off , and the residue was purified by column chromatography with toluene : meoh ( 1:1 ) as eluent . the following products were crystallized from nhexane : ( r)4 as yellow crystals [ 26  mg , yield : 79  % , [ ]d 
 = 37.8 ( c=0.41 in etoh ) , m.p.=145147  c , ee=98  % , r 
 f=0.15 ] , ( s)4 as yellow crystals [ 15  mg , yield : 52  % , [ ]d 
 = + 36.1 ( c=0.4 in etoh ) , m.p.=146147  c , ee=98  % , r 
 f=0.16 ] , ( r)5 as lightyellow crystals [ 8  mg , yield : 38  % , [ ]d 
 = 22.0 ( c=0.4 in etoh ) , m.p.=167168  c , ee=98  % , r 
 f=0.18 ] , ( s)5 as lightyellow crystals [ 9  mg , yield : 38  % , [ ]d 
 = + 21.8 ( c=0.45 in etoh ) , m.p.=168170  c , ee=98  % , r 
 f=0.21 ] , ( r)6 as lightyellow crystals [ 11  mg , yield : 52  % , [ ]d 
 = 29 ( c=0.155 in etoh ) , m.p.=9698  c , ee=96  % , r 
 f=0.14 ] , or ( s)6 as lightyellow crystals [ 5  mg , yield : 28  % , [ ]d 
 = + 29 ( c=0.25 in etoh ) , m.p.=99101  c , ee=98  % , r 
 f=0.18 ] . a mixture of ( )4 ( 30  mg , 0.13  mmol ) , 6  equiv acetic anhydride ( 75  l , 0.8  mmol ) and naoh ( 100  mg , 2.5  mmol ) in ch2cl2 ( 20  ml ) and water ( 20  ml ) was stirred for 48  h at rt . the reaction mixture was then extracted with ch2cl2 ( 315  ml ) . the organic phase was dried on anhydrous na2so4 and evaporated . the resulting darkyellow oil was purified by column chromatography with ch2cl2:meoh ( 30:1 ) as eluent . the product ( )13 ( 18  mg , yield : 49  % , m.p.=191192  c , r 
 f=0.10 ) was obtained as white crystals from etoh and diisopropyl ether ( 1:9 ) . h  nmr ( 400  mhz , cdcl3 ) for ( )13 : =8.588.71 ( br s , 1  h , nh ) , 7.447.49 ( d , j=7.72  hz , 1  h , ar h ) , 7.317.35 ( d , j=8.36  hz , 1  h , ar  h ) , 7.137.20 ( dt , h ) , 5.745.82 ( t , j=6.56  hz , 1  h , ch ) , 3.964.11 ( m , 2  h , ch2 ) , 3.843.93 ( m , 1  h , ch2 ) , 3.433.55 ( m , 1  h , ch2 ) , 2.792.96 ( m , 2  h , ch2 ) , 2.29  ppm ( s , 3  h , ch3 ) . with the above procedure , the reaction of ( r)4 ( 26  mg , 0.11  mmol ) resulted in the desired product ( r)13 as white crystals [ 22  mg , yield : 70  % , [ ]d 
 = + 164 ( c=0.2 in etoh ) , m.p.=201203  c , ee=98  % ] . the h  nmr ( 400  mhz , cdcl3 ) spectroscopic data for ( r)13 were similar to those for ( )13 . l4777 , specification:5000  u  g ) was purchased from sigma  aldrich ; lipase ak ( pseudomonas fruorescens ) was from amano pharmaceuticals . lipase psim ( burkholderia cepacia immobilized on diatomaceous earth ) was from amano enzyme europe ltd . reactions in the continuousflow system were carried out in the hcube from thalesnano inc ( budapest , hungary ) . the stainlesssteel cartridges used ( 70  mm in length , 4  mm in internal diameter and 0.75  ml in volume ) , were also from thalesnano inc . with calb ( 230  mg ) as enzyme charge and a flow rate of 0.1  ml  min ( toluene ) , the experimentally determined ( staining procedure ) residence time within the packed bed of the reactor was 7  min and 40  s. the hcube was used in  no h2  mode . the h  nmr and c  nmr spectra were recorded with a bruker avance drx 400 instrument ( billerica , ma , usa ) . elemental analyses were performed with a perkinelmer chns2400 ser ii elemental analyzer ( waltham , ma , usa ) . microwave ( mw ) reactions were performed in a cem discover mw reactor ( matthews , nc , usa ) . the ee values of the nbocprotected amino alcohols [ ( r)7(r)9 ) and ( s)7(s)9 ] and amino esters [ ( s)10(s)12 ) ] were determined directly , while those of the deprotected enantiomers [ ( r)4(r)6 and ( s)4(s)6 ] were determined after derivatization with boc2o by using highperformance liquid chromatography ( hplc ) with a chiralpak odh column ( 4.6  mm250  mm ) , eluent : nhexane : isopropyl alcohol ( 93:7 ) , flow rate : 0.5  ml  min , detection at 260  nm , at rt . retention times ( min ) : for ( r)7 : 27.7 , ( s)7 : 16.6 , ( r)8 : 38.6 , ( s)8 : 21.9 , ( r)9 : 28.8 , ( s)9 : 15.6 , ( s)10 : 13.8 , ( r)10 : 18.8 , ( s)11 : 17.0 , ( r)11 : 25.3 , ( s)12 : 12.6 , and ( r)12 : 19.9 . the ee value of nacetyl amino alcohol ( r)13 was determined with a chiralpak ia column ( 4.6  mm250  mm ) , eluent : nhexane : isopropyl alcohol ( 95:5 ) , flow rate : 0.5  ml  min , detection at 210  nm , at rt . retention times ( min ) : for ( r)13 : 92.8 and ( s)13 : 88.2 . smallscale experiments in the continuousflow system : the racemic substrate [ ( )7 , 0.0125  mmol ] and the acyl donor ( 1.1  equiv ) were dissolved in the solvent ( 1  ml ) , and the mixtures were pumped with an hplc pump through the heated ( 45  c , 60  c , 70  c , and 80  c ) and compressed ( 1  bar , 20  bar , 40  bar , 60  bar , 80  bar , and 100  bar ) cartridge filled with enzyme ( flow rate : 0.1  ml  min ) . smallscale experiments in batch mode : the racemic compound [ ( )7 , ( )8 , or ( )9 , 0.0125  mmol ] was dissolved in the solvent ( 1  ml ) , and the enzyme ( 30  mg  ml ) and acyl donor ( 2 , 6 , or 8  equiv of acetic anhydride ) were then added . tryptamine hydrochloride ( 1 , 5.9  g , 0.03 mol ) was dissolved in a mixture of water and 2  n hcl ( 15  ml ) . the solution was cooled to 0  c , and a solution of glycolaldehyde dimer ( 2.3  g , 0.02 mol , dissolved in 5  ml water ) was added . the reaction mixture was stirred at 90  c for 4  h. the cooled solution was treated with activated carbon , and then extracted with diethyl ether . to the aqueous layer , 20  % naoh was added until ph  10 , and the mixture was then extracted with etoac ( 330  ml ) . the product ( )4 was purified by column chromatography ( 5.2  g , yield : 87  % , m.p.=146147  c , lightyellow crystals , r 
 f=0.27 , eluent : meoh ) . alcohol ( )4 ( 3.0  g , 0.015 mol ) was dissolved in 80  ml 1,4dioxane and cooled to 0  c , and a solution of naoh ( 0.62  g , 0.016 mol , in 5  ml water ) and then a solution of ditertbutyl dicarbonate ( 3.56  g , 0.016 mol , in 10  ml 1,4dioxane ) were added . the reaction was carried out at 1  h under icecooling , and then at room temperature for 24  h. the reaction mixture was extracted with dichloromethane ( 330  ml ) and the extract was dried on anhydrous na2so4 and evaporated . the resulting nbocprotected amino alcohol ( )7 ( 3.6  g , yield : 81  % , m.p.=115117  c , lightyellow crystals from with diethyl ether . ) was purified by column chromatography [ r 
 f=0.23 , eluent : nhexane : etoac ( 2:1 ) ] . h  nmr ( 400  mhz , cdcl3 ) for ( )4 : =8.128.26 ( br s , 1  h , nh ) , 7.497.56 ( d , j=7.69  hz , 1  h , ar h ) , 7.327.39 ( d , j=8.14  hz , 1  h , ar h ) , 4.184.26 ( t , j=2.30  hz , 1  h , ch ) , 3.773.96 ( m , 2  h , ch2 ) , 3.113.36 ( m , 2  h , ch2 ) , 2.712.87  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )4 : =135.35 , 131.43 , 125.98 , 119.67 , 117.22 , 116.13 , 109.46 , 107.18 , 62.11 , 53.19 , 40.17 , 20.35  ppm ; anal . c 71.26 , h 6.98 , n 13.85 , found : c 71.21 , h 6.93 , n 13.79 . h  nmr ( 400  mhz , dmso ) for ( )7 : =10.6610.87 ( br s , 1  h , nh ) , 7.357.43 ( d , j=7.6  hz , 1  h , ar h ) , 7.287.35 ( d , j=8.0  hz , 1  h , ar  h ) , 7.017.09 ( t , h ) , 6.916.99 ( t , j=7.2  hz , 1  h , ar h ) , ) , 4.885.24 ( m , 2  h , ch2 ) , 4.104.43 ( m , 1  h , ch ) , 3.693.84 ( m , 2  h , ch2 ) , 2.572.74 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )7 : =136.68 , 132.30 , 127.01 , 122.24 , 119.76 , 118.50 , 111.56 , 81.10 , 64.62 , 53.32 , 28.94 , 21.91  ppm ; anal . : c 67.53 , h 7.33 , n 9.26 , found : c 67.43 , h 7.39 , n 9.22 . with the procedure described above [ 5methoxytryptamine hydrochloride ( 2 , 1.0  g , 4.4  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.8  ml ) , glycolaldehyde dimer ( 0.52  g , 4.3  mmol ) ] , the reaction resulted in ( )5 [ 0.52  g , yield : 51  % , m.p.=152153  c , r 
 f=0.25 , eluent : meoh ] as yellow crystals . to a solution of ( )5 ( 0.52  g , 2.26  mmol ) in 1,4dioxane ( 35  ml ) , naoh ( 0.09  g , 2.25  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.54  g , 2.47  mmol ) in 1,4dioxane ( 5  ml ) were added . ( )8 [ 0.65  g , yield : 87  % , m.p.=155156  c from nhexane , r 
 f=0.34 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , cdcl3 ) for ( )5 : =8.088.24 ( br s , 1  h , nh ) , 7.227.24 ( d , 1  h , j=8.80  hz , ar h ) , 6.786.88 ( d , j=8  hz , 1  h , ar h ) , 4.134.26 ( m , 1  h , ch ) , 3.753.97 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 3.043.37 ( m , 2  h , ch2 ) , 2.632.88  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )5 : =152.55 , 132.38 , 130.56 , 126.30 , 110.07 , 109.48 , 107.05 , 98.70 , 62.12 , 53.90 , 53.27 , 40.23 , 20.42  ppm ; anal . c 67.22 , h 6.94 , n 12.06 , found : c 67.20 , h 6.88 , n 12.14 . h  nmr ( 400  mhz , dmso ) for ( )8 : =10.4910.72 ( br s , 1  h , nh ) , 7.167.31 ( d , 1  h , j=8.48  hz , ar h ) , 6.88 ( s , 1  h , arh ) , 6.616.77 ( dd , j=2.2  hz , 8.7  hz , 1  h , ar h ) , 4.905.23 ( m , 2  h , ch2 ) , 4.084.43 ( m , 1  h , ch ) , 3.703.85 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 2.512.61 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )8 : =154.45 , 133.12 , 131.80 , 127.37 , 112.18 , 100.91 , 81.05 , 64.68 , 56.42 , 53.32 , 28.90 , 21.92  ppm ; anal . calcd . for c18h24n2o4 : c 65.04 , h 7.28 , n 8.43 , found : c 65.07 , h 7.19 , n 8.49 . with the procedure described above [ 5fluorotryptamine hydrochloride ( 3 , 1.0  g , 4.6  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.5  ml ) , glycolaldehyde dimer ( 0.55  g , 4.6  mmol ) ] , the reaction resulted in ( )6 [ 0.93  g , yield : 91  % , m.p.=138141  c , r 
 f=0.15 , eluent : toluene : meoh ( 1:1 ) ] as yellow crystals . to a solution of ( )6 ( 0.83  g , 3.77  mmol ) in 1,4dioxane ( 30  ml ) , naoh ( 0.15  g , 3.75  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.91  g , 4.17  mmol ) in 1,4dioxane ( 5  ml ) the product ( )9 [ 0.88  g , yield : 73  % , m.p.=124125  c from nhexane , r 
 f=0.26 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , [ d4]meoh ) for ( )6 : =7.167.28 ( q , j=4.44  hz , 1  h , ar h ) , 4.034.15 ( m , 1  h , ch ) , 3.783.92 ( m , 1  h , ch2 ) , 3.563.66 ( m , 1  h , ch2 ) , 3.253.32 ( m , 1  h , ch2 ) , 2.933.03 ( m , 1  h , ch2 ) , 2.622.78  ppm ( m , 2  h , ch2 ) ; c  nmr : ( 400  mhz , [ d4]meoh ) for ( )6 : =157.62 , 155.31 , 133.72 , 131.84 , 126.26 , 110.07 , 107.34 , 100.86 , 62.02 , 47.39 , 40.16 , 20.28  ppm ; anal . c 65.44 , h 5.95 , n 12.72 , found : c 65.27 , h 5.99 , n 12.85 . h  nmr ( 400  mhz , dmso ) for ( )9 : =10.7810.92 ( br s , 1  h , nh ) , 7.257.34 ( q , h ) , 4.955.19 ( m , 2  h , ch2 ) , 4.114.39 ( m , 1  h , ch ) , 3.693.81 ( m , 2  h , ch2 ) , 2.562.69 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( )9 : =159.37 , 157.04 , 134.25 , 133.13 , 127.32 , 112.03 110.33 , 103.54 , 81.22 , 64.49 , 53.24 , 40.36 , 28.89 , 21.85  ppm ; anal . for c17h21fn2o3 : c 63.74 , h 6.61 , n 8.74 , found : c 63.70 , h 6.71 , n 8.68 . tryptamine hydrochloride ( 1 , 5.9  g , 0.03 mol ) was dissolved in a mixture of water and 2  n hcl ( 15  ml ) . the solution was cooled to 0  c , and a solution of glycolaldehyde dimer ( 2.3  g , 0.02 mol , dissolved in 5  ml water ) was added . the reaction mixture was stirred at 90  c for 4  h. the cooled solution was treated with activated carbon , and then extracted with diethyl ether . to the aqueous layer , 20  % naoh was added until ph  10 , and the mixture was then extracted with etoac ( 330  ml ) . the product ( )4 was purified by column chromatography ( 5.2  g , yield : 87  % , m.p.=146147  c , lightyellow crystals , r 
 f=0.27 , eluent : meoh ) . alcohol ( )4 ( 3.0  g , 0.015 mol ) was dissolved in 80  ml 1,4dioxane and cooled to 0  c , and a solution of naoh ( 0.62  g , 0.016 mol , in 5  ml water ) and then a solution of ditertbutyl dicarbonate ( 3.56  g , 0.016 mol , in 10  ml 1,4dioxane ) were added . the reaction was carried out at 1  h under icecooling , and then at room temperature for 24  h. the reaction mixture was extracted with dichloromethane ( 330  ml ) and the extract was dried on anhydrous na2so4 and evaporated . the resulting nbocprotected amino alcohol ( )7 ( 3.6  g , yield : 81  % , m.p.=115117  c , lightyellow crystals from with diethyl ether . ) was purified by column chromatography [ r 
 f=0.23 , eluent : nhexane : etoac ( 2:1 ) ] . h  nmr ( 400  mhz , cdcl3 ) for ( )4 : =8.128.26 ( br s , 1  h , nh ) , 7.497.56 ( d , j=7.69  hz , 1  h , ar h ) , 7.327.39 ( d , j=8.14  hz , 1  h , ar h ) , 4.184.26 ( t , j=2.30  hz , 1  h , ch ) , 3.773.96 ( m , 2  h , ch2 ) , 3.113.36 ( m , 2  h , ch2 ) , 2.712.87  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )4 : =135.35 , 131.43 , 125.98 , 119.67 , 117.22 , 116.13 , 109.46 , 107.18 , 62.11 , 53.19 , 40.17 , 20.35  ppm ; anal . c 71.26 , h 6.98 , n 13.85 , found : c 71.21 , h 6.93 , n 13.79 . h  nmr ( 400  mhz , dmso ) for ( )7 : =10.6610.87 ( br s , 1  h , nh ) , 7.357.43 ( d , j=7.6  hz , 1  h , ar h ) , 7.287.35 ( d , j=8.0  hz , 1  h , ar  h ) , 7.017.09 ( t , h ) , 6.916.99 ( t , j=7.2  hz , 1  h , ar h ) , ) , 4.885.24 ( m , 2  h , ch2 ) , 4.104.43 ( m , 1  h , ch ) , 3.693.84 ( m , 2  h , ch2 ) , 2.572.74 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )7 : =136.68 , 132.30 , 127.01 , 122.24 , 119.76 , 118.50 , 111.56 , 81.10 , 64.62 , 53.32 , 28.94 , 21.91  ppm ; anal . : c 67.53 , h 7.33 , n 9.26 , found : c 67.43 , h 7.39 , n 9.22 . with the procedure described above [ 5methoxytryptamine hydrochloride ( 2 , 1.0  g , 4.4  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.8  ml ) , glycolaldehyde dimer ( 0.52  g , 4.3  mmol ) ] , the reaction resulted in ( )5 [ 0.52  g , yield : 51  % , m.p.=152153  c , r 
 f=0.25 , eluent : meoh ] as yellow crystals . to a solution of ( )5 ( 0.52  g , 2.26  mmol ) in 1,4dioxane ( 35  ml ) , naoh ( 0.09  g , 2.25  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.54  g , 2.47  mmol ) in 1,4dioxane ( 5  ml ) were added . ( )8 [ 0.65  g , yield : 87  % , m.p.=155156  c from nhexane , r 
 f=0.34 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , cdcl3 ) for ( )5 : =8.088.24 ( br s , 1  h , nh ) , 7.227.24 ( d , 1  h , j=8.80  hz , ar h ) , 6.786.88 ( d , j=8  hz , 1  h , ar h ) , 4.134.26 ( m , 1  h , ch ) , 3.753.97 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 3.043.37 ( m , 2  h , ch2 ) , 2.632.88  ppm ( m , 2  h , ch2 ) ; c  nmr ( 400  mhz , [ d4]meoh ) for ( )5 : =152.55 , 132.38 , 130.56 , 126.30 , 110.07 , 109.48 , 107.05 , 98.70 , 62.12 , 53.90 , 53.27 , 40.23 , 20.42  ppm ; anal . : c 67.22 , h 6.94 , n 12.06 , found : c 67.20 , h 6.88 , n 12.14 . h  nmr ( 400  mhz , dmso ) for ( )8 : =10.4910.72 ( br s , 1  h , nh ) , 7.167.31 ( d , 1  h , j=8.48  hz , ar h ) , 6.88 ( s , 1  h , arh ) , 6.616.77 ( dd , h ) , 4.905.23 ( m , 2  h , ch2 ) , 4.084.43 ( m , 1  h , ch ) , 3.703.85 ( m , 2  h , ch2 overlapping with s , 3  h , ch3 ) , 2.512.61 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr ( 400  mhz , cdcl3 ) for ( )8 : =154.45 , 133.12 , 131.80 , 127.37 , 112.18 , 100.91 , 81.05 , 64.68 , 56.42 , 53.32 , 28.90 , 21.92  ppm ; anal . c 65.04 , h 7.28 , n 8.43 , found : c 65.07 , h 7.19 , n 8.49 . with the procedure described above [ 5fluorotryptamine hydrochloride ( 3 , 1.0  g , 4.6  mmol ) , water ( 40  ml ) , 2  n hcl ( 2.5  ml ) , glycolaldehyde dimer ( 0.55  g , 4.6  mmol ) ] , the reaction resulted in ( )6 [ 0.93  g , yield : 91  % , m.p.=138141  c , r 
 f=0.15 , eluent : toluene : meoh ( 1:1 ) ] as yellow crystals . to a solution of ( )6 ( 0.83  g , 3.77  mmol ) in 1,4dioxane ( 30  ml ) , naoh ( 0.15  g , 3.75  mmol ) in water ( 5  ml ) and ditertbutyl dicarbonate ( 0.91  g , 4.17  mmol ) in 1,4dioxane ( 5  ml ) the product ( )9 [ 0.88  g , yield : 73  % , m.p.=124125  c from nhexane , r 
 f=0.26 , eluent : nhexane : etoac ( 2:1 ) ] was obtained as lightyellow crystals . h  nmr ( 400  mhz , [ d4]meoh ) for ( )6 : =7.167.28 ( q , j=4.44  hz , 1  h , ar h ) , 4.034.15 ( m , 1  h , ch ) , 3.783.92 ( m , 1  h , ch2 ) , 3.563.66 ( m , 1  h , ch2 ) , 3.253.32 ( m , 1  h , ch2 ) , 2.933.03 ( m , 1  h , ch2 ) , 2.622.78  ppm ( m , 2  h , ch2 ) ; c  nmr : ( 400  mhz , [ d4]meoh ) for ( )6 : =157.62 , 155.31 , 133.72 , 131.84 , 126.26 , 110.07 , 107.34 , 100.86 , 62.02 , 47.39 , 40.16 , 20.28  ppm ; anal . : c 65.44 , h 5.95 , n 12.72 , found : c 65.27 , h 5.99 , n 12.85 . h  nmr ( 400  mhz , dmso ) for ( )9 : =10.7810.92 ( br s , 1  h , nh ) , 7.257.34 ( q , h ) , 6.836.91 ( dt , j=2.8  hz , 9.4  hz , 1  h , ar  h ) , 4.955.19 ( m , 2  h , ch2 ) , 4.114.39 ( m , 1  h , ch ) , 3.693.81 ( m , 2  h , ch2 ) , 2.562.69 ( m , 2  h , ch2 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( )9 : =159.37 , 157.04 , 134.25 , 133.13 , 127.32 , 112.03 110.33 , 103.54 , 81.22 , 64.49 , 53.24 , 40.36 , 28.89 , 21.85  ppm ; anal . c 63.74 , h 6.61 , n 8.74 , found : c 63.70 , h 6.71 , n 8.68 . to ( )7 ( 0.5  g , 1.66  mmol ) in toluene ( 30  ml ) , lipase calb ( 900  mg ) and acetic anhydride ( 2  equiv , 310  l ) were added , and the reaction mixture was shaken in an incubator shaker at 60  c for 1.5  h. the reaction was stopped at 50  % conversion ( ee=98  % ) by filtering off the enzyme , and the solvent was then evaporated off . the products were separated by column chromatography on silica [ eluent : nhexane : etoac ( 2:1 ) ] , resulting in the unreacted amino alcohol ( r)7 as lightyellow crystals [ 235  mg , yield : 47  % , [ ]d 
 = + 107.5 ( c=0.34 in etoh ) , m.p.=136137  c , r 
 f=0.24 ] and the product amino ester ( s)10 as white crystals [ 263  mg , yield : 46  % , [ ]d 
 = 102.2 ( c=0.32 in etoh ) , m.p.=124125  c , r 
 f=0.76 ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)7 were similar to those for ( )7 . h  nmr ( 400  mhz , cdcl3 ) for ( s)10 : =7.988.15 ( br s , 1  h , nh ) , 7.527.54 ( d , 1  h , j=8.0  hz , ar h ) , 7.377.39 ( d , 1  h , j=7.6  hz , ar h ) , 5.315.69 ( m , 1  h , ch ) , 4.294.47 ( m , 1  h , ch2 overlapping with m , 2  h , ch2 ) , 3.473.56 ( m , 1  h , ch2 ) , 2.712.96 ( m , 2  h , ch2 ) , 2.15 ( s , 3  h , ch3 ) , 1.46  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)10 : =171.30 , 136.70 , 130.76 , 127.06 , 122.57 , 120.00 , 118.66 , 111.47 , 80.81 , 65.16 , 50.09 , 39.90 28.87 , 21.90 , 21.37  ppm ; anal . c 66.26 , h 7.02 , n 8.13 , found : c 66.29 , h 7.12 , n 8.04 . with the procedure described above , the reaction of ( )8 ( 200  mg , 0.6  mmol ) , in toluene ( 25  ml ) , calb ( 750  mg ) and acetic anhydride ( 8  equiv , 466  l ) after 2.5  h resulted in ( r)8 as white crystals [ 93  mg , yield : 47  % , [ ]d 
 = + 82 ( c=0.23 in etoh ) , m.p.=196198  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 2:1 ) ] and ( s)11 as a yellow oil [ 98  mg , yield : 43  % , [ ]d 
 = 92.3 ( c=0.61 in etoh ) , ee=98  % , r 
 f=0.63 , eluent : nhexane : etoac ( 2:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)8 were similar to those for ( )8 . h  nmr ( 400  mhz , dmso ) for ( s)11 : =10.7210.88 ( d , 1h j=14.04  hz , nh ) , 7.187.25 ( d , 1  h , j=8.4  hz , ar h ) , 6.896.94 ( d , 1  h , j=2.12  hz , ar h ) , 6.696.75 ( dd , 1  h , j=2.34  hz , 8.84  hz , ar h ) , 5.285.47 ( m , 1  h , ch ) , 4.104.50 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 3.75 ( s , 3  h , ch3 ) , 2.552.73 ( m , 2  h , ch2 ) , 1.952.10 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)11 : =171.36 , 154.56 , 131.84 , 127.45 , 112.19 , 100.96 , 80.78 , 65.07 , 56.39 , 50.17 , 28.87 , 21.93 , 21.35  ppm ; anal . c 64.15 , h 7.00 , n 7.48 , found : c 64.26 , h 7.02 , n 7.39 . similarly , the preparativescale reaction of ( )9 ( 500  mg , 1.56  mmol ) in toluene ( 50  ml ) , calb ( 1500  mg ) and acetic anhydride ( 6  equiv , 885  l ) resulted after 2  h in ( r)9 as lightyellow crystals [ 234  mg , isolated yield : 47  % , [ ]d 
 = + 97 ( c=0.21 in etoh ) , m.p.=99100  c , ee=96  % , r 
 f=0.12 , eluent : nhexane : etoac ( 3:1 ) ] and ( s)12 as white crystals [ 255  mg , isolated yield : 45  % , [ ]d 
 = 131.8 ( c=0.38 in etoh ) , m.p.=143145  c , ee=98  % , r 
 f=0.49 , eluent : nhexane : etoac ( 3:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)9 were similar to those for ( )9 . h  nmr ( 400  mhz , dmso ) for ( s)12 : =10.9911.21 ( d , 1  h , j=16  hz , nh ) , 7.277.35 ( 2d , h ) , 7.157.21 ( dd , 1  h , j=2.4  hz , 9.82  hz , ar h ) , 5.315.53 ( d , 1  h , j=27.4  hz , ch ) , 4.104.59 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 2.552.70 ( m , 2  h , ch2 ) , 1.942.12 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)12 : =171.31 , 159.46 , 157.12 , 133.17 , 132.64 , 127.45 , 111.98 , 110.79 , 103.73 , 80.94 , 65.07 , 50.13 , 28.85 , 21.82 , 21.35  ppm ; anal . : c 62.97 , h 6.40 , n 7.73 , found : c 62.89 , h 6.44 , n 7.78 . enantiomeric ( s)10 ( 30  mg , 0.09  mmol ) , ( s)11 ( 40  mg , 0.11  mmol ) , or ( s)12 ( 50  mg , 0.14  mmol ) was dissolved in meoh ( 10  ml ) . k2co3 ( 50  mg , 0.36  mmol ) was added , and the reaction mixture was shaken at 60  c for 10  min . the following products were obtained as white crystals : ( s)7 [ 24  mg , yield : 90  % , [ ]d 
 = 108.8 ( c=0.33 in etoh ) , m.p.=135137  c , ee=98  % , r 
 f=0.48 , eluent : nhexane : etoac ( 1:1 ) ] , ( s)8 [ 31  mg , yield : 88  % , [ ]d 
 = 81 ( c=0.12 in etoh ) , m.p.=195197  c , ee=98  % , r 
 f=0.47 , eluent : nhexane : etoac ( 1:1 ) ] , or ( s)9 [ 33  mg , yield : 75  % , [ ]d 
 = 105 ( c=0.195 in etoh ) , m.p.=98100  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 3:1 ) ] . ( r)7 ( 50  mg , 0.16  mmol ) , ( r)8 ( 30  mg , 0.09  mmol ) , ( r)9 ( 30  mg , 0.09  mmol ) , ( s)10 ( 50  mg , 0.15  mmol ) , ( s)11 ( 40  mg , 0.1  mmol ) , or ( s)12 ( 30  mg , 0.08  mmol ) was suspended in water ( 5  ml ) in a tube , and stirred at 100  c for 1  h under maximum mw irradiation of 150  w. the solvent was evaporated off , and the residue was purified by column chromatography with toluene : meoh ( 1:1 ) as eluent . the following products were crystallized from nhexane : ( r)4 as yellow crystals [ 26  mg , yield : 79  % , [ ]d 
 = 37.8 ( c=0.41 in etoh ) , m.p.=145147  c , ee=98  % , r 
 f=0.15 ] , ( s)4 as yellow crystals [ 15  mg , yield : 52  % , [ ]d 
 = + 36.1 ( c=0.4 in etoh ) , m.p.=146147  c , ee=98  % , r 
 f=0.16 ] , ( r)5 as lightyellow crystals [ 8  mg , yield : 38  % , [ ]d 
 = 22.0 ( c=0.4 in etoh ) , m.p.=167168  c , ee=98  % , r 
 f=0.18 ] , ( s)5 as lightyellow crystals [ 9  mg , yield : 38  % , [ ]d 
 = + 21.8 ( c=0.45 in etoh ) , m.p.=168170  c , ee=98  % , r 
 f=0.21 ] , ( r)6 as lightyellow crystals [ 11  mg , yield : 52  % , [ ]d 
 = 29 ( c=0.155 in etoh ) , m.p.=9698  c , ee=96  % , r 
 f=0.14 ] , or ( s)6 as lightyellow crystals [ 5  mg , yield : 28  % , [ ]d 
 = + 29 ( c=0.25 in etoh ) , m.p.=99101  c , ee=98  % , r 
 f=0.18 ] . a mixture of ( )4 ( 30  mg , 0.13  mmol ) , 6  equiv acetic anhydride ( 75  l , 0.8  mmol ) and naoh ( 100  mg , 2.5  mmol ) in ch2cl2 ( 20  ml ) and water ( 20  ml ) was stirred for 48  h at rt . the reaction mixture was then extracted with ch2cl2 ( 315  ml ) . the resulting darkyellow oil was purified by column chromatography with ch2cl2:meoh ( 30:1 ) as eluent . the product ( )13 ( 18  mg , yield : 49  % , m.p.=191192  c , r 
 f=0.10 ) was obtained as white crystals from etoh and diisopropyl ether ( 1:9 ) . h  nmr ( 400  mhz , cdcl3 ) for ( )13 : =8.588.71 ( br s , 1  h , nh ) , 7.447.49 ( d , j=7.72  hz , 1  h , ar h ) , 7.317.35 ( d , j=8.36  hz , 1  h , ar h ) , 5.745.82 ( t , j=6.56  hz , 1  h , ch ) , 3.964.11 ( m , 2  h , ch2 ) , 3.843.93 ( m , 1  h , ch2 ) , 3.433.55 ( m , 1  h , ch2 ) , 2.792.96 ( m , 2  h , ch2 ) , 2.29  ppm ( s , 3  h , ch3 ) . with the above procedure , the reaction of ( r)4 ( 26  mg , 0.11  mmol ) resulted in the desired product ( r)13 as white crystals [ 22  mg , yield : 70  % , [ ]d 
 = + 164 ( c=0.2 in etoh ) , m.p.=201203  c , ee=98  % ] . the h  nmr ( 400  mhz , cdcl3 ) spectroscopic data for ( r)13 were similar to those for ( )13 . to ( )7 ( 0.5  g , 1.66  mmol ) in toluene ( 30  ml ) , lipase calb ( 900  mg ) and acetic anhydride ( 2  equiv , 310  l ) were added , and the reaction mixture was shaken in an incubator shaker at 60  c for 1.5  h. the reaction was stopped at 50  % conversion ( ee=98  % ) by filtering off the enzyme , and the solvent was then evaporated off . the products were separated by column chromatography on silica [ eluent : nhexane : etoac ( 2:1 ) ] , resulting in the unreacted amino alcohol ( r)7 as lightyellow crystals [ 235  mg , yield : 47  % , [ ]d 
 = + 107.5 ( c=0.34 in etoh ) , m.p.=136137  c , r 
 f=0.24 ] and the product amino ester ( s)10 as white crystals [ 263  mg , yield : 46  % , [ ]d 
 = 102.2 ( c=0.32 in etoh ) , m.p.=124125  c , r 
 f=0.76 ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)7 were similar to those for ( )7 . h  nmr ( 400  mhz , cdcl3 ) for ( s)10 : =7.988.15 ( br s , 1  h , nh ) , 7.527.54 ( d , 1  h , j=8.0  hz , ar h ) , 7.377.39 ( d , 1  h , j=7.6  hz , ar h ) , 5.315.69 ( m , 1  h , ch ) , 4.294.47 ( m , 1  h , ch2 overlapping with m , 2  h , ch2 ) , 3.473.56 ( m , 1  h , ch2 ) , 2.712.96 ( m , 2  h , ch2 ) , 2.15 ( s , 3  h , ch3 ) , 1.46  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)10 : =171.30 , 136.70 , 130.76 , 127.06 , 122.57 , 120.00 , 118.66 , 111.47 , 80.81 , 65.16 , 50.09 , 39.90 28.87 , 21.90 , 21.37  ppm ; anal . c 66.26 , h 7.02 , n 8.13 , found : c 66.29 , h 7.12 , n 8.04 . with the procedure described above , the reaction of ( )8 ( 200  mg , 0.6  mmol ) , in toluene ( 25  ml ) , calb ( 750  mg ) and acetic anhydride ( 8  equiv , 466  l ) after 2.5  h resulted in ( r)8 as white crystals [ 93  mg , yield : 47  % , [ ]d 
 = + 82 ( c=0.23 in etoh ) , m.p.=196198  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 2:1 ) ] and ( s)11 as a yellow oil [ 98  mg , yield : 43  % , [ ]d 
 = 92.3 ( c=0.61 in etoh ) , ee=98  % , r 
 f=0.63 , eluent : nhexane : etoac ( 2:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)8 were similar to those for ( )8 . h  nmr ( 400  mhz , dmso ) for ( s)11 : =10.7210.88 ( d , 1h j=14.04  hz , nh ) , 7.187.25 ( d , 1  h , j=8.4  hz , ar h ) , 6.896.94 ( d , 1  h , j=2.12  hz , ar  h ) , 6.696.75 ( dd , 1  h , j=2.34  hz , 8.84  hz , ar h ) , 5.285.47 ( m , 1  h , ch ) , 4.104.50 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 3.75 ( s , 3  h , ch3 ) , 2.552.73 ( m , 2  h , ch2 ) , 1.952.10 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)11 : =171.36 , 154.56 , 131.84 , 127.45 , 112.19 , 100.96 , 80.78 , 65.07 , 56.39 , 50.17 , 28.87 , 21.93 , 21.35  ppm ; anal . c 64.15 , h 7.00 , n 7.48 , found : c 64.26 , h 7.02 , n 7.39 . similarly , the preparativescale reaction of ( )9 ( 500  mg , 1.56  mmol ) in toluene ( 50  ml ) , calb ( 1500  mg ) and acetic anhydride ( 6  equiv , 885  l ) resulted after 2  h in ( r)9 as lightyellow crystals [ 234  mg , isolated yield : 47  % , [ ]d 
 = + 97 ( c=0.21 in etoh ) , m.p.=99100  c , ee=96  % , r 
 f=0.12 , eluent : nhexane : etoac ( 3:1 ) ] and ( s)12 as white crystals [ 255  mg , isolated yield : 45  % , [ ]d 
 = 131.8 ( c=0.38 in etoh ) , m.p.=143145  c , ee=98  % , r 
 f=0.49 , eluent : nhexane : etoac ( 3:1 ) ] . the h  nmr ( 400  mhz , dmso ) spectroscopic data for ( r)9 were similar to those for ( )9 . h  nmr ( 400  mhz , dmso ) for ( s)12 : =10.9911.21 ( d , 1  h , j=16  hz , nh ) , 7.277.35 ( 2d , h ) , 7.157.21 ( dd , 1  h , j=2.4  hz , 9.82  hz , ar  h ) , 6.876.96 ( dt , h ) , 5.315.53 ( d , 1  h , j=27.4  hz , ch ) , 4.104.59 ( m , 2  h , ch2 overlapping with m , 2  h , ch2 ) , 2.552.70 ( m , 2  h , ch2 ) , 1.942.12 ( m , 3  h , ch3 ) , 1.44  ppm ( s , 9  h , c(ch3)3 ) ; c  nmr : ( 400  mhz , cdcl3 ) for ( s)12 : =171.31 , 159.46 , 157.12 , 133.17 , 132.64 , 127.45 , 111.98 , 110.79 , 103.73 , 80.94 , 65.07 , 50.13 , 28.85 , 21.82 , 21.35  ppm ; anal . c 62.97 , h 6.40 , n 7.73 , found : c 62.89 , h 6.44 , n 7.78 . enantiomeric ( s)10 ( 30  mg , 0.09  mmol ) , ( s)11 ( 40  mg , 0.11  mmol ) , or ( s)12 ( 50  mg , 0.14  mmol ) was dissolved in meoh ( 10  ml ) . k2co3 ( 50  mg , 0.36  mmol ) was added , and the reaction mixture was shaken at 60  c for 10  min . the following products were obtained as white crystals : ( s)7 [ 24  mg , yield : 90  % , [ ]d 
 = 108.8 ( c=0.33 in etoh ) , m.p.=135137  c , ee=98  % , r 
 f=0.48 , eluent : nhexane : etoac ( 1:1 ) ] , ( s)8 [ 31  mg , yield : 88  % , [ ]d 
 = 81 ( c=0.12 in etoh ) , m.p.=195197  c , ee=98  % , r 
 f=0.47 , eluent : nhexane : etoac ( 1:1 ) ] , or ( s)9 [ 33  mg , yield : 75  % , [ ]d 
 = 105 ( c=0.195 in etoh ) , m.p.=98100  c , ee=98  % , r 
 f=0.20 , eluent : nhexane : etoac ( 3:1 ) ] . ( r)7 ( 50  mg , 0.16  mmol ) , ( r)8 ( 30  mg , 0.09  mmol ) , ( r)9 ( 30  mg , 0.09  mmol ) , ( s)10 ( 50  mg , 0.15  mmol ) , ( s)11 ( 40  mg , 0.1  mmol ) , or ( s)12 ( 30  mg , 0.08  mmol ) was suspended in water ( 5  ml ) in a tube , and stirred at 100  c for 1  h under maximum mw irradiation of 150  w. the solvent was evaporated off , and the residue was purified by column chromatography with toluene : meoh ( 1:1 ) as eluent . the following products were crystallized from nhexane : ( r)4 as yellow crystals [ 26  mg , yield : 79  % , [ ]d 
 = 37.8 ( c=0.41 in etoh ) , m.p.=145147  c , ee=98  % , r 
 f=0.15 ] , ( s)4 as yellow crystals [ 15  mg , yield : 52  % , [ ]d 
 = + 36.1 ( c=0.4 in etoh ) , m.p.=146147  c , ee=98  % , r 
 f=0.16 ] , ( r)5 as lightyellow crystals [ 8  mg , yield : 38  % , [ ]d 
 = 22.0 ( c=0.4 in etoh ) , m.p.=167168  c , ee=98  % , r 
 f=0.18 ] , ( s)5 as lightyellow crystals [ 9  mg , yield : 38  % , [ ]d 
 = + 21.8 ( c=0.45 in etoh ) , m.p.=168170  c , ee=98  % , r 
 f=0.21 ] , ( r)6 as lightyellow crystals [ 11  mg , yield : 52  % , [ ]d 
 = 29 ( c=0.155 in etoh ) , m.p.=9698  c , ee=96  % , r 
 f=0.14 ] , or ( s)6 as lightyellow crystals [ 5  mg , yield : 28  % , [ ]d 
 = + 29 ( c=0.25 in etoh ) , m.p.=99101  c , ee=98  % , r 
 f=0.18 ] . a mixture of ( )4 ( 30  mg , 0.13  mmol ) , 6  equiv acetic anhydride ( 75  l , 0.8  mmol ) and naoh ( 100  mg , 2.5  mmol ) in ch2cl2 ( 20  ml ) and water ( 20  ml ) was stirred for 48  h at rt . the reaction mixture was then extracted with ch2cl2 ( 315  ml ) . the organic phase was dried on anhydrous na2so4 and evaporated . the resulting darkyellow oil was purified by column chromatography with ch2cl2:meoh ( 30:1 ) as eluent . the product ( )13 ( 18  mg , yield : 49  % , m.p.=191192  c , r 
 f=0.10 ) was obtained as white crystals from etoh and diisopropyl ether ( 1:9 ) . h  nmr ( 400  mhz , cdcl3 ) for ( )13 : =8.588.71 ( br s , 1  h , nh ) , 7.447.49 ( d , j=7.72  hz , 1  h , ar h ) , 7.317.35 ( d , j=8.36  hz , 1  h , ar  h ) , 7.137.20 ( dt , h ) , 5.745.82 ( t , j=6.56  hz , 1  h , ch ) , 3.964.11 ( m , 2  h , ch2 ) , 3.843.93 ( m , 1  h , ch2 ) , 3.433.55 ( m , 1  h , ch2 ) , 2.792.96 ( m , 2  h , ch2 ) , 2.29  ppm ( s , 3  h , ch3 ) . with the above procedure , the reaction of ( r)4 ( 26  mg , 0.11  mmol ) resulted in the desired product ( r)13 as white crystals [ 22  mg , yield : 70  % , [ ]d 
 = + 164 ( c=0.2 in etoh ) , m.p.=201203  c , ee=98  % ] . the h  nmr ( 400  mhz , cdcl3 ) spectroscopic data for ( r)13 were similar to those for ( )13 . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .