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 .
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 abstractmany alkaloids containing a tetrahydrocarboline skeleton have wellknown therapeutic effects , leading to increased interest in the synthesis of these natural products . 
 enantiomers of nbocprotected 1hydroxymethyl1,2,3,4tetrahydrocarboline [ ( )7 ] , 1hydroxymethyl6methoxy1,2,3,4tetrahydrocarboline [ ( )8 ] , and 1hydroxymethyl6fluoro1,2,3,4tetrahydrocarboline [ ( )9 ] were prepared through enzymecatalyzed asymmetric acylation of their primary hydroxyl group . 
 the preliminary experiments were performed in a continuousflow system , while the preparativescale resolutions were done as batch reactions . 
 excellent enantioselectivities ( e>200 ) were obtained with candida antarctica lipase b ( calb ) and acetic anhydride in toluene at 60  c . 
 the recovered alcohols and the produced esters were obtained with high enantiomeric excess values ( ee96  % ) . 
 the oacylated enantiomers [ ( s)10(s)12 ) ] were transformed into the corresponding amino alcohols [ ( s)7(s)9 ) ] with methanolysis . 
 microwaveassisted boc removals were also performed and resulted in the corresponding compounds ( r)4(r)6 and ( s)4(s)6 without a drop in the enantiomeric excess values ( ee96  % ) . 
Experimental Section
Materials and methods
Smallscale enzymatic resolutions
Syntheses
Synthesis of racemic 
Synthesis of racemic 
Synthesis of racemic 
Enzymatic resolutions
Enzymatic resolution of ()7
Enzymatic resolution of ()8
Enzymatic resolution of ()9
Deacylation of (
Deprotection of (
Synthesis of racemic and enantiomeric 1hydroxymethyl2acetyl1,2,3,4tetrahydro
Supporting information