458 
Mydriatic  Alkaloids. 
( Am.  Jour.  Pharm. 
1     October,  1903. 
resume  of  this  magnificent  research,  which  was  only  accomplished 
after  many  failures,  may  not  be  without  interest : 
Nearly  pure  atropine  of  the  market,  rotating  (a)D=  —  1*39°,  was 
saponified  by  boiling  with  water  under  reflux  condenser  for  about 
twenty-four  hours.  The  reaction  product  was  reduced  to  small 
volume,  strongly  acidified  with  H2S04  to  hold  the  base  tropine  in 
solution,  and  repeatedly  shaken  out  with  ether.  This  removed 
mainly  tropic  acid. 
The  acid,  aqueous  liquid  remaining  was  carefully  neutralized,  con- 
centrated to  small  volume,  mixed  with  powdered  CaO  and  anhydrous 
CaS04,  dried  and  extracted  with  ether.  Upon  evaporation  of  the 
ether,  tropine  was  left  as  a  white  crystalline  residue. 
The  i-tropic  acid,  which  was  first  obtained,  was  split  into  its 
active  components  d-  and  1-tropic  acids  in  a  manner  similar  to  that 
employed  by  Pasteur  in  the  splitting  of  racemic  acid.  The  quinine 
salt  of  inactive  tropic  acid  was  prepared  and  from  the  solution,  upon 
concentrating,  the  d-tropate  of  quinine  separated  first,  leaving  the 
1-tropate  in  solution.  The  latter  was  recovered  from  the  mother 
liquor  after  concentrating.  From  these  two  salts  the  respective 
acids  were  easily  obtained  by  decomposing  with  stronger  acid  and 
then  purifying.  Prepared  in  this  manner  the  d-tropic  acid  rotated 
(a)D  =  -f  71-30°  and  the  1-tropic  acid  (a)D  =  —  7275°. 
Since  Gadamer  showed  that  the  cause  of  optical  inactivity  of 
atropine  and  the  activity  of  hyoscyamine  resided  in  the  tropic  acid 
nucleus  and  not  in  the  tropine,  it  appeared  natural  that  d-hyoscy- 
amine  could  be  prepared  by  coupling  d-tropic  acid  with  tropine. 
This  was  in  fact  accomplished  by  mixing  nearly  equal  quantities  of 
tropine  and  d-tropic  acid  with  25  to  35  volumes  of  5  per  cent.  HQ 
and  evaporating  to  about  3  volumes.  The  solution  was  made 
alkaline  and  repeatedly  shaken  out  with  ether,  which  took  out 
principally  the  new  base  which  has  been  so  long  sought.  Purifica- 
tion was  effected  by  means  of  the  gold  salt,  decomposing  with  H2S 
and  crystallizing.  The  synthesis  of  1-hyoscyamine  was  accomplished 
in  the  same  manner  by  using  the  1-tropic  acid  instead.  As  to  the 
success  of  this  research  it  need  only  be  said  that  a  d-hyoscyamine 
was  obtained  which  rotated  (a)D  =  -f-  23-15°  and  a  1-hyoscyamine 
which  rotated  (a)D  =  —  24-12°. 
Now  that  the  preparation  of  d-hyoscyamine  had  been  accom- 
plished, Dr.  Cushny  was  naturally  very  anxious    to  verify  his 
