528 
Analogues  of  Atropine. 
Am.  Jour.  Pharm. 
July,  1918. 
stereoisomer  is  formed  by  reducing  pseudopelletierine  with  concen- 
trated hydriodic  acid  and  zinc  dust,  which  may  therefore  be  called 
iso-methylgranatoline.  These  two  isomers  have  different  physical 
properties,  as  is  the  case  of  the  two  reduction  products  of  tropinone. 
As  was  stated,  an  important  difference  in  the  properties  of  the 
reduction  products  of  tropinone  lies  in  the  different  physiological 
activities  of  the  esters  of  the  hydroxy  acids  with  these  alcohols. 
Thus  the  tropic  acid  ester  (atropine),  and  the  mandelic  acid  ester 
(homatropine)  of  tropine  have  strong  mydriatic  power,  whereas 
the  tropic  acid  esters  and  the  mandelic  acid  ester  of  pseudotropine 
are  devoid  of  such  properties. 
The  object  of  the  work  undertaken  was:  To  prepare  the  second 
reduction  product  of  pseudopelletierine  which  was  theoretically  pos- 
sible, and  then  to  determine  any  difference  in  the  physiological  ac- 
tivities of  the  tropic  acid  and  mandelic  acid  esters  of  these  two 
stereoisomers. 
The  hydrobrpmides  of  the  mandelic  acid  and  tropic  acid  esters 
of  isomethylgranatoline  were  prepared,  and  were  found  to  have  no 
mydriatic  powers.  These  two  artificial  alkaloids  were  not  obtain- 
able in  a  crystalline  condition,  it  being  necessary  to  isolate  them,  and 
purify  them  in  the  form  of  their  hydrobromides. 
The  hydrobromides  of  the  mandelic  acid  and  tropic  acid  esters 
of  methylgranatoline  were  also  prepared,  and  were  found  to  have 
strong  mydriatic  properties.  The  hydrobromide  of  the  tropic  acid 
ester  was  obtained  as  a  crystalline  powder,  but  the  hydrobromide  of 
the  mandelic  acid  ester  was  obtained  as  a  syrup  only. 
From  the  viewpoint  of  physiological  activity  alone,  tropine  and 
methylgranatoline  should  constitute  one  type  of  stereoisomer,  that 
is,  the  type  whose  hydroxy  acid  esters  have  mydriatic  power, 
whereas  pseudotropine  and  iso-methylgranatoline  are  another  type 
of  isomer  whose  hydroxy  acid  esters  are  lacking  in  mydriatic 
powers. 
From  the  standpoint  of  physical  properties  we  would  predict 
different  results  from  those  found  above,  as  we  would  naturally 
group  tropine  (m.  p.  63  °)  and  iso-methylgranatoline  (m.  p.  65  °) 
together  and  pseudotropine  (m.  p.  1080)  and  methylgranatoline  (m. 
p.  ioo°)  together.  From  the  analogy  in  the  methods  of  preparation 
of  tropine  and  iso-methylgranatoline,  and  of  pseudotropine  and 
methylgranatoline  we  would  classify  these  compounds  into  these  two 
groups  also.    Thus  methylgranatoline  is  prepared  by  reducing  pseu- 
