Studies in the Indole Series. IV. The Synthesis of d, l-Eserethole

THESYNTHESIS OF ~,Z-ESERETHOLE

March, 1!135

563

[CONTRIBUTION FROM THE CHEMICAL LABORATORY OF DEPAUW UNIVERSITY]

Studies in the Indole Series. IV. The Synthesis of d,l-Eserethole B Y PERCY

L.

JULIAN AND JOSEF PIKL

Recently an improved synthesis of substances containing the basic ring structure of the alkaloid, physostigmine (eserine) has been reported,' and the reactions of these substances shown to run exactly parallel with those of natural physostigmine. This work has now been extended to include the synthesis of d,lnoreserethole (XI) and d,Z-eserethole (XII). A synthesis of eserethole represents a complete synthesis of physostigmine (I) since eseroline (11) easily obtained from physostigmine by treatment with alkali, is reconverted int.0 eserine on reaction with methyl isocyanate.

Our method of synthesis follows in the main the course indicated in previous communications on CHs

CHI

I I

I

I H I

CHa CHa Eserine (I)

CH3 CH3 Eseroline (11) CHs Ethyl-fiA -

toluenesulfonate

CHs CHs Eserethole (111)

this subject.1*2 N-Methylphenetidine (IV) is treated with a-bromopropionyl bromide to yield

Br

CH,

d,l-Noreserethole (XI) ( 1 ) Jiiliiln and l'ikl,

l'rlls JOIIKNAL,

67, 539 (l!lX).

I

NaOH

d,l-Eserethole (XII) (2)

J i i l i : ~ ~I'ikl ~,

an