Abstract
In Part I (Cohen and King 1938) it was shown that retention of the bridge carbinol group in the molecule of the cinchona alkaloids (I) was essential for antiplasmodial activity, as tested on bird malaria. Now Giemsa and Oesterlin (1933) have shown that quinicine (II,
R
= OMe;
R
1
=. CH: CH
2
), an isomeride of quinine, is devoid of antiplasmodial action, and it seemed possible that reduction to the carbinol (III), which occurs in two diastereoisomeric forms, might restore activity, since the pictorial resemblance between the dihydroquinicinols (III,
R
= OMe;
R
1
= .CH
2
.CH
3
) and quinine (I,
R
= OMe;
R
1
= .CH:CH
2
) could hardly be greater. Both carbinols which were made according to the method of Heidelberger and Jacobs (1922) proved to be inactive (Table I), as did a methylation product,
d
-
N
-methyldihydroquinicinol (IV). From this result it seemed essential that the piperidine ring system, which is still present in (III), should be as near the quinoline ring system as possible, consistent with retention of the carbinol group. If, therefore, any further progress was to be made in unravelling the factors necessary for antiplasmodial action, it was eminently desirable that substances of the type of (V) should be synthesized, where
R
is H or MeO. An
N
-butyl derivative of such a substance (VI) would be structurally very similar to quinine (I,
R
= OMe;
R
1
= .CH:CH
2
) and would only differ in molecular weight from it by four hydrogen atoms.
Reference19 articles.
1. Ber. dtsch. chem;Braun J.;Ges.,1904
2. B uttle G. A. H . Henry T. A. and Trevan J. W. 1934 Biochem. J. 28 426.
3. Synthese von α- und γ-Oxychinolinen
4. J;Clarke H .;Chem. Soc.,1913
5. Proc. Roy;Cohen A.;Soc. B,1938
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