VOL. 4 (1950) 



CYCLIC PLANT ACIDS AND GLUCOSE 



201 



Our previous papers on the oxidation of quinic acid, shikimic acid and dihydro- 

 shikimic acid by means of periodic acid have made available a series of 1.5-dialdehydes, 

 which, depending on their origin, possess either a free or blocked hydroxyl and carboxyl 

 group, or a carboxyl group alone. The possession of these aldehydes led us to an alkaloid 

 synthesis, along the lines of the lobelanine synthesis of Schopf^^. The condensation, 

 however, was successful only after the elimination of the electro-negative groups and 

 the choice of a 1.5-dialdehyde which no longer contained any hydroxyl groups and only 

 a carboxyl group in the form of its nifrile. This was the dialdehyde, XI, which is obtained 

 by treating the nitrile of the dihydro-shikimic acid with 2 molecules of periodic acid^'^-^-. 



C=N 



H-C 

 HjC/ jCHg NaOCH^ 



AcOChI JcHOAc 

 CHOAc 



2HI04 



/ 



H-C 



C=N 



H,C 



CH, 



H-C=0 C=0 



H-C 



2C,HiCO-CH;-COOH HgCj^ 1CH2 

 NHj-CH, ^ I 



0=C-CH2-H Cv /'CH • CH2-C=0 



C«H, 



X 



XI 



I 



CH3 



XII 



C«H, 



Experimentally the synthesis was carried out in the following way: Triacetyl 

 dihydro-shikimic acid amide, was transformed into the corresponding nitrile X, by 

 heating with acetic anhydride. The nitrile was de-acetylated with a minimum amount 

 of sodium methylate according to Zemplen. and the free nitrile was transformed into 

 the dialdehyde, XI, by the action of 2 molecules of periodic acid. The dialdehyde was 

 not isolated, but was condensed directly in aqueous solution with 2 molecules of benzoyl 

 acetic acid ester and i molecule of monomethylamine at a p^ of 4. 



The 3-cyano-lobelanine, XII, was isolated in a yield of 30% (calculated on the 

 amount of triacetyl dihydro-shikimic acid nitrile), and showed the usual precipitation 

 reaction of alkaloids, e.g. with perchloric acid, picric acid and picrolonic acid. It crystal- 

 lized in long shining silklike needles similar to those of caffein, and showed a melting 

 point of 143°. 



experimental 



Preparation of the acetyl-methylene-shikimic acid nitrile from monacetyl-methylene-quinic acid amide 

 5 g monacetyl-methylene-quinic acid^^ were shaken with 10 g (2^4 molecules) ^-toluene sul- 

 phonyl chloride in 15 ml dry pyridine for a short time until dissolved. The brown coloured solution 

 was kept for seven days at 37°. The solution was then diluted with 20 ml of water, and an oily sub- 

 stance separated. It was allowed to stand with occasional shaking for 15 minutes at room tempera- 

 ture in order to destroy any unused toluene sulphonyl chloride. The solution was then extracted 

 twice with a large volume of chloroform. The united chloroform fractions were next shaken up with 

 small portions of dilute sulphuric acid until all the pyridine was neutralized, and no more acid was 

 used up. The solution was washed with a little water and then dried with sodium sulphate. The mix- 

 ture was next filtered and the filtrate was evaporated in the vacuum of a water pump to remove all 

 solvent. The light-brown oil (4.5 g) remaining was distilled under high vacuum. A light yellow oil 

 (2.3-2.8 g, i.e., 54-65% of the theoretical yield) distilled over at 0.2 mm and a bath temperature 

 of 150-165°. It had a boiling point of 128°. After a second distillation it was almost colourless, but 

 had a slight odour of toluene sulphonic acid and a minimum content of sulphur. 



Preparation of unsaturated nitrile from monacetyl-isopropylidenequinic acid amide^^ 



Reaction and processing follow exactly as described for the corresponding methylene compound. 

 4.3 g {i.e., 77% of the theoretical yield) unsaturated acetyl-isopropylidene nitrile were obtained 



from 6.5 g monacetyl-isopropylidene-quinic acid amide. The compound had a light yellow colour 



and a boihng point of i25°/o.i5 mm. 



References p. 203I204. 



