V-BenzyltetrahydroiSoquinoline Alkaloids

Sendaverine (CXXIV), C18H21NO3 [mp 139°-140° B-HCl, mp 202°-207°], is the name given by Kametani and Ohkubo (192) to the alkaloid F-28, first isolated by Manske (193) from Corydalis aurea Willd. and which was also one of the bases present in the original sample of corpaverine (194) (Section VIII, A, 2). 

On the basis of the earlier chemical data reported by Manske and the analysis of spectral data, sendaverine was assigned the V-benzyltetra-hydroisoquinoline structure OXXIV which was confirmed by synthesis. 

The IR-spectrum presents a hydroxylic band (3546 cm i) and the NMR-spectrum indicates the presence of two methoxyl groups and of six aromatic protons no V-methyl group was present. Four of the aromatic protons gave two doublets centered at 7.24 and 6.81 ppm (J = 8.5 cps) indicating two pairs of ortho protons the other two gave singlets at 6.50 and 6.45 ppm. 

The mass spectrum gave a base peak at m/e 121, which was considered to be due to the ion CXXV in agreement with the isolation of anisic acid by Manske by oxidation of the original corpaverine. The two pairs of aromatic protons derive from this moiety of the molecule. The other main peaks were due to the m/e 150 and 178 ions. The last peak was assigned to ion CXXVI which is transformed into the ion m/e 150 (CXXVII). That the peak m/e 178 was due mainly to ion CXXVI and not to CXXIX received support when the mass spectrum of sendaverine was compared with that of the 1-benzyltetrahydroisoquinoline (CXXVIII) (195). In this case the base peak is the ion m/e 178, to which structure CXXIX is assigned and which is transformed into the radical ion m/e 163 (CXXX), of low abundance in the case of sendaverine. On the other hand, the ion m/e 150 (CXXVII) is not detectable in the spectrum of CXXVIII. 

Sendaverine was synthesized (192) by quaternizing the known 7-benzyloxy-6-methoxy-3,4-dihydroisoquinoline (CXXXI) with 4-meth-oxybenzyl chloride (CXXXII). Reduction in acidic medium of the quaternary salt (CXXXIII) afforded a product identical with the natural base (CXXIV). 

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