Venenatine

Venoxidine (Venenatine N-oxide) Alstonia venenata R.Br. (85) 218-219 -82.4° (82a) C22H28N2O5... 

Epiallo Series. Among alkaloids containing the epiallo yohimbane skeleton, only 3-epi-a-yohimbine (105) was formerly known. In the past decade, four additional members of this alkaloid subgroup have been isolated, namely, quatematine (106) from Alstonia quaternata (84), venenatine (107) and its N-oxide (venoxidine) from Alstonia venenata R.Br. (79, 80, 82a, 85) and 16-epivenenatine (108) also from Alstonia venenata R.Br. (81). 

Among methoxy-substituted yohimbine alkaloids, only 11-methoxy-a-yohim-bine (95) and 1 l-methoxy-3-epi-a-yohimbine (106) were tested for a-adrenergic activity, and they showed only weak a2-adrenoceptor blocking effect (347). On the other hand, venenatine (107) has reserpinelike activity and shows synergism with reserpine (109). Furthermore, alstovenine (96) displays monoamine oxidase inhibitor activity (348). 

Govindachari et al. have recently recorded the extraction of reserpine, venenatine (LXXVII), and 3-isovenenatine from the bark of Alstonia venenata R. Br. (98). 3-Isovenenatine may be identical with alstovenine, isolated earlier from the same species by Ray and Chatterjee (99), together with a second, unnamed base, m.p. 192°. 

In passing it is worth noting that the absolute configuration of (— )-venenatine (46) has been estabUshed by comparison of its ORD spectrum with those of yohimbinoid alkaloids known to possess j8 hydrogen at C-3 (44). The routes used in the total synthesis of ( )-tetrahy-droalstonine (3, 28) have been described above. 

These reactions are characteristic of a methoxyyohimbine, a conclusion which is amply supported by the striking similarity between the mass spectra of venenatine and 3-epi-a-yohimbine, if appropriate allowance is made for the presence of an additional (aromatic) methoxyl group in venenatine (12). The position of this aromatic methoxyl group was rigorously established by selenium dehydrogenation of venenatic acid,... 

Venenatine is thus a 9-methoxyyohimbine and may be formulated as X (stereochemistry so far not defined). The stereochemistry of venenatine was unequivocally deduced as follows. Reaction of venenatine with tert-butyl hypochlorite gave the corresponding 7-chloroindolenine derivative, which was converted by methanolic hydrogen chloride into Zl -dehydro-venenatine. Reduction of the latter with sodium borohydride yielded... 

The reaction of venenatyl alcohol with toluene- -sulfonyl chloride in pyridine yields a quaternary tosylate (XI), which is presumably formed by intramolecular nucleophilic displacement of an initially formed primary tosylate by Ny hence the D/E ring junction must be cis and the hydrogen at C-16 must also be cis with respect to the hydrogen atoms at C-15 and C-20. In contrast, venenatine itself reacts with toluene- -... 

Several new alkaloids of this group have been recently described (see Table I, Part 1). Venenatine, isovenenatine (5, 6), and venoxidine (venenatine-Ai,-oxide) (7) from Alstonia venenata as well as oxygambir-... 

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