Hydroxy indolenines

The vincadifformine-tabersonine group of alkaloids provide a rich field for the study of oxidative rearrangements. New work reported recently101" includes a study of the oxidation of 3-oxovincadifformine (189) with m-chloroper oxy benzoic acid (Scheme 27). The products were 3-oxovincamine (190), 3-oxo-16-ep/-vincamine (191), and a dilactam (192), which is simply the result of oxidative fission of the 2,16 bond. Under carefully controlled conditions, the hydroxy-indolenine (193) was isolated, and it was subsequently shown to be an intermediate (as expected) in the formation of (190)—(192). Photochemical oxidative rearrangement gave similar results. 

Five monomeric alkaloids isolated117d from the leaves of Stenosolen hetero-phyllus (Vahl) Mgf. have been identified as voacangine, voacangine hydroxy-indolenine, conoflorine, pandine, and pandoline. 

With the structure of quinamine firmly established, its other reactions can now be considered (Chart II), all of which proceed via VIII. When the alkaloid was refluxed with acetic anhydride or acetyl chloride, acetyl-apoquinamine (O-acetyl-d3- 14-cinchonamine, XII), picrate, mp 143° was obtained. The change may be formulated, quinamine VIII-XII, with the last step being a special case of a general reaction of hydroxy-indolenines (20). The analogous transformation can be realized very easily when 7-hydroxy-7/f-yohimbine methiodide (X) is boiled in methanol (21). 

Rhazidine (Volume VIII, p. 505) in the form of its chloride has been shown to be the quaternary derivative (XXV) of the 12-hydroxy-indolenine (XXVI Volume VIII, p. 358) which is obtained by oxidation of quebrachamine (XVI) (66). In neutral and acid solution the UV-spectrum (A 236, 293 mp) corresponds to a dihydroindole (neutral spectrum), in strongly alkaline solution or in heptane a hydroxyindo-lenine spectrum (A 210,281, 292, 307 m/a) is observed. The facile ring closure of XXVI at first caused a misinterpretation of the experimental results (66a) although it was known that the 12-hydroxyindolenine (XXVI) and its acetate (XXVII) could be readily obtained from rhazidine and reduced with LiAlH4 to (— )-quebrachamine. 

Two new alkaloids which contain a monoterpene unit that is not derived from loganin have been isolated in extremely small amounts from Aristotelia chilensis (Mol.) Stuntz. The structures of both alkaloids were determined by the A-ray method aristotelinine (94) has the constitution of the hydroxy-indolenine analogue of a hydroxy-aristoteline in view of the comparative ease of oxidation of many indoles and the minute amount of alkaloid isolated it seems possible that aristoteline may be an artefact derived from a hydroxy-aristoteline that is as yet undetected in the plant. The second alkaloid, aristone (95), can be derived from... 

The iboga alkaloids behave differently from the vincadifformine group on photochemical oxidation iboxyphylline is rapidly oxidised at C-16 to give a hydroxy-indolenine, but only in the presence of oxygen and in the absence of cyanide. 

The ultraviolet absorption spectra of most 1-hydroxy-, 1-acyloxy-, and 1-alkoxyindoles are quite similar to those of the corresponding indoles representative examples are listed in Table 11. In general, they show a small shift towards the visible, and this is accentuated in the 1-hydroxyindoles on the addition of alkali when the proton can be removed. The UV spectrum reported (67BSF1296) for 1-hydroxyindole is certainly that of a polymer, for it shows no absorption at —280 nm, which is characteristic of these compounds and of 2,3,3-trimethyl-3//-indolenine 1-oxide, a model for the 3//-tautomer (Table II). 

The substitution reaction may occur on a prototropic nonaromatic form. Both types of tautomerism, i.e., that prevailing in the parent heterocycles (pyrrole-pyrrolenine, indole-indolenine) and that typical of the hydroxy and amino derivatives, must be considered. 

Oxidation of tabersonine hydrochloride with m-chloroperbenzoic acid does not give a 16-hydroxy-derivative, as expected, but a 16-chloro-indolenine derivative (201), presumably via the generation of Cl+ from chloride ion and the oxidant in the presence of an excess of oxidant, the Nh-oxide of (201) is formed.83... 

The condensation of 2,3,3-trimethylinolenine with aryl aldehydes gave the corresponding 2-styrylindolenines. Condensation with 5-nitrosalicylaldehyde and its 3-bromo, 3-methoxy, and 3-nitro derivatives similarly gave the 2-(2-hydroxy-styryl)indolenines (46, 73, 68 and 91% yields, respectively), rather than the corresponding merocyanine or spiropyran forms. These indolenines were neither photochromic nor solvatochromic.53... 

A BIPS having hydrogen rather than alkyl on the l -nitrogen atom could possibly be formed from the reaction between a 2,3,3-trialkylindolenine and a salicylaldehyde. However, the reactions between 4-nitro-2,3,3,7-tetramethylindole-nine and five different substituted salicylaldehydes (3-methoxy-5-nitro 5-nitro 3-bromo-5-nitro 3-nitro-5-methoxy and 3-nitro) gave only the 2-hydroxy(substitu-ted)styryl dyes, which were not solvatochromic or photochromic. The yields were 3-7% based on 5-nitro-2-methylphenylhydrazine, the precursor of the indolenine used. The NMR, UV, and mass spectrometry (MS) evidence excluded spiro or open zwitterionic structures for these products.81... 

Oxidative demethylation. In benzene solution, 1 mole of lead tetraacetate oxidizes 21-desoxyajraaline-17-acetate (1) to the 2-hydroxy derivative (2). Excess oxidant gives the l-demethyl-A -compound (3), an indolenine. 

Hydroxy vincadifformine indolenine (285) can also be rearranged to a mixture of vincamine (286) and 16-epivincamine by pyrolysis or flow thermolysis at 580°C (795). 

In the UV spectrum rhazidigenine TV-oxide gave absorptions at 237 and 293 nm for an indolenine, shifting in alkali to 308 nm. Losses of 17 and 29 mu from the molecular ion (M+ 314) indicated the presence of hydroxy and ethyl groups, and a loss of 16 from M+—17 suggested an N-oxide. Ions at m/e 144, 143, and 130 indicated an unsubstituted indole nucleus. Rhazidigenine N-oxide was assigned structure 200 on this basis. 

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