A Reinvestigation of the Oxidative Rearrangement of Yohimbane‐Type Alkaloids. Part B. Formation of Oxindol (= 1,3‐Dihydro‐2H‐indol‐2‐one) Derivatives

Abstract

The methanolysis of the epimeric 7-chloro-7H-yohimbine derivatives 2 and 3 was reinvestigated. In case of the 7a-epimer 2, the reaction was uneventful and conformed with earlier observations, i.e., under sufficiently mild conditions, only the imino ether 4 ( = imino ether A) was produced. Under the same conditions, the less reactive p-isomer 3 furnished a mixture of both imino ethers 4 and 5, accompanied by the elimination product 11, and by equal amounts of yohimbine (1) and 3,4,5,6-tetradehydroyohimbine (12), which are believed to arise through a disproportionation process of the putative intermediate 5,6-didehydroyohimbine (23). The nature of this divergent reactivity and of the ready equilibration of 4 and 5 was investigated by means of extensive force-field and semi-empirical calculations (AM1 and PM3) of various conformers of the compounds 2-5 and of some possible reaction intermediates.

New Strategies for the Synthesis of Monoterpene Indole Alkaloids

“…The situation is shown in Scheme 21, where it can be seen that the position of the equilibrium is dependent on the acidity of the solvent. In comparison with the results we had obtained in the Aristotelia alkaloid field, discussed above, their findings stroke us as truly remarkable and we decided to re-investigate this issue [81]. On the other hand, 130 is favoured over 129 in a basic medium [74], presumably because the latter is destabilized through a dipol-dipol interaction between the lone-pairs of the heteroatoms.…”

“…CF 3 COOH, 4 h reflux; v, 5 equiv. We were able to reproduce this result and succeeded for the first time in transforming the more labile imino ether B (135) selectively into oxindole B (137) simply by using the even stronger triflic acid (6 h at 0°C) [81]. AcOH, 2 h reflux.…”

“…Mechanistic speculations concerning this and the above reactions can be found in the original paper [81]. It reacted indeed slower than 132: treatment with 0.5 M NaOMe after 3 hours at 24°C produced a mixture that still contained 20% of staring material besides 20% of imino ether A and 60% of imino ether B (entry ii in Scheme 23).…”

“…The above-mentioned synthesis of serratoline (57) via oxidation of aristoteline (1) (77) was isolated from A. australasica and was originally assigned a structure with opposite relative configuration at C(17) [48]. In the context of a different project, indole-protected makomakine (80) was prepared from makomakine (81), which can be synthesized in gramquantities according to the protocol of Stevens and Kenney [51]. In the case of 79, the structure proposal, based on spectroscopic arguments, was secured by a single-crystal X-ray analysis [49].…”

“…In collaboration with Azerad's group in Paris, the three most readily available alkaloids makomakine (81), hobartine (4) and aristoteline (1) were administered to several commercially available microbes and 4 out of 12 tested strains were shown to metabolize these alkaloids [59]. 7 ppm, relative to the starting material (81). 7 ppm, relative to the starting material (81).…”