Quebrachamine alkaloids

Quebracho bark was first examined by Fraude, who isolated aspidospermine, and later by Hesse, who obtained quebrachine (yohimbine) and four other bases, aspidosamine, aspidospermatine, m.p. 162°, [a]n — 72-3°, hypoquebrachine and quebrachamine, of which the last has been confirmed by other workers the first and third, according to Ewins, are possibly decomposition products of aspidospermine. In the course of an investigation of this alkaloid Ewins isolated two unnamed bases. One of these, m.p. 149-150°, is probably quebrachamine the other crystallises from ethjd acetate in octahedra, m.p. 176-7°. 

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

A-Acyliminium ions are versatile intermediates for synthesis of nitrogenous compounds, particularly alkaloids [154]. The conjugate system is very electrophilic such that it can be intercepted by various donors including carbonyl compounds and jt-systems. In comparison with a,p-unsaturated ketones the replacement of the a-carbon with a nitrogen atom accentuates the reactivity of these species. Ingenious applications of the JV-acyliminium ions include service to synthesis of corydaline [155], lycoramine [156], quebrachamine [157], and ajmaline [158], to name a very few. 

From Stemmadenia donnell-smithii, besides iboga alkaloids and voac-amine, the indole (+ )-quebrachamine (L), mp 147°—149°, [a]D +111° (CHCI3), and the indole stemmadenine (LIV, a— x or a— y bond), mp 199°-200° (dec.), [ ]D + 324° (pyridine), were isolated (11). The latter alkaloid also occurs in Diplorrhynchus condylocarpon (43) along with condylocarpine, shown (43a), to be LV (rather than LVI), and into which it was converted by potassium permanganate oxidation (44). Stem-... 

The Vinca minor alkaloids vincadine (II-A) and vincaminoreine (II-B) are the 3-carbomethoxy- and 3-carbomethoxy-Aa-methyl derivatives, respectively, of ( + )-quebrachamine (10a). The same plant also contains ( + )-indolic-A-methylquebrachamine (10b). 

The determination of the structure of quebrachamine (I) followed on that of aspidospermine (II), and was indeed suggested at the time that this latter structure was published (11, 12, 13, 14). In work prior to this, Witkop and his co.-workers were able to show that the two alkaloids were related, since both gave on zinc dust distillation a mixture from which... 

The closure of a bond between positions 12 and 19, presumably involved in the natural synthesis of aspidospermine-type alkaloids from quebrachamine, has been shown (18) to occur during the zinc dust distillation of the latter when a compound IX was isolated whose mass spectrum was exactly comparable with that of the indolenine VII, except for the 30-unit shift in the indole-containing fragments (Table V). Substance IX has subsequently been found in nature (Section II, E). 

The indolenine corresponding to aspidospermidine was also isolated (28,51a). It was denominated Alkaloid 280A [later named 1,2-dehydro-aspidospermidine (51)] and has structure IX. This compound had previously been obtained by the zinc dust distillation of quebrachamine (18, Section II, B) and was subsequently found in R. stricta (51). It is... 

Mass spectrometry was very helpful in determination of the structures of vincaminorine,105 vincaminoreine,105 md-N-methylquebrach-amine,105 106 and a degradation product of rhazidigenine,107 alkaloids closely related to quebrachamine (220) and the dehydro product (221). 

Aspidospermine-Aspidofractine-Eburnamine Group. The leaves of Pandaca minutiftora contain (+)-vincadifformine, which also occurs in the leaves of Amsonia tabernaemontana, together with ten other alkaloids [tabersonine, (+)-l,2-dehydroaspidospermidine, (—)-quebrachamine, lochnericine, ( ) and (—)-vincadine, (-)and ( )-epivincadine, (+)-14,15-dehydrovincadine, and (+)-14,15-dehydroepivincadine] the roots contain the first four alkaloids and ebumamonine. 

Several new sources of quebrachamine (5) (10-16) and, particularly, voaphylline (conoflorine, 6) (15,17-34) have been found in recent years. Other known alkaloids encountered in recent extractions include vincadine (7) (35,36), 14,15-didehydro-epivincadine (8) (37), rhazidine (9) (38), and 12-methoxyvoaphylline (10) (39-41). New alkaloids include quebrachamine hydroxyindolenine (strictanol, 11), which has been found in the fruits (42) and leaves (43) of R. stricta, and voaphylline hydroxyindolenine (12), for which five sources have been reported (20,22,27,34,44). In common with many other hydroxyindolenine derivatives of easily oxidized alkaloids, these may well prove to be artifacts of the extraction process. Ervayunine (13), the enantiomer of voaphylline, occurs in the roots of Ervatamia yunnanensis... 

Three incompletely characterized alkaloids in the quebrachamine group are among the 45 alkaloids isolated from the root bark of T. chippii Stapf (30). Alkaloids TC-A and TC-C gave identical mass spectra, which were in turn identical with that exhibited by synthetically prepared (l SjlS )-voaphyllinediol (18) (50,51). Alkaloids TC-A and TC-C are therefore regarded as (14R,155)-voaphyllinediol and (145,15S)-voaphyllinediol (19 and 18), but in view of the trace amounts of alkaloid isolated, it was not possible to determine which was which. Alkaloid TC-B contains an additional oxygen atom (mass spectrum), probably as a hydroxyl group attached to C-19, the most frequently substituted position in this group of alkaloids. It is therefore tentatively formulated as 20 (30). 

In view of the importance of vindoline (44) as a constituent of the oncolytic bisindole alkaloid vinblastine, methods for the synthesis of both vindorosine (43) and vindoline from members of the quebrachamine and vincadifformine groups have been extensively investigated. The first results... 

The reaction was also applied to thcAspidosperma alkaloids. Thus oxidation of (—)-quebrachamine (4) with mercuric acetate followed by reduction with lithium aluminum hydride gives (+)-aspidospermidine (5). 

Both drug extracts are characterized in (JV-365nm by the blue fluorescent zone of yohimbine at R, 0.45 (T5). A variety of additional alkaloids are seen as ten blue zones in the lower R, range (e.g. quebrachamine, aspidospermine in 5), whereas Yohimbe cortex (4) has two prominent alkaloid zones in the upper R, range (R, 0.7-0,75) and one near the solvent front. 

From the root bark of Aspidosperma fendleri Woods. Medina and coworkers (41) isolated a new crystalline alkaloid, fendlispermine. The UV spectrum indicated the dihydroindole moiety, and the mass spectrum, which showed a molecular ion at m/e 298, suggested a molecular formula of C19H26N20. Reduction of fendlispermine with lithium aluminum hydride gave quebrachamine (82). 

Numerous alkaloids have been isolated from Voacanga africana Stapf., and Poisson and co-workers (85) have reported on two new compounds having the quebrachamine skeleton. 

Three new alkaloids in the vincadine series have also been reported by the Hungarian group (92). The first compound obtained was (+)-14,15-dehydrovincadine (187) [a]D + 65°, whose structure was proved by catalytic hydrogenation to (+)-vincadine (184) and hydrolysis/decar-boxylation to (+)-14,15-dehydroquebrachamine (188). The two other compounds were the C-16 epimers of vincadine (184) and 187. 16-Epivincadine (189) was racemic, and hydrolysis gave (+)-quebrachamine... 

The simplest of all Aspidosperma alkaloids is quebrachamine (82), having only one stereochemical center and no carbomethoxy group. A number of syntheses of quebrachamine have been discussed previously in these volumes (see, e.g., Volume XI, p. 277). 

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