Strychnine-Akuammicine-Ellipticine Group

Strychnine-Akuammicine-Ellipticine Group. A new alkaloid encountered in the culture of cell line 943 of Catharanthus roseus has been formulated, on the basis of its n.m.r. and mass spectra, as the /S-xyloside (147) of 9- (or 12-)hydroxy-akuammicine.42a Akuammicine and 10-methoxyakuammicine are reported to be present in the leaves of Rauwolfia oreogiton.43a Diaboline has been found in the root bark of Strychnos jobertiana Baill., and 11-methoxydiaboline in the root bark of S. 

The three new alkaloids reported recently from the root bark of S. variabilis are 16-hydroxyisoretulinal, rosibiline (150), and strychnopivotine (151), which is unusual in that C-17 is missing. The structure of rosibiline becomes clear from the formation of desacetylretuline on treatment with acid, and is confirmed by the preparation of rosibiline by the reaction of desacetylretuline with formaldehyde in the presence of acetic acid.75 

Galeffi and G. B. Marini-Bettolo, Gazz. Chim. Ital., 1980, 110, 81. 

The leaves and stems of Mostuea brunonis Didr. var brunonis forma augustifolia 

Ellipticine is the major alkaloid of the trunk bark of Ochrosia moorei F. von Muell., in which it occurs in association with 27 other alkaloids, including 10-methoxyellipticine, ellipticine 7Vb-oxide, and 3,14-dihydroellipticine.43rf A point of chemotaxonomic interest is that the genera Ochrosia and Neisosperma can be distinguished on the basis of their ellipticine/10-methoxyellipticine content one or both of these alkaloids are present in Ochrosia species, but absent from Neisosperma species. 

Strychnine-Akuammicine-Ellipticine Group. 11-Methoxyicajine (110)77 and 15-hydroxystrychnine,78 a new alkaloid, have been isolated from Strychnos nux-vomica seeds, and 11-methoxydiaboline from S. rubiginosa.58 10-Hydroxy-akuammicine (sewarine) occurs in the leaves of Rauwolfia volkensii,60 and 11-methoxyakuammicine in Alstonia odontophora.59 

The presence of isoretulinal (111) in the root bark of Strychnos variabilis de Wild, has been confirmed,79 and it has also been shown that retulinal (112), with which it is very easily equilibrated, occurs in smaller amounts in the same extracts both alkaloids exist in two forms, which are amide rotamers, according to their n.m.r. spectra. The 12-hydroxy-derivatives, (113) and (114), form a similar equilibrating pair of alkaloids, and were also isolated from this source. The occurrence of these easily interconvertible C-16 epimers explains the simultaneous occurrence of retuline and isoretuline derivatives in Nature, in both the monomeric and dimeric alkaloid series. 

The first extractions of Strempeliopsis strempelioides K. Schum. (Family Apo-cynaceae), from Cuba, reveal that it is rich in alkaloids. The leaves and stem bark contain, amongst others, (+)-tubotaiwine and (+)-condylocarpine, and the stem bark also contains (-)-apparicine.80 Apparicine (pericalline) also occurs, together with O-acetylvallesamine, 19,20-dihydrocondylocarpine, and eleven other alkaloids, in the wood and stem bark of Ervatamia heyneana (Wall.) T. Cooke,81 and 

Laguna, C. Dolejs, and L. Novotny, Collect. Czech. Chem. Commun., 1980, 45, 1419. 

The two d/e-c/s-fused diastereoisomers of structure (115) have been synthesized,83 but neither proves to be identical with subincanine, which was earlier836 assigned the general structure (115), without stereochemistry. The available evidence indicates that subincanine is very unlikely to be a d/e-transfused isomer of (115) hence its structure remains obscure. 

Strychnine-Akuammicine-Ellipticine Group. Akuammicine has been found in the seeds of Hunteria congolana and Na-methyl-2/3,16 -dihydroakuammicine in the leaves of Vinca minor. Tubotaiwine and condylocarpine occur in Aspid-osperma album tubotaiwine and apparicine have been isolated from Catharanthus ovalis, tubotaiwine also from Pandaca boiteau and Melodinus aeneus Baill., in the last of which tubotaiwine Nb-oxide also occurs.  

New extractions of the root bark of Sri Lankan Strychnos nux vomica have disclosed the presence, besides strychnine, brucine, and isostrychnine, of 12-hydroxystrychnine, 12-hydroxy-11-methoxystrychnine, and a minor base, named protostrychnine (168), because of the obvious possibility that it may be an immediate biosynthetic precursor of strychnine. The overall structure (168), but not necessarily the configuration at C-17, was confirmed by allowing the 18-0-tigloyl ester to react with phosphorus oxychloride in pyridine saponification of the product, followed by treatment with dilute hydrochloric acid, then gave strychnine. 

In addition to desacetylretuline and deoxydiaboline (already noted),the root bark of S. variabilis de Wild, contains retuline, isoretuline, and desacetyl-isoretuline.  

The leaves of Ochrosia oppositifolia contain two new alkaloids, 10-hydr-oxyapparicine (169) and 10-methoxyapparicine (170), whose overall structures became clear from examination of their mass and 300 MHz n.m.r. spectra. The position of the aromatic substituent in (170), which could not be deduced from the spectroscopic data, follows from the typical 5-methoxyindole u.v. absorption of the secondary base (171) and it Nb-acetyl derivative (172), produced by saturation of the 16,17 and 19,20 double-bonds in 10-methoxyapparicine and simultaneous hydrogenolysis of the benzylic 6-Nb bond. Methylation of the second, amorphous alkaloid with diazomethane gave (170) consequently it is 10-hydr-oxyapparicine (169). 

The configuration about the double bond in apparicine (173), which has not previously been rigidly defined, follows from the NOE enhancement of the H-15 absorption on irradiation of the C-18 methyl signal. A similar phenomenon was observed for 10-hydroxyapparicine. In these two alkaloids, and therefore in 

Hunteria zeylanica, and from the leaves of Peschiera echinata. 

Olivacine occurs in the stem and root bark of this last species. 

Eighteen of the twenty-two alkaloids isolated from the root bark and leaves of Sri Lankan S. nux vomica are strychnine derivatives, and include several that have not previously been obtained from this species.The alkaloids identified were strychnine, its lO- and 12-hydroxy derivatives, B-colubrine, brucine, 12-hydroxy-11-methoxystrychnine, the Nj -oxides of strychnine, brucine, 12-hydroxystrychnine and 12-hydroxy-11-methoxystrychnine, isostrychnine I and its 19,20-dihydro derivative, protostrychnine, vomicine, 3-hydroxystrychnine, 3,12-dihydroxy-strychnine, 3,12-dihydroxy-ll-methoxystrychnine, and 3-hydroxy-10, 

The alkaloid content of these specimens of S. nux vomica clearly differentiates them from Indonesian plants, which, for example, contain no 12-hydroxy-11-methoxystrychnine and only traces of 12-hydroxystrychnine. In view of this, it seems likely that the Sri Lankan variety is a hybrid of the true nux vomica and the jungle liane S. wallichiana Steud. ex DC. Certainly the alkaloid content is that expected from such a hybrid, although morphologically S. nux vomica appears to be the dominant plant. 

Some further C n.m.r. data on pyridocarbazoles related to ellipticine have been published. The hydroboration-oxidation of akuammicine results unexpectedly in Markownikov hydration of the 

---

Strychnine-Akuammicine-Ellipticine Group.—Very few new extractions have been recorded during the year under review. (- )-Akuammicine occurs in the leaves of Hunteria elliottii and in the aerial parts of V. major. A cytotoxic constituent of the roots of Tabernaemontana holstii K. Schum. proves to be tubotaiwine N-oxide. Olivacine and apparicine have been found in the leaves of Pagiantha cerifera. ... 

Strychnine-Akuammicine-Condylocarpine-Uleine Group. Details39 have appeared of a synthesis1" of the ( )-dasycarpidones and ( )-epi-uleine. Ellipticine, appari-cine, and isoreserpiline have been isolated from Ochrosia silvatica 0a and the last two, together with 10-methoxy-19,20-dihydrocorynantheol, from O. vieillardii.40b... 

Corynantheine-Heteroyohinbine-Yohimbine Group, and Related Oxindoles Sarpagine-Ajmaline-Picraline Group Strychnine-Akuammicine-Condylocarpine-Ellipticine Group... 

Strychnine-Akuammicine-Condylocarpine-Ellipticine Group. Full details have been given of structural work on hunteracine chloride and of Le Goffic s synthesis " of ellipticine reviewed" in Volume 4. It has been shown that the so-called strychnicine, isolated from leaves of Strychnos ignatii and S. nux-vomica many years ago, is probably vomicine. 11-Methoxydiaboline occurs... 

---