New Erythrina Alkaloids

Up to the most recent reviews published in the years 1995/96 nearly 95 erythrinane and 68 schelhammerane type alkaloids were known (79, 27, 24). In this chapter all the new compounds reported in literature from 1995 to 2004 are listed including the natural source, structure, analytical and spectroscopical informations. 7U1 in all, there are 12 erythrinane and 6 homoerythrinane type compounds compiled in Tables 1 and 2. 

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A new erythrina alkaloid, erythroculine, from Cocculus laurifolius has been shown to have the structure (167). The ester group may be reduced with lithium aluminium hydride and the acetyl ester of the resulting alcohol on treatment with cyanogen bromide affords the hindered diphenyl (168), with loss of hydrogen bromide and methanol. This on reduction to the secondary base, N-methylation, and successive Hofmann degradations affords an olefin that may be oxidised to the tricarboxylic acid (169).The base represents a novel structure in having the additional carbon atom linked to the ring system. 

It appears that the combined g.c.-m.s. method for analysis of crude natural product mixtures can be improved by using it in conjunction with high-resolution field-ionization m.s. studies. ° Such studies on the crude mixture from E. princeps (formerly known as E. lysistemon) have allowed the tentative structural assignments of several new Erythrina alkaloids. ... 

The methanol extract of E. herbacea flowers was subjected to the conventional extraction and isolation procedures for alkaloids. A new Erythrina alkaloid, 10-hydroxy-ll-oxoerysotrine (29), was isolated together with five known compounds. The structure of the new compound was elucidated on the basis of its spectral data, including 2-D NMR and mass spectra (MS). The new compound is a rare C-10 ox ygenated Erythrina alkaloid [49]. 

A new abnormal Erythrina alkaloid, obtained from the leaves of Cocculus laurifolius, was assigned the structure isococculine (7) on the basis of spectral and chemical studies.7... 

In the intervening 13 years the subject has expanded dramatically over 60 compounds are now classified as Erythrina alkaloids, and the structures of most of these have been deduced from a combination of mass spectral fragmentation analysis, H-NMR spectral interpretations, and chemical correlations with alkaloids of known structures. Some unusual alkaloids have been obtained from certain Cocculus species and a new, as yet small, subgroup, the Homoerythrina alkaloids, has been recognized. The biosynthetic pathway from tyrosine through the aromatic bases to the ery-throidines has been elucidated, and some significant advances have been made in methods of total synthesis. Reviews of the Erythrina alkaloids since 1966 have appeared (3-6). 

A new approach to the synthesis of the Erythrina alkaloids involves (134) a Birch reduction of the amide (166) to 167, followed by cyclization, first to 168 with sulfuric acid in DMF, then to the ketolactam (169) with formic... 

In the Erythrina series, Tsuda and co-workers11 have developed new methods for the synthesis of spiro-type compounds that are related to Erythrina alkaloids, either by intramolecular nucleophilic cyclization of dioxopyrrolines or by cycloaddition of activated butadienes to dioxopyrrolines. The conversion of 2-(ethoxycarbonyl)-cycloalkanones (9) into the spiro-type compounds (12), in high yield, via 3,3-disubstituted dioxopyrrolines (11) is shown in Scheme l.12 They also reported... 

Erythrina Alkaloids.—Although a small number of new alkaloids have been discovered, most of these show interesting structural features. Erysotrine has been obtained for the first time from a natural source Erythrina suberosa Roxb.). Erythroculine is the first case of an Erythrina alkaloid which bears a methoxy-carbonyl-substituent at C-15. ... 

A new synthesis of bis(2-arylethyl)amines (7), required in connection with studies in Erythrina alkaloid biosynthesis, may have general applicability (c/. Scheme 1). 

There is sound evidencethat the biosynthesis of Erythrina alkaloids, e.g. erythraline (105), proceeds by the novel pathway shown in Scheme 7. New evidence" of a negative kind supports the previously established role of (S)-N-norprotosinomenine (102) as an intermediate in the biosynthesis of these alkaloids. 

New benzylisoquinoline alkaloids are (+ )-iV-norprotosinomenine (14), found in Erythrina lithosperma Blume (Leguminosae), and A-methylpalaudinium chloride (15), isolated from Thalictrum polygamum Muhl. (Ranunculaceae). ... 

New investigation of bisbenzylisoquinoline biosynthesis is welcome (see ref. 32 also this Report, p. 16). Although aporphine alkaloids are the simplest developments of the benzylisoquinoline skeleton, their biosynthesis need not, as several examples show, be simple. It has, however, been found that the biosynthesis of boldine and isocorydine is straightforward. Further detail has been repor-ted on the biosynthesis of Erythrina alkaloids, which were established to be modified benzylisoquinolines some time ago. Further detail on the biosynthesis of morphine (23) and related alkaloids continues to be published. Of particular R. B. Herbert, in ref. 9, p. 11. 

The present contribution will give a brief classification of the Erythrina alkaloids, a compilation of new alkaloids isolated from 1997 to 2004 covering source, structure, analytical/spectral data, a new pathway of their biosynthesis, an overview of all the synthesis strategies hitherto known for the erythrinane alkaloids including several approaches to the homoerythrinane group, and finally a short review of their biological activities. 

Not only because of their attractive structure, but also of their pharmacological potential, mainly that of the pure compounds, the synthesis of the Erythrina alkaloids will remain an important goal challenging the synthesis chemists in the forthcoming years. It is hoped, that this review along with the powerful arsenal of modem synthesis methods can stimulate the development of new efficient strategies to the Erythrina alkaloids and possibly to related new active agents. 

Folkers K, Unna K (1938) Erythrina Alkaloids, n. A Review, and New Data on the Alkaloids of Species of the Genus Erythrina. J Am Pharm Assoc 27 693... 

Folkers K, Koniuszy F (1940) Erythrina Alkaloids. VIL Isolation and Characterization of the New Alkaloids, Erythraline and Erythratine. J Am Chem Soc 62 436... 

Dagne E, Steglich W (1983) Erymelanthine, a New Type of Erythrina Alkaloid Containing a 16-Azaerythrinane Skeleton. Tetrahedron Lett 24 5067... 

Sharma SK, Chawla HM (1998) Structure Elucidation of Erythrosotidienone and Erythromotidienone - Two New Isoquinoline Alkaloids from Erythrina variegata Flowers. J Indian Chem Soc 75 833... 

Tanaka H, Tanaka T, Etoh H, Goto S, Terada Y (1999) Two New Erythrinan Alkaloids from Erythrina x bidwillii. Heterocycles 51 2759... 

Ozawa, M. Kawamata, S. Etoh, T. Hayashi, M. Komiyama, K. Kishida, A. Knroda, C. Ohsaki, A. Structures of new Erythrinan alkaloids and nitric oxide production inhibitors from Erythrina crista-galli. Chem. Pharm. Bull 2010, 58, 1119-1122. 

Quinolines and Related Compounds.— The Erythrina alkaloids have an interesting molecular architecture, and new routes to the skeleton and to the alkaloids themselves have been described recently. One approach requires the synthesis of the dibenzazonine system, which is now readily available by nickel-promoted coupling of a bis(iodophenyl)ethylamine (Scheme 90). An attempt to utilize an intramolecular [4 + 2] cycloaddition of enamines and enamides for the construction of the Erythrina carbon skeleton failed, but nevertheless provided an interesting synthesis of bridged bicyclotetrahydroisoquinolines (Scheme 91). ... 

The isolation of these new 8-oxo-alkaloids adds two further examples to a growing family of 8-oxo-erythrina alkaloids, other examples being erythrabine (Id) and erysotramidine (If) (Ito et al. 1973) isolated from E.arborescens and crystamidine (In) from E.crysta-galli (Ito et al. 1973) whilst two other oxo-alkaloids have been found in Cocculus laurifolius (Uprety and Bhakuni 1975), (Bhakuni and Jain 1980). 

Boar RB, Widdowson DA (1970) Mass spectra of the Erythrina Alkaloids - A novel fragmentation of the spiran system. J Chem Soc (B) 1591-1595 Boekelheide V (1960) In Manske RHF, Holmes HL (eds) The alkaloids, chap 11. Erythrina alkaloids. Academic Press, London New York, pp 201-227 Boekelheide V, Grundon MF (1953) A characterisation of a-Erythroidine. J Am Chem Soc 75 2563-2568... 

CTiawla AS, Chunchatprasert S, Jackson AH (1983) Studies of Erythrina alkaloids VII C-NMR Spectral Studies of some Erythrina alkaloids. Org Mag Res 21 39-41 Chawla AS, Redha FMJ, Jackson AH (1985) Alkaloids in the seeds of E.brucai, E.cochleata, E.thollonia 2ind E.caribea Isolation of a new Dienoid Alkaloid, Erythrocarine. Phytochemistry (in press)... 

Mondon A (1970) In Pelletier SW (ed) Chemistry of the alkaloids, Erythrina alkaloids. Van Nostrand Reinhold, New York, pp 173-196... 

Because of the postulated biosynthetic derivation of the Cephalotaxus alkaloids from the Homoerythrina bases, the former, relatively new group is included in this chapter. Anticancer activity has been found in certain members of the Cephalotaxus group, so the subject has already been reviewed several times (7-9). Annual coverage is given to the Erythrina, Homoerythrina, and Cephalotaxus alkaloids in the Specialist Periodical Reports of the Chemical Society (10-1 la). 

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