Erythrina skeleton

Erythrina alkaloids, possessing curare-like activity, are a large class of natural products found in Erythrina plants (Leguminosae). In a study towards construction of the erythrina skeleton, disfavored 5-endo-trig cyclizations were achieved by Ikeda et al. by BusSnH-mediated radical cyclization of an //-vinylic a-chloroacetamide to give five-membered lactams... 

The studies of the biosynthesis of erythrina alkaloids got off to a false start. In a beautiful experiment, A. I. Scott and colleagues showed49,50 that the whole erythrina skeleton could be constructed in one simple phenolate coupling radical reaction. 

A new approach to the Erythrina skeleton involves Birch reduction of the readily available amide (21) and two successive cyclizations, (22)->(23) and (23)->(24) (Scheme 3). Compound (24) was correlated with several known alkaloids and degradation products. A similar acid-catalysed cyclization of the enamido-ketone... 

This section will discuss the Cephalotaxine [e.g., (23)] and the Homoerythrina [e.g., (19)] alkaloids as well as the normal Erythrina types/ The last two groups are clearly biogenetically related while the Cephalotaxine structure may be regarded as a rearranged Erythrina skeleton. 

Very recently, a highly efficient synthesis of the erythrina and B-homoerythrina skeleton by an AlMe3-mediated three-step domino condensation-type/iminium ion formation/iminium ion cyclization sequence has been reported by Tietze and co-... 

The biosynthetic pathway suggested for cephalotoxine (Scheme 8) includes intermediates whch are homologous with those for Erythrina alkaloids (see above). It depends in part on the fact that homo-Erythrina alkaloids co-occur naturally with those having the cephalotaxine skeleton. 

A domino reaction catalyzed by AlMe3 leads to the skeleton of the Erythrina and /3-homo-/<.ry thrift a alkaloids (Scheme 49) <2004AGE5391>. The mechanism is believed to proceed via an iV-acyliminium ion and a metalled amide. 

Moreover, the 4-azaazulene skeleton has been found in natural products, such as Cephalotaxus alkaloids and Erythrina alkaloids (78MI1) (Section V,B). 

Two alkaloids possessing the 4-azaazulene skeleton have been isolated from leaves of Dysoxylum lenticellare (Meliaceae), namely 3-e/u-schelhamericine (188a) and dihydrohomoerysotrine (188b) (83MI2). For a report on Erythrina and related alkaloids, see (84MI1). 

The desilylation route (Section II,B) has also been used effectively to construct the skeletons of erythrina alkaloids (86JOC1159). Thus, reaction of... 

In 1957, at the time of writing the previous review of the Erythrina alkaloids in this series 1), the structures of the major alkaloids had only recently heen elucidated. Preliminary reports had appeared of syntheses of the parent skeleton which confirmed the unusual spiroamine framework of these alkaloids. Little chemical evidence was available concerning the stereochemistry, though an X-ray study had confirmed the structure and shown the relative configuration of erythraline, one of the aromatic subgroup. 

Oxidation of 2-ethoxycarbonylnorprotosinomenine (3) with potassium ferricyanide in the presence of ammonium acetate and ammonia (pH 9.2) affords the proerythrin-adienone (4) in about 2 % yield. The product has a basic skeleton of the key intermediate in the probable biogenesis of Erythrina alkaloids.3... 

The spectroscopic properties of the homoerythrina skeleton parallel those of the Erythrina group. The IR and H-NMR spectral characteristics are similar, particularly in rings A and B. The stereochemistry at C-3 may be assigned from chemical shift and coupling constants. 

Tsuda, Y., Ishiura, A., Hosoi, S., and Isobe, K., Studies toward total synthesis of non-aromatic Erythrina alkaloids. Part 2. A general method for synthesis of perhydro-6/7-pyrido[2,l-z]indole derivatives. Synthesis of isoerythroidine skeleton, Chem. Pharm. Bull., 40, 1697, 1992. 

There was a hidden agenda here too. A second cyclisation onto an electron-rich benzene ring was planned to build up the skeleton of the Erythrina alkaloids and it occurred to Tamura17 that a sulfide (X = SMe below) might control both cyclisations. Therefore the anhydride 106 was combined with an imine 105 already having the aromatic ring tethered to the nitrogen atom. 

A related cyclization was recently used by Mariano and coworkers as the key step in a construction of the skeleton of the Erythrina alkaloids. Photocyclization of 3,4-dihydroisoquinolinium perchlorate (131) afforded a 60% yield of tricycle (132 Scheme 48). This spiro tricycle was converted in eight additional steps to 15,16-dimethoxy-c/s-erythrinan. °2 ° ... 

The greater electrophilicity of the A -acyliminium ion as compared with an ordinary iminium ion was nicely illustrated as early as 1957. In experiments directed at the total synthesis of erythrina alkaloids, cyclization of iminium ion (60) to the erythrinane skeleton (61) fails (equation 34). However, A(-acylim-inium ions (62) and (63) can both be converted into the desired skeleton in good yields. A recent il-... 

It seems likely that the ring system of the homoerythrina alkaloids is derived by a route analogous to that involved in the formation of the erythrina alkaloids for which a l-benzyl-l,2,3,4-tetrahydroisoquinoline precursor has been established (36, 37). On the basis of this analogy the homoerythrina skeleton could be formed from a sequence of an oxidative coupling reaction through a l-phenethyl-l,2,3,4-tetrahydroisoquinoline derivative, as shown in Chart 18. 

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 erythrina-type alkaloids are characterized by their unique tetracyclic spiroamine framework. They are generally classified into two main groups Alkaloids predominantly possessing a 6-5-6-6-membered indoloisoquinoline core are called erythrinanes and those exhibiting a 6-5-7-6-membered indolobenzazepine skeleton are generally called schelhammeranes or homoerythrinane alkaloids (see Fig. 1). 

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

El Bialy SAA, Braun H, Tietze LF (2004) A Highly Efficient Synthesis of the Erythrina and B-Homoeiythrina Skeleton by an AlMes-Mediated Domino Reaction. Angew Chem Int Ed 43 5391... 

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