Homoerythrinan alkaloids

Photocycloaddition of 2-TMSO-buta-1,3-diene to enone (89) affords the adduct (90) which is a key intermediate in an approach to the synthesis of homoerythrinan alkaloids. The principal product obtained by irradiation (298-310 nm) of the dione (91) in the presence of the isoxazolone (92) has been identified as (93, 38%). ... 

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). 

The biosynthesis of homoerythrinane alkaloids has been proposed to proceed by the same pathway as that of the erythrinanes according to... 

The synthesis of the 3-epimeric schelhammericines, being the first synthesis approach to a homoerythrinane alkaloid at all (111), is based... 

Tsuda Y, Sano T (1996) Erythrina and Related Alkaloids. In Cordell GA (ed) The Alkaloids vol. 48. Academic Press, Inc. (Erythrinane and Homoerythrinane alkaloids)... 

Bick IRC, Panichanun S (1991) Homoerythrina and Related Alkaloids. In Pelletier SW (ed.) Alkaloids Chemical and Biological Perspectives Vol. 7. Springer, Berlin (Homoerythrinane alkaloids exclusively)... 

Toda J, Niimura Y, Takeda K, Sano T, Tsuda Y (1998) General Method for Synthesis of Erythrinan and Homoerythrinan Alkaloids (1). Synthesis of a Cycloerythrinan, as a Key Intermediate to Erythrina Alkaloids, by Pummerer-Type Reaction. Chem Pharm Bull 46 906... 

Tsuda Y, Ohshima T, Hosoi S, Kaneuchi S, Kiuchi F, Toda J, Sano T (1996) Total Synthesis of Homoerythrinan Alkaloids, Schelhammericine and 3-Epischelhammer-... 

Tsuda Y, Murata M, Hosoi S, Ikeda M, Sano T (1996) Synthesis of Homoerythrinan Alkaloids of 1(2)-Alkene and 1,6-Diene Types Total Synthesis of Comosine,... 

The Erythrina alkaloids contain four linked rings, labeled A, B, C, and D (Figme 1), and can be divided or classified into two main groups alkaloids possessessing a 6,5,6,6 indoloisoquinoline ring system called erythrinans, and those with a 6,5,7,6 ring system, the homoerythrinan alkaloids (Figure 3). 

There are two groups of Cephalotaxus alkaloids the cephalotaxine - har-ringtonine group and the group represented by alkaloids II and III. The latter are often called homoerythrinan alkaloids. 

Although biosynthesis of the phenethylisoquinoline alkaloids has not yet been studied in full, that of androcymbines, homoaporphines, and homoerythrinans has been examined by work with radioactive tracers. In this section tracer experiments as well as hypothetical biogenetic routes in the synthesis of the phenethylisoquinoline alkaloids are discussed. 

Dibenz[i7,/]azecines (see Cephalotaxus alkaloids) have been discussed as intermediates (formula II in the biosynthesis of cephalotaxin) of homoerythrinan-Cephalotaxus alkaloids. 

In the late 1960s ring C-homologues of erythrinane alkaloids have been anticipated firom the biosynthetic pathway of certain alkaloids, which are known to be generated from 1-phenethyl-isoquinoline derivatives as precursors (75, 16). Only a short time later such compounds named homoerythrinanes, homoerythrina alkaloids, or schelhammeranes indeed have been found in the plant kingdom 17) (parent compound 2, Fig. 1). 

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. 

The aromatic erythrinanes and homoerythrinanes as the most important members of the Erythrina alkaloids show substimtion patterns of... 

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. 

Fig. 3. Phenethylisoquinolines 47 and 48 isolated from plants, which produce homoerythrinane and dibenzazecine alkaloids 49, 50, and 51...

In this classification C-homoerythrinane syntheses remain out of consideration, since the construction of their framework is far more difficult than that of the erythrinanes. Nevertheless, several useful approaches to this alkaloid group are included in this section (see below). 

Figure 3. Ring systems of the alkaloids eiythrinanes and homoerythrinans.

A possible pathway of the biosynthesis of Cephalotaxus alkaloids is shown in Fig. 5.2.13 (120). A similarity has been pointed out between this scheme and that of Erythrina alkaloids (Sect. 5.2.2.5.T). The starting open-ring intermediate in the present case is phenethylisoquinoline, instead of benzylisoquinoline for the Erythrina alkaloids. On this basis, homoerythrinan-type alkaloids are also called phenethylisoquinoline-type alkaloids. 

A study of the constituents of Cephalotaxus plants was made by using a young plant grown in a controlled environment (33). The concentration of free alkaloids (homoerythrinan-type alkaloids and cephalotaxine) did not increase with age, but that of cephalotaxine esters did. Total alkaloid concentrations increased in the older leaves and decreased in the older stems. Hydrolytic cleavage... 

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