Homoerythrina

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-... 

Five new homoerythrina alkaloids have been isolated from this plant in addition to others which were known. Their properties and... 

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). 

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). 

The C-Homoerythrina alkaloids are a relatively recently identified group, the first examples being isolated and identified from Schelhammera pedunculata F. Muell. in 1968 (81). Homoerythrina alkaloids have been isolated from all three species of Schelhammera (Liliaceae), in which they constitute a further addition to the various biosynthetically related alkaloids within the family Liliacea (82-85)-, from the leaves of species of Phelline (Ilicacea), where their presence raises some doubts about the taxonomic classification of the genus (86-88)-, and from the roots and stems of species... 

Many members of the Homoerythrina group occur with their C-3 epimers, in contrast to the Erythrina group, and despite the fact that they appear in relatively few plant species, over 20 individual Homoerythrina alkaloids have been isolated, although the structures of two of them remain incomplete because of insufficient amounts of samples. Those alkaloids of known struc-... 

The Homoerythrina alkaloids have not been reviewed before, except briefly in conjunction with Cephalotaxus alkaloids, with which they occur in Cephalotaxus species (9). 

Nomenclature for the Homoerythrina group is a problem because only a few of the alkaloids have been given trivial names. Since the structures of the Homoerythrina group parallel those of the Erythrina group we have... 

Scheme 17. Major fragmentation pathway for l, 6-diene-type Homoerythrina alkaloids.

The alkaloids were best isolated from the ethanol extract of the plant material, partially fractionated by counter-current distribution, and subsequently purified by preparative chromatography. Of the 11 known Cephalotaxus alkaloids (105-115 in Figs. 8 and 9), cephalotaxine (105a) is ubiquitous and the most abundant (up to 64% of the total alkaloid extract) in all species examined. C. wilsoniana Hay., which yields only minor quantities of cephalotaxine, is the exception, however it is rich in Homoerythrina alkaloids,... 

Recently, a GC-MS method for the separation and quantitative identification of extracts from Cephalotaxus species (97) has been described. Most of the alkaloids were resolved, particularly the biologically active esters. The seven Homoerythrina alkaloids were only resolved into two groups of five and two components, respectively, under the conditions described. Acetylcephalotaxine (106), 11-hydroxycephalotaxine (114), and desmethyl-cephalotaxinone (113) were not resolved by retention time, but could be identified within the mixture by their MS fragmentation patterns. Cepha-lotaxinone (112) gave two GC peaks after silylation, presumably due to a contribution from the enol component. The artifact peak overlaps partly with the peak for drupacine (115) and hence introduces a slight error for this component and makes it difficult to quantify cephalotaxinone. 

The first two homoerythrina alkaloids to be isolated (82) were schelham-merine (80a) and schelhammeridine (77a), and since various species of... 

Lilaceae also contain 1-phenethylisoquinoline alkaloids, it was suggested [82) that the homoerythrina derivatives are biosynthesized along a pathway analogous to that followed by the Erythrina alkaloids themselves (Scheme 35). Some preliminary results from feeding experiments (121) support this view ( )-[2-14C]tyrosine causes specific labeling of C-8 in 77a. 

Arguing from structural similarities, it was originally suggested (10) that the Cephalotaxus alkaloids could be derived in vivo from the same precursor as the aromatic erythrina bases, but since Cephalotaxus and homoerythrina alkaloids have been isolated (90) from E. wilsoniana, it has been postulated (10b, 89) that both groups have a 1-phenethyltetrahydroisoquinoline as a common precursor (Scheme 36). Tyrosine is incorporated (122) into cepha-lotaxine, but the labeling pattern did not seem to be consistent with a... 

The ring system of the homoerythrina alkaloids has been prepared (149) by oxidative coupling of the 1-phenethyltetrahydroisoquinoline (206, R = COCF3) (Scheme 44). The diphenol (208) was obtained in 76% yield from 207, but all attempts to oxidize the A-trifluoroacetate of 208 to a dipheno-quinone failed—probably because the two aromatic rings are orthogonal to each other. However, oxidation of the secondary amine (208) itself with potassium ferricyanide gave a mixture of 209 (45% yield) and 210 (15%) ... 

Dibenzazecines are probably biogenetically derived from a phenethyliso-quinoline such as 112 via the homoproerythrinadienone 113 (Scheme 33). The resulting dibenzazecine can either give dysazecine 114 or be further oxidized to a homoerythrina derivative such as 115. This biogenetic pathway parallels that of the Erythrina alkaloids (see Scheme 32). 

It should be noted that several domino reactions exist where the Michael/SN-type processes are reversed. For instance, bicylo[3.3.1]nonane ring systems, applicable as synthons for the construction of various natural products [96], have been synthesized by Srikrishna and coworkers using a domino SN/Michael process [97]. This type of domino reaction was also used by the group of Bunce to synthesize N-pro-tected pyrrolidines and piperidines bearing functionalized side chains at C-2 [98], For a domino alkylation/spiroannulation process to give homoerythrina alkaloids 2-177 [99], Desmaele/dAngelo and coworkers have treated the 2-tetralones 2-179 with 2-180 in the presence of Cs2C03 as base (Scheme 2.42) [100],... 

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