Erythroidine a- and

The first crystalline pharmacologically active alkaloid was isolated from Erythrina americana mentioned above (7) and was called ery-throidine. This name had already been used by Altamirano referring, however, to the unknown constituents of the plant (774). Further analytical investigations revealed the material isolated to be a mixture of isomeric alkaloids, which were subsequently named a- and /3-erythroidines (14 and 225, see Figs. 2 and 4). 

Barton DHR, Cohen T (1957) In Festschrift Dr A Stoll, Birkhauser, Basel, p 117 Barton DHR, Kirby GW, Taylor JB, Thomas GM (1963) Phenol oxidation and biosynthesis, part VI. The biogenesis of amaryllidaceae alkaloids. J Chem Soc 4545—4558 Barton DHR, Hesse RH, Kirby GW (1965) Phenol oxidation and biosynthesis, part VIII. Investigations on the biosynthesis of berberine and protopine. J Chem Soc 6379-6389 Barton DHR, Bracho RD, Potter CJ, Widdowson DA (1974) Phenol oxidation and biosynthesis, part XXIV. Origin of chirality in the erythrinan system and derivation of the lactone rings of a- and ]3-erythroidine. J Chem Soc Perkin Trans 1 2278-2283 Basmadjian GP, Paul AG (1971) The isolation of an O-methyltransferase from peyote and its role in the biosynthesis of mescaline. Uoydia 34 91-93 Basmadjian GP, Hussain SF, Paul AG (1978) Biosynthetic relationships between phenethylamine and tetrahydroisoquinoline alkaloids in peyote. Lloydia 41 375-380 Battersby AR, Binks R, Francis RJ, McCaldin DJ, Ramuz H (1964) Alkaloid biosynthesis, part IV. 1-Benzylisoquinolines as precursors of thebaine, codeine and morphine. J Chem Soc 3600-3610... 

From all the pure alkaloids tested a- and yS-erythroidine exhibit the highest activity (727). They have been assumed to be the principles responsible for the hypnotic activity of the extracts of the flowers of E. americana 19). /)-Eyrthroidine (225) and its more potent 2,7-dihydro-derivative 226 have been used as muscle relaxant in numerous clinical applications 114, 120). This activity is attributed to an antagonistic action of dihydro-/3-erythroidine to nicotinic acetylcholine receptors, which is now well known and is frequently used in the experimental pharmacology (79, 725, 726). 

In our own studies in Cardiff we have also isolated 8-oxo-a- and j3-erythroidine (4a) and (4b) (Chawla et al. 1982) from E.herteroana as well as 8-oxo-erysodine from E.tahitensis (Chunchatprasert 1983) it thus seems likely that 8-oxo- analogues of many of the other dienoid alkaloids are also likely to be found accompanying the parent alkaloid, albeit in small amounts. However, the relatively high polarity makes them less amenable to GC-MS and only 8-oxo-i3-erythroidine (4b) has been detected by GC, presumably because the derivatization of the lactone residue by the silylat-ing reagent makes it much more volatile. (The TMS derivative of 3-erythroidine itself has the shortest retention time of all the Erythrina alkaloids we have studied so far). 

Soto-Hernandez, M. and Jackson, A. H. 1993. Studies of alkaloids in foliage of Erythrinia berteroana and E. poeppigiana detection of 3-erythroidine in goats milk. Phytochemical Analysis, 4 97-99. 

Cocculolidine, an alkaloid with striking insecticidal properties isolated from the leaves of Cocculus trilohus DC, has recently been isolated and assigned the structure (XCIV) of a lower homolog of -erythroidine 50). The degradation reactions reported closely parallel those of /3-erythroidine. This makes the second report of Erythrina alkaloids in Cocculus species, dihydroerysodine having been isolated earlier from C. laurifolius 51). 

Weinstock and Boekelheide introduced Amberlite IRA-400 (OH ) for conversion of alkyltrimethylammonium iodides into the corresponding quaternary ammonium hydroxides. The procedure is simpler than the conventional silver oxide method and avoids undesirable side reactions sometimes encountered. In the case of a derivative of /3-erythroidine, this technique raised the yield in a Hofmann degradation from 40 to 78%. 

Erythrina alkaloids except erythroidine. Boekelheide and coworkers (97) have shown that erythroidine and its derivatives are represented by XX-XXII. Boekelheide (97) suggested a biogenetical relationship between /3-erythroidine and the aromatic Erythrina alkaloids. 

In general, /3-erythroidine, demethoxy-/3-erythroidine, and their derivatives which contain the spiran ring-system exhibit curariform activity to some degree, even though in many cases it is masked by other effects such as ganglionic block. On the other hand, apo-/3-erythroidine, which no longer is a spiran, and its derivatives all exhibit central depressant activity and have no curare-hke effects (97). 

All of the aromatic alkaloids (except for erythratine) and -erythroi-dine possess two asymmetric carbon atoms—the spiro carbon (C-5) and the carbon substituted by methoxyl (C-3). a-Erythroidine has an additional center of asymmetry at C-12. Chemical, spectroscopic, and crystallographic methods have been used to assign relative and absolute configurations at the asymmetric centers. 

A chemical determination of the absolute configuration at C-3 by Boekelheide and Wenzinger corroborated this conclusion 19). The di-hydropyran derivative (L) derived from tetrahydro-j8-erythroidine... 

XLIX) was degraded by Hofmann eliminations (Fig. 6) to a mixture of dienes which w as oxidized to X( — )-3-methoxyadipic acid. The absolute configuration of this acid was knowui from earlier work in which it had been a key intermediate in establishing the absolute configuration of sterols 20) and led to the 3 R configuration for j8-erythroidine. 

H2O), pK st(3) 7.4 Recrystallise a-erythroidine from pentane. It is best prepared freshly from the more stable hydrochloride. The hydrochloride (1.3g) in H2O (20mL) is basified with NaHC03 to pH 8 and extracted with C6H6 (6 X lOmL). The combined extracts are evaporated to a small volume and refrigerated. The free base separates as white hygroscopic crystals m 52-55°, which are recrystallised from pentane. Although stable in solution, the crystals turn brown on exposure to air. 

In acute slices, a mixed response, which consists of fast a7-like and slow components, has been described in interneurons of the stratum oriens (36%of all interneurons). The slow response is sensitive to mecamylamine (I/aM) and to a certain extent to dihydro-/3-erythroi-dine (100 nM), but resistant to the o 3j32 antagonist a-conotoxinMII (200nM). In its moderate sensitivity to dihydro-jS-erythroidine, this response may resemble more o 3j34-like responses (type III) than o 4j82 type II responses (218), although it has been suggested... 

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