Erythramine

In view of the fact that the conversion of tertiary into quaternary base other hand, hydrogenation in this series ma have 110 effect on activity (cf. erythraline and its dihydro-derivative ery thramine) or may enhance it (cf. -erythroidine and its dihydride) or mai diminish it (cf. erythramine and its dihydride). 

Alkynyl azomethine ylides containing an aryl bridge have been shown to undergo cyclization. Thus, tautomerization of imine (137) afforded an azomethine ylide which cyclized to give two diastereomeric dihydropyrroles and traces of aromatized product (Scheme 42).56 The activated cyclic ylide (138), generated via the desilylation route, underwent cyclization to afford dihydropyrrole (139) in 42% yield.67b The structure of (139) is closely related to erythramine. The structurally related non-stabilized azomethine ylide (140) did not cyclize, tautomerizing to the corresponding enamine instead. 

Azomethine ylids derived from amidines undergo internal [3 + 2]cyclization reactions with a styrenic double bond present in the starting amidine. This strategy has been applied to the synthesis of physostigmine and erythramine. 

Erythramine, a natural alkaloid extracted from bark of Mulungu tree, has a potent curariform activity. Unfortunately, the erythramine skeleton could not be formed using this cyclization process, and the acetylenic enamine is formed instead.162,292,465... 

Erythramine (47), previously known as a reduction product of erythraline (4) (62), was detected in E. crysta galli and in E. glauca Willd. (now classified as E. fusca Loureiro) (19). Since there was insufficient sample isolated, erythramine was prepared from erythraline and its structure established by NMR. In addition, erythramine was prepared by an alternative route from erythratine (42) (see Scheme 8) by chlorination and reduction. Since 42 could also be converted to erythraline (79), an alkaloid of known stereochemistry (63), the position of the double bond as well as the configurations at C-3 and C-5 in erythramine were firmly established. 

Erysotrine (le) does not occur naturally but is a common transformation product of the other aromatic alkaloids. In addition to the members shown, two dihydroderivatives occur in nature dihydroerythraline (erythramine) and dihydroerysodine. 

Eight known bases were isolated from this plant, namely, erysopine, erythraline, erythramine, erysodine, erysotrine, erythratine, N,N-dimethyltryptophan, and hypaphorine. In addition three alkaloids, not previously known to occur naturally, were isolated, namely, N-norprotosinomenine (CigHaiO N hydrochloride, mp 242-244° [a] +18°) (74), protosinomenine (picrolonate, mp 172-174°) (75) which was methylated to laudanosine (mp 83-85°), and j8-erythroidine (76) (92). 

Folkers K, Koniuszy F (1940) Erythrina alkaloids. VIII. Studies on the Constitution of Erythramine and Erythraline. J Am Chem Soc 62 1673... 

Desmaele and co-workers reported an interesting annulation process based on a tandem i7 -allylpalladium complex alkylation-Michael addition for the approach of erythramineJ It was well known that arylnitronate anions react with 7r-allylpalladium derivatives to give C-aUcylated products. The unsaturated ester 260 was prepared as described in Scheme 59. Treatment of a mixture of diester 260 and arylnitronate 261 with DBU and LiCl in the presence of a catalytic amount of Pd(PPh3)4 and PPhs gave, in a one-pot reaction, nitro esters 262 in 57% yield. Such nitro esters could be suitable intermediates for the synthesis of Erythria alkaloids, exemplified by erythramine. 

Erythramine, CisHjiOjN. This base occurs in various Erythrina species but was first isolated by FoUcers and Koniuszy from E. sandidcensis and E. suhumhrans along with hypaphorine. It has m.p. 104-5°, or 103-4° (solvent-free) b.p. 125°/3-9 X 10 mm., [a]f, ° -f 227-6° (EtOH). It is isolated as the hydriodide, orange-yellow needles, m.p. 249° (dec.),... 

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