Synthesis Of Emetine Research Articles

Synthesis of substituted allyl acetates from heterocyclic dienes by Pd-promoted arylation-acetoxylation cascade

Pd-catalysed arylation?acetoxylation cascade, a previously reported methodology, was applied in the functionalisation of unsymmetrical dienes. Both explored classes of compounds, isoquinoline and ?-carboline-derived dienes, afforded single regioisomers. Although further improvements of the process are necessary, primarily due to lower yields, the described functionalisation of the studied compounds might be useful in the synthesis of emetine and related naturally occurring compounds.

A New Stereoselective Synthesis of Emetine and Related Alkaloids

A New Stereoselective Synthesis of Emetine and Related Alkaloids

The synthesis of emetine and related compounds. VII. The utility of Bi-functional catalysts in amine-ester interactions.

Bi-functional catalysts such as 2-hydroxypyridine are shown to be valuable in promoting the reaction between a variety of aliphatic amines and non-activated esters to give substituted amides; they are less effective with aniline. This method has been applied to the synthesis of the emetine intermediate, an N-substituted benzo[a] quinolizineacetamide (II), and analogues.

The synthesis of emetine and related compounds. IX. The use of Wittig-type reagents in the synthesis of 2,3-dehydroemetine.

The (±)-ketone (I)(3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxybenzo[a]quinolizin-2-one) is converted in one operation through the mixture of isomeric 2-ethoxycarbonylmethylene derivatives (IIb) and (IIIb) into ethyl 3-ethyl-1,4,6,7-tetrahydro-9,10-dimethoxy-11bH-benzo[a]quinolizine-2-acetate (Vb), which gives, in 75% overall yield from (I), the (±)-N-(3,4-dimethoxyphenethyl) amide (VI) required for production of racemic 2,3-dehydroemetine (IX). Similarly, the (–)-ketone (I) gives the (–)-amide (VI) corresponding to (–)-2,3-dehydroemetine (IX).The emetine skeleton has also been synthesised by linking together the benzo[a] quinolizine and isoquinoline moieties directly. The novel 3,4-dihydro-6,7-dimethoxyisoquinolin-1-ylmethylenetriphenylphosphorane (XIV) obtained from the chloromethyldihydroisoquinoline hydrochloride (XI) condenses with the ketone (I) to form 2,3-dehydro-O-methylpsychotrine (VIII) or its isomer (X), depending on the reaction conditions. Treatment of 1,2,3,4-tetrahydro-6,7-dimethoxyisoquinolin-1-ylmethyltriphenylphosphonium bromide hydrobromide (XVI) with sodium methylsulphinylmethanide produces methylenetriphenylphosphorane as well as the 1,2,3,4-tetrahydro-6,7-dimethoxyisoquinolin-1-ylmethylenetriphenylphosphorane (XVIII) and the latter reacts with the ketone (I) to give the 2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinolin-1-ylmethylene) derivative (XXI) of (I).Fusion of 2-(2-acetamidoethyl)-4,5-dimethoxyphenacylidenetriphenylphosphorane (XXVII) with the ketone (I) leads to a variety of fragmentation products.

The synthesis of emetine and related compounds. Part VI. Improvements in the synthesis of 3-alkyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxybenzo[a]quinolizin-2-ones and 3-alkyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-ones. Formation of some related diazabicyclo[3,3,1]nonanes

A simplified procedure is reported for the almost quantitative conversion of the dihydroisoquinoline(II) into the benzo[a] quinolizines (I; R = alkyl). A by-product formed in the preparation of the 3-unsubstituted compound (Ic) is assigned the pentacyclic structure (VII). 3,4-Dihydro-β-carboline condenses with Mannich bases in the presence of carbon dioxide to give the indolo[2,3-a]quinolizines (XII; R = alkyl) in good yield. The unsymmetrical di-Mannich base (XIII) condenses with two molecules of the dihydroisoquinoline (II) to give the 9,18-methanodiisoquino[2,1-a : 1′,2′-d][1,5]diazocine (XV); the symmetrical di-Mannich base (XVI), or the 4-oxopiperidinium salt (XIX), gives the substituted 9,18-methanodi-isoquino[2,1-a: 2′,1′-e][1,5]diazocine (XVIII), together with a trace of the dipentacyclic ketone (XXII).

The synthesis of emetine and related compounds. 8. The synthesis of tubulosine and isotubulosine.

The constitution (Ic) assigned to tubulosine {3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2-(1,2,3,4-tetrahydro-6-hydroxy-β-carbolin-1-yl)-2H-benzo[a]quinolizine} has been confirmed by total synthesis from the (–)-ester (II)(ethyl 3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a] quinolizine-2-acetate) of known configuration. Isotubulosine (Vc), also produced in the synthesis, has been identified with an alkaloid subsequently isolated from Alangium lamarckii.

Dehydroemetine

Emetine has long been important in acute amoebiasis. The symptoms of acute amoebic dysentery are most effectively relieved by parenteral emetine hydrochloride, though parasites frequently persist unless another amoebicidal drug, such as tetracycline, is given as well. Amoebic hepatitis is treated with emetine hydrochloride injections together with chloroquine by mouth. Unfortunately emetine is rather toxic; and this has stimulated the search for substitutes. Dehydroemetine is closely related structurally to natural emetine and was first synthesised in the laboratories of Roche in Switzerland during work on the synthesis of emetine.1 It is claimed to be as effective as emetine and less toxic. The drug is made by Roche, who do not sell it in Britain, and by Glaxo (Mebadin). Dehydroemetine hydrochloride is intended for injection and the resinate, which slowly releases dehydroemetine, for oral use.

276. The synthesis of emetine and related compounds. Part IV. A new synthesis of 3-substituted 1,2,3,4,6,7-hexahydro-9,10-dimethoxy-2-oxo-11bH-benzo[a]quinolizines

276. The synthesis of emetine and related compounds. Part IV. A new synthesis of 3-substituted 1,2,3,4,6,7-hexahydro-9,10-dimethoxy-2-oxo-11bH-benzo[a]quinolizines

973. The synthesis of emetine and related compounds. Part III. The reaction of some isoquinoline derivatives with acrylonitrile

973. The synthesis of emetine and related compounds. Part III. The reaction of some isoquinoline derivatives with acrylonitrile

Syntheseversuche in der Emetin‐Reihe. 5. Mitteilung. Eine neue Totalsynthese von Emetin

AbstractA new synthesis of emetine and its unnatural antipode is described. As indicated previously it has now been demonstrated that rac. 2‐dehydro‐emetine (II), a highly effective amoebicide has probably the same configuration at carbon atoms 1′ and 11b as the natural product.

Studies on the Synthesis of Emetine. II

Studies on the Synthesis of Emetine. II

499. The synthesis of emetine and related compounds. Part II. The synthesis of (±)-rubremetinium bromide

499. The synthesis of emetine and related compounds. Part II. The synthesis of (±)-rubremetinium bromide

80. Studies on the Synthesis of Emetine and its Analogues (IV)

80. Studies on the Synthesis of Emetine and its Analogues (IV)

81. Studies on the Synthesis of Emetine and its Analogues (V)

81. Studies on the Synthesis of Emetine and its Analogues (V)

106. Studies on the Synthesis of Emetine and its Analogues (III)

106. Studies on the Synthesis of Emetine and its Analogues (III)

Studies on the Synthesis of Emetine and its Analogues (Preliminary Report). The Oxidation of N-β-Phenethyl-3-carbalkoxy-pyridinium-Salt

Studies on the Synthesis of Emetine and its Analogues (Preliminary Report). The Oxidation of N-β-Phenethyl-3-carbalkoxy-pyridinium-Salt