New Natural Colchicinoids: Indications of Two Possible Catabolic Routes for the Colchicine Alkaloids

Abstract

Colchicum ritchii of Jordanian origin has yielded the three non-nitrogenous colchicinoids colchicone [1], 3-demethylcolchicone [2], and comigerone [3], as well as the amidic (-)-colchibiphenyline, which in CDClj solution exists as a mixture of isomers 4a and 4b. Ketones 1-3 may exemplify one catabolic route for the colchicine alkaloids, while (-)-colchibiphenyline [4a,4b], and the accompanying and previously known (-)-androbiphenyline [5a,5b] may exemplify another.Five Colchicum species (Liliaceae) are native to Jordan. These are Colchicum crocifolium Boiss., Colchicum decaisnei Boiss., Colchicum triphyllum G. Kuntze, Colchicum steveni Kunth, and Colchicum ritchii R. Br. (1). The last of these, namely C. ritchii, has been the subject of an investigation that has revealed the presence of a number of diphenolic phenethyltetrahydroisoquinoline-, androcymbine-, and colchicine-type alkaloids (2).The present study was focused on the acid-insoluble components of C. ritchii. Extensive chromatography of the acid-insoluble extracts furnished three closely related ketonic and non-nitrogenous compounds, which also incorporate a tropolone system.The first of these, colchicone [1], C20H20O6, had a mass spectrum showing a molecular ion peak m!z 356 (54%) and base peak mtz 328 [M -CO]+. The presence of two carbonyls was indicated by the ir spectrum, which included a strong band at 1610 cm-1 for the tropolonic carbonyl and another at 1710 cm-1 for the ketonic group of ring B.The existence of these two carbonyls was confirmed by the 13C-nmr spectrum, which displayed downfield singlets for the carbonyl carbons at 179 37 (ring C) and at 205.66 (ring B).Extensive 1H-nmr spin decoupling and nOe experiments resulted in the detailed 'H-nmr values summarized around structure 1. Four methoxyl singlets were in evidence with the most upfield, at 3.55, assigned to the highly hindered 1-OMe, while the most downfield, at 4.00, represented the tropolonic 10-OMe. It was even possible to differentiate between the two remaining methoxyl singlets at 3.86 and 3.87, with the former due to 2-OMe and the latter to 3-OMe. Four aromatic proton signals, two appearing as two singlets and the two others as two doudsgem '3.7

Synthesis of naturally occurring tropones and tropolones

“…15 A small number of non-nitrogen containing colchicine derivatives, such as colchicone, have also been reported. 67 …”

Notizen: New Colchicine and Homoaporphine- N-Oxide Alkaloids from Colchicum Ritchii: The First Homoaporphine TV-Oxide Found in Nature

“…The addition of alkali caused no noticeable shift com pared to (-)speciosine (2) [4], indicating that the hydroxyl function in (-)-speciosine (2) should be alkylated in com parison to the related (-)-O -m ethylspeciosine (1). Additionally, the H-bonded phenolic function ob served in the IR spectrum of (-)-speciosine (2) is absent in the IR spectrum of O-methylspeciosine.…”

“…During an extensive study of the colchicine-type alkaloids and related compounds found in species belonging to the Liliaceae family, the structures of several minor alkaloids from colchicum ritchii and colchicum decaisnei were characterized and two possible catabolic pathways for the colchicine-type alkaloids were proposed [1][2].…”

“…Additionally, the H-bonded phenolic function ob served in the IR spectrum of (-)-speciosine (2) is absent in the IR spectrum of O-methylspeciosine. More im portant, however, is the information ob tained from the fragm entation pattern noticed in the mass spectrum of O-methylspeciosine (1). The molecular ion of com pound 1 is present at m/z 491, 14 daltons higher com pared to the m/z peak of (-)-speciosine (2).…”

Attempted Oxidative Deamination ofN-Deacetylcolchicinoids with 3,5-Di(tert-butyl)-1,2-benzoquinone: Synthesis of 2H-1,4-Benzoxazine-Type Adducts

“…In the frame of a systematic study on the pharmacological properties of new and known colchicinoids, we intended to investigate extensively the biological properties of the non-N-containing compounds 7-deacetamido-7-oxocolchicine (2), a metabolite of colchicine [3], and 7-deacetamido-7-oxothiocolchicine (3), the so-called colchicone and thiocolchicone, respectively (thiocolchicine 10-demethoxy-10-(methylthio)colchicine). Both compounds are readily prepared in excellent yield by oxidative deamination of N-deacetylcolchicine (4) [4] and N-deacetylthiocolchicine (5) [5], respectively, with the Rapoport reagent (4-formyl-1-methylpyridinium benzenesulfonate) [6], following the protocol developed by Banwell et al [4].…”