Thc reactions leading to the establishment of structure I for lycopodine are discussed. S t r u c t~~r e s are proposed for three cyclizatioll products derived from lycopodine.I n a short comlnunication (1) we proposed structure I for lycopodine. This structure has been confirmed by the worlt of Anet (2), who succeeded in interconverting several Lycopodiz~m alkaloids, among which was lycopodine. In this paper we wish to give a full account of our worlt on the elucidation of the structure of the alltaloid and t o discuss the structures of the tetracylic compounds obtained on elimination of hydrogen halide from lycopodine methiodide and a-and P-cyanobromolycopodine.
Acid hydrolysis of 5,6-dihydro-2-methyl-I,4-oxathiin-3-carboxanilide gives 2-(2-hydroxyethy1thio)-acetoacetanilide enol. 3-Carbonyl-substituted 5.6-dihydro-l,4-oxathiins were found to undergo ring cleavage by nucleophilic nitrogen attack on C-2. Thus the following reactions were observed: 3-acetyl-5,6-dihydro-2-methyl-1,4-oxathiin o n treatment with hydrazine gives 4-(2-hydroxyethylthi0)-3,5-dimethylpyrazole, instead of the hydrazone. The 1,4-oxathiins, N-(5,6-dihydro-2-methyl-1,4-oxathiin-3-ylcarbony1)-N'-phenylurea and 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxylic acid hydrazide rearrange to give 5-(2-hydroxyethy1thio)-6-methyl-I-phenylracil and 4-(2-hydroxyethy1thio)-3-methyl-2-pyrazolin-5-one, respectively. Finally, treatment of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride with 2-aminopyridine and with 2-aminopyrimidine affords 4H-3-(2-hydroxyethy1thio)-2-methylpyrido[l,2-nlpyrimidin-4-one and 4H-3-(2-hydroxyethylthio)-2-methylpyrimido[l,2-a]pyrimidin-4-one, respectively, a s the predominant products.
Evidence is furnished which establishes the structure of a new allcaloid isolated from Lyro)odiz~nl flabellifornze.In the present publication we wish to report evidence which enables the assignment of structure I to a new allialoid obtained froin Lyco;bodiz~mJEabelliforme.The alkaloid, for ivhich the name flabellifornline seenls appropriate, is sparingly soluble in cold ether. Advantage was taken of this property in its isolatioil from the bases obtained, after the separation of lycopodine from the crude alkaloid mixture.Analysis of flabellifonnine, I , fits the formula C161-12j02N. The infrared spectrunl of the allialoid, measured in chloroform solution, shows lietonic carbonyl absorption a t 1705 cm-I and a hydroxyl band a t 3560 cm-l. Reduction of the carbonyl group with sodium borohydride affords the diol 11, C16H270?N. T h e hydroxyl group appears to be attached to a tertiary carbon atom, since flabelliforinine is recovered unchanged after treatment with chromium trioxide and its i1.m.r. spectrunl shows no absorption below a T-value of 6.5.Treatment of the allialoid with hydrogen iodide replaces the hydroxyl group with hydrogen; the reaction product is identical with lycopodine, I11 (1-4). Flabelliformine, therefore, is formally derived from lycopodine by replacement of a methine hydrogen by a hydroxyl group.Dehydration ol I , effected by both phosphoric acid and ;b-toluenes~~lphonic acid, affords a non-crystalline product, IV, which was converted to a crystalline methiodide, V, C17f1260NI. Compound IV has the properties of an a,p-unsaturated ketone. The ultraviolet spectrum of this substance shows I~~X~I~L I I~ absorption a t 245 mp and the infrared spectrum, measured in carbon tetrachloride solution, has bands of equal intensity a t 1685 and 1617 cm-l. The i1.m.r. spectrum of IV has a triplet a t a T-value of 3.01 which is attributed to a proton on the p-carbon of the a,p-unsaturated carboilyl system ( 5 , 6).
Annotine, C~J I~I O~N , is shown to be pentacyclic and to contain a tertiary hydroxyl group, a lactone function, a tertiary nitrogen atom, and a dialkylated double bond. The position of the double bond and the tertiary hydroxyl group relative t o the nitrogen atom has been established by Emde degradation of annotine methiodide. The presence of a lactone function is inferred from the reduction of annotine to dihydroannotinol, a hemiacetal, which reacts with 1 mole of ethyl mercaptan. T h e reduction of the lactone to a diol in a n annotine derivative has been carried out. T h e chemical studies and the examination of annotine and its derivatives by modern instrumental methods allow the assignment of a plausible structure to the alkaloid.Annotine, C16H2103N (I), was first isolated from L. annotinz~m of Canadian origin by hiIanslte and Marion and designated alkaloid L . l l (1). I t was subsequently found in European plant material by Bertho and Stoll (2), who assigned the name annotine t o it, and by Achmatowicz and Rodewald (3). An examination of the functional groups of annotine was carried out by Perry and MacLean (4), who concluded that the alltaloid contained a tertiary nitrogen atom, a double bond, a hydroxyl group, a ketonic carbonyl group, and a third inert oxygen function, which they ascribed t o a n ether linkage other than an epoxide.In this coinmunication we wish t o report further studies on annotine by chemical and modern instrumental methods. These studies have shown that annotine is a lactone and have thereby established the nature of the third inert oxygen function. They have also allowed a n assignment of the position of the double bond and the hydroxyl group in the n~olecule relative t o the nitrogen atom and have led t o the development of a plausible structure for the molecule.Nuclear magnetic resonance (n.m.r.) spectroscopy has been used extensively in this study and has provided useful information about the functional groups and their environment in annotine and its derivatives. The n.m.r. spectrum of annotine has a quartet centered a t T = 4.04 (J = 10 c.p.s.) with a n intensity corresponding to two protons. This H\ band indicates the presence of the grouping /C=C\ and is an example of an intermediate case of an AB spectrum in which the chemical shift between the two nuclei is comparable to the coupling constant between them (5). I t was possible t o resolve each component of the quartet into a triplet in each of which the splitting was the same. These data indicate the presence of a methylene group adjacent to the double bond, as in theA singlet occurring a t T = 8.57 with an intensity corresponding to three protons points to the presence of a methyl group attached t o a quaternary carbon. The low T value of the C-methyl group in this system can possibly be explained by the deshielding effect of a carbonyl group beta t o the methyl protons. I t has been postulated that the deshielding effect in such a system is due to the anisotropy of the carbonyl group and that the deshielding e...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.