New Azafluorene Alkaloids from Oxandra xylopioides

Abstract

ABsmcT.-Three new azafluorene alkaloids were isolated from Oxandra xylopioidies. The structures of the alkaloids, as determined by organic syntheses andor spectral analyses, were shown to be 4-azafluorenones, 6-hydroxyonychine [3),5-hydroxy-6-methoxyonychine 141, and 2,6-dimethoxy-7-hydroxyonychine 15). The syntheses also provided three additional azaflourenone alkaloids, which were identified as 5,6-dimethoxyonychine 161, 8-hydroxyonychine [n, and 5,8dimethoxyonychine 181. The physical and spectral properties of these azafluorene alkaloids are discussed.In 1976, De Almeida et a f . (1) isolated the novel alkaloid onychine from Onychopetafum arnuzonicum (Annonaceae). Its structure was assigned as 1-aza-4-methylfluoren-9-one 111. In 1979, Koyama et a f . (2) synthesized both 1-aza-4-methylfluoren-9-one E l ] and its structural isomer, l-methyl-4-azafluoren-9-one 121. Based upon the nmr data of these synthetic products and onychine, they suggested that the structure of onychine be revised to l-methyl-4-azafluoren-9-one 121, although a direct comparison of the synthetic products with onychine was not carried out. Later, reference (3) to and isolation [from Cfeistophofispatm (Annonaceae)] (4) of onychine still regarded the structure as 1. This was also the case when 6-methoxyonychine was reported (5) without reference to the revised (2) structure for onychine.In our laboratory three new alkaloids were isolated from Oxandra xyfopioides Diels (Annonaceae). Spectral data suggested they were onychine analogues. At this point erroneous structures were published (6,7) for these compounds, based upon the prior references that regarded the structure of onychine as 1. In view of the uncertainty of the structure of onychine, synthetic methods were employed to produce several 4-azaflouren-9-one derivatives via phenylnicotinic acids (8) in order to establish firmly the structures of the isolates.The three alkaloids isolated from 0. xyfopioih were shown to be 6-hydroxyonychine {37, 5-hydroxy-6-methoxyonychine 141, and 2,6-dimethoxy-7-hydroxyonychine 151. The syntheses provided three additional azafluorene alkaloids, 5,6-dimethoxyonychine 167, 8-hydroxyonychine 17, and 5,8-dimethoxyonychine 181.The uv and ir data of the three natural products indicated they were analogues of onychine ( l-methyl-4-azafluoren-9-one) [ 2 ] . The mass spectra showed molecular ions at m/z 2 11 (16 amu higher than 2), 24 1 (46 amu larger than 2), and 27 1 (76 arnu higher than 2) suggesting hydroxy-, hydroxy-methoxy-, and dimethoxy-hydroxy-derivatives, respectively.

Grindstone chemistry: one-pot synthesis of spiro[diindenopyridine-indoline]triones and spiro[acenaphthylene-diindenopyridine]triones

“…1). 1 Indenopyrazoles A and indenopyridazines B have been investigated as cyclin-dependent kinase 2 and selective monoamine oxidase B (MAO-B) 3 inhibitors, respectively. Indenopyridines C exhibit cytotoxic, 4a phosphodiesterase inhibitory, 4b adenosine A2a receptor antagonistic, 4c antiinflammatory/ antiallergic, 4d coronary dilating 4e , and calcium-modulating activities.…”

Activated Alumina Balls under Neat Conditions: A Green Catalyst for the Synthesis of Spiro‐Heterocyclic Scaffolds by Ring‐Opening versus Annulation of the Isatin Moiety

“…These indole‐fused heterocycles possess anti‐bacterial and anti‐fungal activities . The indenopyridine organic framework is the most familiar structural unit of the 4‐azafluorenone group of alkaloids, represented by its simplest member onychine . If we consider the various synthetic protocols used over the past decades for the construction of spirocyclic fragments, the adoption of “cleaner production” methods is an urgent priority because of serious pollution problems.…”

Ceric ammonium nitrate (CAN) catalyzed one-pot synthesis of fully substituted new indeno[1,2-b]pyridines at room temperature through multi-component reaction

“…2 The indenopyridine nucleus is present in the 4-azafluorenone group of alkaloids, represented by its simplest member onychnine. 3 Many indenopyridine derivatives were found to exhibit adenosine A2a receptor binding and phosphodiesterase inhibiting activities for the treatment of neurodegenerative disorders and inflammation related diseases. 4 They also behave as calcium antagonistic activators, 5 and herbicides.…”

“…Several methods are available describing the synthesis of the 5H-indeno[1,2-b]pyridin-5-ones: reaction of the Knoevenegal products of several 1,3-indandiones and aromatic aldehydes with some substituted cyanoacetamide (or phenyl acetonitrile or ethyl phenylacetate and ammonium acetate), 7 oxidative thermal rearrangement of 2-indanone oxime O-allyl ethers, 8 direct cyclization of 2-aryl-3-methylpyridines to give 5H-indeno[1,2-b]pyridines followed by oxidation, 9 cyclization of 2-aryl-3-nicotinic acids by the use of polyphosphoric acid, 9,10 Pummerer reaction of imidosulfoxides, 11 Pd(0)-catalyzed cross-coupling reaction 12 between arylboronic acids and 2-halopyridines. Tu et al developed the synthesis of substituted indeno[1,2-b]pyridines by the multi-component reaction of aldehydes, 1,3-indandione or 1-indenone and aromatic ketones in the presence of ammonium acetate under microwaveirradiation.…”