7-Oxoaporphines

The new oxoaporphines oxoanolobine (55a) and peruvianine (55b) have been isola- 

This result indicates that some of the natural oxoaporphines characterized in the past may actually exist in the plant as the corresponding N-metho salts. 

Known oxoaporphines that have been recently reisolated, and their natural sources, are listed below. 

Lysicamine Annona acuminata Siparuna gilgiana Nandazurine 79 

Photocyclization of a series of substituted 2,3-diaryl-A-pyrroline-4,5-diones 

Glaunine (67) and glaunidine (68) are two new oxoaporphines from Glaucium fimbrilligerum (Papaveraceae).47 Arosine, found in G. flavum Cr. var. vestitum, must be identical with glaunidine, while arosinine, from the same source, possesses structure (69).48 Oxidation of the aporphine corydine with iodine and 

Photolysis of the hydrochloride of (71) gave the corresponding oxoaporphine O-methylatheroline, in 38% yield, which was converted into the aporphine glau-cine by successive methylation and reduction with zinc in hydrochloric acid.49 

Following the isolation of liriodenine and oxolaureline from the bark of Laurelia novae-zelandiae, a careful n.m.r. analysis has revealed that H-ll of oxoaporphines does not necessarily absorb downfield from H-8.50 

Ocotea minarum contains the known oxoaporphines dicentrinone and thalic-minine.4 Liriodenine is present in Rhigiocarya racemifera15 and in Pachygone ovata9b and lanuginosine is found in Anona squamosa.19 

A new oxoaporphine alkaloid is oxostephanine (38) from Stephania japonica. Imerubrine, found together with a variety of oxoaporphines and azafiuoranthenes in the South American vines Abuta imene and A. rufescens has been tentatively 

Jackman, J. C. Trewella, J. L. Moniot, and M. Shamma, unpublished results. 

Reaction of morphine with cone. H2SO4 yields the blue ortho quinone (42) whose 1,2-methylenedioxy analogue has been found as a natural product in Corydalis cava  

A full paper on the isolation and characterization of lanuginosine and liriodenine, as well as the noraporphine michelanugine, from Michelia lanuginosa has appeared. Known oxoaporphines recently reisolated are  

Stephania japonica Liriodendron tulipifera Triclisia patens Liriodendron tulipifera Eupomatia laurina Cananga odorata Talauma mexicana  

Lead Tetraacetate-Mediated Hydroxylation of Isoquinoline Alkaloids 

As mentioned above (see Section ILA), a diastereomeric mixture of ( )-4)3- and ( )-4a-acetoxy-O-acetylthaliporphines (18 and 19) was formed as a by-product on acid treatment of the p-quinol acetate derived 

Similar stereoselective acetoxylation at C-4 in C-homoaporphines was performed (JS). Thus, ( )-C-homoaporphines 127 and 128 were converted quantitatively to ( )-2,10,11-trimethoxy- and ( )-2-methoxy- 

Reagents Q. Pb(OAc), AcOH b. AC2O, pyridine c.lOWCI d. CH2N2, MeOH e. MeOH 

LTA oxidation of four tetrahydroprotoberberines has been investigated (110,111). Namely, LTA oxidation in AcOH of ( )-govanine (366) and ( )-10-hydroxy-2,3,l 1-trimethoxytetrahydroprotoberberine (369) afforded the corresponding p-quinol acetates 367 and 370 quantitatively. Treatment of acetate 367 with acetic anhydride including concentrated sulfuric acid gave only ( )-2,5 -diacetoxy-3,10,11-trimethoxy tetrahydroprotoberberine (368) in 90.9% yield, whereas that of acetate 370 resulted in acetoxylation at C-13 to lead to ( )-10,13q - and ( )-10,13 /3-diacetoxy- 

An interesting and unusual aporphinoid obtained from Telitoxicum peruvianum (Menispermaceae) is the reddish-brown telazoline, which possesses two nitrogen atoms. The tentative structure (62) has been advanced for this compound.73 

Several known oxoaporphines have been re-isolated, as indicated in Table 3. 

Conclusive support for the identity of glauvine with corunnine (65) has been provided. Reduction of so-called glauvine (65) with zinc in acetic acid did not give norlirioferine (66), as previously claimed, but instead supplied the known thaliporphine (69). Authentic norlirioferine and its A,O-diacetyl derivative (67) were then obtained via reduction of oxolirioferine (68), which was synthesized by two independent routes.74 

Oxidation of noraporphines and aporphines with Fremy s salt gives oxoaporphines and oxoaporphinium salts, respectively.75 Aerial oxidation of dehydro-aporphines in the presence of alkali provides the corresponding oxoaporphines, 4,5-dioxoaporphines, and A-methylaristolactams.76 An analysis of the 13C n.m.r. 

Liriodenine (70) and other oxoaporphines were evaluated for their antibacterial and antifungal activity against several micro-organisms. Only (70) showed significant activity.78 

Splendidine (37), a new oxoaporphine, has been obtained from Abuta rufescens Aublet ( = A. splendida) (Menispermaceae). Following its structural elucidation, its total synthesis was achieved via a Reissert-Pschorr sequence The known phenolic oxoaporphine subsessiline, found in a Guatteria species (Annonaceae), has been established to possess structure (39) instead of the 

Marsaioli, F. de A. M. Reis, A. F. Magalhaes, and E. A. Riiveda, Phytochemistry, 1979,18,165. J. C. Trewella, Ph.D. Thesis, Department of Chemistry, The Pennsylvania State University, 1979. M. Shamma and D. M. Hindenlang, C-13 NMR Shift Assignments of Amines and Alkaloids , Plenum Press, N.Y., 1979. 

Known oxoaporphines re-isolated from natural sources include those shown in Table 2. 

9-Trimethoxyoxoaporphine and the 1,2,9- and 1,2,10-isomers have been synthesized by a Bischler-Napieralski-Pschorr sequence/  

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The oxoaporphine alkaloids Teliglazine (126), Corunnine (127), Nandazurine (128), PO-3 (129), A-Methylliriodendronine (130), and A,(9-Dimethylliriodendronine (131) contain the 6-methyl-7-oxo-dibenzo [Je,g]quinolinium-l-olate ring system 125 which is isoconjugate with the l-methyl-7-methylene-7H-benzo[Je]anthracene anion (Scheme 46). Therefore, these alkaloids belong to class 1, i.e., heterocyclic mesomeric betaines isoconjugate with odd alternant hydrocarbon anions. Another... 

In the Philippines, the sap expressed from the stem is drunk to alleviate headache. Using antiplatelet aggregation as a guide to fractionation, Chen et al. isolated a series of aporphines including actinodaphnine, N-methylactinodaphnine, launobine, dicentrine, O-methylbulbocapnine, hernovine, bulbocapnine, and oxoaporphines dicentrinone and liriodenine were isolated from the stems of I. luzonensis (13). 

Camacho, M. del R. 2000. Oxoaporphine alkaloids and quinones from Stepha-nia dinklagei and evaluation of their antiprotozal activities. Planta Medica, 66 478 80. 

Hufford, C. D., Sharma, A. S. and Oguntimein, B. O. 1980. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids. Journal of Pharmaceutical Science, 69 1180-1182. 

Clark, A. M., Watson, E. S., Ashfaq, M. K. and Hufford, C. D. 1987. In vivo efficacy of antifungal oxoaporphines alkaloids in experimental disseminated candidiasis. Pharmacological Research, 4 495 98. 

Reissert alkylation and Pschorr cyclization have frequently been utilized for the synthesis of oxoaporphine alkaloids by Cava and co-workers. Their synthetic... 

The mass spectra of 4,5-oxoaporphine alkaloids are characterized by a direct loss of CO (M — 28) from the molecular ion (base peak) leading to a prominent peak at miz 265 (27%). Subsequent loss of a methyl group accounted for the other significant peak at mIz 250 (51%) (64). 

A useful and timely supplementary listing of new aporphines, oxoaporphines, phenanthrenes, and 4,5-dioxoaporphines has appeared.1 The alkaloids of Glaucium species, which include several aporphines and oxoaporphines, have been tabulated2 and a general discussion of the chemistry and biogenesis of isoquinoline alkaloids, including the aporphines, has been presented.3... 

Alternatively, reduction of the keto-imine (20) with sodium borohydride gave a mixture of two carbinols corresponding to N-demethylated (16) and (17). Irradiation of this mixture produced norushinsunine together with a little noroliveroline. Photolysis of the alcohol (21) gave rise to the oxoaporphine liriodenine (22).21 Synthetic routes to those aporphines that incorporate a hydroxyl group at C-7 that is trans to the proton at C-6a are already known.22 23 A novel synthesis of aporphines via 3-phenylphenethylamines has been developed, and is described in Scheme 1. The aporphine (23) and related species were then synthesized by a modified route.24... 

Aerial oxidation of the dehydroaporphines (52)—(54) with alkali catalysts gives the corresponding oxoaporphines, 4,5-dioxoaporphines, and JV-methyl -aristolactams in low yields. The 4,5-dioxoaporphine (55) from the oxidation of (54) corresponds to 4,5-dioxodehydronantenine, which is found as a natural product in the dried fruits of Nandina domestica.34... 

The dehydrogenation of 66 to 6a,7-dehydroglaucine (79) proceeded in a yield of 60% with Fusarium solani ATCC 12823. This microorganism also produced a 21% yield of the oxoaporphine 80, but control experiments indicated that the latter was an artifact produced by air oxidation of 79 during the incubation. 

N,O-DimethyIIiriodendronine (95), isolated in fairly large amounts from G. chrysopetala (21), stands out among the oxoaporphine alkaloids found in Guat-teria in that it is a zwitterion related to the highly colored compounds of Glau-cium (Papaveraceae). Neutral and basic solutions of the rather insoluble N.O-... 

Oxoisocalycinine (106), which cooccurs with the ring D-9,11-dioxygenated isocalycinine (74) and discoguattine (75) in G. discolor (24), is the only example to date of an oxoaporphine with this unusual substitution pattern. The alternative oxocalycinine and oxoisocalycinine structures were suggested by mass and H-NMR spectra, which are quite unexceptional, and the actual positions of the substituents were established by zinc-hydrochloric acid reduction to isocalycinine (74) (24). 

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