Phenanthridine skeleton

At first, acid-catalyzed cyclization of Hofmann degradation products was undertaken however, the cyclization proceeded via the 5-exo-trigonal mode instead of the 6-endo-trigonal mode, resulting in no benzo[c]phenanthridine skeleton. Dyke and Brown (114-117) reinvestigated Perkin s results (118,119) and established the structure of the cyclized products 196 and 197 derived from the methine base 194 (Scheme 36). Onda et al. (120,121) obtained the five-membered spiro compounds 198 and 199 by treatment of 195 with dilute hydrochloric acid. 

Lead tetraacetate oxidation was applied to construct a benzo[c]-phenanthridine skeleton. The Hofmann degradation product 224 derived from the phenolic protoberberine 59a was oxidized with lead tetraacetate to afford the p-quinol acetate 225, which was cyclized to the benzo[c]-... 

The intermediacy of aryne intermediates generated by dehydrohalogenation of the corresponding aryl bromide is useful in preparing polycyclic isoquinolines with the phenanthridine skeleton <99T5195, 990L985>. 

Numerous Amaryllidaceae alkaloids include phenanthridine skeletons, one of whose constructive methods constitutes an IEDA strategy. In some cases, the functionality on the dienophile influences the stereochemistry of cyclo addition reactions under high-pressure conditions. For example, the reactions of ( )-buta-l,3-dienyl acetate (6) and the quinolin-2(lH)-ones 7 gave rise to different configurations in the products 8 and 9, depending on the functional groups at the 4-position of 7 (Scheme 3). These results reflect... 

The phenanthridine skeleton is synthesized by photocyclization of the enamides prepared from cyclohexanonimines and benzoyl chlorides (17,18). The benzo[c]phenanthridine skeletons are formed from the enamides prepared from 2-tetralonimines and benzoyl chlorides (19,20). More conveniently, the skeletons of protoberberine alkaloids are readily synthesized from the enamides prepared by simple acylation of 1 -methyl-3,4-dihy-droisoquinolines with benzoyl chlorides (21-24). This berbine synthesis is one of the most typical examples of the application of enamide photocyclization to alkaloid synthesis and can be further extended to the facile synthesis of the skeletons of the yohimbine group of indole alkaloids (25,26). 

Coiydalis alkaloids. General name for a series of iso-quinoline alkaloids with aporphine, protoberberine, or benzo[c]phenanthridine skeletons tom the roots of the yellow fumitory and some other Corydalis species (see aporphine, protoberberine, and benzo[c]phenanthri-dine alkaloids). Some of the C.a. have narcotic, muscle paralyzing activities and the powdered root stocks of the C. a.-containing plants had traditional use as anthelmintic and menstruation-promoting agents. 

This type of Amaryllidaceae alkaloids owns an unique pyrrolo[t/,e]phenanthridine skeleton and is one of the most common alkaloids in plants of the family Amaryllidaceae (Table 17.3). Usually, they have a trans-junction in the B/C ring,... 

The Skeleton of Lycorine-Type Alkaloids. In the course of photochemical studies on 1-aroylindoles, Carruthers and Evans (76) synthesized pyr-rolo[3,2,l-i/,e phenanthridin-7-one (35), the basic skeleton of lycorine, in 10% yield by irradiation of 1-o-iodobenzoylindole (34). However, photocyclization of the corresponding indole analogs proceeded quite differently as shown in Scheme 29. 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

The azepino[3,2,l-/i,/]indole skeleton has been formed by intramolecular Friedel-Crafts cycli-zation of l-(2-methylthioethanoyl)-4,5-dihydro-benz[ft]azepine with NCS <88JHC937>. Treatment of the hydrazinophosphonium tetrafluoroborate (119) with nitrosonium hexafluorophosphate in acetonitrile brings about ring contraction to phenanthridine together with a smaller amount of 5H-dibenz[c,c]azepine <82ZN(B)88l>. 

The alkaloids of this group are derivatives of the pyrrolo[de]phenanthridine (lycorine type) and the 2-benzopirano-[3,4-gf]indole (homolycorine type) skeletons, and both types originate from an ortho-para phenol oxidative coupling (Fig. 4). 

This group includes the alkaloids derived from 5,10b-ethanophenanthridine (crinine and hemanthamine types), 2-benzopyrano[3,4-c]indole (tazettine type), phenanthridine (narciclasine type), and 5,11-methanomorphanthridine (montanine type) skeletons, originating from a para-para phenol oxidative coupling (Fig. 8). 

The benzophenanthridine skeleton is encountered in approximately 30 alkaloids, principally of the family Papaveraceae (Cordell, 1978a). In contrast to the biosynthesis of protopine alkaloids, phenanthridine alkaloids are synthesized in the cytoplasm (Hartmann, 1991). This type of system arises from a protoberberine precursor by fission of the C-6-N bond and recyclization. The biogenetic sequence leading to chelidonine (80) biosynthesis in Chelidonium majus has been supported by feeding experiments with multiply-labeled (-t-)-reticuline [(5)-reticuline] (20) and with labeled stylopine (79) (Fig. 32.25) (Hutchinson, 1986 Sim ek, 1985 Tanahashi and Zenk, 1988). (5)-Z-V-Methylstylopine and protopine (60) have been shown to be metabolites in this pathway. Reticuline is oxidatively cyclized to ( —)-scoulerine (72). Formation of two methylenedioxy groups results in the formation of stylopine (79) (Hartmann, 1991). 

Banwell, M. G. Cowden, C. J. Mackay, M. F. 1994. Concise synthetic ronte to both enantiomeric forms of 2,3,4,4a-tetrahydro[l,3]dioxolo[4,5-j]phenanthridin-6(5H)-one. Tetracyclic skeleton associated with the narcissus alkaloids lycoricidine and narciclasine. J. Chem. Soc. Chem. Commun. 61-62. 

By inventing an intramolecular imino-Diels-Alder cycloaddition of a diene formed by the thermolysis of an oxime-ether, the construction of the alkaloid skeleton, and the usefulness of this methodology, was successfully exemplified, first by the total synthesis of the benzo[c]phenanthridine alkaloid, chelidonine, and then in a beautiful total synthesis of lysergic acid (1). 

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