Benzophenanthridines, synthesis

X-ray crystal structure, 6, 516 Benzophenanthridines synthesis from anils, 2, 416 Benzophenanthridines, tetrahydro-synthesis, 2, 469 Benzo[c]phenanthridines synthesis, 2, 414 from aryl isocyanides, 2, 411 from benzynes, 2, 432 Benzo[i]phenanthridines synthesis, 2, 414 Benzophenanthridinones... 

Pyrolysis of anils has long been known to give polycycles, as shown by the synthesis of phenanthridine (120) (1889CB3340) and of the two benzophenanthridines (121) and (122) <1891LA(266)155>. More recently, quinoline has been obtained by flash vacuum pyrolysis of the dianil (123) <80JCS(P1)2200). 

Badger and Sasse have described the preparation of 2-, 3-, and 8-bromophenanthridine by the cyclization of the appropriate bromo-formamidobiphenyl with polyphosphoric acid.25 In the case of 2-bromo-2 -formamidobiphenyl a higher concentration of phosphorus pentoxide in the acid was necessary to effect ring closure, and a simple steric effect was invoked.26 Nevertheless, the Morgan-Walls reaction has been used to obtain several overcrowded compounds in which unfavorable steric factors operate. Following the original report of the preparation of the 1,10-dimethylphenanthridine (5a) by this procedure,27 several other examples have been described, notably the synthesis of the related phenanthridine (5b),28 the l,2-(6)29 and 9,10-benzophenanthridines (7),30 and the 1,2 9,10-dibenzophenanthridine (8).29... 

SCHUMACHER, H.-M., GUNDLACH, H FIEDLER, F ZENK, M.H., Elicitation of benzophenanthridine alkaloid synthesis in Eschscholtzia califomica cell cultures. Plant Cell Rep., 1987,6,410-413. 

A, few isochroman-3-ones occurs in nature The importance of isochroman-3-ones however is because they are valuable intermediates for the synthesis of isoquinolines. A most interesting use of isochroman-3-ones is that they provide benzocyclobutenes which are valuable synthons for berbines, spiro-benzylisoquinolines, 3-aryl isoquinoline, benzophenanthridines, benzocarbazoles, yohimbin, tetracycline, steroids etc. 

Homophthalic anhydrides have been used for the synthesis of isocoumarins, isoquinolones, berbines and benzophenanthridine alkaloids. Some of the recent examples are given below. 

The thermal decomposition of tetrahydroberberine methine base hydrochloride has been shown to yield an epimeric mixture of the rearranged product (216).215 An interesting transformation of a protoberberine into a benzophenanthridine alkaloid is discussed in Section 3J. Other work dealing with the synthesis of proto-berberine-type structures has been reported.216—218 A procedure for the preparation of radioiodinated (131I) berberine has appeared.219... 

The synthesis of the parent ring-system of the protopine alkaloids using Perkin s method has been described.224 The preparation of examples of the indeno[l,2-c]isoquinoline ring system (219), exhibited by a rearrangement product of cryptopine, has been described.225 The transformation of protopine to benzophenanthridine alkaloids will be described in Section 3 J. 

A photocyclization which may involve a similar electrocyclic reaction and which may be useful for benzophenanthridine alkaloid synthesis has been described in preliminary form.239 For example, irradiation of the enamide (257) gave an approximately 1 1 mixture of the octahydrophenanthridines (258 R1 = H, R2 + R3 = 0CH20) and (258 R1 + R2 = 0CH20, R3 = H). In this connection, an alternative synthesis of phenanthridines (260) by the reaction of diazonium salts (259) with sodium iodide in acetone may be noted.240 A series of compounds, e.g. (261), temptingly related to benzophenanthridine alkaloids, have been synthesized.241... 

Useful general syntheses of benzophenanthridines have been developed. This is illustrated by the synthesis of oxynitidine and oxyavicine via photocyclization of the... 

There are several others that inhibit DNA replication. Fagaronine and nitidine have ben mentioned previously as intercalating agents, and this intercalation evidently inhibits the action of DNA polymerase [334]. Several benzophenanthridines and protoberberines inhibit reverse transcriptase, which catalyzes the synthesis of DNA with an RNA template [356, 357]. Mimosine at the cellular level, rather than directly on the process, is an inhibitor of DNA synthesis because it chelates iron [358] and because it blocks the synthesis of thymidylate, an essential precursor of DNA [359]. Vincristine may also act as an inhibitor of thymidylate synthesis, perhaps because it alkylates an essential thiol group of an enzyme [360]. 

The syntheses of benzophenanthridine bases were also studied (132, 771-776). Much interest was shown in the synthesis of the alkaloids of this group, particularly after their antitumor activity in mouse leukemia L-1210 (LE) and P-388 (PS) as well as some selected antimicrobial activities had been established (776). On photocyclization, protopine, tetrahydroprotober-berine, and 13-methyltetrahydroprotoberberine yielded sanguinarine via anhydroprotopine (114) (680, 681, 777, 778) (Schemes 33 and 40). 

This methodology has since been applied to constructing [6]-an-nelated carbazoles, and benz[/]indole, and the tetracyclic skeleton of the benzophenanthridine alkaloids. Arynes used in this type of reaction include 3,4-didehydropyridine in the synthesis of ellipticine 8 and isoellipticine 9," 3,4-(methylenedioxy)benzyne, and 2,3-naphthalyne. ... 

Progress in asymmetric organocatalyzed Michael addition/hemi-amino-acetalization/acylimminium-cyclization cascade reactions and application of this type of reactions in the synthesis of alkaloids 13CJ01. Progress in synthesis of benzophenanthridine alkaloids and their derivatives 12CJO1605. 

Battersby and his group have recently reported the details of an extensive study of biogenetic interrelations among tetrahydroprotoberberines, benzophenanthridines, rhoeadines, and phthalideisoquinolines. A key step in this study of the stereospecificity of enzyme reactions was the use of horse liver alcohol dehydrogenase to prepare the complementary R- and 5-benzyl alcohols shown. These tritiated materials were needed for the synthesis of chirally labeled scoulerine. 

This approach has been used by Ninomiya, Ishii, and their co-workers in the synthesis of such aromatic benzophenanthridine alkaloids as dihydro-nitidine and dihydroavicine. ... 

The above sequence has been adapted to a synthesis of the deoxy analog 12 of corynoline. Berberine-acetone, easily prepared from berberine, was converted to the enamine 9 whose photolysis yielded two pseudobases, 10 and 11. These could be reduced with sodium borohydride to the angularly methylated benzophenanthridine 12 (see Scheme 21.4). ... 

Moore s group has also exploited his methodology for the synthesis of a variety of 7V-heterocyclic quinones and hydroquinones such as piperidinoquinones 37, dihydrophenanthridinediols 38, benzophenanthridine 39, and assoanine 40, a member of a series of biologically active pyrrolophenanthridine alkaloids. ... 

Numerous other examples of the dienamide photocyclization reaction in the synthesis of berbine, protoberberine, benzophenanthridine, Amaryllidaceae, and indole alkaloids have been discussed elsewhere. ... 

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