Heptacyclic alkaloids

We have recently characterized the heptacyclic alkaloid chilocorine from the ladybird (coccinellid) beetle Chilocorus cacti (23). In spite of its superficial complexity, this structure is easily dissected into two tricyclic moieties, A and B, each of which can be regarded as an acetogenin which has been elaborated from a straight chain of 13 carbon atoms stitched together at three points by a trivalent nitrogen atom. 

Finally, the examination of Chilocorus renipustulatus, a European member of the Chilocorus genus, led to the isolation and structure determination of chilocorine D (22), a new heptacyclic alkaloid constituted of a hippodamine moiety linked to a modified octahydro-azaacenaphthylene skeleton encompassing a seven-membered ring [36]. 

H. Interrelation of Minovincine with Hexa- and Heptacyclic Alkaloids. . . 236... 

Kopsine. Kopsine is a heptacyclic alkaloid which at first sight would appear to offer little hope of rapid structure elucidation, but the reader should remember how much information can be gotten out of quite simple measurements. The nature of its chromophoric moiety followed from its ultraviolet absorption spectrum the infrared revealed its carbonyl functionalities. From the above, the elemental composition, Zeisel and Kuhn-Roth determinations and behaviour towards hydrogenation it seemed to be a heptacyclic-N-methoxycarbonylindoline containing a keto-carbonyl and a hydroxyl group. 

The second Chilocorini species studied, Chilocorus cacti, contained several alkaloids closely related to the former. The structure of the heptacyclic chilo-corine A (19) was deduced from a series of NMR experiment (DEPT, HMQC, DQ-COSY, TOCSY) and from a comparison of its spectral properties with those of exochomine (18) from which it differ by having two C-C linkages between the two tricyclic partners. However, the configuration at the asymmetric center in the azaacenaphthylene ring was not established [33]. 

In the last ten years, research in the field of insect defensive chemistry has made remarkable breakthroughs which would not have been possible without the advances in separation techniques, structure determination methods, and synthetic methodology. The structures of structurally complex compounds can now be determined on less than 1 mg of material, as exemplified by the hexa- and heptacyclic coccinellid alkaloids. Moreover, in-depth investigations on the biosynthetic origins of some of the defensive compounds are now made possible and will surely bring interesting data in the future. 

Vinca minor, cultivated in Georgia, USSR, has been shown to contain ( )-vincadifformine and vincine, both already known to occur in this species, together with apovincamine and 11-methoxyvincadifformine.92 Voaphylline, voaphylline hydroxyindolenine, and 11-hydroxytabersonine have been isolated from the leaves of Tabernanthe pubescens,43/ and 5,22-dioxokopsane (177) from the root bark of Alstonia venenata R. Br. 93 this is the first report of an alkaloid of the heptacyclic kopsine group in this species. 

The useful synthetic utilities of photosensitized oxidation of furans were demonstrated. A notable example was the oxidation of the trisubstituted furan 29 shown in Scheme 16 to the (Z)-7-keto-o,/ -unsaturated ester intermediate 30, a crucial step for the construction of the ABC ring system of the complex heptacyclic marine alkaloid norzoanthamine <2004SCI495>. 

Similarly, in a total synthesis of strychnine, the optical resolution was carried out by separation of the sulfinyl lactam diastere-omers (7) and (8), which were obtained from the heptacyclic indole alkaloid precursor (6) this was first transformed with (/ )-(+)-p-tolylsulfinylacetic acid into the corresponding sulfinyl amide and then converted to the diastereomeric lactams (7) and (8) by an intramolecular conjugate addition (eq 3). ... 

Plants of the genus Kopsia have proven to be a particularly rich source of aspidofractinine-type alkaloids. Early studies in the sixties by Battersby (144,145) and Schmid (146,147) of Kopsia frulicosa, an ornamental Kopsia widely cultivated in Malaysia, yielded the heptacyclic bridged alkaloids, fruticosine (186), fruticosamine (187) and kopsine (188). 

Delnudine 020 25 03). This unusual new alkaloid was found in D. denudatum. Its empirical formula (C20H25NO3) coupled with the presence of a carbonyl and exocyclic methylene group (5 4.72, 4.96) indicated a heptacyclic structure. The proximity of the ketone and double bond was concluded from the u.v. absorption Umax 300 nm, log< 1.76) (see Section 2B). The presence of a carbinolamine was shown by formation of an N-acetyl ketone on acetylation, and that of a secondary hydroxyl near the nitrogen by the drop of two units when it was oxidised to a carbonyl group. 

This ring system can be seen in the pentacyclic alkaloids ascididemin 28, 2-bromoleptoclinidone 29, 11-hydroxyascididemin 30, 8,9-dihydro-ll-hydroxyascididemin 31, calliactine 32, the heptacyclic eilatin 33, and the octacyclic biemnadin 34. (See Section II,D,1 on pyrido[2,3,4-/c/]acridines.)... 

Rao et al. in 1984 isolated the first member of the new class of alkaloids, zoanthamine (5), CsoHuNOs, [a]D 18° (CHC13), which was obtained as a white crystalline solid. The molecular formula required that compound 5 be heptacyclic and have both a fully substituted nitrogen atom and an ether linkage. Analysis of the 13C NMR data revealed the presence of a ketone [S 212.0 (s)], an a,/3-unsaturated ketone [S 197.2 (s), 159.9 (s), and 126.8 (d)], and an ester [5 172.5 (s)]. The structure was unambiguously assigned by single X-ray diffraction analysis (20). 

These alkaloids were described briefly in Volume VIII (p. 444) and they could then be ascribed the partial structure CXCII in which the ketonic carbonyl group should be placed in a six-membered ring. Subsequent work (80-82) has shown that the bases are indeed heptacyclic (perhydrogenation NMR) like kopsine and has led to structure CXCIII for fruticosine while fruticosamine has structure CXCIV, epimeric at C-3. 

In 1988, Kashman et al. reported the isolation and structure elucidation of a novel, highly symmetrical, heptacyclic, aromatic alkaloid, eilatin (413) (ca 0.001% dry wt.), from the marine tunicate Eudistoma sp. collected in the Gulf of Eilat and/or the Straits of the Gulf of Suez, in the Red Sea 178,179). 

Williams and co-workers reported the non-enantioselective total syntheses of the heptacyclic indole alkaloids notoamide B (227) and stephacidin A (225) (Scheme 43) [168], and of their probable biogenetic precursor, notoamide C (213) (Scheme 41) [169]. The notoamides are fungal indole alkaloids from Aspergillus species collected fi-om the common mussel Mytilus edulis off Noto Island in the Sea of Japan [170, 171]. There is also a synthesis of the closely related notoamide J (217) (Scheme 42) [172]. 

Myrmicarins. Pyrrolo[2,l,5-cd]indolizine alkaloids from the poison gland secretion of the African mtMyr-micaria opaciventris e.g., the monomeric M. 213 B (1) heptacyclic M. 430 A (2), and the most complex... 

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