Aporphine-type alkaloids

Magnoflorine is a quaternary alkaloid first isolated from a Magnoliaceae, Magnolia grandiflora (115). From the bark of this plant, magnoflorine was obtained in a yield of 0.013%. The same alkaloid was later isolated from other plants, such as Zanthoxylum planispium (Rutaceae), the bark and wood of which contain 0.02% magnoflorine. 

Alkaloids having the same fundamental skeleton as magnoflorine are called aporphine-type alkaloids (58, 140). This class of alkaloids is widely distributed in nature. At least 18 families are known to contain aporphine-type alkaloids. Some of them are Annonaceae, Magnoliaceae, Lauraceae, and Hernandiaceae (Magnoliales), Ranunculaceae, Berberidaceae, and Menispermaceae (Ranun-culales), Aristrochiaceae (Aristrochiales), Papaveraceae (Fumariaceae) (Papavera-les), Rutaceae (Rutales), and Rhamnaceae (Rhamnales). 

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Hansel, R. and Leuschke, A. (1976) Bin Aporphinalkaloid aus Piper sanctum. Phytochemistry, 15,1323. Hansel, R., Leuschke, A. and Gomez-Pompa, A. (1975) Aporphine-Type Alkaloids from Piper auritum. Lloydia, 38, 529—530. 

Aporphine-type alkaloids are formed by the intramoleculer oxidative coupling of the benzyhsoquinoline alkaloid, S-reticuline. Thus, from the ortho, ortho -, and ortho, para -intramolecular coupling of the biradicals formed from S-reticuline, bulbocapnine- and isoboldine-type aporphine alkaloids are formed, respectively. When para, ort/zo -intramolecular coupling of the biradicals formed from S-reticuline occurs, the morphine... 

Aporphine-type alkaloids. Aporphines, e.g., isoboldine, are built by radicalic coupling (C 2.3.1) from tetrahydroisoquinolines. In dependence on the position of the hydroxy group attacked by phenol oxidases and the locations of the free radicals either alkaloids of the isoboldine type (Fig. 281) or via dienones and their further rearrangement alkaloids of isothebaine structure are formed (Fig. 282). 

Aristolochic acids, nitrocompounds found in Aristolochia species, are derived from aporphine-type alkaloids by oxidative degradation (Fig. 288). Probably intermediates are involved which are hydroxylated at position 4. Aristolochic acids are taken up with the diet by larvae of butterflies feeding on Aristolo-chiaceae. They protect the animals from potential predators (E 5.1). 

The pseudobenzylisoquinoline alkaloids are fairly widespread in nature, being found among members of Berberidaceae, Annonaceae, Fumariaceae, and Ranunculaceae. The biogenesis of the pseudobenzylisoquinoline alkaloids assumes their formation from protoberberinium salts by C-8—C-8a bond scission in a Baeyer-Villiger-type oxidative rearrangement to produce the enamides of type 73 and 74. These amides may be further biotransformed either to rugosinone (76) type alkaloids by hydrolytic N-deformylation followed by oxidation or to ledecorine (75) by enzymatic reduction. These transformations were corroborated by in vitro studies (80-82). It is suggested that enamide seco alkaloids may be precursors of aporphine alkaloids (80), on one hand, and of cularine alkaloids (77), on the other. 

Finally, an alkaloid of undetermined structure was studied to demonstrate the utility of these methods. The FABMS of the alkaloid was first determined, followed by derivitization of the alkaloid to its bismethiodide (MeI/Me2CO - room temperature), and subsequent determination of the FABMS of the derivative. The unknown alkaloid exhibited fragmentation characteristic of a type A aporphine-benzylisoquinoline alkaloid with one methoxy and one hydroxy group in... 

The dienone-phenol rearrangement is widely employed for the synthesis of many polycyclic structures, the formation of which demands an expansion of one of the cycles. Thus, the aporphine-type plant alkaloids 307-310 can be obtained via the dienone-phenol rearrangement of orientalinone 305 and dienol-benzene rearrangement of orientaUnol 306 (equation 148). 

Related work not directly dealing with total synthesis of proaporphine, aporphine, or homoproaporphine alkaloids has appeared. A series of homopro-aporphine-type compounds (110) have been prepared, as shown in Scheme 9.12 7 Compound (106), readily prepared from 3,4-dimethoxy-/ -phenethylamine and the appropriate keto-acid derivative, was transformed by reduction and acetylation to (107). Acetylation effectively blocked any complications from the cyclohexane oxygen function during the subsequent Bischler-Napieralski cyclization. Consecutive reduction, alkylation, and hydrolysis gave the key intermediate (109) which was transformed into the tetracyclic spiro-system (110) by reaction with polyphosphate ester under strictly defined conditions. Other conditions and... 

Some years ago a general synthetic method 52) for the morphinan-dienone-type alkaloids was discovered by modifying the Pschorr reaction which had been used widely for the synthesis of the aporphine alkaloids and this method was applied to a synthesis of the homo-morphinandienone-type compounds. 

The plants of Hernandiaceae comprise about sixty-five species in four generic kinds. The plants of Hernandia ovigera L. are widespread in the tropics and the subtropics. In Japan, these plants grow on the beaches of Okinawa and Ogasawara islands. In the Okinawa region, the plants have been used as therapeutic agents. A number of groups have been involved in the isolation and structure elucidation of aporphine-type and isoquinoline-type alkaloids from these plant materials as well... 

L. var. lecoquii (Lamotte) Fedde, some authors (38,39) found berberine (209b) as the major alkaloid, whereas in the material studied by us (40) the major alkaloids were rhoeadine (389) and isorhoeadine (389), though in some instances berberine was also detected. The plant P. commutatum also was shown to contain either alkaloids of the rhoeadine or those of the aporphine type and papaverine or all of these alkaloids simultaneously. Noticeable is the high content of isorhoeagenine glycoside (390) (41). 

Nozaka, T., R Watanabe, S. Tadaki, et al. 1990. Mutagenicity of isoquinoline alkaloids, especially of the aporphine type. Mutat. Res. 240(4) 267-279. 

The pharmacological activity of certain bisbenzylisoqui-noline alkaloids has been reviewed (Buck, 1987 Schiff, 1987). Many of these compounds have weak to moderate antimicrobial activity. Two types of bisisoquinoline alkaloids possess antitumor activity. These are bisbenzylisoqui-noline and aporphine-benzylisoquinoline alkaloids [e.g., tetrandrine (99) and thalicarpine (100), respectively]. Both have pronounced side effects (Cordell, 1978b). 

It has been indicated that isoquinolone alkaloids originate in plants from oxidation of simple benzylisoquinolines. A parallel assumption is that hernan-daline is formed by oxidation of a thalicarpine-type aporphine-benzyliso-quinoline. It is self-evident from the structure of baluchistanamine that in vivo oxidation of an oxyacanthine type alkaloid to an isoquinolone-benzyliso-quinoline dimer, as well as of a simple monomeric benzylisoquinoline to an isoquinolone, is an intrinsic feature of the alkaloidal catabolic process within B. baluchistanica. 

Most of the alkaloids containing an isoquinoline structure that are considered are presented in the following order simple iso quinolines, isoquinolones, and phenethylammonium compounds benzyltetrahydroi-soquinolines bisbenzylisoquinolines and bisbenzyltetrahydroisoquino-lines protoberberines and tetrahydroprotoberberines proaporphines aporphinoids dehydroaporphines 7-substituted aporphines oxoapor-phines phenanthrenes miscellaneous isoquinohne-type alkaloids and nonisoquinoline alkaloids. 

The presence of the isopavine alkaloids amurensine (34) and amurensinine (35) can be considered to be of chemotaxonomic significance for the section Scapiflora. All the ssp. of P. alpinum contain rhoeadine-type alkaloids alpinine and alpini-genine, but rhoeadine itself has not been isolated. In contrast to these findings, rhoeadine is present in several of the varieties of P. nudicaule. The promorphinan alkaloid amurine (30) is present in all of the ssp. of P. alpinum and the majority of the varieties of P. nudicaule. Aporphine alkaloids have not yet been found in species of the section Scapiflora. 

A curious situation is presented by the unusual aporphine alkaloid melosmine (Zabel et al. 1982). This compound is aromatic in ring B and dialkylated at C-7, so that it cannot readily be degraded by any of the above routes. Here, nature adopts a completely different course. The cularine-type alkaloid gouregine is the metabolic product, resulting from oxidation of ring D with subsequent expansion of ring C of melosmine as shown in Fig. 4 (Leboeuf et al. 1982). 

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