Aporphine alkaloids degradation

These domino reactions have also been employed by us for the total synthesis of pharmacologically important [50,51] aporphine alkaloids namely dehydronomuciferine (1) and ( ) N-nomuciferine (2)(Scheme 1), and biologically active [52] phenanthrene alkaloids namely N-noratherosperminine (3) and atherosperminine (4)(Scheme 2). Incidentally, phenanthrene alkaloids are related to the aporphines, from which they can be obtained by degradative procedures [37],... 

The phenanthrene alkaloids are a small group of optically inactive bases derived in vitro and probably in vivo by Hofmann degradation of quaternary aporphine salts. Of the more than one hundred aporphine alkaloids presently known, only three possess a methylenoxy bridge. However, five of the fourteen known phenanthrene alkaloids incorporate this bridge. 

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). 

Most phenanthrene alkaloids are easily synthesized by degradation of the corresponding aporphines. Many phenanthrenes were first prepared as aporphine derivatives for characterization or in the course of structural studies, and only later were they found in nature. Although the ready availability of most aporphines from natural sources makes this strategy very simple, it often does not constitute a formal total synthesis, and some approaches from simpler compounds have been published (29,105). Degradation of the morphine alkaloid thebaine (151) gives rise to a number of unnatural phenanthrenes (93,94,102, 104,113). 

Hoffmann degradation is a classic way to transform aporphines into phe-nanthrene alkaloids. This transformation involves the thermolysis of the quaternary ammonium hydroxide formed by sequential treatment of an aporphine with an alkylating agent and silver oxide. This degradation was extensively used in initial degradative studies of the structure of aporphines. The alkylations are usually done with methyl iodide (20,30,45,60,85,86,88) or dimethyl sulfate... 

II) t3q>es. The absolute configuration of (-f )-norlaudanosine was elucidated by adopting a degradative method (isolation of i T-a-carb-oxyethyl-L-aspartic acid) 115), which in turn permitted the establishment of the absolute configuration of the proaporphine, aporphine, pro-morphinane, morphinane, and tetrahydroprotoberberine alkaloids (Scheme 20). The optical rotatory data 63), the ORD-curves 2, 41,120, 122), and the CD-curves 73) have led to an accumulation of sufficient information for the determination of the absolute configuration even of... 

In continuation of their chemical investigation of peptide alkaloids obtained from Zizyphus amphibia (see Vols. 3 and 4 of these Reports), Tschesche and coworkers have elucidated the structures of the new amphibines F (40), G (41), and H (42) by the established spectroscopic and degradative methods. Amphibine I (43), an alkaloid of obvious mixed biogenesis, has been isolated from Z. am-phibia. Interestingly, the aporphine base (—Fnuciferine was also obtained from this species. 

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). 

A relevant and very recent development is the isolation and characterization by Beal, Doskotch, and co-workers, of the new alkaloid ( + )-thaliadine from Thalictrum minus L. race B (Ranunculaceae). This alkaloid is accompanied in the plant by such aporphine-benzylisoquinoline dimers as (-h)-adiantifoline, (+)-desmethyladiantifoline, and (-h)-thaliadanine (Sec. 12.1), and must be formed from their oxidative degradation. ... 

Most of the congeners of thalmine, C20H23O3N (see Volume V, p. 325), are aporphines but this alkaloid proved to be the first of a new structural type. There are two methoxyls in the molecule and the third oxygen is present as hydroxyl. Acetylation yields a neutral 0,V-diacetyl derivative and Hofmann degradation yields in two stages a compound formulated as LXXXVI (mp 212°). This on oxidation generates 5,6 -dimethoxydiphenic acid which is also obtained by oxidation of the alkaloid. Reduction of LXXXVI leads to the formation of a dihydro derivative (mp 173°) which on oxidation yields the diphenic acid as well as propionic acid. The proposed structure (LXXXV) accounts for these reactions but equally satisfactory would be one in which the piperidine nucleus is inverted with the nitrogen at the top in the formula (231). 

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