Alkaloids, proaporphine

C. Aporphine, oxa-aporphine, and proaporphine alkaloids (including dioxo-... 

The 13C chemical shifts of several reduced (61-64) and nonreduced (65, 66) proaporphine alkaloids (Fig. 11 and Table XI) have been reported by Ricca and Casagrande (41). The authors studied several pairs of diastereo-mers and found the 13C chemical shifts to be sensitive to the relative stereochemistry in these compounds. 

N-Methyl-litsericine (1), a new proaporphine alkaloid, has been isolated from Neolitsea aurata.5... 

New proaporphine alkaloids are (-l-)-isocrotsparinine (1), (-I-)-N-methyliso-crotsparinine (2), and ( )-tetrahydroglaziovine (3), all obtained from Croton spar-siflorus. The stereochemistry of crotsparinine has been defined as in structure (4). Jacularine and Base-E, two minor alkaloids previously isolated from C. linearis have been assigned stereo formulas, with the former being enantiomeric with (1), and the latter being represented by (5)/... 

In an eady attempt to understand the genesis of alkaloids from amino acids it was postulated (56) that intramolecular phenolic coupling should lead from benzylisoquinoline bases such as laudanosine (77, R = CH3), before it was completely methylated, to aporphine bases such as isothebaine (81). For example, between a benzylisoquinoline derived from laudanosoline (77, R = H), such as orientaline (82), and an aporphine alkaloid such as isothebaine (81), there should be a proaporphine alkaloid such as orientalinone (83) (56). The isolation of 83 lent credence to the hypothesis. Indeed, the fragile nature of 83 (it readily undeigoes the dienone—phenol rearrangement on acid treatment) required unusual skill in obtaining it from total plant extract. 

On reductive cleavage (JOO) with sodium in liquid ammonia the proaporphine alkaloids with dienone structure are converted into benzyl-isoquinoline bases (IV I XIV XIII). By treatment with W-hydro-chloric acid the dienone alkaloids are transformed (69, 349) into the aporphine alkaloids (Schemes 1 and 2) by dienone-phenol rearrangement (IV -> II XIV -5- XV, XVI, and XVII). Substitution of the proaporphine base at C-9 by a methoxyl function involves rearrangement which gives rise to two isomers, i.e., XV and XVI. On the other hand, by reduction of dienone with sodium borohydride (formation of two dienols) and following treatment with hydrochloric acid these dienols are converted (65,66, 68, 69, 349) into the aporphine alkaloids with formation of a new aromatic ring (VI and VII III XVIII XIX and XX). 

Mass spectrometry (22, 96,181, 530, 531) and NMR spectroscopy (65, 69,181,209,431) have been recorded. The UV spectra of the dienone alkaloids differ in the extinction maxima (proaporphine alkaloids at 220 nm (e 24800) and 285 nm (c 3000) promorphinane alkaloids 230 nm (e 24,000) and 285 nm (e 7500)). IR Spectroscopy reveals characteristic frequencies of the cross-conjugated dienone at 1655, 1630, and 1613 cm"i. On polarography the proaporphine and the promorphinane dienone compoimds are reduced (335) at a half-wave potential similar to that of aromatic aldehydes. 

The term aporphinoids covers aporphines and their close biogenetic precursors, the proaporphines. Alkaloids derived from relatively straightforward biological transformations of proaporphines or of aporphines are also encompassed, so that proaporphine-benzylisoquinolines, aporphine-benzylisoquinolines, aporphine-pavines, oxoaporphines, dioxoaporphines, aristolactams, and aristolochic acids, as well as phenanthrenes, will be discussed. Azafluoranthenes are also included within the scope of aporphinoids for reasons which will become clear toward the end of the present chapter. 

Previous knowledge of the proaporphine alkaloids has been summarized in two reviews (10,391) and in the book by Shamma (/). These three publications also draw attention to the UV, IR, and NMR spectra, but no assessment of the data is made. 

This material is supplementary to The Alkaloids, Vol. XII, p. 349. t The proaporphine alkaloids of the cyclohexadienone type or those with a partially reduced ring D occur not only in the Papaveraceae but in many other plant families, such as Euphorbiaceae, Lauraceae, Menispermaceae, Monimiaceae, and Nymphaceae (1,393). Their widespread occurrence permits a study of the isolation and the synthesis of these compounds on a large scale. 

Four major reactions (Pschorr, phenol oxidative coupling, photocyclization, and benzyne-mediated synthesis) continue to play key roles in the total synthesis of aporphine and proaporphine alkaloids. Coninnine (96) was synthesized according to Scheme 5, employing the Pschorr reaction as the key step. An... 

The mass spectral behaviour of proaporphine alkaloids has been analysed. Microcrystalloscopic determination of phenanthrene-isoquinolines using antimony acid complexes has been carried out. ... 

The hypervalent iodine-promoted oxidation of enamide 257 in the presence of a base leads to the spiroe-namide 258, which is a key intermediate product in the total synthesis of annosqualine (Scheme 3.106) [325], A similar oxidative cyclodearomatization approach has been utilized in the total synthesis of a proaporphine alkaloid, ( )-stepharine [326],... 

Azafluoranthene and Tropoloisoquinoline Alkaloids Aporphine Alkaloids Biogenesis Biological Activity Aristolactams and Aristolochic Acid Eupomatia Alkaloids Proaporphine Alkaloids... 

Although the mechanisms above were postulated before compounds resembling the proposed intermediates were known, compounds such as orientalinone (50) were later isolated. Both (- )-orientaline (29) and (+ )-orientalinone (50) (a proaporphine alkaloid) serve as precursors for isothebaine (49) in Papaver orientate (Fig, 32.12) (Geissman and Grout, 1969). 

Proaporphine alkaloids are known from the Euphor-biaceae, Lauraceae, Menispermaceae, Monimiaceae, Ne-lumbonaceae, and Papaveraceae (Santavy, 1979). 

Fig. 32.17. Formation of aporphine alkaloids via the intermediacy of proaporphine alkaloids (modified from Geissman and Grout, 1969).

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