Dienone alkaloid

Comparison of NMR data for coyhaiquine and other dienone alkaloids showed that the relative stereochemistries can be assigned easily. In coyhaiquine the chemical shifts of H-l 1 and H-12 (8 6.37 and 7.06, respectively) differ by 0.69 ppm a similar difference (0.70 ppm) is observed for pakistanamine (46). How-... 

Several bisbenzylisoquinolines that are found in Berberis species of northern Pakistan can be derived, formally at least, from the naturally occurring spiro-dienone alkaloid pakistanamine (54).48 It is notable that the relative abundance of alkaloids derived by formal dienone-phenol rearrangement in (54) by mechanism (a) is greater than that of more hindered alkaloids formed by mechanism (b). 

Seven isomeric dienone alkaloids of molecular composition CieH2iN02 have been isolated and their structures and absolute configurations have been determined. 

Pseudoepi-isoelaeocarpiline (24) (a colorless gum [a]p +222° in CHCI3 picrate, mp 230-235° dec) was shown to have the molecular formula O16H21NO2, isomeric with the conjugated dienone alkaloids. The IR (vjnax 1665 cm ) and UV 75 nm, e 7600) spectra showed the presence of an a,j8-unsaturated carbonyl group, and the close... 

Comparison of the reduction products formed from the aromatic alkaloids and the dienone alkaloids with sodium boro-hydride in ethanol provides evidence for the assignment of the relative stereochemistry at C-16 in (— )-isoelaeocarpiline [4, 5, 9). 

It has been suggested 10, 13) that the aromatic and dienone alkaloids having the elaeocarpine-isoelaeocarpine ring skeleton can be formally derived from appropriate condensations of an ornithine unit and a polyketide chain (Chart 2a) and the C alkaloids of Elaeomrpus could similarly be derived from ornithine and a C polyketide (Chart 2b). Elaeocarpidine was considered to be derived from condensation of tryptamine, ornithine, and a C unit as indicated in Chart 2c (15). Onaka 8) has drawn attention to the possibility that, by analogy with elaeocarpidine, elaeocarpine could be derived as shown in Chart 2d and he has noted that elaeocarpidine and 2-methyl-6-hydroxyacetophenone have both been isolated from the same plant as ( )-elaeocarpine and (+ )-isoelaeocarpine 4). This alternative biosynthetic route seems less attractive, however, when the C dienone alkaloids are taken into account. 

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. 

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

Upon tissue disruption, the isoxazoline alkaloids 76 and 78 are converted to aeroplysinin-1 (79), which subsequently provides the dienone (80) (Scheme 21). 

Coupling ortho to the phenol group in the tetrahydroisoquinoline and para to the phenol in the benzyl substituent then yields the dienone salutaridine, found as a minor alkaloid constituent in the opium poppy. Only the original benzyl aromatic ring can be restored to aromaticity, since the tetrahydroisoquinoline fragment becomes coupled para to the phenol function, a position that is already substituted. 

Oxidative phenolic coupling.1 A new hiomimetic approach to morphine alkaloids involves oxidative intramolecular coupling of the reticuline derivative 1 to a salutaridine derivative 2 with VOCl3 in ether.1 If the reaction is conducted in CH2C12 2 is obtained in markedly lower yield and the undesired aporphine 3 is formed as a major product. The dienone 2 has been converted into 2-hydroxycodeine (4). 

Application of the above procedure to the known N-protected phenol 342, derived from L-tyrosine and veratraldehyde, resulted in smooth oxidative cyclisation to the dienone 343 in 66% yield. Since the latter had been previously converted [90] via (+)-epimaritidine (344) into (+)-maritidine (345) [91] in six steps with an overall yield of 1.26%, the preparation of 343 constituted a formal synthesis of the alkaloid. 

Chitraline is obtained from B. baluchistanica under neutral conditions, so it is an actual alkaloid and not an artifact from acid-catalyzed dienone-phenol rearrangement of a proaporphine-benzylisoquinoline dimer (61). Chitraline has also been isolated from B. zebiliana Schneider (62), and B. calliobotrys (62). A possible biosynthetic scheme relating chitraline with co-occurring alkaloids has been proposed (62, see Section VII,C). 

Studies directed toward the synthesis of amaryllidaceae alkaloids provide instructive examples of the combined use of spirocylization and Michael addition pathways in phenolic oxidations (03MI1). For example, treatment of the norbelladine derivative 164 with BTIB leads, by way of C,C-bond formation, to the spiroannulated azepine 165 (Scheme 47) (96JOC5857, 98JOC6625). Hydrolysis of the amide moiety in 165 results in Michael addition of the nitrogen center to the dienone ring and affords ( )-oxomaritidine (166). BTIB-oxidation of the appropriate... 

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