Pavines and Isopavines

Isopavines have been synthesised from urethane acetals by cyclisat- 

Norargemonine and bisnorargemonine have been isolated from Cryptocarya longifolia14 and amurensinine from Papaver tauricola.108 

Partial reduction of the benzylisoquinolines (33 R1 = Me, R2 = CH2Ph) and (33 R1 = CH2Ph, R2 = Me) with sodium borohydride gives the corresponding 1,2-dihydro-compounds, which are cyclized by phosphoric and formic acids (with removal of the benzyl group) to the pavines caryachine (34 R1 = Me, R2 = H) and isocaryachine (34 R1 = H, R2 = Me),66 but attempts to repeat 

Roberts, C. H. Williams, S. D. Waldman, S. T. Simpson, C. Trim, and J. Brazile, Thermoregul. Mech. Their Ther. Implic., Int. Symp. Pharmacol. Thermoregul., 4th, 1979 (publ. 1980), p. 137. 

Few new alkaloids of these relatively small sub-groups have been reported, but there have been significant developments in the synthesis of both structurers. 

Quinol acetates, easily obtained by the oxidation of phenolic benzylisoquinolines with lead (IV) acetate can be cycli-sed to isopavines in good yield in trifluoro-acetic acid. 

Two aporphine-pavine dimers, pennsylpavoline (171, R=H) and pennsylpavine (171, R=Me), together with their aporphine-benz-ylisoquinoline dimer precursors, pennsylvamine and pennsylvan-amine, have been isolated from Thalictrum polyganum (Shamma and Moniot, J.Amer.chem.Soc., 1974, 96, 3338). 

0-Methylcryptaustoline iodide (175, R=Me) has been synthesised from the keto-acid (172, R=H), via the nitro-compound (172, R= NO2) and the amine (173), which on heting is converted into the lactam (174) which is reduced and quaternised to (175, R= Me) (P.W. Elliott, J.org.Chem., 1982, 5398). Cryptaustol- 

Four unusual alkaloids of this group, with bridged ring systems, have been discovered. These are solidaline (178), from Corydalis solida (R.H.F. Manske et al., Canad.J.Chem., 1978, 

Syntheses of 0-methylthalisopavine (59b) have been recorded. In one of these the construction of the carbon-nitrogen skeleton was effected by oxidative cyclization of the lactam (58) to the lactam (59a) by vanadium oxyfluoride in acetonitrile, in 40% yield. Reduction of (59a) by diborane in tetrahydrofuran gave the tertiary amine (59b). An alternative synthesis involved the cyclization, with sulphuric acid, of the acetal (60), prepared from deoxyveratroin.  

Nakamoto, Y. Arashina, and S. Seno, Gan to Kagaku Ryoho, 1979,6,175. 

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Pavines and isopavines are two relatively small subgroups of the isoquinoline alkaloids, being represented by 22 and 11 compounds, respectively. Few new examples have been reported in the last decade, which stands in contrast to the rapid increase in the number of known natural compounds in recent years as a consequence of improved isolation techniques and spectral methods of structure elucidation. 

The pavine and isopavine alkaloids of the Papaveraceae have been discussed in Vols. 4, 10, 12, and 17 of this treatise (2-5), and only brief references have been made to occurrences outside this botanical family. Individual chapters have been devoted to the pavine and isopavine alkaloids in the two books by Shamma (6,7), covering developments until 1977, and also in Rodd s Chemistry of Carbon Compounds (8), published in 1978. A listing of naturally known pavines and isopavines up to 1975, with references to physical and spectral data, appeared in Kametani s Chemistry of the Isoquinoline Alkaloids 9,10). A more recent compilation by Gozler and co-workers 11) has covered references to mid-1982. Relevant literature has also been summarized regularly in Vols. I-XIII of Spe-... 

It has been emphasized that either pavines or isopavines can be obtained selectively depending on the choice of acid conditions used in the aforementioned cyclization process (777). It is also apparent that acid-catalyzed cycliza-tion at room temperature results almost solely in the production of isopavines, whereas application of heat at this stage, which promotes dehydration of the 4-hydroxy intermediate, affords a mixture of pavine and isopavine alkaloids in varying ratios (770,772). 

References relevant to the spectral analyses of naturally occurring pavine and isopavine bases are presented in Tables XIII and XIV. An exhaustive numerical compilation of spectral data of these alkaloids may also be consulted (77). 

The absorption maximum of isopavine alkaloids appear at 290-294 nm. The shoulder at 250 nm, which is missing in the spectra of pavines, provides complementary information in distinguishing between pavine and isopavine alkaloids (7,67,69). Additionally, the Hofmann degradation products of the two nuclei have been shown to differ greatly in their UV spectral behavior (67,69,75). 

The fact that pavine and isopavine alkaloids have the same absolute configuration also suggests an alternative biosynthetic sequence where both nuclei are derived from a common 4-hydroxybenzyltetrahydroisoquinoline precursor (Scheme 35) (77,135). A dehydration reaction to afford a 1,2-dihydrobenzyliso-quinoline, followed by cyclization, would yield a pavine. Alternatively, dis-... 

An interesting variation on the above theme for the biosynthesis of the pavines and isopavines has been proposed by Dyke (169). This proceeds via a quinone methine intermediate. The precursor, a l-benzyltetrahydroisoquinoline-3-car-boxylic acid 165 oxidizes to a quinone methide 166, which then decarboxylates to afford a reactive enamine 167. Cyclization then readily furnishes a pavine. Alternatively, hydration of the enamine 167 at C-4 would ultimately result in formation of an isopavine (Scheme 36). 

Undoubtedly, work with labeled precursors is in order at this point to establish with certainty the exact biosynthesis of the pavine and isopavine bases. 

The presence of pavines and isopavines has been used to provide assistance for taxonomic classifications, and to determine intergeneric and phylogenic relationships in the genera Papaver and Argemone. The results of extensive chemical research on Papaver species demonstrated that morphologically distinct sections are also chemically distinguishable by virtue of their alkaloidal profile (170). Out of nine well-defined sections of Papaver, the Section Scapiflora, which displays... 

The H-NMR and mass spectral data of homopavines and homoisopavines are in conformity with those of the pavine and isopavine bases, respectively. A brief note should be made, however, on a divergent mode of fragmentation in the mass... 

In addition a range of oxidised cularines matching that of the oxidised aporphines is also known. The bases limousamine (92) and 4-hydroxysarcocapnine (93) represent hydroxy substitution unknown in the benzylisoquinoline and.bisbenzylisoquinoline series (probably because of the ease with which such compounds can be converted into pavines and isopavines) but... 

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