Alkaloids pavine

Reviews on the isopavine alkaloids have appeared dealing with various synthetic approaches and with that using lead tetra-acetate oxidation in particular/ The preparation of a number of argemonine analogues (47) by transannular addition of various biogenic amines, e.g. 5-methoxytryptamine to the dione (48), has been reported/  

Cryptausoline (49 R = R = R = Me, R = H) and cryptowoline (49 R = Me, R = H, R R = CH2) have been synthesized by cyclization of bromobenzyltetrahyd-roisoquinolines (50). ° In this type of reaction the product is stable only if a free phenolic group is present at Otherwise Hofmann degradation occurs with 

Komiyama, T. Ogawa, Y. Takahagi, T. Yokomatsu, and S. Shibuya, Chem. andPharm. Bull. 

Komiyama, K. Nawa, and S. Shibuya, Chem. and Pharm. Bull. (Japan), 1976, 24, 310. S. Kano, T. Yokomatsu, and S. Shibuya, Heterocycles, 1976, 4, 933. 

---

A tertiary base isolated from Thalictrum strictum was assigned a pavine structure based on the spectral data (27). Three methoxyl and one methylenedioxy functions were detected with the aid of mass spectroscopy. Structure 3 was proposed as the most probable representation for this new pavine alkaloid, which indeed is the first example of a pentasubstituted pavine base. However, when the reported aromatic proton chemical shifts (8 6.23, 6.36, and 6.54) were evaluated in the light of empirical rules about the H-NMR absorptions of pavine bases (Section V,B), and it seemed possible that the two upfield absorptions belong to H-4 and H-10 rather than to H-1 and H-10. Therefore, alternative structure 4 cannot presently be completely excluded from consideration. 

It is a general feature of alkaloid chemistry that less is known about the quaternary alkaloidal components than the tertiary bases due to the difficulties encountered in handling the isolation and analyses of these highly polar compounds. It is interesting to note, however, that in the pavine series, 5 naturally occurring A -metho salts as against a total of 15 tertiary pavine alkaloids have been recognized. 

Brief reference should also be made to indolopavine derivatives 85 which were synthesized as illustrated in Scheme 13 (130). Since the utilized process, which is the classical route leading to pavines, also represents the probable biosynthetic sequence for the natural pavine alkaloids, it has been suggested that the future discovery of naturally occurring indolopavines is not an unlikely possibility (130). 

A base peak corresponding to a 6,7 (or 7,8)-disubstituted isoquinolinium ion is the prime criterion in considering a pavine or an isopavine structure. In the case of a pavine, the presence of the expected peaks may only confirm the structure deduced by other spectral and chemical means. In isopavines, however, mass spectroscopy is an exceptionally powerful tool in differentiating this group from the pavine alkaloids, as well as from other related isoquinoline bases. 

References for Spectral Properties of Naturally Occurring Pavine Alkaloids... 

Various pharmacological activities have been attributed to the pavine alkaloids, but no pavinoid species has been claimed as a therapeutic agent. A... 

H. Guinaudeau, M. Leboeuf, and A. Cave, J. Nat. Prod. 42, 133 (1979). Dimeric aporphine-benzylisoquinoline and aporphine-pavine alkaloids. Tabulates physical properties, sources, and references to synthesis of 28 alkaloids. 

The 13C chemical shifts of the symmetrical pavine alkaloids argemonine (47) (6) and eschscholtzine (48) (77) (Fig. 9) are presented in Table IX. The difference in chemical shifts between the two alkaloids in large measure... 

Reversed regioselectivity in aryl radical additions to enamides and enamines can also be observed with aryl substituents on the alkene [86]. This cyclization type has been successfully applied in the synthesis of protoberberines and the pavine alkaloids. Argemonine (39) was obtained from a 6-exo cyclization of 40 passing through a well-stabilized benzylic radical (Scheme 15). 

It has been suggested164 that (+ )-reticuline (163) is the precursor of the pavine alkaloids, but the racemate was not incorporated into... 

EP-10 (82), C39H42OgN2 (666.2941), mp 205-210°, was isolated from an extract (EtOH) of the whole plant of the Taiwanese T. fauriei Hayata in 1986 [35]. The UV spectrum showed absorption maxima at 210, 270, 294, and 300 nm, and was similar to those of the aporphine-pavine alkaloids pennsylpavine (83) and pennsylpavoline (84) that had been isolated from T. polygamum Muhl. some twenty years earlier [135]. The specific rotation of the alkaloid was not reported, nor was any CD spectral data provided. The high resolution EIMS showed a parent ion and base peak at m/z 666.2953 (666.2641, calcd. for C39H42OgN2) with other important fragment... 

Preliminary biological testing of the new aporphine-pavine alkaloid EP-10, isolated from extracts of the whole plant of the Taiwanese Thalictrum fauriei Hayata in 1986, demonstrated that the alkaloid possessed weak in vitro activity, as compared with thalicarpine, in the lysis of Hela cells [35]. 

B. Pavine Alkaloids.—Eschscholtzine (70 R = Me) has been isolated from Eschscholtzia californica.89a The structure of ( )-bis-norargemonine (70 R = H) has been confirmed by synthesis.90 The key intermediate (69), prepared by two unexceptional methods, was converted into (70 R = H) in three steps. Interestingly, 1,2-dihydroisoquinoline derivatives do not give this type of product but rather undergo a variety of other reactions if excess acid is avoided [see reactions of compound (58)]. 

---