Cularine

D. cucullaria (L) Bernh. Bicuculline, corlumine, cryptopine, a-aZZocryptopine, cularidine, cularine, ochotensine, protopine. Manske was unable to confirm from his specimen the presence of cucullarine recorded by Black et al. ... 

D. eximia (Ker) Torr. d-Corydine, cularine, d-dicentrine, eximidine,... 

Minor Corydalis Alkaloids. The following four alkaloids have been isolated by Manske from various Corydalis species but have not yet been assigned to chemical groups. Cularine has been compared pharmacologically with papaverine and hydrastine, and may prove to be related to one of these alkaloids. 

Pharmacological Action. As already pointed out, cularine shows some resemblance to papaverine and hydrastine in action (p. 196). The M.L.D. (mgm./kilo.) for mice by intravenous injection of ochotensine is 10-6 i 0-54 so that it seems to be the most toxic of the fifteen corydalis alkaloids examined by Anderson and Chen, who also state that it stimulates isolated guinea-pig or rabbit uterus, inhibits isolated rabbit-intestine and induces a fall in blood pressure on intravenous injection in etherised cats. 

The pseudobenzylisoquinoline alkaloids are fairly widespread in nature, being found among members of Berberidaceae, Annonaceae, Fumariaceae, and Ranunculaceae. The biogenesis of the pseudobenzylisoquinoline alkaloids assumes their formation from protoberberinium salts by C-8—C-8a bond scission in a Baeyer-Villiger-type oxidative rearrangement to produce the enamides of type 73 and 74. These amides may be further biotransformed either to rugosinone (76) type alkaloids by hydrolytic N-deformylation followed by oxidation or to ledecorine (75) by enzymatic reduction. These transformations were corroborated by in vitro studies (80-82). It is suggested that enamide seco alkaloids may be precursors of aporphine alkaloids (80), on one hand, and of cularine alkaloids (77), on the other. 

Secocularine (228) and secocularidine (229) were synthesized by Hofmann degradation of the corresponding cularine and cularidine methiodides, respectively (181). Both secocularidine (229) and norsecocularine (230) were transformed to secocularine (228) by O- and N-methylation, respectively (181,182). Total synthesis of noyaine (231) was achieved by Ullmann condensation of 8-hydroxy-7-methoxy-2-methyltetrahydroisoquinoIine (232) with 6-bromoveratric acid methyl ester followed by oxidation of the intermediate 233 (183) (Scheme 35). 

Rodrigues,]. A. R. Abramovitch, R. A. de Sousa,]. D. F. Leiva, G. C. Diastereoselective Synthesis of Cularine Alkaloids via Enium Ions and an Easy Entry to Isoquinolines by Aza-Wittig Electrocyclic Ring Closure.]. Org. Chan. 2004, 69, 2920-2928. 

Cularine (67) and related alkaloids constitute a small group of 1-benzyliso-quinoline-related alkaloids, which are distinguished from the main group by... 

Jackson et al. (22) reported the biomimetic total synthesis of ( )-cularine (67) itself (Scheme 11). Benzyolation of isoquinoline 68 in the presence of potassium cyanide gave Reissert compound 69, the anion of which was alkylated with 3-benzyloxy-4-methoxybenzyl chloride, resulting in intermediate 70. After al-... 

There are several reports of tetrahydroisoquinolines with a fused furan ring that could be argued (for the sake of the classification used in this collection) as an oxidative attack by the a-hydrogen of the 1-benzyl onto the 8-HO substituent, in a manner similar to the formation of a seven-membered ether ring seen in the cularines. It can also be seen as a similar oxidative attack from an a-hydroxy group (a commonly encountered benzyl substituent) on the 8-hydrogen position. The first of these two mechanisms (illustrated above) is used in this collection. 

Cularines are isoquinoline alkaloids, which occur mainly in the Fumaraceae family, and are used as muscle relaxants. Total syntheses of (+)-cularine (171)... 

To our knowledge the biological effects of the alkaloids of the cularine group have not been studied. 

---