Secophthalideisoquinoline alkaloids

The first secoisoquinoline alkaloid discovered was the secophthalideisoquinoline, narceine (106), isolated from opium by J. Pelletier in 1832 (7). Up til now 19 natural bases belonging to this group have been isolated, and 6 others have been synthesized. Secophthalideisoquinoline alkaloids have been described in several reviews papers by Shamma et al. 2,4,5), by Santavy (7), and most recently, in 1985, by MacLean (5). 

This arrangement of subgroups is due to the hypothetical biosynthetic sequence. It assumes that precursors for these alkaloids are the Af-methylphth-alideisoquinolinium salts, whose presence in plants is well documented. Enol lactones may be the initial degradation products formed in a Hofmann-type jft-elimination process. They could be hydrated to the keto acids and in the next step oxidated in air to the diketo acids. Diketo adds may undergo further oxidative cleavage to yield simple alkaloids of the fumariflorine (87) type 85,86), which seem to be the final products of the metabolism of phthalideiso-quinoline alkaloids. 

In Table VI secophthalideisoquinoline alkaloids and their precursors are presented. They form four series of seco bases from enol lactones to diketo adds ending with ene lactams, which in all probability are not true alkaloids but products arising during the extraction process. The classic precursors of 

Parent phthalideisoquinoline alkaloid Configuration Enol lactone Configuration Keto acid Diketo acid Ene lactam Configuration 

Bicuculline (88) Erythro Aobamidine (96) Z Adlumidiceine Bicucullinine Fumaramine Z 

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A second series of phthalideisoquinoline alkaloids, the secophthalideisoquinoline alkaloids, involves additional cleavage (Fig. 32.28). These compounds are found only in the Papaveraceae and Fumariaceae (MacLean, 1985). 

In this chapter the proposed (5) division of secophthalideisoquinolines into the four subgroups and the nomenclature have been preserved. Since the publication of the most recent review (5), information about the synthesis of the missing ( )-narceine enol lactone (102) (87), the isolation of ( )-fumaramine (112) from Fumaria vailanti (88), and the discovery of a new seco alkaloid, coryrutine (118), from Corydalis rutifolia (89) has appeared. In the former plant fumaramine (111) (55) and in the latter N-methylhydrasteine... 

The secophthalideisoquinoline enol lactones may exist as Z or geometric isomers. Three pairs of such isomers are known aobamidine (96) (Z) and adlumidiceine enol lactone (97) ( ), /V-methylhydrastine (98) (Z) and (E)-N-methylhydrastine (99) ( ), (Z)-narceine enol lactone (101) and ( )-narceine enol lactone (102). Three of these enol lactones (99, 101, 102) are synthetic products. Lists of these alkaloids, the plant species in which they occur, as well as their spectral data and other references are provided in the review papers (4,5,8). Narceine enol lactones (101 and 102) are described in Refs. 87 and 90. 

Secophthalideisoquinoline enol lactones of type 128 were used by Klotzer et al. (95,103-105) for the synthesis of benzazepine system 129 which was further transformed to alkaloids of rhoeadine type. 

S)-(+)-reticuline (20) and orientaline (25). The alkaloids of the Papaveraceae and Fumariaceae can be subdivided into several constitutional types (Fig. 3), viz., simple isoquinolines, benzylisoquinolines, pavines, isopavines, cularines, proaporphines, aporphines, promorphinanes, morphinanes, protoberberines, retroprotoberberines, secoberbines, benzophenanthridines, protopines, phthali-deisoquinolines, secophthalideisoquinolines, indenobenzazepines, spirobenzyl-isoquinolines, and rhoeadines. 

The Papaveraceae and Fumariaceae DC. are closely related families. Their relationship as well as their independence are well demonstrated by the external stmcture of the flowers, the various anatomical characteristics of their different organs, and alkaloid content. As in the Papaveraceae, the protoberberines, ben-zophenanthridines, and protopines are chemotaxonomically significant for the Fumariaceae. Characteristic for the Fumariaceae is the presence of spirobenzylis-oquinolines, indenobenzazepines, secophthalideisoquinolines, phthalideiso-quinolines, and cularines. The Fumariaceae also contain quaternary highly polar alkaloids, insoluble in nonpolar solvents (16). 

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