Narceine enol lactone

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. 

The enol lactones were synthesized by Hofmann degradation of metho salts of classic phthalideisoquinoline alkaloids. The biogenetically relevant transformations were highly stereospecific. In this way aobamidine (96) was obtained from the methiodide of (erythro) bicuculline (88) (2), and ad-lumidiceine enol lactone (97) was produced from both (threo) isomeric adlumidiceine (89) and capnoidine (90) methiodides (14,15,91-93). (Z)- (98) and ( )-N-methylhydrastine (99) were obtained from / - (91, erythro) and a-N-methylhydrastinium (92, threo) iodides (5,87,91,96-98), respectively, as were (Z)- (101) and (JE)-narceine enol lactones (102) synthesized from a- (94, erythro) and /J-narcotine (95, threo) quaternary N-metho salts (87,90), respectively. In a similar process /J-hydrastine (91) JV-oxide heated in chloroform yielded enol lactone 124 of Z configuration (99) however, a-narcotine (94) N-oxide was transformed to benzoxazocine 125 (99). ... 

Both Z and E isomeric enol lactones undergo photoisomerization to yield mixtures of isomers (5,14,87) in which the thermodynamically more stable one prevails. It is the Z form in hydrastine series (5) and the E isomer in the more hindered narcotine series (87). Relative stabilities of isomeric enol lactones (98 versus 99 and 101 versus 102) were determined by comparing their rates of methanolysis. Keto esters of type 126 were formed (87). It turned out that both ( )-N-methylhydrastine enol lactone (99) and (Z)-narceine enol lactone (101) solvolyzed faster than their geometric partners. 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Enol lactones can also be obtained from keto acids by enolization-dehydration. Adlumidiceine (103) as well as N-methylhydrasteine (104) when heated in toluene with acetic anhydride or p-toluenosulfonic acid were transformed to enol lactones 97 (97) and 98 (5,102), respectively. Narceine (106) under the influence of PC13 yielded 101 (87,100). 

Adlumiceine, adlumiceine enol lactone, adlumidiceine, adlumidiceine enol lactone, bicucullinidine, bicucullinine, fumaramidine, fumaramine, fumaridine (= hydrastine imide), fumschleicherine, A-methylhydrasteine, IV-methylhydrastine, narceine imide, narceine imine, narlumidine, A-methyloxohydrasteine... 

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