Narceine imide

A series of N-substituted narceine amides (Section III,D,1) was prepared from 101 under the action of primary amines (100). Acid-catalyzed dehydration transformed these amides to corresponding imides (ene lactams) of the ( )-narceine imide (117) type (100). Similar transformations were performed in the hydrastine series (101). JV-Methylhydrastine (98) when treated with dilute ammonium hydroxide gave hydroxy lactam 127, which was dehydrated to (Z)-fumaridine (113) (5). Sodium borohydride was able to reduce the stilbene double bond in 98 to produce saturated lactone 132 (5). 

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... 

Ene lactams can be obtained directly from quaternary phthalideisoquino-linium salts by treating them with concentrated ammonium hydroxide. In this way fumaramine (111) was synthesized from bicuculline (88) methiodide (121,124), fumaridine (113) from methiodides of both diastereomeric / - (91) and a-hydrastines (92) (5,124-126), and narceine imide (116) from narcotine (94) methiodide (122,127,128). In the case of the hydrastines (91 and 92) the Hofmann degradation of their methiodides in ammonia was not stereospecific but yielded the thermodynamically more stable Z isomer (113) (5). It seems, however, that from narcotine (94) a mixture of the Z and E forms was produced rather than a single isomer (123,127). 

The less stable isomers were obtained from the more stable ones by photoisomerization. (Z)-Fumaridine (113) when exposed to sunlight was isomerized to a separable 3 2 mixture of geometric isomers (5). The Z form of narceine imide (116) is unstable and in daylight equilibrates easily to a mixture of Z and E forms (123). 

A great number of transformations has been performed on narceine imide (116) by Czech researchers. Oxidation with potassium permanganate in acetone or with nitric acid caused the cleavage of the alkaloid, giving rise to hemipinic imide (127). A similar result was noted by Rdnsch (129,130) during Lemieux-Johnson oxidation of ene lactam 152 (129,130) in this reaction the basic component (156) was isolated as well. The use of hydrogen peroxide in acetone converted 116 to (Z)-narceine imide N-oxide, which under the action of acetic anhydride underwent N-dealkylation (135). 

Lamblin, M. Couture, A. Deniau, E. Grandclaudon, P. A concise first total synthesis of narceine imide. Org. Biomol. Chem. 2007, 5,1466-1471. 

Thermal decomposition of narceine imide methiodide 73a in the presence of 30% aqueous potassium hydroxide afforded 91.4% of a mixture of ZjE-narceone imides 74, along with the azaazulenone 75 (R = OMe) (1.5%), which was also formed (8%) from 74 under the same conditions (75CCC681). 

From a Polonowski reaction of narceine imide Af-oxide 73b N-bridgehead bicycles 75 were obtained containing functional groups in the 5-position. Reaction of 75 (R = OAc) with ethanolic sulfonic acid gave 75 (R = OC2H5), together with the azaazulen-3-one derivative 76 (82MI1). 

Thermal decomposition of narceine imide methohydroxide (158) affords a mixture of (Z)- and (E)-narceone imides (159) together with a smaller amount of the dibenzyl dibenzopyrrocoline derivative (160). Cyclization of the narceone imides (159) in acid gave (160) (cf. Scheme 16) while cyclization in an alkaline medium gave the previously reported benzazepine derivative (161) (cf. Vol. 5). The structure of anhydro-N-oxynarceine (162 R =H R —OMe), which is obtained by refluxing... 

Treatment of the methiodide of narceine imide (186) with aqueous potassium hydroxide solution provided a low yield of the benzazepine derivative (187),... 

Phthalideisoquinolines.—The new alkaloid narceine imide (162) has been obtained from extracts of Papaver somniferum L. (Papaveraceae). Gnoscopine [( )-narcotine] has been synthesized by a classical route. 

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... 

Thermal decomposition of narceine imide methiodide in the presence of 30% potassium hydroxide yields the Hofmann products 28 and 29, as well as the aporhoeadane derivative 30 which can be further reduced to 31 and 32 ... 

In contrast, thermal decomposition of narceine imide methohydroxide gives a 55% yield of 28 and 29, as well as a small amount of the rearranged lactam 33. ... 

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