Phthalideisoquinoline alkaloid

Work on alkaloid isolation is summarized in Table Corledine (154  

Z-(155 R = Me), obtained from C. ochotensis var. raddeana, had similar u.v. absorption to the urethan Z-(155 R = C02C6H4Br-p) of established structure. The alkaloid was prepared from adlumidine methiodide by the action of dilute aqueous NaOH to give J5-(155 R = Me) followed by photochemical isomerization. The structure of bicucullinine (156 R R = CH2), a new alkaloid isolated from C. ochroleuca, was elucidated with the help of spectral data available for the analogous benzil, oxo-N-methylhydrasteine (156 R = R = Me) (c/. Vol. 4). °  

The kinetics and mechanism of hydrolysis of narcotine and of lactonization of narcotic add have been studied/ Another report deals with the instability of bicuculline under physiological conditions/ 8-Ethylnarcotoline hydrochloride had antitussive properties similar to codeine phosphate but the hydrochlorides of narcotoline and 8-benzylnarcotoline were weaker/  

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In addition to the foregoing five phthalideisoquinoline alkaloids obtained from opium, Manske has isolated from genera of the Rhceadales six more alkaloids definitely assigned to, and three, including base F38 (p. 173), which he considers may belong to this group. Hydrastine, already dealt with (p. 162), is also a phthalidcMoquinoline derivative. 

Methoxyberberinephenolbetaine (131) possesses an interesting structural feature, namely, an 8,14-dioxygenated berberine skeleton and a masked carboxylic acid at C-8. It has been converted to phthalideisoquinoline alkaloids (Section V,D,1). Treatment of 131 with methyl iodide, hydrochloric... 

Phthalideisoquinoline alkaloids have been reviewed (1,2,176-179) and compiled (180). Because of the potential usefulness of phthalideisoquinoline alakloids such as bicuculline, a competitive antagonist of y-aminobutyric acid, many synthetic methods for these alkaloids have been developed. Several attractive transformations from protoberberines have also been reported. 

The first conversion of protoberberines to phthalideisoquinoline alkaloids was achieved by Moniot and Shamma (88,89). 8-Methoxyberberinephenol-betaine (131), derived from berberine (15) (Section III,B,2), is an attractive compound having a carboxyl group masked as an imino ether in ring B. The masking was uncovered by hydration with water-saturated ether to furnish dehydronorhydrastine methyl ester (367) (Scheme 65). On N-methylation (68%) and subsequent sodium borohydride reduction (90%), 367 provided (+ )-/ -hydrastine (368) and ( )-a-hydrastine (369) in a 2 1 ratio. Compound 367 was converted to dehydrohydrastine (370), which also afforded 368 and 369 by catalytic hydrogenation. 

Phthalideisoquinoline alkaloids have been suggested to be biosynthesized from 13-oxyberbines with retention of the configuration at C-13 and C-14 through regioselective C-8—N bond cleavage (185). Based on this biogenetic viewpoint, ( )-ophiocarpine and ( )-epiophiocarpine were converted to ( + )-a- and ( )-/ -hydrastine, respectively (Scheme 70) (186). Treatment of... 

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

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). ... 

Directed lithiation has ako proved useful in synthesis of phthalideisoquinoline alkaloids, as shown in equation (II)... 

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