Spiro-benzylisoquinolines

Some physiological effects of bicuculline have been studied. 11 Spiro-benzylisoquinolines 

Fumariline, ledecorine, and parfumine have been isolated from 22 

Fumaria vaillantii. Several alkaloids previously assigned 

Fumariline has been isolated from Fumaria indica.125 

Cyclization of amides of the type (91) yields dehydro-phthalide isoquinolines (94), which are enamines and which can be reduced by di-isobutylaluminium hydride in tetrahydrofuran, at -10 °C, with the formation of spirobenzyl-isoquinolines. Starting from the amides used for the synthesis of adlumine and adlumidine (described above), the diastereoisomeric alkaloids corydaine R R2 = CH2,R3 = H,R4 - OH) and sibiricine (95 RJR2 = CH2, R3 = OH, R4 = H) and the related pair yenhusomidine (95 R1 = R2 = Me, R3 = H, R4 = OH) and raddeanone (95 R1 = R2 = Me, R3 = OH, R4 = H) have 

Hanaoka, K. Nagami, and T. Imanishi, Chem. Pharm. Bull., 1979, 27, 1947. 

MacLean, Symp. Pap. lUPACInt. Symp. Chem. Nat. Prod. 11th, 1978, 4, 204. 

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Application of LTA-mediated hydroxylation to the synthesis of spiro-benzylisoquinoline alkaloids has been reported by Blasko et al. 128. 2,3,9-Trimethoxy- and 9-methoxy-2,3-methylenedioxy- IO-hydroxy-8-keto-spirobenzylisoquinolines (457 and 458) underwent acetoxylation at C-13 on treatment of LTA in AcOH to afford the corresponding 5yn-13-... 

A, few isochroman-3-ones occurs in nature The importance of isochroman-3-ones however is because they are valuable intermediates for the synthesis of isoquinolines. A most interesting use of isochroman-3-ones is that they provide benzocyclobutenes which are valuable synthons for berbines, spiro-benzylisoquinolines, 3-aryl isoquinoline, benzophenanthridines, benzocarbazoles, yohimbin, tetracycline, steroids etc. 

Photoinduced itniniutn ion-benzylsilane cydizations have also been employed to construct the protoberberine and spiro benzylisoquinoline alkaloid skeletons. For example, the spiro benzylisoqui-noline (138) can be accessed in 50% yield by the photocyclization of isoquinolinium salt (137). Photo-cyclization of the electron rich isoquinolinium salt (118) gave a 70% yield of ( )-xylopinine (Scheme 45). This photocyclization is claimed to proceed more cleanly and with higher efficiency than the corresponding fluoride-promoted ground state cyclization. 

When tetrahydroberberine methiodides are heated under reflux with sodium bis-(2-methoxyethoxy)borohydride in dioxan, Stevens rearrangement to spiro-benzylisoquinolines and 8-methyltetrahydroberberines occurs. Thus xylopinine (104) gives the bases (105) and (106). Using deuterium-labelled material, it has been shown that the quasi-axially oriented hydrogens at C-8 and C-14 are independently extracted. In the b C-cw salt series the products are spiro-compounds with retention of configuration at C-8 and inversion at C-14 and... 

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