No abstract

Mannich reaction of 1 -(2-bromo-5-hydroxy-4-methoxybenzyl) -1;2,3,4-tetrahydro-6 7-methylenedioxyisoquinoline (1x1 gave 12-bromonandinine (11) which was debrominated to afford (i)-nandinine (I). Methylation of (i)-nandinine with diazomethane gave (i) -canadine (111). dehydrogenation of which with iodine afforded berberine iodide (XI). NANDININE (I), C&,,NO,, and canadine (III), C20H21N0,, have been isolated from Nandirta domestics and CorydaZis 3 species, respectively. Their structures were elucidated from degradative evidence and by total synthesis.** We are investigating a modified Mannich reaction which selectively affords protoberberines cyclised ortho to the hydroxy group. This reaction has been

Diazotization of 6 '-aminopapaverine (5) in dilute sulfuric acid, followed by treatment with copper, gave the indazole 7 as the major product; the oxoaporphine 8, derived from the normal Pschorr product 9, was the minor product. In contrast, diazotization of 5 in 46% sulfuric acid, followed by Pschorr cyclization, gave papaverine (10, 4.3%), the 1-oxoaporphine 12 (2.4%), and the indenoisoquinoline 11 (30%). Acid treatment of 11 affords 12 almost quantitatively. Chemical conversions of 11 and 12 to the known aporphine bases glaucine (1) and thaliporphine (18), respectively, are described.

Phenolic oxidative coupling of 1 -( 3.4-dihydroxybenzyl) -1,2,3,4-tetrahydro-7-hydroxy-6-methoxy-2,2-dimethylisoquinolinium iodide gave 2.3.5-trihydroxy-6-methoxyaporphine methopicrate, which w a s methylated with diazomethane to give glaucine methopicrate, identical with a n authentic sample obtained by an alternative syn-Sendai, Japan thetic method.JACKSON and MARTIN have recently reported that phenolic oxidative coupling of the benzylisoquinoline (I) leads to two isomeric 2,4-dienones. Reduction of one of the above isomers with sodium borohydride followed by treatment with hydrochloric acid gave isocorytuberine (11) ; alternatively, reaction under anhydrous conditions gave corydine (111) .l Shamma and Slusarchyk also reported the synthesis of glaucine (IV) by phenolic oxidation of the same benylisoquinoline (I) followed by dienol-benzene rearrangement .2 Regarding other aporphine syntheses by phenolic oxidative coupling of quaternary benzyltetrahydroisoquinolines, Franck and his co-workers 394 reported that two phenolic bases (VIIa) and (VIIb) were obtained by phenolic oxidation of laudanosoline methiodide (Va) , isolaudanosoline methobromide (Vb) , and 8-hydroxylaudanosoline methobromide (Vc). Albonico et aL5 also obtained (+)-laurifoline (VIIc) by phenolic oxidative coupling of (+) -tembetarine chloride (Vd) with ferric chloride.We now report our investigation with 1-(3,4-dihydroxybenzyl) -1,2,3,4-t etrahydro-7-hydroxy-6-methoxy-2,2,-dimethylisoquinolinium iodide (VI) , whose phenolic oxidative coupling has not previously been

41) NB. The concentrations of the substrate and of bromine in this mixture were thus half that In the Initial solutions. (42) Sadtler32 uv spectrum no. 16495. (43) A