Total synthesis of (±)-glaucine methopicrate by phenolic oxidative coupling

Abstract

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

Alkaloids from the Chinese Vine Gnetum montanum

“…As for compound 1, the synthesis of 2 has been previously reported. 15 Our data is in accordance with the UV spectrum of the literature.…”

“…Compound 3 is thus the trifluoroacetate salt of 1,9,10-trihydroxy-2-methoxy-6-methyl aporphinium, This is the first report of 3 as a natural product. Its synthesis has been reported by the same group as that of of 2 15 , this latter structure being the starting point to get 3 by oxidative coupling. Our data is in accordance with the 1 H NMR and UV spectra from the literature.…”

Alkaloids

“…The aporphine alkaloids have been synthesized by the Pschorr reaction [136], either from the accessible 1-(2-aminobenzyl)isoquinolines [137][138][139] or from the 8-aminoisoquinolines, which are difficult to synthesize [140]. Decomposition of the diazonium intermediates by photolysis instead of the usual thermolysis improved the yields [141].…”

Aryne Formation from 2-Bromolaudanosine. Fate of the 5,6,12,12a-Tetrahydrodibenzo[b,g]indolizinium Ion and an Alternative Synthesis of Glaucine

“…From a previous similar experiment using 2-bromolaudanosine (2.0 g), compound 11 was isolated according to an earlier procedure (9). The product was decolorized (charcoal) and crystallized three times from methanol to give colorless needles (0.3 g, 18%) of 11, m.p.…”

“…spectral correlations and by known conversion to (A )-glaucine, 12, (Scheme 3) which was characterized as the methiodide (9). External addition of amide ion to the aryne had thus occurred preferentially at the carbon atom remote from the methoxygroups as expected (1); interestingly, 4-aminoveratrole had been previously identified as the main product from reaction of Cbromoveratrole with potassamide in ammonia.…”