Of -nupharolutine

Demethyldeoxynupharidine (5) was synthesized from (—)-castoramine (59) in six steps (Scheme 6) (26). Syntheses of ( )-nupharolutine (50) and of ( )-7-epinupharolutine (60) were completed from cyclopentanone derivative 61 (Scheme 7) (62). A stereocontrolled synthesis of ( )-anhydronupharamine (62) was achieved in six steps from cyclopentanone derivative 63 (Scheme 8) (63). Tufariello (64) pointed out the possibility of synthesizing of 7-demethylodeoxy-nupharidine (5) from nonfunctionalized nitrones such as 64 (Scheme 9). Compound 65, after cyclization and removal of the ketone group, would furnish a synthesis of alkaloid 5. 

Scheme 7. Synthesis of ( )-nupharolutine (50) and ( )-7-epinupharolutine (60) from cyclopen-tanone derivative 61.

The reaction of endoperoxides of derivatives of 1,2-dihydropyridine with vinyl ethers, effected by stannous chloride cf. Vol. 10, p. 35), has been used in another synthesis of ( )-nupharolutine (19) (Scheme 3).20 The crystalline quinolizidine (21) was separated from its isomer that is epimeric at C-4. 

Nupharolutine (50) was selectively transformed to A7-dehydronupharolutine (51), a compound prepared for the first time. Treatment of 51 with methyl iodide produced the corresponding methiodide 52, which retained a trans ring junction... 

For the C, 5 Nuphar alkaloids containing quinolizidine rings, deoxynupharidine (14), 7-epideoxynupharidine (15), nupharolutine (50), and 7-epinupharolutine (60), and also for the synthetic model compounds 3(e)-methyl-3(a)-methylthio-methylquinolizidine (68) and 3(a)-methyl-3(e)-methylthiomethylquinolizidine (69), the diagnostic carbon atoms that determine the conformation of the methyl and methylthiomethyl substituents are the carbon atoms of those groups as well as the carbon atoms of the quinolizidine ring at which the substituents are situated (67). For substituents in an axial conformation, the above-mentioned carbon... 

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