Nupharolutin synthesis

Nucleoside antibiotics biosynthesis, 1, 88-90 Nucleosides oxa analogues, 3, 1085 as pharmaceuticals, 1, 153 protected, 5, 316 Nucleosidin occurrence, 5, 603 Nupharolutine synthesis, 2, 393 Nybomycin applications, 6, 667 Nybomycin, deoxy-applications, 6, 667 Nystatin antifungal agent veterinary use, 1, 211... 

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. 

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