Adaline, synthesis

The well-known Robinson-Schbpf reaction has been applied to the synthesis of JZ-adaline (107) from ketoglutaric acid (457), ammonium chloride, and keto-aldehyde (458) (Scheme 58) 338). The second synthesis of starts with nitrone 459 462). Reaction of 459 with pentylmagnesium bromide gave a hydroxylamine (460) which was oxidized to yield a mixture of nitrones 461 and 462. Without separation of the nitrones (461 and 462), successive treatments with allylmagnesium bromide and then mercuric oxide gave a mixture of desired nitrones 466 and 467 and by-product 468. Nitrones 466 and 467 are capable of 1,3-dipolar cycloaddition and, on heating in chloroform, 466 and 467... 

Gnecco Medina, D. H., Grierson, D. S., and Husson, H. P., 2-Cyano-A -pipcrideines X biomimetic synthesis of the Ladyburg alkaloids of the adaline scries. Tetrahedron Lett., 24, 2099. 1983. 

A total synthesis of adaline (550) has been performed (73BSB699). The vinyl ketone 547 was submitted to hetero Diels-Alder reaction with methyl vinyl ether to yield the dihydropyran derivative 548 in 60% yield. Acid hydrolysis of 548 produced the keto aldehyde 549. Finally, a Mannich reaction involving... 

Synthesis by Other Cyclizations. The epimeric amines (49) have been made by means of a novel S 2 reaction of the corresponding 2-bromo-6-amino-cyclohexanone derivative. Double Michael addition of (+)-a-methylbenzyl-amine to cyclo-octa-2,7-dienone derivatives forms the basis of a synthesis of the enantiomeric forms of adaline (50). Intramolecular Friedel-Crafts alkylation has been used in the synthesis of derivatives of the 2,6-methanobenz-azepine, 2,6-methano-3-benzazocine, 2,6-methano-3-benzazonine, and... 

A biomimetic synthesis of the 9-azabicyclo[3.3. llnonan-3-one skeleton of the adaline alkaloids (68) is noted as are syntheses of derivatives of the 3-aza-nonan- 9-one. 2-aza- ° and 3-aza- nonane relatives. Other published syntheses include routes to 1-substituted-C norbenzomorphans 2.5-methano-3-benzazocines and 1.2.3.4.5.6-hexahydro-1.6-methano-3-benzazocines. ... 

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