Benzazocine derivatives

Win 42156-2) is a benzazocin derivative, a mixed OPIOID RECEPTOR AGONIST and OPIOID RECEPTOR ANTAGONIST with OPIOID ANALGESIC activity, tonazocine mesylate tonazocine. 

A number of investigators have synthesized benzazocine derivatives by treating reduced quinolines and isoquinolines with dimethylacetylene di-carboxylate (DMA) or with other acetylenes (Eqs. 6-9).274-277... 

Syntheses of analgesics. HI. Synthesis of l,2,3,4,5,6-hexahydro-3-benzazocine derivatives. 2... 

The morphine-fragment type of compound has continued to attract interest. An improved synthesis and new pharmacological data on the analgesic morphan (102) have been described and its IR,5S absolute configuration has been established by X-ray crystallography. Of two series of benzazocine derivatives which were... 

A controlled crisscross annulation strategy has been used to construct the eight-membered ring compound (457) has been prepared in five steps. The key reaction was conducted under electrolytic reduction conditions to afford the benzazocine derivative (458), which was transformed to (459) in 20 steps. Oxidation of the alcohol and further treatment with /-butyldimethylsilyltriflate gave the tricyclic compound (460) (Scheme 32) <88JOC5355>. 

The benzo-fused azodne derivatives are diverse, hence grouping them together and presenting strategic synthetic routes becomes rather intricate. Benzazocine derivatives are mostly formed as unexpected cyclized products, as intermediates, or as one of the other products in a reaction. But a desirable benzazocine can be easily separated from other products by flash chromatography. 

SCHEME 79 Synthesis of benzazocine derivatives from 2-vinylazetidines [106]. 

X ]-antara,antara-Copc rearrangement Dimethyl acetylenedicarboxylate has been used in [2 + 2]cycloadditions with enamines to give cyclobutenes, which in turn have been used as intermediates in preparations of dihydrothiepins and benzo[h]oxepins. Stable bicyclic 1,2-dimethoxycarbonylcyclobutenes have also been obtained from dimethyl acetylenedicarboxylate with 1-alkyl-1,4-dihydropyridines and 1-alkyl-1,4-dihydroquinolines. The former products showed no tendency to isomerize whereas benzazocine derivatives could be obtained from the latter compounds simply by refluxing them in benzene. 

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