Benzazocines syntheses

Total synthesis of antitumor antibiotic ER900482, 3.9-epoxy-3//-azirino[2,3-c]-l-benzazocine. 97YGK946. 

Dopamine, the free catechol corresponding to (1-1), plays an important role as a neurotransmitter, particularly in the CNS. The synthesis of a dopamine-related sedative agent starts with the condensation of homoveratramine (1-1) with styrene oxide (1-2) to afford the carbinol (1-3). Treatment of that product with a strong acid leads to an attack on the electron-rich aromatic ring by the resulting carbocation there is thus obtained the benzazocine (1-4). The secondary amine is then methylated by reaction with formaldehyde and formic acid to yield trepipam (1-5) [1]. 

Snieckus reported a combination directed ortho-metalation (DoM)-RCM strategy for the synthesis of benzazepine, benzazocine, and benzannulated sulfonamide heterocycles <00SL1294> (Scheme 60). For example, the Boc-protected aniline (75) was sequentially allylated to give 76 which underwent RCM in excellent yield to give benzazepine 77. Use of similar methodology led to 78 and 79 starting from Y-methylbenzamide and p-tolylsulfonamide, respectively. 

Multi-dimensional NMR was also the tool in the structure elucidation of dihydroazocine 10 in order to prove the addition regioselectivity <2003JOC1447>, and in the synthesis of various benzazocines via Beckmann rearrangement <2006TL4721>. 

A series of unusual amidinium benzomorphans has been described by Strauss et a/.<53 55) where some members of the series exhibit narcotic antagonist properties. Their synthesis involves a meta bridging process of di- and trinitronaphthalenes (116) with a-phenyl N,N-dimethylacetamidine (117) to produce two isomeric benzazocine amidinium nitronates as their a-phenyl-N,N-dimethylacetamidinium salts (AmH+). The benzomorphan 118 is formed in ethanolic solution, whereas the isomeric benzazocine (119) results from reaction in dimethylsulfoxide. 

The first preparation of a benzazocine (105 R = S02Ph) was carried out by Braun and Bayer via the cyclization of ethyl A/-benzenesulfonyl-A-(4-phenylbutyl)amino acetate.230 Numerous methods for the synthesis of benzazocines utilizing aromatic electrophilic substitution have been reported. For example, 106 was prepared by cyclization of the appropriate... 

The 93-propyl levo Isomer (3c) was considerably more potent subcutaneously than morphine, while the 9oi-propyl levo Isomer (3d) was equipotent with morphine as an analgesic. None of the optical isomers suppressed withdrawal signs in monkeys the 9f5-propyl levo isomer exacerbated the withdrawal syndrome, indicating that it possesses some narcotic antagonist activity.The most active compound (4) of six homobenzomorphans was as potent subcutaneously as morphine (measured by pressure stimuli on mouse tail).115,116 Simplified procedures for the synthesis of the 6,7-benzomor-phan series have been described.117,118 Several 11-hydroxy and 11-alkoxy-2,6-methano-3-benzazocines display as potent analgesic and narcotic antagonist activity as cyclazocine.H ... 

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... 

Synthesis and analgetic activity of 1,2,3,4,5,6-hexahydro-1,6-methano-3-benzazocines... 

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

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