Synthesis, stereochemistry and anti-tetrabenazine activity of bicyclo analogues of 2-phenylmorpholines

✍ Scribed by G. Evan Boswell; David L. Musso; Ann O. Davis; James L. Kelley; Francis E. Soroko; Barret R. Cooper

• Book ID: 102892829
• Publisher: Journal of Heterocyclic Chemistry
• Year: 1997
• Tongue: English
• Weight: 669 KB
• Volume: 34
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570340629

✦ Synopsis

A series of bicyclo analogues of several 2-phenylmorpholines were synthesized and tested for anti-tetrabenazine activity in mice. Most of the target compounds were prepared by reaction of 2-bromopropiophenone (22) with the appropriate amino alcohol to form 2-phenylmorpholinols. Reduction of the 2-phenylmorpholinols with sodium borohydride gave amino diols, which were cyclized to morpholines with acid. Alternatively, oxazines 17 and 18 were synthesized by alkylation of phenyl-(2-pyrrolo)carbinol (32a) and phenyl-(2-piperidyl)carbinol (32b) with 2-bromoethanol, followed by cyclization of the resulting amino diols with acid. Only the spirocyclic compounds 8 and 9 had i.p. anti-tetrabenazine activity comparable to the non-cyclic compounds (2 \mathrm{a}-3 \mathrm{~b}), but 8 and 9 were less active by the oral route of administration.