Y MIKI; H HACHIKEN; K NOGUCHI; M OHTA; A NAKANO; K TAKAHASHI; S TAKEMURA
CHEMICAL & PHARMACEUTICAL BULLETIN PHARMACEUTICAL SOC JAPAN 38 (12) 3257 - 3260 0009-2363 1990/12
[Refereed] The synthesis of two kinds of propranolol analogues, A and B, with a rigid skeleton was investigated. The compounds were designed to help identify the conformation involved in beta-adrenergic receptor-propranolol interaction.1) The key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained starting from acenaphthenone (1). On sequential dehydration, hydroboration, and oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphthol[1,8-bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13 followed by reduction and alkylation produced the desired compound B. The beta-blocking activities of A and B were examined.