Octahydrophenanthrene Analogs of Tetrabenazine

Abstract

Acid-catalyzed treatment of 1,9,10,10a-tetrahydro-3(2H)-phenaiithrenones with ethylene glycol led to kefcalization with accompanying double-bond migration. Catalytic hydrogenation, followed by cleavage of the ketals gave the corresponding B/C-cfs hexahvdrophenanthrenones. Metal in liquid ammonia reduction of the unsaturated ketals followed by hydrolysis gave the B/C-trans hexahydrophenanthrenones. Both series of compounds were converted to 2-alkyloctahydro-3-ketophenanthrenes which were of interest as nitrogen-free analogs of tetrabenazine.

Vesicular monoamine transporter 2: Role as a novel target for drug development

“…55 , 88 Thus, a basic amine nitrogen at position 5 is a prerequisite for TBZ-like activity. 89 Also, methoxy groups at positions 9 and 10 appear to be essential for TBZ-like activity; the methylenedioxy compound 11 ( Figure 5 ) was 3 orders of magnitude less potent than Ro 4-1284 ( 6 ). 90 Replacing the carbonyl oxygen in TBZ with a bis -methylthio group (compound 12 , Figure 5 ) affords a compound with similar activity to TBZ.…”

Total synthesis of an estrajervatetraene

“…(a) From the Ketal 2b. The ketal (2b) and its B/C cis isomer were obtained by the potassium-ammonia reduction of the 4a(10a)-unsaturated ketal as described by Fahrenholtz et al 8 The isomers were present in a 4:1 ratio as determined from the distinctive dioxolane absorption of the two materials (irons-ketal, <5 4.03; cisketal, 3.96). Separation was possible by recrystallization from Et20 and then from MeOH.…”

“…Hydrolysis gave the known irons-ketone 2a. 8 Conversion of the benzdecalone 2a to the benzindanone 4a was accomplished by well-established methodology.9 The furfurylidene ketone 3 was prepared in 87% yield by treatment of the ketone 2a with furfural in methanolic base. Cleavage of the ketone with basic peroxide provided a crystalline diacid 5a in 68% yield.…”