cis-Bicyclo[3.3.0]octane-3,7-dione

Uses

cis-Tetrahydro-2,5(1H,3H)-pentalenedione is an intermediate in the synthesis of Loganin (L469405), an iridoid glycoside that exhibits protective effects against hepatic injury and other diabetic complications associated with abnormal metabolic states and inflammation caused by oxidative stress and advanced glycation endproduct formation. A potential anti-amnesic agent.

Synthesis Reference(s)

Synthesis, p. 529, 1984 DOI: 10.1055/s-1984-30893
Tetrahedron, 38, p. 63, 1982 DOI: 10.1016/0040-4020(82)85046-1

Synthesis

Step 2 (cis) - Synthesis of bicyclo[3.3.0]octane-3,7-dione: Tetracyclohexyl[3.3.0]octane-3,7-dioxo-2,4,6,8-tetracarboxylate 14b (6.75 g, 0.02 mol) was dissolved in 3.3 mL of acetic acid, followed by addition of 30 mL of 1 M hydrochloric acid solution. The reaction mixture was heated to reflux and maintained for 3.5 hours and subsequently cooled to room temperature. The reaction mixture was extracted with dichloromethane (50 mL × 3). The organic phases were combined, concentrated under reduced pressure, and phase separation was carried out by adding 100 mL of dichloromethane and slowly adjusting the pH to 7 by dropwise addition of saturated sodium bicarbonate solution. The organic phase was dried with anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to afford the target product cis-dicyclo[3.3.0]octane-3,7-dione (14c, 2 g, yield: 80.0%) as a white solid.

References

[1] Patent: EP2481739, 2012, A1. Location in patent: Page/Page column 43
[2] Patent: US2012/184543, 2012, A1. Location in patent: Page/Page column 46
[3] Journal of the American Chemical Society, 1960, vol. 82, p. 6347 - 6353
[4] Tetrahedron, 1981, vol. 37, # 25, p. 4521 - 4542