gibberic acid synthesis

Yield:427-78-1 76.5%

Reaction Conditions:

with hydrogenchloride in water at 100; for 3 h;Wagner-Meerwein Rearrangement;

Steps:

(4bS,7S,9aS,10R)-1,7-Dimethyl-8-oxo-4b,6,7,8,9,10-hexahydro-5H-7,9a-methanobenzo[a]azulene-10-carboxylic acid(2).

Gibberellic acid (1.92 g, 5.54mmol) was suspended inaqueous hydrochloric acid (2.4M, 250 mL) in a round bottomflask equipped with a reflux condenser. The reactionmixture was refluxed for 3 h at 100 °C. After reaction, themixture was cooled down to the room temperature and thenextracted with EtOAc (3 × 200 mL). The combined organiclayer was washed with brine (2 × 300mL), dried overanhydrous Na2SO4 and concentrated in a vacuum. The residuewas subjected to column chromatography (PE/EtOAc=3:1) to afford product 2 as a white solid (1.20 g, 76.5%). 1HNMR(400MHz, CDCl3): δ 7.24 (t, J=7.5 Hz, 1 H), 7.08 (d,J=7.5 Hz, 1 H), 6.99 (d, J=7.5 Hz, 1 H), 4.68 (s, 1 H), 3.03(t, J=7.6 Hz, 1H), 2.92 (d, J=17.8 Hz, 1 H), 2.57 (dd, J=17.8, 3.7 Hz, 1 H), 2.25 (s, 3 H), 2.17-2.08 (m, 1 H), 2.05(dd, J=11.9, 3.5 Hz, 1 H), 1.95-1.85 (m, 1 H), 1.81-1.71(m, 1 H), 1.69-1.59 (m, 1 H), 1.55 (d, J =12.0 Hz, 1 H), 1.09(s, 3 H). 13C-NMR (100MHz, CDCl3): δ 173.0, 145.4,136.7, 135.3, 129.3, 129.1, 120.6, 67.1, 51.5, 50.8, 50.1,48.0, 38.5, 34.2, 22.9, 21.5, 20.2. FTIR (MeOH): νmax=3356, 2923, 2866, 1739, 1634, 1455, 1336, 1261, 1196,1159, 1021 cm-1. HRMS (ESI): m/z calcd for C18H20O3Na[M+Na]+: 307.1310, found: 307.1308.

References:

Zhu, Shi-ying;Luo, Fa-zeng;Sun, Ping-Hua [Medicinal Chemistry Research,2020,vol. 29,# 8,p. 1341 - 1354]