A novel synthesis of a tricyclo (7.5.01,5.01,9) tetradecane ring system related to gascardic acid.

Synthesis of novel molecular probes inspired by harringtonolide

“…The ester 9 (2.73 g, 11.0 mmol) was dissolved in 1 M NaOH (90% methanol in water, 60 mL) and stirred at room temperature for 3 h. The reaction mixture was concentrated, dissolved in water (50 mL), acidified with 5 M HCl (12 mL) and extracted with ethyl acetate (3 ¥ 40 mL). The organic extract was washed with brine (2 ¥ 40 mL), dried over anhydrous sodium sulfate, filtered and concentrated at reduced pressure to afford the crude product which was purified on a silica column (hexane : ethyl acetate, 85 : 15) to yield the title compound 29…”

“…0.93 (d, J = 6.5 Hz, 6H, CH(CH 3 ) 2 ); d C (125 MHz, CDCl 3 ) 155.90 (C7), 145 (C8b), 134.58 (4a), 121.84 (C5), 121.07 (C8a), 108.13 (C6), 76.89 (C1), 67.17 (OCH 2 ), 55.70 (OCH 3 ), 41.70 (C2a), 39.19 (OCH 2 CH 2 ), 35.65 (C4), 35.37 (C3), 31.67 (C8), 29.74 (C2), 25.33 (CH), 22 A solution of 20a (100 mg, 0.12 mmol) in dry THF (1.0 mL) was added slowly to a stirred and cooled suspension sodium hydride (60% dispersion in oil, 79 mg, 1.96 mmol) in dry THF (1.2 mL). Upon complete addition, the reaction mixture was stirred at ambient temperature for 1 h under argon.…”

“…δ H (500 MHz, CDCl 3 ) 7.07 (d, J = 8.5 Hz, 1H, H-8'), 6.70 (dd, J = 2.5, 8.5 Hz, 1H, H-7'), 6.60 (d, J = 2.5 Hz, 1H, H-5'), 4.17 (q, J = 7.1 Hz, 2H, CO 2 CH 2 CH 3 ), 3.76 (s, 3H, OCH 3 ), 3.29 (m, 1H, H-1'), 2.75 (m, 2H, CHCH 2 CO), 2.66 (dd, J = 5.0, 10.0 Hz, 1H, H-4'), 2.48 (dd, J = 10.0, 14.75 Hz, 1H, H'-4'), 1.92-1.65 (m, 4H, H-2', H'-2', H-3', H'-3'), 1.27 (t, J = 7.2 Hz, 3H,COCH 2 CH 3 ); δ C (125 MHz, CDCl 3 ) 173.02 (CO), 157.83 (C6'), 138.48 (C4'a), 131.69 (C8'a), 129.36 (C8'), 113.83 (C5'), 112.31 (C7'), 60.46 (CH 2 CH 3 ), 55.34 (OCH 3 ), 42.34 (CH 2 CO), 34.09 (C1'), 30.04 (C4'), 28.56 (C2'), 19.72 (C3'), 14.42 (CH 2 CH 3 ); (+) LRESIMS m/z 271 [M+Na] + .6'-Methoxy-1',2',3',4'-tetrahydro-1'-naphthylacetic acid (10)The ester 9 (2.73 g, 11.0 mmol) was dissolved in 1M NaOH 20 (90% methanol in water, 60 mL) and stirred at room temperature for 3 h. The reaction mixture was concentrated, dissolved in water (50 mL), acidified with 5M HCl (12 mL) and extracted with ethyl acetate (3 × 40 mL). The organic extract was washed with brine (2 × 40 mL), dried over anhydrous sodium sulfate, filtered and concentrated at reduced pressure to afford the crude product which was purified on a silica column (hexane:ethyl acetate, 85:15) to yield the title compound29 as a white solid (2.37 g, 97.8%): mp 80-82 °C; δ H (500 MHz, CDCl 3 ) 7.10 (d, J = 8.5 Hz, 1H, H-8'), 6.72 (dd, J = 2.5, 7.7 Hz, 1H, H-7'), 6.62 (d, J = 2.0 Hz, 1H, H-5'), 3.77 (s, 3H, OCH 3 ), 3.32 (m, 1H, H-1'), 2.81-2.70 (m, 3H, CH 2 CO, H-4'), 2.56 (dd, J = 10.0, 15.5 Hz, 1H, H'-4'), 1.98-1.92 (m, 1H, H-2'), 1.87-1.71 (m, 3H, H'-2', H-3', H'-3'); δ C (125 MHz, CDCl 3 ) 178.82 (CO), 157.92 (C6'), 138.53 (C4'a), 131.30 (C8'a), 129.30 (C8'), 113.91 (C5'), 112.43 (C7'), 55.35 (OCH 3 ), 41.93 (CH 2 CO), 33.89 (C1'), 29.99 (C4'), 28.43 (C2'), 19.66 (C3'); (+)-LRESIMS m/z 243 [M+Na] + ; (+)-HRESIMS m/z 243.0992, C 13 H 16 O 3 [M+Na] + requires 243.0992.3-(6'-Methoxy-1',2',3',4'-tetrahydro-1'-naphthyl)-1-diazopropane-2-one (11) The title compound was prepared according to the method reported by Mander et. al.…”