A synthetic approach to tacamonine. Access to 3-epitacamonine and 14-epitacamonine

General Strategy for the Syntheses of Corynanthe, Tacaman, and Oxindole Alkaloids

“…15 is a member of the relatively small group of tacaman indole alkaloids and was first isolated in 1984 from Tabernaemontana eglandulosa (Apocynaceae), the root of which is used to treat snake bites in Central Africa 14b. Although tacamonine has been prepared before, it occurred to us that 4 was nicely suited as an intermediate, and we developed a facile one-pot procedure for its transformation into 14 , which had been previously converted in two simple steps into 15 15b. Thus, following reduction of 4 by catalytic hydrogenation [10% Pd/C, H 2 (1 atm)], POCl 3 was added, and the reaction was heated at 100 °C for 3 h to give 14 in 92% yield (Scheme ).…”

Stereoselective synthesis of (−)-desethyleburnamonine, (−)-vindeburnol and (−)-3-epitacamonine: observation of a substrate dependent diastereoselectivity reversal of an aldol reaction

“…The concentration of the organic layer in vacuo followed by silica gel (60-120 mesh) column chromatographic purification of the resulting residue using ethyl acetate-petroleum ether (8 : 2) as an eluent afforded the required lactamol 6 (7 : 3 dr) as a white foam (1.65 g, 82% yield). 1 H NMR (CDCl 3 , 500 MHz) δ 1.78-1.93 (m, 1H), 1.96 (s, 1H), 2.08 (s, 2H), 2.15-2.35 (m, 1H), 2.29 (s, 1H), 2.30 (s, 2H), 2.35-2.60 (m, 2H), 2.90-3.05 (m, 2H), 3.48-3.90 (m, 2.70H), 4.50-4.55 (br s, 0.30H), 4.78-4.90 (m, 1H), 4.93 (s, 1H), 7.13-7.35 (m, 4H), 7.37 (s, 1H), 7.55-7.60 (m, 1H), 7.65-7.80 (m, 2H), 7.90-8.00 (m, 1H); 13 20.5, 20.8, 21.0, 21.5, 23.7, 27.3, 29.2, 45.4, 45.9, 69.4, 69.9, 79.6, 81.3, 113.6, 119.6, 119.9, 123.1, 123.2, 124.8, 126.7, 129.8, 130.7, 134.9, 135.0, 144.9, 169.5, 169.96, 170.0, 170.5; ESIMS (m/z) 493 [M + Na] + ; HRMS (ESI) calcd for C 24 H 26 N 2 O 6 SNa 493.1404, found 493.1397; IR (neat) ν max 3312, 1739, 1620 cm −1 .…”

“…The aqueous layer was extracted with CH 2 Cl 2 (50 mL × 3) and the combined organic layer was washed with brine and dried over Na 2 SO 4 . The concentration of the dried organic layer in vacuo followed by silica gel (230-400) column chromatographic purification of the resulting residue using ethyl acetate-petroleum ether (3 : 2) as an eluent gave pure amido-lactone (−)-3 as a gummy solid (11.12 g, 82% yield) (m, 3H), 2.79 (t, J = 8 Hz, 2H), 2H),4.69 (t,J = 8 Hz,1H),6.50 (t,J = 6 Hz,1H),4H),7.27 (s,1H), 7.37 (dd, J = 6 and 2 Hz, 1H), 7.64 (d, J = 10 Hz, 2H), 7.84 (d, J = 8 Hz, 1H); 13 C NMR (CDCl 3 , 50 MHz) δ 21. 5, 24.9, 25.7, 27.4, 38.6, 77.3, 113.6, 119.17, 119.23, 123.1, 123.3, 124.8, 126.7, 129.9, 130.5, 135.0, 135.1, 144.9, 169.4, 175.8 3321, 1784, 1733, 1677 cm −1 (4).…”

“…The concentration of the dried organic layer in vacuo followed by silica gel (230-400 mesh) column chromatographic purification of the resulting residue using petroleum ether-ethyl acetate (1 : 1) as an eluent yielded (S)-hydroxyglutarimide (−)-4 as a white solid (2.92 g, 68% yield; 99.6% ee). Mp 168-170 °C; [α] 25 D −49.37 (c 0.5 CHCl 3 ); 1 H NMR (CDCl 3 , 500 MHz) δ 1.86 (dq, J = 10 and 5 Hz, 1H), 2.27-2.35 (m, 1H), 2.36 (s, 3H), 2.62 (ddd, J = 20, 15 and 5 Hz, 1H), 2.82-2.91 (m, 1H), 2.93 (t, J = 10 Hz, 2H), 3.55 (s, 1H), 3.96-4.05 (m, 1H), 4.06-4.12 (m, 1H), 4.16 (dd, J = 10 and 5 Hz, 1H), 7.25 (d, J = 5 Hz, 1H), 7.29 (t, J = 10 Hz, 1H), 7.34 (t, J = 10 Hz, 1H), 7.43 (s, 1H), 7.66 (d, J = 5 Hz, 1H), 7.79 (d, J = 5 Hz, 2H), 8.00 (d, J = 5 Hz, 1H); 13 C NMR (CDCl 3 , 125 MHz) δ 21.5, 23. 3, 25.2, 30.7, 39.9, 68.2, 113.6, 118.9, 119.5, 123.2, 123.6, 124.8, 126.8, 129.8, 130.7, 135.0, 135.3, 144.9, 171.1, 175…”

“…The concentration of the organic layer in vacuo followed by silica gel (60-120 mesh) column chromatographic purification of the resulting residue using petroleum etherethyl acetate (6 : 4) as an eluent afforded pure acetoxyimide (−)-5 as a white solid (6.20 g, 94% yield). Mp 135-138 °C; [α] 25 D −44.57 (c 2.1 CHCl 3 ); 1 H NMR (CDCl 3 , 200 MHz) δ 2.09-2.21 (m, 2H), 2.22 (s, 3H), 2.34 (s, 3H), 2.52-2.78 (m, 1H), 2.80-3.05 (m, 1H), 2.89 (t, J = 8 Hz, 2H), 3.85-4.20 (m, 2H), 5.45 (dd, J = 12 and 8 Hz, 1H), 7.22 (d, J = 8 Hz, 2H), 7.20-7.38 (m, 2H), 7.40 (s, 1H), 7.67 (dd, J = 6 and 2 Hz, 1H), 7.76 (d, J = 8 Hz, 2H), 7.97 (dd, J = 6 and 2 Hz, 1H); 13 C NMR (CDCl 3 , 50 MHz) δ 20. 7, 21.5, 23.1, 23.3, 30.3, 39.9, 68.5, 113.6, 119.0, 119.7, 123.2, 123.5, 124.7, 126.7, 129.8, 130.6, 135.0, 135.2, 144.8, 169.1, 169.8, 170.5; ESIMS (m/z) 491 [M + Na] + ; HRMS (ESI) calcd for C 24 H 24 N 2 O 6 SNa 491.1247, found 491.1238; IR (CHCl 3 ) ν max 1743, 1685 cm −1 .…”