16-epi-Panarine, a New Betaine-Type Alkaloid from Stemmadenia minima

General Approach for the Synthesis of Sarpagine Indole Alkaloids. Enantiospecific Total Synthesis of (+)-Vellosimine, (+)-Normacusine B, (−)-Alkaloid Q3, (−)-Panarine, (+)-Na-Methylvellosimine, and (+)-Na-Methyl-16-epipericyclivine

“…Oxidation of the aldehyde 1 at C-17 to provide the ester 39 was accomplished in 85% yield by using I 2 and KOH in MeOH. , The optical rotation of synthetic 39 [[α] D +4.6 ( c 1.00, MeOH)] was in agreement with that of Büchi and not of Quaisuddin. , Subsequent quaternization of the N b -nitrogen moiety in 39 with MeI provided the N b -methiodide salt 40 which was, upon exposure to AgCl, converted into the chloride 4 in 85% yield. The 1 H NMR spectrum and optical rotation of 4 were in good agreement with that of the reported values . Hydrolysis of the ester function of 4 with 0.1 N NaOH followed by neutralization with 0.1 HCl afforded panarine ( 5 ) in 90% yield.…”

“…The excess AgCl and formed AgI were removed by filtration and washed with MeOH (3×10 mL). After removal of the solvent under reduced pressure, the crude product was purified by chromatography on silica gel (CHCl 3 /MeOH = 9:1) to afford alkaloid Q 3 ( 4 ) (29 mg, 85%): [α] D = −21.3 ( c 0.15, MeOH) [lit . [α] D = −23 ( c 0.15, MeOH)]; FTIR (NaCl) 3040, 1594 cm -1 ; 1 H NMR (300 MHz, CD 3 OD) δ 1.68 (3H, ddd, J = 8.3, 2.3, 2.2 Hz), 2.26 (1H, dd, J = 13.3, 3.2 Hz), 2.58 (1H, ddd, J = 12.1, 10.3, 1.7 Hz), 3.03 (1H, dd, J = 7.7, 1.8 Hz), 3.08 (1H, br d, J = 17.5 Hz), 3.17 (3H, s), 3.33 (1H, m), 3.41 (1H, dd, J = 17.4, 4.9 Hz), 3.60 (1H, m), 3.76 (3H, s), 4.30 (1H, d, J = 15.5 Hz), 4.45 (1H, m), 4.56 (1H, dt, J = 15.5, 2.4 Hz), 4.98 (1H, d, J = 10.2 Hz), 5.58 (1H, q, J = 6.8 Hz), 7.1 (1H, ddd, J = 8.0, 7.1, 1.1 Hz), 7.2 (1H, ddd, J = 8.2, 7.1, 1.2 Hz), 7.40 (1H, dt, J = 8.1, 0.8 Hz), 7.52 (1H, dt, J = 7.8, 0.9 Hz); 13 C NMR (75.5 MHz, CD 3 OD) δ 11.43, 23.41, 27.20, 30.95, 46.83, 47.17, 51.57, 60.39, 62.51, 64.24, 100.02, 111.17, 117.93, 119.53, 120.79, 122.46, 125.87, 126.59, 130.52, 137.38, 170.52; EIMS ( m / e , relative intensity) 336 (M + , 14), 322 (100), 307 (37), 291 (11), 263 (44), 225 (20), 168 (71).…”

“…Alkaloid Q 3 ( 4 ) (37 mg, 0.1 mmol) was treated with 0.1 N NaOH (1 mL) in MeOH (4 mL) at rt for 6 h. The solution that resulted was brought with 0.1 N HCl to pH 7. The solvent was removed, and the crude product was purified by chromatography on silica gel (CHCl 3 /MeOH = 6:1) to afford panarine ( 5 ) (29 mg, 90%): [α] D = −24.0 ( c 0.10, MeOH) [lit . [α] D = −28 ± 10 ( c 0.05, MeOH)]; IR (KBr) 1738 cm -1 ; 1 H NMR (300 MHz, CD 3 OD) δ 1.53 (3 H, d, J = 6.7 Hz), 2.07 (1 H, dd, J = 13.2, 3.8 Hz), 2.43 (1 H, t, J = 12.3 Hz), 2.51 (1 H, d, J = 7.6 Hz), 2.88 (1 H, d, J = 17.3 Hz), 3.03 (1 H, s), 3.24 (1 H, dd, J = 17.3, 5.0 Hz), 3.36 (1 H, bs), 4.11 (1 H, d, J = 15.4 Hz), 4.16 (1 H, t, J = 6.4 Hz), 4.28 (1 H, d, J = 15.4 Hz), 4.80 (1 H, d, J = 5.0 Hz), 5.47 (1 H, q, J = 6.7 Hz), 7.11 (1 H, t, J = 7.3 Hz), 7.22 (1 H, t, J = 7.1 Hz), 7.43 (1 H, d, J = 8.1 Hz), 7.51 (1 H, d, J = 7.9 Hz).…”

“…Its structure has been established unequivocally by 1 H and 13 C NMR spectra and X-ray crystallographic analysis . Another related quaternary alkaloid 16-epipanarine ( 6 ) was isolated from Stemmadenia minima in 1991 by Achenbach et al To directly compare an authentic sample of 6 with 5 and establish the correct configuration of 6 , chemical correlations were carried out. The three steps included esterification with thionyl chloride in methanol to provide 7 , epimerization on treatment of 7 with potassium tert -butyl alcoholate to obtain 4 , and alkaline hydrolysis to afford 5 as the only product.…”

Indole alkaloids from the Marquesan plant Rauvolfia nukuhivensis and their effects on ion channels

“…Consequently, 10 was named 10-methoxypanarine. Due to the conservation of the configuration at C-16, these three sarpagine derivatives should be biosynthetically related (Scheme 1) (Achenbach et al, 1991). A third family of indole alkaloids was isolated from this plant.…”