Chemie und Stereochemie der Iridoide, XVI. EPC‐Synthese von (−)‐Hypnophilin

Abstract

Chemistry and Stereochemistry of Iridoids, XVfi). -EPC-Synthesis of ( -)-HypnophilinThe synthesis of enantiomerically pure ( -)-hypnophilin (27) from (6R,?R)-( -)-?-hydroxy-3-oxabicyclo[4.3.0]non-1-en-9-one (1) is described. 1 was obtained in 93% yield from catalpol, which is readily available from the aqueous sodium carbonate extract of Picrorhiza kurrooa (Scrophulariaceae). The specific rotation, MS, 'H-and I3C-NMR data of synthetic ( -)-hypnophilin were identical with those of the natural product.Ausgewertet "'nach AMX, "nach ABX. Liebigs Ann. Chem. 1991, 893-902 OVCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1991 0170-2041/91/0909-0893 $ 3.50+ .25/0 I 2 3 R = Bz 24R= H 25 26 27 Liebigs Ann. Chem. 1991, 893 -902 Chemie und Stereochemie der Iridoide, XVI

Stereoselective Hydrogenation and Ozonolysis of Iridoids. Conversion into Carbocyclic Nucleoside Analogues

“…The residue was purified as described for 23 to give acetonide 24 (135 mg, 90%): mp 187-188 °C (from MeOH-EtOH-hexanes), [R] 20 D -98°(c 0.8, MeOH); 1 H NMR (methanol-d4, 500 MHz) δ 5.13 (1H, br s, H-1), 4.00 (1H, dt, Ja,b ) J3a,4b ) 11. 5 Hz and J3a,4a ) 2. 5 Hz, H-3a), 3.91 (1H, br d, J ) 5.…”

“…Hz, H-10a), 4.17 (1H, br d, Ja,b ) 14 Hz, H-10b), 3.71 (3H, s, 11-MeO), 3.18 (1H, q-like, J ) 8. 5 Hz, H-1′), 3.73 (1H, obsc., H-6a′), 3.49 (1H, dd, Ja,b ) 10.5 Hz, J5′,6b′ ) 6.5 Hz, H-6b′), 3.37 (1H, t, J2′,3′ ) J3′,4′ ) 9.5 Hz, H-3′), 3.36 (1H, obsc., H-5′), 3.26 (1H, t, J3′,4′ ) J4′,5′ ) 9.5 Hz, H-4′), 3.25 (1H, br t, J ) 9 Hz, H-2′), 1.31, 1.30 (each 3H, s, 4′,6′-Me2C); 13 Alternate Preparation of Geniposide Acetonides 14 and 16. Geniposide (9, 12.0 g) and PPTS (1.5 g) in dry Me2-CO-DMP (1:1, 300 mL) was kept for 14 h at room temperature followed by 1.5 h at 50 °C, when more DMP (50 mL) and PPTS (1.0 g) were added.…”

“…Elution with hexane-Me2CO (2:1 to 1:1.3) gave first a 1:1.5 mixture of acetonides 23/24 (121 mg, 24%); then came pure 23 (311 mg, 62%): mp 157-158 °C (from Me2-CO-hexanes), [R] 20 D -120°(c 0.9, MeOH); 1 H NMR (methanol-d4, 500 MHz) δ 5.15 (1H, d, J1,9 ) 4 Hz, H-1), 4.04 (1H, br dd, J ) 9, 4 Hz, H-6), 3.97 (1H, ddd, J ) 12, 8.5, 3.5 Hz, H-3a), 3.75 (1H, dd, Ja,b ) 11 Hz, J8,10a ) 7 Hz, H-10a), 3.53 (1H, obsc., H-10b), 3.50 (1H, obsc., H-3b), 2.47 (1H, br sextet, J ) 8 Hz, H-8), 2.30 (1H, m, H-9), 2.27 (1H, m, H-5), 1.85 (1H, br d, J ) 9 Hz, H-7a), 1.84 (1H, dd, J ) 9, 1.5 Hz, H-7b), 1.62 (1H, m, H-4a), 1.37 (1H, m, H-4b), 4.67 (1H, d, J 1′,2′ ) 8 Hz, H-1′), 3.88 (1H, dd, Ja′,b′ ) 10.5 Hz, J5′,6a′ ) 5. 5 Hz, H-6a′), 3.76 (1H, t, J ) 10. 5 Hz, H-6b′), 3.54-3.46 (2H, m, H-3′ and H-4′), 3.28 (1H, dd, J2′,3′ ) 9 Hz, J1′,2′ ) 8 Hz, H-2′), 3.25 (1H, m, H-5′), 1.51, 1.38 (each 3H, s, 4′,6′-Me2C); 13 Hydrogenation of Acetonide 20 with Pd/C as Catalyst.…”

“…5 Hz, H-6a′), 3.76 (1H, t, J ) 10. 5 Hz, H-6b′), 3.54-3.46 (2H, m, H-3′ and H-4′), 3.28 (1H, dd, J2′,3′ ) 9 Hz, J1′,2′ ) 8 Hz, H-2′), 3.25 (1H, m, H-5′), 1.51, 1.38 (each 3H, s, 4′,6′-Me2C); 13 Hydrogenation of Acetonide 20 with Pd/C as Catalyst. Acetonide 20 (100 mg) in MeOH (5 mL) and Et3N (0.14 mL) was hydrogenated (as described below for 24) for 24 h in the presence of 5% Pd/C (15 mg).…”

“…The iridoids aucubin ( 19 ), catalpol, and asperuloside have previously been used synthetically as precursors of cyclopentanoids such as prostaglandins, − methyl jasmonate, and triquinanes . Also, the aglucone of geniposide ( 9 ), genipin, has been the starting material in semisyntheses of diterpenes from marine algae. − In addition, iridoid aglucones have been converted into pyridine monoterpene alkaloids and monoterpene piperidines .…”