Synthesis of (2R,4S,5S)-epiallomuscarine, (2S,3R,5S)-isoepiallomuscarine, and (2S,3S,4S,5S)-3-hydroxyepiallomuscarine from .alpha.-D-glucose

Abstract

2fi,4S,5S)-Epiallomuscarine iodide (4) and two new muscarine analogues (5 and 6) have been synthesized from -D-glucose. Fur an ose 10, obtained in 64% overall yield from -D-glucose, was reduced by lithium aluminum hydride to afford a 3:2 mixture of alcohols (11a and lib). Acetylation of 11a gave acetate 13. Hydrolysis of 13 was followed by oxidation to carboxylic acid 14, which upon treatment with oxalyl chloride and subsequent treatment with dimethylamine afforded dimethylamide 15. Reduction of 15 with lithium aluminum hydride

Total synthesis of racemic triptolide and triptonide

“…of lactones 9. An analytical sample was prepared by recrystal- 1.5-2.8 (9 H, m), 2.S-3.6 (3 H, m), 3.70 (3 H, s), 4.0-4.4 (2 H, m), 6.97 (1 H, d, J = 10 Hz), 7.18 (1 H, d, J = 10 Hz); UV (ethanol) 267 nm (t 475); MS m/e 344 (M+). Anal.…”

“…The ether layer was dried (MgS04) and concentrated to give 6.27 g (83%) of 11 as a pale yellow oil that was sufficiently pure for further use. An analytical sample (colorless oil) was prepared by chromatography on silica gel (ethyl acetate): IR (CHC13) 2733, 1716,1630 cm"1; NMR (CDC13) 1.24 (6 H, d, J = 7 Hz), 1.47 (3 H, s), 1.5-3.5 (18 H, m), 3.72 (3 H, s), 6.S-7.4 (2 H, m), 9.73 (1 H, s); MS m/e 387 (M+). Anal.…”

“…The combined organic layers were concentrated under reduced pressure to give 330 mg (98%) of epoxides 18 as white, crystalline material. The major isomer, assigned the -epoxide structure, was isolated by recrystallization from 1% ether/ethanol: mp 188-190 °C; IR (KBr) 1780 cm"1; NMR (CDClg, 250 MHz) 1.22 (6 H, d, =7 = 7 Hz), 1.34 (3 H, s), 3.73 (3 H, s), 4.35 (1 H, d, =7 = 10.3 Hz), 4.39 (1 H, d, =7 = 10.3 Hz), 6.98 (1 H, d, =7 = 8.5 Hz), 7.11 (1 H, d, =7 = 8.5 Hz); 13C NMR (CHClg) 17.7, 21.1, 23.0, 23.9, 26.2, 28.5, 28.7, 36.7, 37.0, 60.6, 66.3, 66.9, 69.2, 120.8, 124.7, 127.6, 139.4, 142.9, 155.2, 176.0; high-resolution mass spectrum, caled for C2iH2604 m/e 342.18160, found 342.18160.…”

“…The resulting slurry was stirred for 1 h at 20-25 °C and extracted with three 50 mL portions of ether. The combined ether extracts were worked up in the usual manner, and purification by preparative TLC (silica gel) gave 19 (95 mg, 92%) as pale yellow crystals that were recrystallized from ethanol: mp 148-150 °C; IR (KBr) 1750,1660 cm"1; UV (ethanol) XmM 268 (e 12000), 205 (18000); NMR (CDClg, 250 MHz) 1.19 (3 H, s), 1.21 (3 H, d, =7 = 7 Hz), 1.27 (3 H, d, =7 = 7 Hz), 3.77 (3 H, s), 4.97 (2 H, m), 6.18 (1 H, dd, =7 = 5.7, 2.0 Hz), transand cis-3b,4,5,9b,10,1 l-Hexahydro-6-methoxy-9bmethyl-7-( l-methylethyl)phenanthro[ 1,2-c Jfuran-1 (3Jf)-one (16,17). Diene 19 (420 mg, 1.36 mmol) in anydrous ethyl acetate (20 mL) was reduced in a Parr hydrogenation apparatus with Pd/C (10%, 420 mg) and 50 psi of H2 over a period of 1.5 h. The reaction mixture was suction filtered through a short solumn of Celite.…”

“…Benzylic ketone isomer with cis A/B ring fusion was isolated (4%) from oxidation of the minor amount of 17 present as an impurity: mp 172.5-173.5 °C; IR (CHClg) 1755, 1679 cm"1; NMR (CDClg) 1.22 (6 H, d, =7 = 6 Hz), 1.48 (3 H, s), 1.6-3.1 (7 H, m), 3.30 (1 H, septet, «7 = 7 Hz), 3.74 (3 H, s), 4.77 (2 H, m), 7.19 (1 H, d, =7 = 8 Hz), 7.50 (1 H, d, «7 = 8 Hz); high-resolution mass spectrum, caled for C21H2404 m/e 340.1675, found 340.1669. trans-3,3b*4,9b, 10, ll-Hexahydro-6-hydroxy-9b-methyl-7-(l-methylethyl)phenanthro[ 1,2-c ]furan-l,5-dione (22). To a solution of 20 (99.7 mg, 2.93 mmol) in 5 mL of CH2C12 at 0 °C under nitrogen was added boron tribromide (238 mg, 90 /¿L).…”