Total synthesis of (±)-prostaglandin E₂methyl ester from exo-2-bromo-endo-3-hydroxybicyclo[3.2.0]heptan-6-one using dimethyl-t-butylsilyl protected intermediates

Abstract

Peracetic acid oxidation a t -78 "C of the dihydroxybicyclo[3.2.0] heptan-6-one (23) afforded the dihydroxylactone (24) which was protected as its bisdimethyl-t-butylsilyl ether (26) and reduced to the corresponding lactol (27). A Wittig reaction on ( 27), carried out in benzene with a short reaction time, gave mainly the required 11 ccsilyl ether (28) together with a trace of the 9a-silyl ether (29) which results from 1,5-migration of the silyl group.Oxidation of (28) followed by quantitative deprotection using aqueous H F in acetonitrile afforded (f) methyl ester (20). This short stereo-and regio-selective total synthesis proceeds in an overall yield of 10% starting from cyclopentadiene.

Facile stereoselective reductions of enediones and cage diketones suing sodium borohydride-cerium(III) chloride

“…The two products were separated by chromatography on silica gel. The NMR of the faster moving product was identical with 8, while the NMR of the less mobile product indicated demethylation at the 6 position: NMR (CDC13)7 3.83 (3 H, s, 3-OCHa), 2.38 (3 H, s, N-CH3), 4.35 (1 H, s, 5a proton), 5.40 and 5.70 (2 H, ABq, J = 10 Hz, vinylic protons).…”

“…addition of 25 mL of diethyl ether, a white precipitate formed. The powdery solid was filtered, washed with ether, and air dried to yield 3.63 g (877c): mp 178-183 °C; NMR (CDC13)7 5 3.82 (3 H, s, 3-OCHg), 3.50-3.55 (3 H, m, 6-OCH3), 2.43 (3 H, s, N-CHS), 4.66 (1 H, s, 5a proton), 5.42 to 5.95 (2 H, m, vinylic protons).…”

“…The salt was recrystallized from methanol/ether: mp 208-214 °C; TLC (2-propyl alcohol/concentrated NH4OH, 10:1), one product, R¡ 0.42; NMR (D20)7 3.82 (3 H, s, 3-OCHs), 3.56 (3 H, s. 6-OCH,). 2.39 (3 H, s, N-CH3); NMR (CDC13) free base, 4.84 (1 H, s, 5a proton), 5.60 and 5.74 (2 H, ABq, J = 8 Hz, vinylic protons). Anal.…”

“…Caled for C29H34N205: C, 70.99; H, 6.99; N. 5.71. Found: C. 70.80; H, 6.88; N, 5.51. 6-Desmethyl-7a-(aminomethyl)-6,14-endo-ethenotetrahydrothebaine (5). A solution of 3 (500 mg, 1.31 mmol) in THF (6 mL, distilled from LAH) and CC14 (0.5 mL, 5.2 mmol) was added dropwise to a mixture of LAH (740 mg, 19.5 mmol) in THF (6 mL).…”

“…The solvent was removed under reduced pressure to yield 384 mg of a light brown solid (727c); NMR (CDC13) 2.35 (3 H, s, N-CH;,). 4.33 (1 H, s, 5a proton), 5.33 and 5.72 (2 H, ABq, J = 9 Hz, vinylic protons).…”