Total synthesis of 12-fluoroprostaglandin F2? methyl ester

C-12 substituted prostaglandins: synthesis and biological evaluation of (.+-.)-12-hydroxyprostaglandin F2.alpha. methyl ester

“…Removal of the solvent under reduced pressure gave 1.08 g of an oil which was purified by column chromatography using 40 g of silica gel. Elution 4.95 (m, 1 H, -CHOCO), 4.01-3.70 (m, 3 H, -CH20, -CHOH), 2.87-2.65 (m, 3 ), 2.30-2.01 (m, 3 ), 1.45 (s, 6 H); mass spectrum m/e (rel intensity) 213 (100, M+ -Me), 172 (11), 153 (15), 142 (12), 98 (17), 59 (10). Anal.…”

“…The product was purified on 40 g of silica gel. Elution with hexaneethyl acetate (1:5) provided 525 mg (77%) of pure alcohol 24 as a clear oil: IR (CHCI3) 3600, 3500, 3030, 3010, 2990, 2940, 2875,1770,1460, 1421,1415,1390,1380,1370,1355,1334,1301,1240,1198,1170,1148, 1120,1090,1040,1020,996, 970,960,900 cm-1; NMR (CDC13) 5.02 (t, 1 H, J = 5 Hz, -CHOCO), 4.67 (d, 1 H, J = 5 Hz, -CHO-C), 3.66 (s, 2 H, -CH2OH), 3.10 (s broad, 1 H, OH), 3.00-2.00 (m, 5 ), 1.45 (s, 3 ), 1.40 (s, 3 H); mass spectrum m/e (rel intensity) 213 (100, M+ -Me), 197 (6), 171 (5), 135 (4), 107 (3), 59 (3), 58 (10), 43 (10). Anal.…”

“…In a second series of experiments the higher melting hydroxy ester 8 was methylated (94%) [sodium hydride, tetrahydrofuran, methyl iodide, room temperature, 21 h] giving rise to methyl ether 14. Hydrolysis [acetic acid-water (1:1), 95 °C, 3 h] of the ketal function provided (90%) keto ester 15 [IR (CHC13) 1760,1735 cm"1; NMR (CDC13) 4.08 (q, 1 H, J = 5 Hz, 8 Hz, -CHBr), 3.81 (s, 3 H, -COOCH3), 3.40 (s, 3 Ci;SO ; I), DEL , EhCH^, reflux, ? (' hr; v, i.OM HC1, TH F, 15 hr;…”

“…The crude product was purified on 40 g of neutral silica gel (SilicAR CC-7). Elution with hexane-ether (1:1) gave 680 mg (86%) of pure silyl ether 30 as a colorless solid: IR 974, 954, 940, 895, 876, 838 cm"1; NMR (CC14) 5.72 (m, 2 ), 4.80 (t, broad, 1 H, J = 5 Hz), 4.44 (d, broad), 1 H, J = 6 Hz), 4.15 (m, 1 H), 1.41 (s, 3 ), 1.24 (s, 3 ), 0.90 (s, 9 ), 0.00 (s, 6 H).…”

“…We have been involved in the synthesis and biological evaluation of C-12 substituted derivatives of natural PGF2a in order to investigate the effect on luteolytic activity. Our early work centered on the preparation of (±)-12-methyl-PGF2a (2).3 More recently we have described the synthesis of (±)-12-fluoro-PGF2n methyl ester (3)4 and (±)-12-hydroxymethyl-PGF2(, methyl ester (4). 5 We detail below the synthesis of (±)-12-hydroxy-PGF2n methyl ester (5) and present the preliminary biological data.…”