New pathways towards bufadienolides. Synthesis of 5β,14α-bufa-20,22-dienolide from cholanic acid

Mass spectrometry in structural and stereochemical problems. CCXXX. Preparation of 5.alpha.,20.alpha. and 5.alpha.,17.alpha.,20.alpha.-cholestane-3.beta.,6.alpha.-diol. Electron impact induced fragmentation of steroidal .DELTA.17(20), .DELTA.20(21) and .DELTA.20(22) olefins

“…The required starting ketone 5a-pregnane-3d,6adiol-20-one diacetate18 wras prepared by hydroboration of A5-pregnenolone acetate 20-ethylene ketal,19 followed by reacetylation of the hydroxyl functions and acidcatalyzed cleavage of the ketal. Treatment of this ketone or of A6-pregnenolone acetate with the Grignard complex of l-bromo-4-methylpentane or 1-bromo-4-methyl-3-pentene (prepared by reaction of hydrobromic acid with cyclopropyldimethylcarbinol20) according to the general procedure of Petrow* and Stuart-Webb21 furnished the desired 20-hydroxy steroids (12)(13)(14)(15). The expected 20a stereochemistry of the resulting carbinols w*as confirmed by nmr spectroscopy.…”

“…cm"1 (C=0); CD (MeOH) 029" -2367; nmr 0.66, 0.84 (C-18,-C-19 CHa), 0.86 (d, J = 6.0 Hz, C-26,C-27 CHS) 2.00 (s, 6 H, 2 OOCCHs), 4.60 (c, 2 H, CHOAc); 502. 5a (retention time 18 min): oil (80%); ir Xmax (CHCla) 1720 cm"1; CD (MeOH) 629" +1732; nmr S 0.66, 0.84 (0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)CHs), 0.86 (d, J = 6.0 Hz, C-26,C-27 CHa), 2.00 (s, 6 (CHClg) 1700 cm-1; CD (MeOH) 028g -2042; nmr 0.66, 0.84 (s, C-18, C-19 CH,), 0.87 (d, J = 6 Hz, C-26, C-27 CH,), 3.58 (c, 2 H, CHOH); M+ 418.34228 (caled for C27H4e03, 418.34467); mass spectrum m/e (rel intensity) 400 (7, M+ -H20), 361 (6%, M+ -C4Hg), 318 [100, M+ -CH2=C(0H)C4Hg], 303 (32, 318 -CH,), 300 (318 -, ), 289 (16, M+ -side chain + 2 H), 285 (21, 303 -H20), 231 (7, ring D cleavage + H20 + 1 H), 213 (11, 231 -, ), 161 (14), 141 (21), 127 (37), 122 (58), 95 (57), 85 (57), 81 (43), 57 (53), 43 (36), 41 (35).…”

“…This method has been extensively used for the synthesis of naturally occurring steroids including cholesterol,7 dihydrobrassicasterol,8 campesterol,9 ecdysone,10 and 20-hydroxyecdysones.11 More recently 20(22) steroids, obtained by dehydration of 20-hydroxy precursors, have served as intermediates in synthesis of ß-sitosterol12 and bufadienolides. 13 Whereas the preparation of 20(22) olefins by Wittig reaction generally results in poor yield,14 the 20( 21) olefinic linkage has been introduced15 by Wittig reaction of 21-nor-20-keto steroids (easily accessible from the corresponding etioallocholanic acid derivatives and organocadmium derivatives) and it, in turn, provides a facile entry16 into 21-functionalized steroids of the 20S (a) configuration.…”

“…The expected 20a stereochemistry of the resulting carbinols w*as confirmed by nmr spectroscopy. 22Dehydration of the 20-hydroxylated steroids (12)(13)(14)(15) gave varying proportions of the isomeric olefins ( 17 (20), 20(21>, 20(22)) depending on the reaction conditions (see Table I). It is important to note that our results differ from those reported for 20-hydroxycholanic acid derivatives13 (16) [SOCk/Py -80%…”