Steroids: reactions and partial synthesis

Bufadienolides of plant and animal origin

“…Other relevant steroid reactions were covered in the series 'Steroids: Reactions and Partial Synthesis' in this journal. 151 The main difficulty encountered in the synthesis of bufadienolides, as discussed by Sondheimer 152 in 1965, was building both an -pyrone ring and a labile 14 -hydroxy (or epoxide) on the D-ring while keeping thermodynamically unstable configurations. Thirty years later, this problem has still not been solved satisfactorily.…”

Synthesis of Enantiopure Estrone via a Double Heck Reaction

“…Purification by column chromatography afforded 95 mg of 28 (94%) as colorless solid: Rf 0.28 (petroleum ether/CH2Cl2 ) 3:1); mp 60.9 °C (MeOH); [R] -37.8 (c ) 0.5, CHCl3); UV (CH3CN) λmax (log ) 200.5 (4.585), 272.5 (3.685); IR (KBr): 2972, 2870, 1608; 1 H NMR (500 MHz, CDCl3) δ 0.87 (s, 3 H), 1.11 (s, 9 H), 1.41 (ddd, J ) 23.6, 10.7, 5.7 Hz, 1 H), 1.46-1.54 (m, 2 H), 1.62 (dddd, J ) 8.6, 8.6, 5.7, 2.0 Hz, 1 H), 1.70 (dddd, J ) 8. 8,8.6,4.4,4.3 Hz,1 H),1.81 (tdd,J ) 13.4,4.8,4.6 Hz, 1 H), 1.93 (dddd, J ) 13.5, 9.4, 9.4, 6.2 Hz, 1 H), 2.34 (mc, 1 H), 2.53 (ddd, J ) 16.0, 4.4, 4.3 Hz, 1 H), 2.75 (ddd, J ) 16.0, 11.7, 4.3 Hz, 1 H), 3.47 (mc, 1 H), 3.47 (dd, J ) 7.4, 7.1 Hz, 1 H), 3.77 (s, 3 H), 5.94 (dd, J ) 9.9, 3.7 Hz, 1 H), 5.98 (dd, J ) 9.9, 0.9 Hz, 1 H), 6.61 (d, J ) 2.8 Hz, 1 H), 6.74 (dd, J ) 8.6, 2.8 Hz, 1 H), 7.22 (d, J ) 8.6 Hz, 1 H); 13 C NMR (75 MHz, CDCl3) δ 14. 94, 22.91, 25.29, 26.20, 28.71, 31.48, 31.86, 38.67, 42.30, 44.53, 55.15, 72.30, 76.76, 112.1, 113.3, 128.6, 129.0, 131.5, 135.4, 138.6 (+)-17β-tert-Butoxy-3-methoxyestra-1,3,5(10)-triene (29a).…”

“…However, the number of total syntheses of steroids is rather limited compared to the nearly numberless publications which deal with the partial synthesis of steroids and selective functionalizations of mostly every position of the steroidal tetracycle. 8 In recent years, palladium-catalyzed bond forming processes have evolved as very powerful tools for constructing complex natural compounds. 9 The syntheses of morphine, calcitriol, CC-1065, paclitaxel, camptothecin, and cephalotaxine employing the Heck reaction demonstrate their broad potential.…”

“…They all allow the construction of the steroidal skeleton in one step. However, the number of total syntheses of steroids is rather limited compared to the nearly numberless publications which deal with the partial synthesis of steroids and selective functionalizations of mostly every position of the steroidal tetracycle …”

Asymmetric total synthesis of (+)-equilenin utilizing two types of cascade ring expansion reactions of small ring systems

“…However, the number of total syntheses of steroids is rather limited compared to the volume of literature dealing with the partial synthesis of steroids and selective functionalizations of the steroidal tetracycles. 8 Here we describe a novel strategy for the enantioselective synthesis of the steroid (ϩ)-equilenin 1, using two types of cascade ring expansion reactions of small ring systems. 9 The first ring expansion reaction is the asymmetric epoxidation-ring expansion reaction, which involves the asymmetric epoxidation of an aryl-substituted cyclopropylidene derivative to form the chiral oxaspiropentane, followed by its enantiospecific rearrangement to the chiral cyclobutanone (Scheme 1).…”