将沙蟾毒精(83 mg, 0.2 mmol)、酸(0.3 mmol)、DMAP(24.4 mg, 0.2 mmol)和5 ml干燥的二氯甲烷加入到25 ml烧瓶中,氩气保护下逐份加入EDCI(115 mg, 0.6 mmol)。室温反应过夜,反应完全后蒸去溶剂,残余物经柱色谱纯化后得目标产物2a−2j (洗脱剂为二氯甲烷∶甲醇=100∶1)。
2a: 白色固体,收率13.9%。1H NMR (500 MHz, CDCl3) δ: 7.68 (d, 1H), 7.36 (s, 1H), 6.28 (d,1H), 5.43 (s,1H), 5.18 (d,1H), 4.14 (d, 1H), 4.05 (d, 2H), 3.91 (q, 1H), 2.15 (d, 2H), 2.02~2.11 (m, 1H), 1.86 (m, 9H), 1.40 (s, 4H), 1.26 (d, 2H), 1.14 (s, 3H), 0.97 (s, 3H)。
2b: 白色固体,收率为55.5%。1H NMR: (CDCl3, 500 MHz) δ: 7.76 (d, 1H), 7.41 (s, 1H), 6.27 (d, 1H), 5.30 (s, 1H), 4.33 (d,1H), 4.11 (d,1H), 3.84 (s, 1H), 2.43 (d, 1H), 2.30 (t, 2H), 2.05~2.09 (m, 2H), 1.86~1.94 (m, 2H), 1.75~1.80 (m, 5H), 1.63~1.73 (m, 4H), 1.45 (d,1H), 1.33~1.44 (m,15H), 1.27 (s, 3H), 0.86~0.88 (m, 3H)。
2c: 白色固体,收率15.2%。1H NMR (500 MHz, CDCl3) δ: 7.74 (d, 1H), 7.40 (d, 1H), 6.30 (d, 1H), 5.08 (s, 1H), 4.35 (d, 1H), 4.11 (m, 1H), 3.84 (d, 1H), 2.45 (d, 1H), 2.08 (s, 3H), 1.65~1.92 (m, 11H), 1.46~1.53 (m, 1H), 1.26~1.42 (m, 5H), 1.21 (s, 3H), 0.92 (s, 3H)。
2d: 白色固体,收率46.7%。1H NMR: (CDCl3, 500MHz) δ: 8.85 (s, 1H), 8.40 (m, 2H), 7.62~7.77 (m, 2H), 7.41 (s, 1H), 6.29 (d, 1H), 5.38 (s, 1H), 4.36 (m, 1H), 4.13 (d, 1H), 3.86 (d, 1H), 2.56 (d, 1H), 1.72~2.24 (m, 11 H), 1.32~1.51 (m, 6H), 1.23(s, 3 H), 0.94 (s, 3H)。
2e: 白色固体,收率43.5%。1H NMR (500 MHz, CDCl3) δ: 7.66~7.74 (m, 1H), 7.37 (d, 1H), 7.08~7.20 (m, 3H), 6.27 (t,1H), 5.30 (s, 1H), 4.36~4.26 (m, 1H), 4.00~4.15 (m, 2H), 3.81 (m, 1H), 3.56 (d, 1H), 2.27~2.41 (m, 3H), 2.04 (m, 2H), 1.80~1.86 (m, 3H), 1.70~1.79 (m, 4H), 1.64 (s, 3H), 1.26~1.42 (m, 6H), 1.18 (s, 1H), 1.13 (s, 1H), 1.01 (d, 1H), 0.91 (d, 3H)。
2f: 白色固体,收率50.3%。1H NMR (500 MHz, CDCl3) δ: 7.94 (d, 1H), 7.72 (d, 1H), 7.53 (d, 1H), 7.40 (s, 1H), 7.32 (d, 1H), 6.29 (d, 1H), 5.36 (s, 1H), 5.30 (s, 1H), 4.35 (t, 1H), 4.06~4.16 (m, 1H), 3.85 (d, 1H), 2.51 (d, 1H), 1.97~2.13 (m, 3H), 1.74~1.89 (m, 8H), 1.45~1.54 (m, 1H), 1.31~1.45 (m, 3H), 1.25 (s, 1H), 1.21 (s, 3H), 0.93 (s, 3H)。
2g: 白色固体,收率42.6%。1H NMR (500 MHz, CDCl3) δ: 10.11 (s, 1H), 8.20 (d, 2H), 7.97 (d, 2H), 7.72 (d, 1H), 7.40 (s, 1H), 6.29 (d, 1H), 5.37 (s, 1H), 5.30 (s, 1H), 4.36 (m, 1H), 4.12 (t, 1H), 3.81~3.93 (m, 1H), 2.55 (d, 1H), 2.08 (t, 2H), 1.84~2.00 (m, 4H), 1.76~1.84 (m, 5H), 1.61 (s, 3H), 1.38 (d, 3H), 1.25 (s, 3H), 0.93 (s, 3H)。
2h: 白色固体,收率12.5%。1H NMR: (CDCl3, 500MHz) δ: 7.73 (m, 1H), 7.40 (s, 1H), 6.27 (d, 1H), 5.23 (s, 1H), 4.35(q, 2H), 4.36~4.40 (m, 1H), 4.04~4.14 (m, 1H), 2.46 (d, 1H), 1.69~2.26(m, 10H), 1.57 (d, 1H), 1.22~1.50 (m, 8H), 1.20 (s, 3H), 0.91 (s, 3H)。
2i: 白色固体,收率52.3%。1H NMR (500 MHz, CDCl3) δ: 7.74 (m, 1H), 7.61 (d, 1H), 7.42 (s, 1H), 6.79 (s, 2H), 6.38 (d, 1H), 6.32 (d, 1H), 5.32 (s, 1H), 5.23 (s, 1H), 4.37 (m, 1H), 4.08~4.19 (m, 1H), (3.92 (d, 9H), δ3.87 (d, 1H), 2.51 (d, 1H), 1.84 (m,, 10H), 1.40 (t, 3H), 1.28 (s, 3H), 1.25 (s, 3H), 0.95 (s, 3H)。
2j: 白色固体,收率39.2%。1H NMR (500 MHz, CDCl3) δ: 7.84 (d, 1H), 7.74 (m, 1H), 7.50 (t, 1H), 7.42 (s, 1H), 7.02 (t, 2H), 6.32 (d, 1H), 5.35 (s, 1H), 4.37 (m, 1H), 4.18~4.09 (m, 1H), 3.92 (d, 3H), 3.87 (d, 1H), 2.52 (d,, 1H), 2.09 (d, 1H), 1.78~2.00 (m, 7H), 1.59 (s, 3H), 1.28~1.46 (m, 6H), 1.25 (s, 3H), 0.96 (s, 3H)。