CN109320581A - 五环三萜衍生物及其制备方法、药物组合物和用途 - Google Patents
五环三萜衍生物及其制备方法、药物组合物和用途 Download PDFInfo
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Abstract
本发明提供了一种五环三萜衍生物及其制备方法、药物组合物和用途，五环三萜衍生物的结构通式为：
Description
技术领域：
本发明涉及五环三萜衍生物及其制备方法、药物组合物和用途。
背景技术：
三萜及其皂苷广泛存在于自然界、菌类、蕨类、单子叶植物、双子叶植物中，在部分动物及海洋生物钟也有分布。游离型三萜主要来源于菊科、豆科、大戟科、卫茅科、茜草科、橄榄科、唇形科等植物中。据文献报道，三萜类化合物具有溶血、抗肿瘤、抗炎、抗菌、抗病毒、降低胆固醇、抗生育等生物活性，且毒性较低。
根据不同的生物合成方式，三萜类化合物可分为链状三萜、单环三萜、双环三萜、三环三萜、四环三萜和五环三萜等结构类型。其中，五环三萜类化合物在自然界种类繁多、分布广泛，资源丰富。大量研究表明，五环三萜类化合物具有广泛的药理作用和重要的生物活性，尤其在抗炎、护肝、抗肿瘤以及机体免疫调节等方面已经显现出令人关注的药理特性。齐墩果酸(Cas:508-02-1)、熊果酸(Cas:77-52-1)、甘草次酸(Cas:508-02-1)是其中的代表化合物，其结构式分别为。
齐墩果酸是从龙胆科植物獐牙菜属的青叶胆全草或女贞子的果实中分离提取而得一种五环三萜类化合物，具有广谱抗菌活性，临床上用于护肝降酶，治疗支气管炎、肺炎、急性扁桃体炎、牙周炎、菌痢、急性肠胃炎、泌尿系统感染。此外，临床上还用于治疗急性肝炎。熊果酸是存在于唇形科植物夏枯草(Prunella vulgaris L.)的全草，冬青科冬青属铁冬青(Ilex rotunda Thunb.)的叶等许多植物中三萜类化合。研究表明，熊果酸具有抗致癌、抗促癌、诱导F9畸胎瘤细胞分化和抗血管生成作用；此外，熊果酸还对多种致癌、促癌物有抵抗作用，研究发现熊果酸能明显抑制HL-60细胞增殖，并诱导其凋亡；能使小鼠的巨噬细胞吞噬功能显着提高，能抑制人舌鳞癌细胞株TSCCa细胞增殖。甘草次酸是由甘草中提取得到的化合物，具有抗菌、抗肿瘤及肾上腺皮质激素样作用。
上述三个代表性的五环三萜化合物尽管具备了一定药理活性，但对于肿瘤细胞的抑制活性仍然偏弱，熊果酸、齐墩果酸和甘草次酸在体外肿瘤细胞增殖试验中，对大多数癌细胞的杀伤能力不足，IC50值均大于50uM。此外，现有技术中五环三萜化合物还存在制备方法复杂的问题。
发明内容
为解决前述问题，本发明提供了一种五环三萜衍生物，含有作为活性成分的五环三萜衍生物及至少一种可药用载体的治疗癌症药物组合物，以及制备新型五环三萜衍生物的方法。
为了实现本发明的上述目的，本发明提供如下的技术方案：
一种如式(I)所示的五环三萜衍生物：
式(I)中，
R3为氢或羰基；
R4为氢或甲基；
R5为氢或甲基；
R6选自氢、甲基、-C(O)-N(Ra)2或其中Ra选自氢、烷基、环烷基或-(CH2)m-NH-Rc；Rb选自氢、烷基、酰基烷基、酰基环烷基、酰基羟基、酰基氨基、酰基芳基、烯基烷基、烯基酯基、烯基氨基、烯基环烷基、烯基羟基；m为1～6；Rc选自酰基烷基、酰基芳基、磺酰基氨基芳基、酰基烷基酯基、酰基烷基酯基芳基、酰胺基芳基、酰胺基；
R7选自氢、甲基、-C(O)-N(Rd)2或其中Rd选自氢、烷基、环烷基或-(CH2)n-NH-Rf，Re选自氢、烷基、酰基烷基、酰基烯基、酰基环烷基、酰基环烷基烯基、酰基烯基烷基、酰基烯基酯基、酰基烯基羟基、酰基烯基三氟甲基；n为1～6；Rf选自酰基烷基、酰基芳基、酰基取代芳基、酰胺基芳基、酰胺基取代芳基、磺酰基氨基芳基、磺酰胺基取代芳基、酰基烷基酰胺芳基、酰基烷基炔基、酰基烯基、酰基烯基烷基、酰基烯基环烷基、酰基烯基氨基、烯基烯基芳基、酰基烯基酯基。
本发明提供的五环三萜衍生物，优选为具有式(Ia)的化合物；
R7优选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R7a，其中，R7a优选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-烷基-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，-NH-芳基，-C(O)-NH-(CH2)-NH-S(O)-NH-芳基。
本发明提供的五环三萜衍生物，还优选为具有式(Ib)的化合物；
R7优选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R7a，其中，R7a优选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-CH2-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，-NH-芳基，-C(O)-NH-(CH2)-NH-S(O)-NH-芳基；Re优选自-CH＝CH-烷基(碳原子数1～5)，-CH＝CH-环烷基(碳原子数5～8)，-CH＝CH-CH2-三氟甲基，-CH＝CH-(CH2)-二甲胺基，-CH＝CH-酯基。
本发明提供的五环三萜衍生物，还优选为具有式(Ic)的化合物；
R6优选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R6a，其中，R6a优选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-CH2-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，、-NH-芳基、-C(O)-NH-(CH2)-NH-S(O)-NH-芳基；Re优选自-CH＝CH-烷基(碳原子数1～5)，-CH＝CH-烷基羟基，-CH＝CH-环烷基(碳原子数5～8)，-CH＝CH-CH2-三氟甲基，-CH＝CH-(CH2)-二甲胺基，-CH＝CH-酯基。
本发明提供一种五环三萜衍生物优选为下表中的化合物：
不同R8对应的化合物分别为化合物U4-U26，化合物U4-U26中R8的结构式为表1所示：
表1熊果酸衍生物结构通式(U4-U26)
或者，结构式为：不同R9对应的化合物分别为化合物O2-O20，化合物O2-O20中R9的结构式为表2所示：
表2齐墩果酸衍生物结构通式(O2-O20)
或者，结构式为：不同R10对应的化合物分别为化合物G1-G19，化合物G1-G19中R10的结构式为表3所示：
表3甘草次酸衍生物结构通式(G1-G19)
本发明还提供了通式(I)所示化合物的制备方法，所述制备方法为：
化合物的制备路线如下：
化合物的制备路线如下：
化合物的制备路线如下：
本发明还提供通式(I)所示的五环三萜衍生物在制备治疗癌症药物中的应用。
本发明还提供通式(I)所示的五环三萜衍生物在在制备有益于癌症功能性食品中的应用。
本发明还提供了一种治疗癌症的药物组合物，其特征是含有作为活性成分的至少一种式(I)所述化合物和至少一种可药用的辅料。药物组合物被提供用作治疗各种癌症，包括：妇科癌类，例如：卵巢癌、子宫颈癌、阴道癌、阴部癌、子宫/子宫内膜癌、妊娠滋养细胞肿瘤、输卵管癌、子宫肉瘤；内分泌癌类，例如：肾上腺皮质癌、脑垂体癌、胰癌、甲状腺癌、副甲状腺癌、胸腺癌、多发性内分泌肿瘤；骨癌类，例如：骨肉瘤、尤因肉瘤、软骨肉瘤等；肺癌类，例如：小细胞肺癌、非小细胞肺癌；脑和CNS肿瘤，例如：神经母细胞瘤、听神经瘤、神经胶瘤和其他脑肿瘤，脊髓肿瘤、乳癌、结肠直肠癌、晚期结肠直肠腺癌；胃肠癌类，例如：肝癌、肝外胆管癌、胃肠类癌性肿瘤、胆囊癌、胃癌、食道癌、小肠癌；泌尿生殖器癌类，例如：阴茎癌、翠丸癌、前列腺癌；头和颈部肿瘤类，例如：鼻癌、鼻窦癌、鼻咽癌、口腔癌、唇癌、唾腺癌、喉头癌、下咽癌、正咽癌；血癌类，例如：急性骨髓性白血病、急性淋巴性白血病、儿童白血病、慢性淋巴性白血病、慢性骨髓性白血病、发状细胞性白血病、急性早幼粒细胞白血病、血浆细胞性白血病；骨髓癌血液病症，例如：骨髓分化不良症候群、骨髓增生性病症、范禾尼贫血、再生障碍性贫血、特发性巨球蛋白血症；淋巴癌类，例如：霍奇金病、非霍奇金氏淋巴瘤、周围T-细胞林巴瘤、皮肤型T-细胞淋巴瘤、AIDS相关性淋巴瘤；眼癌类，包括：视网膜母细胞瘤、葡萄膜黑色素瘤；皮肤癌类，例如：黑色素瘤、非黑色素瘤皮肤癌、梅克尔细胞癌；软组织肉瘤类，例如：卡波希肉瘤、儿童软组织肉瘤、成人软组织肉瘤、泌尿系统癌症，例如：肾癌维尔姆斯肿瘤、膀肤癌、尿道癌和转移性细胞癌。优选用于乳腺癌、结直肠癌、肺癌的治疗。
本发明提供了一种新型五环三萜衍生物，能够显著提高其用于癌症等疾病治疗时的效果，同时提供一种简便易行的制备新型五环三萜化合物的方法；在药理实验中我们发现，本发明提供的新型五环三萜衍生物，具有明显的体外和体内的抗癌活性。
具体实施方式
除有定义外，以下实施例中所用的技术术语具有与本发明创造所属领域技术人员普遍理解的相同含义。以下实施例中所用的试验试剂，如无特殊说明，均为常规生化试剂；所述实验方法，如无特殊说明，均为常规方法。
为了理解本发明，下面以实施例进一步说明本发明，但不意于限制本发明的保护范围。
实施例1：
化合物2的制备
0℃、氩气保护下，将熊果酸(3g，6.569mmol)溶解在N,N-二甲基甲酰胺(60ml)中，加入N,N-二异丙基乙胺(5.43ml，32.845mmol)，然后在加入HATU(5g，13.14m-mol)，10min后加入单Boc乙二胺(3.16g，19.71mmol)，1小时后，将体系移至室温搅拌过夜，1NHCl洗(200ml)，乙酸乙酯萃取(150ml×2)，再用饱和碳酸氢钠(200ml)洗有机相，干燥浓缩，柱层析纯化(石油醚：乙酸乙酯＝5:1至2:1)得化合物2(白色固体，3.9g，产率：99％)。
mp 194-196℃；[ɑ]24 D+38°(c 1.10,CHCl3)；IR(KBr):3571,3331,2929,2829,1685,1646cm-1.1H NMR(400MHz,CDCl3)δ6.33(s,1H),5.33(s,1H),4.97(s,1H),3.41(dt,J＝13.5,6.3Hz,1H),3.21(dh,J＝13.5,7.8Hz,3H),3.09(dd,J＝13.1,5.5Hz,1H),1.92(dd,J＝18.5,10.3Hz,4H),1.80(d,J＝13.1Hz,1H),1.69(d,J＝14.3Hz,2H),1.65–1.57(m,4H),1.54–1.48(m,3H),1.42(d,J＝8.1Hz,12H),1.29(t,J＝11.5Hz,3H),1.07(s,3H),0.97(s,4H),0.91(d,J＝9.1Hz,7H),0.85(d,J＝6.5Hz,4H),0.76(d,J＝5.3Hz,6H),0.70(d,J＝11.6Hz,1H).13C NMR(100MHz,CDCl3)δ179.0,156.8,139.5,125.9,79.6,79.1,55.3,53.6,47.8,47.7,42.5,40.5,39.8,39.6,39.1,38.9,38.8,37.4,37.1,32.9,31.0,28.6,28.6,28.57,28.3,28.0,27.3,27.0,24.9,23.5,23.5,21.4,18.4,17.3,17.0,15.7,15.6.HRMS(ESI)calculated for C37H62N2NaO4 +:621.4602,found 621.4606.
实施例2：
化合物3的制备
0℃下，将化合物2(4.5g，7.58mmol)溶解在二氯甲烷(70ml)中，然后加入戴斯-马丁氧化剂(6.4g，15.2mmol)，搅拌3h，反应完成后用饱和硫代硫酸钠洗(200ml)，乙酸乙酯萃取(200ml)，有机相再用饱和碳酸氢钠洗(200ml)，干燥浓缩，柱层析纯化(石油醚：乙酸乙酯＝5:1至3:1)得化合物3(白色固体，4.3g，产率：95％)。
mp 197-199℃；[ɑ]24 D+23°(c 0.78,CHCl3)；IR(KBr):3394,2965,2929,1649,1631,cm-1.
1H NMR(400MHz,CDCl3)δ6.34(s,1H),5.37(d,J＝4.1Hz,1H),4.89(s,1H),3.41(dt,J＝12.9,6.2Hz,1H),3.30–3.20(m,2H),3.14(dd,J＝11.7,6.5Hz,1H),2.54(td,J＝10.5,9.8,5.5Hz,1H),2.42–2.35(m,1H),2.01(d,J＝9.7Hz,2H),1.94(d,J＝10.9Hz,1H),1.88(dd,J＝7.5,4.2Hz,1H),1.82(d,J＝13.6Hz,1H),1.73(s,1H),1.67(s,3H),1.63–1.60(m,1H),1.43(d,J＝9.2Hz,16H),1.34–1.29(m,2H),1.25(d,J＝4.1Hz,2H),1.09(d,J＝6.1Hz,6H),1.05(d,J＝4.7Hz,6H),0.95(s,3H),0.87(d,J＝6.4Hz,3H),0.82(s,3H).13CNMR(100MHz,CDCl3)δ217.7,178.8,156.8,139.6,125.6,79.6,55.4,53.6,47.8,47.5,46.9,42.6,40.7,40.3,39.8,39.6,39.4,39.1,37.4,36.8,34.3,32.4,31.0,28.6,28.6,28.6,28.0,26.7,24.8,23.7,23.4,21.6,21.3,19.7,17.3,17.0,15.4.HRMS(ESI)calculated for C37H60N2NaO4 +:619.4445,found 619.4439.
实施例3：
化合物4的制备
将化合物3(5.36g，9mmol)溶解于N,N-二甲基甲酰胺(100ml)中，加入碳酸钾(9.3g，67.5mmol)，加入多聚甲醛(8.6g，288mmol)，油浴下升温至105℃，5h后反应完全，饱和食盐水洗(200ml×3)，乙酸乙酯萃取(150ml×2)，干燥浓缩，柱层析纯化(石油醚：乙酸乙酯＝5:1至4:1)得化合物4(白色固体，3.3g，产率：60％)。
mp 193-195℃；[ɑ]24 D+23°(c 0.28,CHCl3)；IR(KBr):3364,2975,2928,1629,1641,cm-1.
1H NMR(400MHz,CDCl3)δ6.36(s,1H),5.98(d,J＝2.8Hz,1H),5.38(d,J＝3.8Hz,1H),5.15(s,1H),4.96(s,1H),3.39(dt,J＝12.6,6.2Hz,1H),3.29–3.10(m,3H),2.65(d,J＝15.1Hz,1H),2.16(d,J＝15.2Hz,1H),2.00(ddd,J＝23.3,11.8,6.8Hz,4H),1.82–1.77(m,1H),1.67(dq,J＝20.7,8.2,7.7Hz,4H),1.43(s,18H),1.24(s,1H),1.11(d,J＝4.0Hz,6H),1.05(s,3H),0.93(d,J＝6.4Hz,6H),0.87(d,J＝6.4Hz,3H),0.82(s,3H).13C NMR(100MHz,CDCl3)δ207.4,178.8,156.9,142.0,139.6,125.6,123.8,79.6,54.2,53.7,47.9,47.1,46.0,45.4,42.7,40.7,40.3,39.8,39.5,39.1,37.4,36.8,32.3,31.0,28.6,28.6,28.6,28.5,28.0,24.8,23.7,23.4,22.9,21.3,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C38H60N2NaO4 +:631.4445,found 631.4448.
实施例4：
化合物5的制备
0℃下，将化合物4(50mg，0.082mmol)溶解于二氯甲烷(1ml)中，然后缓慢滴加三氟乙酸(1ml)，30min后反应完全，浓缩干得化合物5粗品(黄色油状液体，68mg)。
实施例5：
化合物U1的制备(方法同化合物2的制备)
mp 206-208℃；[ɑ]24 D+44°(c 1.40,CHCl3)；IR(KBr):3511,3321,2925,2869,1673,cm-1.
1H NMR(400MHz,CDCl3)δ6.01–5.86(m,1H),5.30(d,J＝3.8Hz,1H),3.20(d,J＝10.4Hz,1H),2.71(d,J＝4.1Hz,3H),1.93(m,J＝23.2,9.4Hz,2H),1.87–1.78(m,2H),1.73(d,J＝13.7Hz,1H),1.62(d,J＝12.7Hz,3H),1.57–1.50(m,3H),1.46(s,1H),1.41(d,J＝4.3Hz,4H),1.34–1.23(m,3H),1.08(d,J＝3.3Hz,3H),1.02–0.89(m,12H),0.85(t,J＝4.6Hz,4H),0.76(m,J＝10.5,3.2Hz,6H).13C NMR(100MHz,CDCl3)δ178.9,140.3,125.7,79.0,55.3,53.9,47.8,47.7,42.6,39.9,39.6,39.3,38.9,38.8,37.1,37.0,32.7,31.0,28.3,28.0,27.3,26.3,25.1,23.5,23.4,21.4,18.4,17.4,16.7,15.7,15.6.
HRMS(ESI)calculated for C31H51NNaO2 +:492.3812,found 492.3815.
实施例6：
化合物U2的制备(方法同化合物3的制备)
mp 209-211℃；[ɑ]24 D+30°(c 0.40,CHCl3)；IR(KBr):3327,2935,2869,1686,1653cm-1.
1H NMR(400MHz,CDCl3)δ5.90(s,1H),5.34(t,J＝3.5Hz,1H),2.73(t,J＝3.6Hz,3H),2.60–2.49(m,1H),2.38(ddd,J＝12.5,6.9,3.4Hz,1H),2.02(dd,J＝8.7,3.3Hz,2H),1.89(dt,J＝16.6,6.6Hz,3H),1.75(d,J＝14.2Hz,1H),1.62(t,J＝4.6Hz,4H),1.51–1.41(m,7H),1.33(dt,J＝14.0,4.8Hz,3H),1.25(s,1H),1.12–1.03(m,12H),0.95(s,3H),0.87(dd,J＝6.8,2.6Hz,3H),0.81(d,J＝2.6Hz,3H).13C NMR(100MHz,CDCl3)δ217.7,178.9,140.5,125.5,55.4,54.1,47.9,47.6,47.0,42.7,40.0,39.6,39.5,39.3,37.1,36.8,34.3,32.3,31.0,28.0,26.7,26.4,25.13,23.7,23.4,21.7,21.4,19.7,17.5,16.7,15.4.HRMS(ESI)calculated for C31H49NNaO2 +:490.3656,found 490.3654.
实施例7：
化合物U3的制备(方法同化合物4的制备)
mp 219-221℃；[ɑ]24 D+25°(c 1.20,CHCl3)；IR(KBr):3421,2925,2869,1713,1687,1641cm-1.1H NMR(400MHz,CDCl3)δ5.98(s,1H),5.91(q,J＝5.0Hz,1H),5.34(d,J＝3.8Hz,1H),5.14(s,1H),2.71(d,J＝4.7Hz,3H),2.65(d,J＝15.1Hz,1H),2.16(d,J＝15.2Hz,1H),2.03(dt,J＝9.8,4.1Hz,2H),1.95(dd,J＝13.7,3.9Hz,1H),1.88(d,J＝11.4Hz,3H),1.74(d,J＝14.0Hz,1H),1.69–1.60(m,2H),1.51–1.37(m,8H),1.34(d,J＝3.8Hz,1H),1.24(s,1H),1.11(d,J＝3.1Hz,6H),1.05(s,3H),0.93(d,J＝5.7Hz,6H),0.87(d,J＝6.5Hz,3H),0.81(s,3H).13C NMR(100MHz,CDCl3δ207.3,178.7,142.0,140.4,125.4,123.8,54.2,54.1 47.9,47.1,46.0,45.4,42.8,39.9,39.5,39.3,37.1,36.8,32.1,31.0,28.5,27.9,26.4,25.1,23.6,23.3,22.9,21.3,20.2,17.4,16.5,15.3.HRMS(ESI)calculated for C32H49NNaO2 +:502.3656,found 502.3655.
实施例8：
化合物U4的制备
0℃、氩气保护下，将化合物5(68mg)的粗品溶解于二氯甲烷(2ml)中，滴加N,N-二异丙基乙胺至体系为碱性，加入HATU(62mg，0.164mmol)，加入α-苯基肉桂酸(20mg，0.0902mmol)，反应过夜，1NHCl洗(20ml)，乙酸乙酯萃取(20ml)，有机相分别再用饱和碳酸氢钠洗(20ml)、饱和食盐水洗(20ml)，干燥浓缩，制备板分离纯化(二氯甲烷：甲醇＝50:1)得化合物U4(白色固体，20mg，产率60％)。
mp 130-132℃；[ɑ]24 D+27°(c 0.53,CHCl3)；IR(KBr):3364,3055,2924,1714,1650,1514,1450cm-1.1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.43(d,J＝5.0Hz,3H),7.24–7.11(m,5H),6.97(d,J＝7.6Hz,2H),6.44(s,1H),5.99(d,J＝7.4Hz,2H),5.40(s,1H),5.13(s,1H),3.42(ddt,J＝21.2,15.4,8.2Hz,3H),3.15(dd,J＝11.1,6.1Hz,1H),2.60(d,J＝15.0Hz,1H),2.14(d,J＝15.1Hz,1H),2.02–1.93(m,4H),1.75–1.68(m,2H),1.65–1.60(m,2H),1.40(td,J＝25.1,22.3,15.2Hz,9H),1.25(s,2H),1.10(d,J＝5.9Hz,6H),1.05(s,3H),0.95(s,3H),0.92–0.87(m,6H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.4,178.9,168.2,142.0,139.4,137.6,136.0,134.9,134.2,130.5,130.5,129.9,129.9,129.8,129.8,128.8,128.8,128.3,128.3,125.7,123.8,54.2,53.6,47.9,47.1,46.0,45.3,42.6,40.4,40.1,39.9,39.5,39.2,37.5,36.8,32.2,31.0,28.4,28.0,24.8,23.7,23.4,22.9,21.3,20.2,17.4,16.8,15.3.HRMS(ESI)calculated for C48H62N2NaO3 +:737.4653,found737.4650.
实施例9：
化合物U5的制备(方法同化合物U4的制备)
mp 159-161℃；[ɑ]24 D+32°(c 0.17,CHCl3)；IR(KBr):3289,3064,2924,1712,1665,1629,1527,1454cm-1.1H NMR(400MHz,CDCl3)δ8.73(d,J＝4.5Hz,1H),8.58(d,J＝5.1Hz,1H),7.81(t,J＝6.3Hz,1H),7.58(dd,J＝15.7,4.7Hz,1H),7.29(dd,J＝12.5,6.5Hz,2H),6.51(td,J＝13.6,11.4,5.1Hz,2H),5.98(d,J＝4.7Hz,1H),5.43–5.35(m,1H),5.14(s,1H),3.59–3.44(m,3H),3.29(dq,J＝12.0,6.2,5.7Hz,1H),2.60(dd,J＝15.2,4.6Hz,1H),2.14(d,J＝15.2Hz,1H),1.99(d,J＝11.0Hz,4H),1.83–1.78(m,1H),1.74–1.62(m,3H),1.41(dt,J＝33.6,20.4Hz,9H),1.25(d,J＝4.4Hz,2H),1.11(d,J＝4.7Hz,6H),1.03(d,J＝4.7Hz,3H),0.94(d,J＝4.4Hz,3H),0.87(d,J＝5.1Hz,6H),0.81(d,J＝4.6Hz,3H).13C NMR(100MHz,CDCl3)δ207.4,180.3,166.1,150.4,149.4,141.9,139.5,137.2,134.5,130.9,125.7,123.9,123.9,123.3,54.2,53.7,48.5,47.1,46.0,45.3,42.7,41.15,39.97,39.86,39.51,39.11,37.55,36.76,32.20,30.97,28.43,27.91,25.0,23.6,23.3,22.9,21.3,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C41H57N3NaO3 +:662.4292,found 662.4288.
实施例10：
化合物U6的制备(方法同化合物U4的制备)
mp 127-129℃；[ɑ]24 D+29°(c 0.6,CHCl3)；IR(KBr):3306,2927,2864,1682,1651cm-1.
1H NMR(400MHz,CDCl3)δ6.56(d,J＝5.2Hz,1H),6.39(t,J＝5.4Hz,1H),5.99(d,J＝2.3Hz,1H),5.42–5.36(m,1H),5.16(d,J＝2.5Hz,1H),3.42(ddt,J＝20.1,10.3,5.7Hz,2H),3.32–3.18(m,2H),2.65(d,J＝15.1Hz,1H),2.30(t,J＝7.4Hz,2H),2.24(td,J＝6.9,2.6Hz,2H),2.16(d,J＝15.2Hz,1H),2.06–1.98(m,3H),1.96–1.92(m,2H),1.83(d,J＝7.1Hz,2H),1.81–1.78(m,1H),1.65(dd,J＝11.1,7.2Hz,3H),1.52–1.38(m,8H),1.24(s,3H),1.12(d,J＝2.6Hz,6H),1.06(s,3H),0.95(d,J＝2.5Hz,3H),0.92(s,3H),0.88(d,J＝6.5Hz,3H),0.81(s,3H).
13C NMR(100MHz,CDCl3)δ207.4,179.9,173.2,142.0,139.6,125.7,123.9,83.6,69.3,54.3,53.8,48.0,47.1,46.0,45.3,42.7,40.8,40.0,39.9,39.5,39.1,37.5,36.8,35.2,32.3,31.00,28.5,27.9,24.9,24.4,23.6,23.3,22.9,21.3,20.2,18.1,17.3,16.8,15.3.
HRMS(ESI)calculated for C39H58N2NaO3 +:625.4340,found 625.4337.
实施例11：
化合物U7的制备(方法同化合物U4的制备)
mp 143-145℃；[ɑ]24 D+29°(c 0.7,CHCl3)；IR(KBr):3342,2927,2864,1684,1657cm-1.1H NMR(400MHz,CDCl3)δ6.77(t,J＝4.9Hz,1H),6.68(t,J＝3.9Hz,1H),6.46(t,J＝5.5Hz,1H),5.99(d,J＝2.4Hz,1H),5.37(d,J＝3.4Hz,1H),5.15(d,J＝2.4Hz,1H),3.54–3.47(m,1H),3.39(th,J＝9.2,4.9Hz,2H),3.21(dq,J＝14.3,4.9Hz,1H),2.64(d,J＝15.1Hz,1H),2.22–2.12(m,5H),2.00(dt,J＝12.1,6.5Hz,4H),1.86–1.75(m,2H),1.66(dq,J＝8.8,3.2Hz,4H),1.61–1.56(m,2H),1.51–1.37(m,7H),1.36–1.29(m,2H),1.24(s,2H),1.11(d,J＝4.5Hz,6H),1.05(s,3H),0.94(d,J＝2.5Hz,3H),0.90(s,3H),0.87(d,J＝6.4Hz,3H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.4,179.9,169.3,142.0,139.5,134.3,132.6,125.7,123.9,54.2,53.6,48.0,47.1,46.0,45.3,42.7,41.1,39.9,39.5,39.1,37.5,36.8,32.3,31.0,28.5,27.9,25.6,24.9,24.3,23.6,23.3,22.8,22.4,21.7,21.3,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C40H60N2NaO3 +:639.4496,found639.4499.
实施例12：
化合物U8的制备(方法同化合物U4的制备)
mp 144-146℃；[ɑ]24 D+33°(c 0.38,CHCl3)；IR(KBr):3363,3077,2925,1680,1633cm-1.1H NMR(400MHz,CDCl3)δ6.80(dq,J＝13.9,6.7Hz,1H),6.64(t,J＝5.1Hz,1H),6.46(t,J＝5.3Hz,1H),5.98(s,1H),5.80(d,J＝15.3Hz,1H),5.37(d,J＝3.8Hz,1H),5.15(s,1H),3.50–3.35(m,3H),3.21(dt,J＝14.7,4.9Hz,1H),2.64(d,J＝15.1Hz,1H),2.15(d,J＝15.2Hz,1H),2.02–1.95(m,4H),1.83(d,J＝6.8Hz,3H),1.77(d,J＝14.0Hz,1H),1.65(dd,J＝15.3,9.0Hz,3H),1.51–1.38(m,7H),1.34(d,J＝13.9Hz,2H),1.24(s,2H),1.11(d,J＝4.6Hz,6H),1.05(s,3H),0.94(s,3H),0.90(s,3H),0.87(d,J＝6.4Hz,3H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.4,179.8,167.0,142.0,139.9,139.5,125.7,125.2,123.9,54.2,53.6,48.0,47.1,46.0,45.3,42.7,40.5,40.1,39.9,39.5,39.1 37.5,36.8,32.2,31.0,28.5,27.9,24.9,23.6,23.3,22.9,21.3,20.2,17.8,17.3,16.8,15.3.HRMS(ESI)calculated for C37H56N2NaO3 +:599.4183,found 599.4184.
实施例13：
化合物U9的制备(方法同化合物U4的制备)
mp 164-166℃；[ɑ]24 D+23°(c 0.36,CHCl3)；IR(KBr):3419,3071,2928,2867,1682,1636cm-1.
1H NMR(400MHz,CDCl3)δ6.89(s,1H),6.80(dt,J＝14.1,6.5Hz,1H),6.42(d,J＝6.5Hz,1H),6.06(d,J＝15.4Hz,1H),6.00(d,J＝2.4Hz,1H),5.38(t,J＝3.5Hz,1H),5.16(s,1H),3.61–3.31(m,4H),3.26(d,J＝6.7Hz,2H),2.65(d,J＝15.1Hz,1H),2.40(s,6H),2.18(s,1H),2.05–1.98(m,3H),1.94(d,J＝10.5Hz,1H),1.83–1.78(m,1H),1.71(d,J＝14.2Hz,1H),1.68–1.60(m,2H),1.44(dd,J＝26.7,12.6Hz,6H),1.29(d,J＝33.8Hz,5H),1.12(d,J＝4.4Hz,6H),1.06(s,3H),0.95(s,3H),0.91(s,3H),0.88(d,J＝6.4Hz,3H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.4,179.9,165.7,141.9,139.5,129.1,125.7,125.7,123.90,59.4,54.2,53.6,48.0,47.1,46.0,45.3,44.3,44.3,42.7,40.7,39.8,39.8,39.5,39.1,37.5,36.8,32.2,31.0,28.5,27.9,24.9,23.6,23.3,22.9,21.3,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C39H61N3NaO3 +:642.4605,found 642.4601.
实施例14：
化合物U10的制备(方法同化合物U4的制备)
mp 96-98℃；[ɑ]24 D+28°(c 0.46,CHCl3)；IR(KBr):3353,2927,2867,1714,1685,1649cm-1.1H NMR(400MHz,CDCl3)δ8.93(t,J＝5.7Hz,1H),6.40(t,J＝4.7Hz,1H),5.99(t,J＝2.3Hz,1H),5.35(t,J＝3.6Hz,1H),5.15(d,J＝2.3Hz,1H),3.67(s,3H),3.49(ddq,J＝9.8,7.1,3.5Hz,2H),3.38(tt,J＝9.1,4.3Hz,1H),3.19–3.12(m,1H),2.64(d,J＝15.2Hz,1H),2.16(d,J＝15.2Hz,1H),1.98(dq,J＝9.1,4.7,4.1Hz,4H),1.80–1.74(m,2H),1.67(ddd,J＝9.0,6.8,3.5Hz,4H),1.57(q,J＝2.5,1.7Hz,2H),1.51–1.38(m,7H),1.38–1.32(m,2H),1.30–1.23(m,2H),1.11(d,J＝6.9Hz,6H),1.05(s,3H),0.94(d,J＝2.3Hz,3H),0.91(s,3H),0.87(d,J＝6.4Hz,3H),0.81(s,3H).13C NMR(100MHz,CDCl3)δ207.5,178.4,173.8,170.0,142.0,139.5,125.5,123.8,54.2,53.6,52.5,47.8,47.1,46.0,45.3,42.6,40.7,39.8,39.5,39.2,39.2,37.5,36.8,32.3,31.0,28.5 28.0,26.2,24.8,23.6,23.4,22.9,21.4,20.3,20.3,20.2,17.4,16.8,15.3.HRMS(ESI)calculated for C39H58N2NaO5 +:657.4238,found 657.4242.
实施例15：
化合物U24的制备(方法同化合物U4的制备)
mp 142-144℃；[ɑ]24 D+39°(c 0.29,CHCl3)；IR(KBr):3323,2926,2870,1684,1636,1605,1530,1509,1454cm-1.
1H NMR(400MHz,CDCl3)δ11.41(s,1H),7.55(ddd,J＝13.7,7.9,4.1Hz,3H),6.97(t,J＝8.7Hz,2H),6.41(t,J＝5.7Hz,1H),5.99(d,J＝2.3Hz,1H),5.39(t,J＝3.5Hz,1H),5.15(d,J＝2.3Hz,1H),3.51–3.44(m,1H),3.30(q,J＝6.0Hz,3H),2.64(d,J＝15.1Hz,1H),2.15(d,J＝15.2Hz,1H),2.02(qd,J＝12.3,10.4,6.7Hz,3H),1.92(d,J＝11.0Hz,1H),1.88–1.83(m,1H),1.74(t,J＝4.4Hz,3H),1.68–1.62(m,2H),1.51(dd,J＝12.2,4.6Hz,2H),1.46–1.30(m,9H),1.25(s,1H),1.16(d,J＝3.3Hz,1H),1.11(d,J＝7.3Hz,6H),0.98(s,3H),0.95(s,3H),0.88(d,J＝4.9Hz,6H),0.79(s,3H).
13C NMR(100MHz,CDCl3)δ207.2,181.8,173.8,167.9,160.4,141.8,139.7,134.7,125.9,124.0,121.7,121.6,115.7,115.4,54.2,54.0,48.2,47.1,46.0,45.2,43.3,42.9,39.9,39.5,39.1,39.0,37.4,36.8,32.2,30.9,28.4,27.9,27.3,25.0,23.6,23.2,22.8,21.3,20.1,18.5,18.5,17.3,16.8,15.3.
HRMS(ESI)calculated for C44H60FN3NaO4 +:736.4460,found 736.4455.
实施例16：
化合物U26的制备(方法同化合物U4的制备)
mp 149-151℃C；[ɑ]24 D+26°(c 0.40,CHCl3)；IR(KBr):3278,3078,2975,2936,1726,1675,1640cm-1.1H NMR(400MHz,CDCl3)δ7.47(t,J＝4.8Hz,1H),6.91(d,J＝15.5Hz,1H),6.77(d,J＝15.4Hz,1H),6.41(t,J＝5.4Hz,1H),5.99(d,J＝2.4Hz,1H),5.38(d,J＝3.5Hz,1H),5.15(d,J＝2.3Hz,1H),4.23(q,J＝7.1Hz,2H),3.53–3.39(m,3H),3.26(dt,J＝15.3,5.4Hz,1H),2.64(d,J＝15.1Hz,1H),2.15(d,J＝15.2Hz,1H),2.04–1.93(m,4H),1.81–1.76(m,1H),1.72–1.61(m,3H),1.51–1.37(m,7H),1.36(s,1H),1.30(t,J＝7.1Hz,5H),1.24(s,1H),1.11(d,J＝2.1Hz,6H),1.05(s,3H),0.94(s,3H),0.91–0.86(m,6H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.3,180.3,165.7,164.6,141.9,139.5,136.5,130.4,125.8,123.9,61.3,54.2,53.8,48.1,47.1,46.0,45.3,42.8,41.3,39.9,39.7,39.6,39.1,37.5,36.8,32.2,31.0,28.5,27.9,24.9,23.6,23.3,22.9,21.3,20.2,17.3,16.8,15.3,14.3.HRMS(ESI)calculated for C39H58N2NaO5 +:657.4238,found 657.4243.
实施例17：
化合物U12的制备(方法同化合物U4的制备)
mp 133-135℃；[ɑ]24 D+24°(c 0.80,CHCl3)；IR(KBr):3362,3076,2975,2925,1731,1665,1628,1584,1527,1485cm-1.1H NMR(400MHz,CDCl3)δ7.55(d,J＝15.6Hz,1H),7.31(td,J＝7.9,5.7Hz,1H),7.26(s,1H),7.24–7.16(m,2H),7.03(td,J＝8.4,2.5Hz,1H),6.50(t,J＝5.0Hz,1H),6.45(d,J＝15.6Hz,1H),5.97(d,J＝2.4Hz,1H),5.39(d,J＝3.4Hz,1H),5.12(s,1H),3.50(td,J＝13.4,6.1Hz,3H),3.27(td,J＝9.6,4.7Hz,1H),2.58(d,J＝15.1Hz,1H),2.12(d,J＝15.1Hz,1H),1.99(d,J＝10.3Hz,4H),1.79(d,J＝12.7Hz,1H),1.73–1.61(m,3H),1.40(dd,J＝32.4,9.6Hz,7H),1.33–1.23(m,4H),1.10(s,6H),1.02(s,3H),0.93(s,3H),0.89–0.84(m,6H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.1,166.5,164.4,161.9,141.9,139.7,139.4,137.3,130.4,125.7,124.0,123.9,122.4,116.5,114.2,54.2,53.7,48.0,47.1,46.0,45.3,42.7,40.7,40.2,39.9,39.5,39.1,37.6,36.8,32.2,31.0,28.4,27.9,24.9,23.6,23.3,22.9,21.3,20.2,17.3,16.8,15.2.HRMS(ESI)calculated for C42H57FN2NaO3 +:679.4245,found 679.4246.
实施例18：
化合物U11的制备
室温下，将化合物5(68mg)的粗品溶解于二氯甲烷(2ml)中，滴加N,N-二异丙基乙胺至体系为碱性，加入4-氯-3-三氟甲基异氰酸苯酯(18mg，0.082mmol)，反应过夜，饱和食盐水洗(20ml)，乙酸乙酯萃取(20ml)，干燥浓缩，制备板分离纯化(二氯甲烷：甲醇＝30:1)得化合物U11(白色固体，22mg，产率61％)。
mp 217-219℃；[ɑ]24 D+31°(c 1.00,CHCl3)；IR(KBr):3358,3123,2927,2868,1690,1618cm-1.1H NMR(400MHz,CDCl3)δ8.44(s,1H),7.71(s,1H),7.65(d,J＝8.9Hz,1H),7.35(d,J＝8.7Hz,1H),6.74(d,J＝5.1Hz,1H),6.42(s,1H),6.00(s,1H),5.39(d,J＝3.5Hz,1H),5.17(s,1H),3.44(h,J＝6.8,6.4Hz,2H),3.31(dd,J＝11.0,5.7Hz,1H),3.17(q,J＝6.7,5.7Hz,1H),2.62(d,J＝15.1Hz,1H),2.15(d,J＝15.3Hz,1H),2.06–1.93(m,4H),1.73(d,J＝12.9Hz,1H),1.68–1.59(m,3H),1.52–1.34(m,7H),1.30(d,J＝12.5Hz,2H),1.25(s,2H),1.10(d,J＝7.4Hz,6H),1.04(s,3H),0.88(d,J＝6.5Hz,6H),0.84(d,J＝6.4Hz,3H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.5,180.5,156.6,141.8,139.0,138.9,131.9,128.4,126.1,124.5,124.1,122.4,121.5,117.4,54.1,53.5,48.1,47.0,46.0,45.2,42.6,41.1,39.8,39.4,39.0,38.9,37.7,36.7,32.1,30.8,28.5 27.9,25.0,23.6,23.34,22.9,21.1,20.1,17.2,16.8,15.2.HRMS(ESI)calculated forC41H55ClF3N3NaO3 +:752.3776,found 752.3773.
实施例19：
化合物U13的制备(方法同化合物U11的制备)
mp 173-175℃；[ɑ]24 D＝+25°(c 0.35,CHCl3)；IR(KBr):3334,2927,2867,1685,1611cm-1.1H NMR(400MHz,CDCl3)δ7.46(s,1H),7.23(d,J＝8.5Hz,2H),6.80(d,J＝8.4Hz,2H),6.74(d,J＝4.8Hz,1H),6.09–6.01(m,1H),5.99(s,1H),5.38(d,J＝3.5Hz,1H),5.15(s,1H),3.76(s,3H),3.45–3.35(m,2H),3.26(q,J＝7.6,7.0Hz,1H),3.16(dd,J＝10.8,5.0Hz,1H),2.62(d,J＝15.1Hz,1H),2.13(d,J＝15.3Hz,1H),2.02–1.94(m,4H),1.73(d,J＝13.1Hz,1H),1.64(dd,J＝15.7,11.0Hz,3H),1.50–1.35(m,7H),1.30(d,J＝12.8Hz,2H),1.24(s,2H),1.11(s,3H),1.08(s,3H),1.04(s,3H),0.91–0.87(m,6H),0.84(d,J＝6.3Hz,3H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.5,179.7,157.5,156.0,141.9,139.1,132.1,125.8,123.9,122.4,122.4,114.3,114.3,55.6,54.2,53.4,47.9,47.0,46.0,45.3,42.6,41.2,39.8,39.5,39.3,38.9,37.5,36.7,32.2,31.0,28.5,27.9,24.8,23.6,23.4,22.9,21.3,20.2,17.2,16.8,15.3.HRMS(ESI)calculated for C41H59N3NaO4 +:680.4398,found 680.4401.
实施例20：
化合物U14的制备(方法同化合物U11的制备)
mp 180-182℃；[ɑ]24 D+23°(c 0.15,CHCl3)；IR(KBr):3324,2925,2868,1687,1603,1548,1513,1454cm-1.1H NMR(400MHz,CDCl3)δ7.46(s,1H),7.23–7.20(m,2H),7.06(d,J＝8.1Hz,2H),6.69(t,J＝5.1Hz,1H),6.04(s,1H),5.99(t,J＝2.4Hz,1H),5.39(t,J＝3.6Hz,1H),5.16(d,J＝2.2Hz,1H),3.41(dtd,J＝12.6,9.1,7.4,3.9Hz,2H),3.27(dt,J＝8.3,5.2Hz,1H),3.16(dt,J＝13.1,4.7Hz,1H),2.62(d,J＝15.1Hz,1H),2.28(s,3H),2.14(d,J＝15.0Hz,1H),2.01–1.94(m,4H),1.76–1.72(m,1H),1.69–1.61(m,3H),1.51–1.47(m,1H),1.44–1.36(m,6H),1.35–1.28(m,2H),1.25(d,J＝3.2Hz,2H),1.11(s,3H),1.09(s,3H),1.05(s,3H),0.90–0.87(m,6H),0.85(d,J＝6.4Hz,3H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.5,179.8,157.2,142.0,139.1,136.6,132.7,129.6,129.6,125.9,123.9,120.3,120.3,54.2,53.4,48.0,47.1,46.0,453,42.6,41.1,39.8,39.5,39.4,38.9,37.5,36.8,32.2,31.0,28.5,27.9,24.9,23.6,23.4,22.9,21.3,20.9,20.2,17.2,16.8,15.3.HRMS(ESI)calculated for C41H59N3NaO3 +:664.4449,found 664.4452.
实施例21：
化合物U15的制备(方法同化合物U11的制备)
mp 155-157℃；[ɑ]24 D+21°(c 0.63,CHCl3)；IR(KBr):3327,3190,2925,1688,1602,1546,1491cm-1.1H NMR(400MHz,CDCl3)δ7.90(s,1H),7.33(d,J＝8.3Hz,2H),7.22–7.17(m,2H),6.68(d,J＝6.2Hz,1H),6.27(d,J＝5.5Hz,1H),6.00(s,1H),5.39(s,1H),5.17(s,1H),3.42(dd,J＝12.5,6.6Hz,2H),3.28(q,J＝7.8,7.3Hz,1H),3.17(q,J＝8.9Hz,1H),2.62(d,J＝15.1Hz,1H),2.17–2.12(m,1H),2.02–1.92(m,4H),1.73(d,J＝13.0Hz,1H),1.69–1.60(m,3H),1.51–1.36(m,7H),1.33(d,J＝12.0Hz,2H),1.27(d,J＝12.3Hz,2H),1.11(d,J＝8.7Hz,6H),1.05(s,3H),0.91–0.84(m,9H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.5,180.3,156.8,141.9,139.1,138.3,128.9,128.9,127.4,126.0,124.0,120.3,120.3,54.2,53.5,48.1,47.0,46.0,45.3,42.6,41.0,39.8,39.5,39.3,39.0,37.6,36.8,32.2,30.9,28.5,27.9,25.0,23.6,23.4,22.9,21.2,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C40H56ClN3NaO3 +:684.3902,found 684.3907.
实施例22：
化合物U16的制备(方法同化合物U11的制备)
mp 155-157℃；[ɑ]24 D+38°(c 0.33,CHCl3)；IR(KBr):3324,2925,2868,1618,1640,1599,1527,1497cm-1.1H NMR(400MHz,CDCl3)δ7.87(s,1H),7.47–7.36(m,2H),7.29(d,J＝7.5Hz,1H),7.22(d,J＝7.8Hz,2H),6.97(t,J＝5.1Hz,1H),6.43(d,J＝6.0Hz,1H),5.99(d,J＝2.5Hz,1H),5.36(s,1H),5.16(d,J＝2.6Hz,1H),3.85(s,1H),3.66(dd,J＝14.0,5.8Hz,1H),3.51(dt,J＝13.9,6.7Hz,1H),3.26(dq,J＝11.1,5.3Hz,1H),2.64(d,J＝15.0Hz,1H),2.15(d,J＝15.3Hz,1H),2.03–1.92(m,4H),1.72–1.56(m,4H),1.43(dd,J＝21.9,11.9Hz,7H),1.36–1.31(m,2H),1.25(s,2H),1.13–1.11(m,3H),1.09(s,3H),1.06(d,J＝1.9Hz,3H),0.92(d,J＝11.2Hz,6H),0.88–0.85(m,3H),0.77(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.4,179.7,141.9,139.6,136.3,130.1,130.1,127.3,125.7,125.4,125.4,123.9,54.2,53.6,47.9,47.1,46.0,45.3,42.7,42.7,39.9,39.5,39.4,39.1,37.2,36.8,32.2,31.0,28.5,27.9,24.8,23.6,23.3,22.9,21.3,20.2,17.3,16.7,15.3.HRMS(ESI)calculated for C40H57N3NaO2S+:666.4064,found 666.4058.
实施例23：
化合物U17的制备(方法同化合物U11的制备)
mp 145-147℃；[ɑ]24 D+29°(c 0.50,CHCl3)；IR(KBr):3315,3208,2963,2928,1690,1615,1554,1510,1457cm-1.1H NMR(400MHz,CDCl3)δ7.97(s,1H),7.41(d,J＝8.6Hz,2H),7.10(d,J＝8.5Hz,2H),6.67(d,J＝5.4Hz,1H),6.33–6.23(m,1H),6.00(d,J＝2.2Hz,1H),5.40(d,J＝3.7Hz,1H),5.16(s,1H),3.43(dq,J＝12.1,7.2,6.6Hz,2H),3.29(td,J＝8.9,8.0,4.7Hz,1H),3.18(q,J＝9.3Hz,1H),2.63(d,J＝15.1Hz,1H),2.15(d,J＝16.4Hz,1H),2.01–1.94(m,3H),1.87(s,1H),1.74(d,J＝13.1Hz,1H),1.65(td,J＝13.0,11.5,5.2Hz,3H),1.54–1.47(m,1H),1.45–1.37(m,5H),1.32(d,J＝7.5Hz,2H),1.26(d,J＝12.6Hz,3H),1.11(d,J＝6.9Hz,6H),1.05(s,3H),0.88(d,J＝3.2Hz,6H),0.85(d,J＝6.4Hz,3H),0.81(s,3H).13C NMR(101MHz,Chloroform-d)δ207.4,180.3,156.7,144.1,141.9,139.1,138.5,126.0,124.0,121.8,121.8,119.9,119.9,119.4,54.2,53.5,48.1,47.0,46.0,45.3,42.7,41.0,39.8,39.5,39.3,39.0,37.6,36.8,32.2,30.9,28.5,27.9,25.0,23.6,23.4,22.9,21.2,20.2,17.2,16.8,15.3.HRMS(ESI)calculated forC41H56F3N3NaO4 +:734.4115,found 734.4118.
实施例24：
化合物U18的制备(方法同化合物U11的制备)
mp 181-183℃；[ɑ]24 D+27°(c 0.75,CHCl3)；IR(KBr):3333,3209,2927,2865,1710,1610,1545,1454cm-1.1H NMR(400MHz,CDCl3)δ8.17(s,1H),7.49(t,J＝7.3Hz,4H),6.66(d,J＝5.0Hz,1H),6.38(s,1H),6.00(d,J＝2.2Hz,1H),5.42(d,J＝3.3Hz,1H),5.17(s,1H),3.46(h,J＝7.6Hz,2H),3.30(dt,J＝10.4,6.6Hz,1H),3.20(q,J＝7.9,6.3Hz,1H),2.62(d,J＝15.1Hz,1H),2.15(d,J＝15.2Hz,1H),2.07–1.93(m,4H),1.75(d,J＝13.1Hz,1H),1.64(dd,J＝11.2,7.5Hz,3H),1.50(d,J＝11.5Hz,1H),1.40(dq,J＝11.8,6.0Hz,5H),1.28(d,J＝24.9Hz,6H),1.11(d,J＝5.7Hz,6H),1.05(s,3H),0.90–0.84(m,9H),0.81(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.5,156.5,143.0,141.8,139.2,126.2,126.2,126.1,125.8,124.1,124.1,118.2,118.2,54.2,53.5,48.1,47.0,46.0,45.2,42.7,40.9,39.8,39.5,39.2,39.0,37.6,36.8,32.2,30.9,28.5,27.9,25.0,23.6,23.3,22.9,21.1,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C41H56F3N3NaO3 +:718.4166,found718.4165.
实施例25：
化合物U19的制备(方法同化合物U11的制备)
mp 152-154℃；[ɑ]24 D+19°(c 0.63,CHCl3)；IR(KBr):3310,3075,2926,2866,1685,1614,1524,1457cm-1.1H NMR(400MHz,CDCl3)δ8.50(s,1H),7.76(s,1H),7.62(d,J＝8.2Hz,2H),7.49(s,2H),6.51(t,J＝5.8Hz,1H),6.00(d,J＝2.2Hz,1H),5.33(d,J＝3.6Hz,1H),5.16(s,1H),3.86(s,1H),3.69(d,J＝10.1Hz,1H),3.52(d,J＝8.5Hz,1H),3.31(dq,J＝14.7,5.5Hz,1H),2.63(d,J＝15.1Hz,1H),2.15(d,J＝15.1Hz,1H),1.97(dt,J＝21.2,7.6Hz,4H),1.83(s,1H),1.63(dd,J＝11.1,6.8Hz,2H),1.57–1.37(m,8H),1.31–1.23(m,4H),1.12(s,3H),1.08(s,3H),1.05(s,3H),0.90(d,J＝8.2Hz,6H),0.84(d,J＝6.4Hz,3H),0.75(s,3H).13C NMR(100MHz,CDCl3)δ207.3,181.3,180.7,141.8,140.7,139.4,126.6,126.6,125.9,125.9,125.4,124.0,124.0,122.7,54.2,53.6,48.0,47.1,46.0,46.0,45.2,42.7,39.8,39.5,39.0,37.3,36.8,32.2,30.9,29.8,28.4,27.9,24.9,23.6,23.3,22.9,21.2,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C41H56F3N3NaO2S+:734.3938,found734.3941.
实施例26：
化合物U20的制备
0℃、氩气保护下，将化合物5(68mg)的粗品溶解于干燥的二氯甲烷(2ml)中，滴加干燥的三乙胺调PH至碱性，缓慢滴加对溴苯甲酰氯，再加一滴干燥的N,N-二甲基甲酰胺，2h后，饱和食盐水洗(20ml)，乙酸乙酯萃取(20ml)，干燥浓缩，制备板分离纯化(二氯甲烷：甲醇＝33:1)得化合物U20(白色固体，19mg，产率58％)。
mp 145-147℃；[ɑ]24 D+30°(c 0.50,CHCl3)；IR(KBr):3318,2925,2866,1684,1643,1593,1528,1477cm-1.1H NMR(400MHz,CDCl3)δ7.94(t,J＝4.5Hz,1H),7.72(d,J＝8.1Hz,2H),7.55(d,J＝8.1Hz,2H),6.49(t,J＝5.7Hz,1H),5.98(s,1H),5.35(t,J＝3.5Hz,1H),5.15(s,1H),3.61(dd,J＝13.7,6.3Hz,1H),3.51(q,J＝5.0Hz,2H),3.33(dq,J＝14.7,5.0Hz,1H),2.61(d,J＝15.0Hz,1H),2.13(d,J＝15.2Hz,1H),2.07–1.93(m,3H),1.86–1.76(m,2H),1.70(d,J＝14.2Hz,1H),1.60(t,J＝8.7Hz,2H),1.51–1.32(m,8H),1.24(t,J＝6.6Hz,3H),1.10(d,J＝3.4Hz,6H),1.03(s,3H),0.94(s,3H),0.87(d,J＝6.2Hz,3H),0.82(s,3H),0.73(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.0,166.7,141.9,139.5,132.8,131.8,131.8,128.9,128.9,126.2,125.8,123.9,54.2,53.7,48.1,47.1,46.0,45.2,42.7,42.5,39.9,39.6,39.5,39.1,37.5,36.7,32.2,30.9,28.4,27.9,25.0,23.5,23.2,22.9,21.3,20.2,17.3,16.8,15.2.HRMS(ESI)calculated for C40H55BrN2NaO3 +:713.3288,found713.3287.
实施例27：
化合物U21的制备(方法同化合物U20的制备)
mp 73-75℃；[ɑ]24 D+21°(c 0.55,CHCl3)；IR(KBr):3293,2959,2927,1718,1686,1639cm-1.1H NMR(400MHz,CDCl3)δ6.58(d,J＝5.4Hz,1H),6.44(d,J＝5.8Hz,1H),5.99(s,1H),5.38(d,J＝3.7Hz,1H),5.16(s,1H),3.47–3.35(m,2H),3.30–3.18(m,2H),2.65(d,J＝15.1Hz,1H),2.32(t,J＝7.5Hz,1H),2.19–2.13(m,3H),2.04–2.00(m,2H),1.95(d,J＝10.8Hz,1H),1.82–1.77(m,1H),1.70(d,J＝16.0Hz,1H),1.65–1.58(m,4H),1.49–1.38(m,7H),1.26(dd,J＝10.3,4.8Hz,12H),1.11(d,J＝3.3Hz,6H),1.05(s,3H),0.95(s,3H),0.92(s,3H),0.87(t,J＝4.6Hz,6H),0.81(s,3H).13C NMR(100MHz,CDCl3)δ207.4,179.9,174.4,141.9,139.5,125.7,123.9,54.2,53.7,48.0,47.1,46.0,45.3,42.7,40.6,40.0,39.9,39.5,39.1,37.5,36.9,36.8,32.2,31.8,31.0,29.5,29.2,28.5,27.9,25.9,24.9,23.6,23.3,22.9,22.8,21.3,20.2,17.3,16.8,15.3,14.2.HRMS(ESI)calculated forC41H66N2NaO3 +:657.4966,found 657.4967.
实施例28：
化合物U22的制备(方法同化合物U20的制备)
mp 141-143℃；[ɑ]24 D+29°(c 0.46,CHCl3)；IR(KBr):3311,2926,2869,1783,1686,1648,1534,1503,1455cm-1.1H NMR(400MHz,CDCl3)δ7.85(dt,J＝9.1,4.7Hz,3H),7.09(t,J＝8.5Hz,2H),6.47(t,J＝5.9Hz,1H),5.99(d,J＝2.9Hz,1H),5.36(d,J＝3.7Hz,1H),5.15(s,1H),3.63(dq,J＝12.0,5.7Hz,1H),3.52(q,J＝4.9Hz,2H),3.35(dt,J＝14.0,5.2Hz,1H),2.61(d,J＝15.1Hz,1H),2.13(d,J＝15.2Hz,1H),2.07–1.94(m,3H),1.86(dd,J＝12.0,2.7Hz,1H),1.79(d,J＝13.5Hz,1H),1.71(d,J＝14.2Hz,1H),1.61(dd,J＝11.1,5.4Hz,2H),1.42(ddd,J＝30.0,15.6,11.0Hz,7H),1.26(d,J＝12.3Hz,4H),1.10(s,6H),1.04(s,3H),0.94(s,3H),0.88(d,J＝6.2Hz,3H),0.83(s,3H),0.75(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.0,166.6,163.6,141.9,139.5,130.2,129.6,129.5,125.8,123.9,115.7,115.5,54.2,53.8,48.1,47.1,46.0,45.2,42.8,42.7,39.9,39.5,39.5,39.1,37.5,36.7,32.2,30.9,28.5,27.9,25.0,23.5,23.2,22.9,21.3,20.2,17.3,16.8,15.3.HRMS(ESI)calculated for C40H55FN2NaO3 +:653.4089,found 653.4093.
实施例29：
化合物U23的制备(方法同化合物U20的制备)
mp 149-151℃；[ɑ]24 D+33°(c 0.72,CHCl3)；IR(KBr):3310,3078,2925,2869,1658,1602,1526,1488,1455cm-1.1H NMR(400MHz,CDCl3)δ8.42(d,J＝4.2Hz,1H),8.27(d,J＝8.2Hz,2H),8.03(d,J＝8.2Hz,2H),6.50(t,J＝6.0Hz,1H),5.99(s,1H),5.38(d,J＝4.2Hz,1H),5.15(s,1H),3.63(dt,J＝12.1,5.8Hz,1H),3.54(q,J＝4.8Hz,2H),3.39(dt,J＝14.6,5.3Hz,1H),2.61(d,J＝15.0Hz,1H),2.14(d,J＝15.3Hz,1H),2.08–1.94(m,3H),1.88(d,J＝11.7Hz,1H),1.82–1.78(m,1H),1.72(d,J＝13.9Hz,1H),1.66–1.57(m,2H),1.51–1.35(m,7H),1.26(d,J＝13.5Hz,4H),1.11(d,J＝2.8Hz,6H),1.03(s,3H),0.94(s,3H),0.88(d,J＝6.4Hz,3H),0.83(s,3H),0.75(s,3H).13C NMR(100MHz,CDCl3)δ207.2,181.7,165.3,149.7,141.8,139.6,139.6,128.4,128.4,125.9,124.0,123.8,123.8,54.2,53.9,48.2,47.1,46.0,45.2,43.5,42.8,39.9,39.5,39.3,39.1,37.5,36.7,32.2,30.9,28.4,27.8,25.0,23.6,23.2,22.9,21.3,20.1,17.3,16.8,15.3.HRMS(ESI)calculatedfor C40H55N3NaO5 +:680.4034,found 680.4036.
实施例30：
化合物U25的制备(方法同化合物U20的制备)
mp 131-133℃；[ɑ]24 D+27°(c 0.50,CHCl3)；IR(KBr):3323,2963,2928,1686,1649,1528cm-1.1H NMR(400MHz,CDCl3)δ6.51(dt,J＝22.3,5.3Hz,2H),5.99(t,J＝2.4Hz,1H),5.40(t,J＝3.6Hz,1H),5.16(d,J＝2.3Hz,1H),3.47–3.37(m,2H),3.34–3.27(m,1H),3.22(dt,J＝13.3,4.7Hz,1H),2.65(d,J＝15.1Hz,1H),2.16(d,J＝15.2Hz,1H),2.02(dt,J＝13.0,6.8Hz,3H),1.94(d,J＝10.8Hz,1H),1.88(q,J＝5.1,4.5Hz,1H),1.83–1.79(m,1H),1.68(dd,J＝16.4,12.4Hz,3H),1.58(dd,J＝15.1,7.3Hz,2H),1.51–1.38(m,9H),1.29(d,J＝37.6Hz,4H),1.11(d,J＝3.3Hz,6H),1.05(s,3H),0.94(s,3H),0.92(s,3H),0.87(t,J＝7.2Hz,9H),0.82(s,3H).13C NMR(100MHz,CDCl3)δ207.4,179.8,176.9,142.2,139.6,125.7,123.9,54.2,53.7,51.4,47.9,47.1,46.0,45.3,42.7,40.5,40.3,39.9,39.5,39.1,37.4,36.8,32.2,31.0,28.5,27.9,25.8,25.7,25.0,23.6,23.3,22.9,21.3,20.2,17.4,16.8,15.3,12.4,12.3.HRMS(ESI)calculated for C39H62N2NaO3 +:629.4653,found629.4650.
实施例31
化合物7的制备(方法同化合物2的制备)
mp 131-133℃；[ɑ]24 D+40°(c 0.95,CHCl3)；IR(KBr):3373,2945,2873,1698,1643cm-1.1H NMR(400MHz,CDCl3)δ6.35(t,J＝5.2Hz,1H),5.36(t,J＝3.5Hz,1H),5.11(t,J＝5.8Hz,1H),3.40(dq,J＝12.3,6.1,5.6Hz,1H),3.16(ddq,J＝29.9,12.9,5.7Hz,4H),2.53(dd,J＝13.2,4.3Hz,1H),1.99–1.85(m,3H),1.75–1.66(m,2H),1.62–1.50(m,8H),1.41(s,9H),1.39(s,3H),1.33(d,J＝11.6Hz,1H),1.23(dd,J＝9.4,2.8Hz,1H),1.16(t,J＝5.6Hz,1H),1.12(s,3H),1.02–0.98(m,1H),0.96(s,3H),0.94–0.90(m,1H),0.89–0.85(m,9H),0.82(dd,J＝9.3,3.4Hz,1H),0.75(s,3H),0.72(s,3H).13C NMR(100MHz,CDCl3)δ179.1,156.7,144.6,123.0,79.4,78.9,55.2,47.6,46.8,46.3,42.0,40.6,40.3,39.4,38.8,38.6,37.0,34.2,33.1,32.7,32.5,30.8,28.5,28.5,28.5,28.2,27.4,27.2,27.0,25.9,23.7,23.7,23.6,18.4,17.0,15.7,15.4.HRMS(ESI)calculated for C37H62N2NaO4 +:621.4602,found 621.4600.
实施例32：
化合物8的制备(方法同化合物3的制备)
mp 94-96℃；[ɑ]24 D+56°(c 0.32,CHCl3)；IR(KBr):3377,2947,2867,1703,1644cm-1.1H NMR(400MHz,CDCl3)δ6.36(s,1H),5.40(t,J＝3.6Hz,1H),4.97(d,J＝6.8Hz,1H),3.42(dt,J＝11.8,6.7Hz,1H),3.21(dt,J＝24.3,8.3Hz,3H),2.55(ddt,J＝18.5,11.2,5.5Hz,2H),2.35(ddd,J＝15.8,6.7,3.5Hz,1H),1.98(tt,J＝9.9,3.4Hz,2H),1.88(dq,J＝9.6,3.5Hz,1H),1.79–1.69(m,2H),1.69–1.51(m,6H),1.48(d,J＝6.1Hz,3H),1.43(s,9H),1.39–1.27(m,4H),1.16(s,5H),1.08(s,3H),1.04(d,J＝3.7Hz,6H),0.90(d,J＝2.8Hz,6H),0.80(s,3H).13C NMR(101MHz,Chloroform-d)δ217.7,179.0,156.8,144.7,122.8,79.6,55.4,47.6,47.0,46.8,46.4,42.2,42.1,40.7,40.5,39.5,39.3,36.9,34.3,34.2,33.1,32.8,32.1,30.9,28.6,28.6,28.6,27.5,26.5,25.9,23.8,23.8,23.7,21.6,19.7,16.9,15.2.HRMS(ESI)calculated for C37H60N2NaO4 +:619.4445,found 619.4447.
实施例33：
化合物9的制备(方法同化合物4的制备)
mp 129-131℃；[ɑ]24 D+54°(c 0.35,CHCl3)；IR(KBr):3309,2948,2867,1690,1654cm-1.
1H NMR(400MHz,CDCl3)δ6.38(d,J＝6.9Hz,1H),5.98(t,J＝2.3Hz,1H),5.48–5.39(m,1H),5.15(d,J＝2.3Hz,1H),5.00(s,1H),3.41(dt,J＝11.6,5.4Hz,1H),3.26–3.13(m,3H),2.61(t,J＝11.4Hz,2H),2.12(d,J＝15.1Hz,1H),1.99(dddd,J＝13.7,10.6,6.4,2.9Hz,3H),1.80(s,1H),1.73(d,J＝14.7Hz,1H),1.69–1.65(m,1H),1.64–1.57(m,3H),1.56–1.49(m,2H),1.47(t,J＝5.1Hz,2H),1.43(s,9H),1.36–1.31(m,2H),1.26(d,J＝11.6Hz,2H),1.21–1.19(m,1H),1.17(s,3H),1.12(s,3H),1.05(s,3H),0.93–0.88(m,9H),0.81(s,3H).13C NMR(100MHz,CDCl3)δ207.5,179.0,156.8,144.6,142.0,123.8,122.7,79.6,54.2,46.9,46.7,46.4,46.0,45.4,42.3,42.1,40.6,40.5,39.3,36.9,34.2,33.1,32.8,31.8,30.8,28.5,28.5,28.5,28.3,27.4,25.8,23.8,23.7,23.7,22.9,20.2,16.7,15.1.HRMS(ESI)calculated for C38H60N2NaO4 +:631.4445,found 631.4441.
实施例34：
化合物10的制备(方法同化合物5的制备)
实施例35：
化合物O2的制备(方法同化合物U11的制备)
mp 133-135℃；[ɑ]24 D+56°(c 0.52,CHCl3)；IR(KBr):3306,3061,2930,2861,1684,1637,1602,1528,1458cm-1.1H NMR(400MHz,CDCl3)δ7.89(s,1H),7.41(t,J＝7.7Hz,2H),7.29(d,J＝7.4Hz,1H),7.21(d,J＝7.7Hz,2H),6.97(t,J＝5.2Hz,1H),6.47(t,J＝5.6Hz,1H),5.98(t,J＝2.4Hz,1H),5.46–5.39(m,1H),5.16(d,J＝2.3Hz,1H),3.89(s,1H),3.66(dt,J＝14.5,5.5Hz,1H),3.53(ddd,J＝13.8,10.3,5.5Hz,1H),3.26(dt,J＝13.8,5.5Hz,1H),2.65–2.56(m,2H),2.11(d,J＝15.0Hz,1H),1.95(td,J＝9.1,3.7Hz,3H),1.75–1.65(m,2H),1.57–1.48(m,3H),1.45(d,J＝10.0Hz,3H),1.41–1.36(m,2H),1.29(dd,J＝12.6,3.4Hz,2H),1.24(s,2H),1.20–1.17(m,1H),1.15(s,3H),1.12(s,3H),1.05(s,3H),0.90(d,J＝4.3Hz,9H),0.76(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.4,179.8,144.6,142.0,136.2,130.1,130.1,127.3,125.4,125.4,123.9,122.9,54.2,46.9,46.7,46.5,46.1,45.4,42.2,42.0,39.5,39.3,39.3,36.9,34.2,33.1,32.7,31.8,30.9,28.3,27.4,25.8,23.8,23.7,23.7,22.9,20.2,16.6,15.1.
HRMS(ESI)calculated for C40H57N3NaO2S+:666.4064,found 666.4066.
实施例36：
化合物O3的制备(方法同化合物U11的制备)
mp 163-164℃；[ɑ]24 D+50°(c 0.40,CHCl3)；IR(KBr):3318,2943,2864,1685,1639,1511,1461cm-1.1H NMR(400MHz,CDCl3)δ8.52(s,1H),7.75(s,1H),7.61(d,J＝8.2Hz,2H),7.49(s,2H),6.54(t,J＝5.8Hz,1H),5.98(t,J＝2.3Hz,1H),5.40(t,J＝3.6Hz,1H),5.16(d,J＝2.3Hz,1H),3.91(s,1H),3.69(s,1H),3.54(s,1H),3.32(dt,J＝14.2,5.4Hz,1H),2.64–2.53(m,2H),2.11(d,J＝15.1Hz,1H),1.94(ddd,J＝10.5,7.3,3.6Hz,3H),1.74–1.64(m,2H),1.52–1.37(m,8H),1.29(d,J＝12.6Hz,2H),1.24(s,2H),1.20–1.17(m,1H),1.15(s,3H),1.12(s,3H),1.04(s,3H),0.86(d,J＝13.1Hz,9H),0.74(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.4,180.7,144.3,141.9,140.8,126.6,126.6,125.4,124.0,123.9,123.9,123.1,122.7,54.1,46.8,46.6,46.5,46.0,45.3,42.2,42.0,39.6,39.3,39.3,36.8,34.10,33.0,32.7,31.7,30.8,28.3,27.3,25.7,23.8,23.7,23.6,22.8,20.2,16.6,15.1.HRMS(ESI)calculated for C41H56F3N3NaO2S+:734.3938,found 734.3943.
实施例37：
化合物O4的制备(方法同化合物U11的制备)
mp 144-146℃；[ɑ]24 D+61°(c 0.38,CHCl3)；IR(KBr):3307,2946,2864,1749,1687,1641cm-1.1H NMR(400MHz,CDCl3)δ7.65(s,1H),7.12(d,J＝8.3Hz,2H),6.94–6.89(m,2H),6.69(t,J＝5.3Hz,1H),6.45(t,J＝5.7Hz,1H),5.98(t,J＝2.3Hz,1H),5.46–5.40(m,1H),5.16(d,J＝2.3Hz,1H),3.86(s,1H),3.81(s,3H),3.64(dt,J＝13.9,5.5Hz,1H),3.52(ddd,J＝14.1,7.8,3.7Hz,1H),3.24(dt,J＝14.0,5.4Hz,1H),2.64–2.55(m,2H),2.11(d,J＝15.0Hz,1H),2.00–1.89(m,3H),1.74(d,J＝13.3Hz,1H),1.70–1.66(m,1H),1.55–1.37(m,8H),1.33–1.27(m,2H),1.24(s,2H),1.19(d,J＝3.8Hz,1H),1.15(s,3H),1.12(s,3H),1.05(s,3H),0.93–0.88(m,9H),0.76(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.9,179.7,159.1,144.6,142.0,128.5,127.9,127.9,123.9,122.9,115.3,115.3,55.7,54.2,46.9,46.7,46.5,46.1,45.4,42.2,42.0,39.6,39.3,39.3,36.9,34.3,33.1,32.7,31.8,30.9,28.3,27.4,25.8,23.8,23.7,23.7,22.9,20.2,16.6,15.1.HRMS(ESI)calculated forC41H59N3NaO3S+:696.4169,found 696.4174.
实施例38：
化合物O5的制备(方法同化合物U20的制备)
mp 131-133℃；[ɑ]24 D+56°(c 0.34,CHCl3)；IR(KBr):3290,2946,2865,1687,1649,1603,1579,1531,1489cm-1.1H NMR(400MHz,CDCl3)δ7.85–7.80(m,2H),7.63(t,J＝4.4Hz,1H),7.50–7.45(m,1H),7.42(dd,J＝8.2,6.4Hz,2H),6.52(t,J＝5.4Hz,1H),5.98(t,J＝2.3Hz,1H),5.43(t,J＝3.6Hz,1H),5.15(d,J＝2.3Hz,1H),3.58(th,J＝13.4,4.7Hz,3H),3.39(dq,J＝9.4,5.5,4.8Hz,1H),2.61(dd,J＝18.3,12.3Hz,2H),2.10(d,J＝15.1Hz,1H),2.01(td,J＝13.8,3.8Hz,1H),1.90(td,J＝10.0,8.4,3.5Hz,2H),1.76(d,J＝13.3Hz,2H),1.68–1.61(m,3H),1.52(dd,J＝8.8,4.5Hz,1H),1.43–1.38(m,2H),1.37–1.32(m,2H),1.25(s,4H),1.21(s,1H),1.16(s,3H),1.11(s,3H),1.03(s,3H),0.88(d,J＝7.1Hz,6H),0.83(s,3H),0.74(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.7,167.9,144.5,142.0,134.0,131.6,128.6,128.6,127.2,127.2,123.9,122.9,54.2,46.9,46.7,46.6,46.0,45.4,42.3,42.1,42.0,39.8,39.3,36.8,34.2,33.1,32.8,31.8,30.8,28.4,27.4,25.7,23.9,23.6,23.6,22.9,20.2,16.7,15.1.HRMS(ESI)calculated for C40H56N2NaO3 +:635.4183,found 635.4188.
实施例39：
化合物O6的制备(方法同化合物U11的制备)
mp 149-150℃；[ɑ]24 D+65°(c 0.33,CHCl3)；IR(KBr):3324,2945,2864,1687,1621,1553,1510,1462cm-1.1H NMR(400MHz,CDCl3)δ7.29(s,1H),7.25–7.20(m,2H),6.83–6.78(m,2H),6.71(t,J＝5.1Hz,1H),5.98(d,J＝2.4Hz,1H),5.93(d,J＝6.2Hz,1H),5.42(d,J＝3.6Hz,1H),5.15(d,J＝2.3Hz,1H),3.76(s,3H),3.46–3.28(m,3H),3.18(dt,J＝12.0,5.3Hz,1H),2.66–2.56(m,2H),2.10(d,J＝15.2Hz,1H),1.99(d,J＝3.7Hz,1H),1.93(d,J＝9.3Hz,2H),1.74(d,J＝13.4Hz,1H),1.69–1.65(m,1H),1.59(t,J＝8.3Hz,3H),1.52–1.38(m,5H),1.30–1.24(m,4H),1.19(dd,J＝4.8,2.2Hz,1H),1.15(s,3H),1.11(s,3H),1.04(s,3H),0.89–0.85(m,9H),0.78(s,3H).13C NMR(100MHz,CDCl3)δ207.5,179.8,157.4,156.1,144.3,142.0,132.0,123.9,122.9,122.9,122.8,114.4,114.4,55.6,54.2,46.8,46.7,46.5,46.0,45.4,42.2,41.9,41.1,39.7,39.3,36.9,34.2,33.1,33.0,31.8,30.8,28.4,27.4,25.8,23.8,23.6,23.6,22.9,20.2,16.7,15.1.HRMS(ESI)calculatedfor C41H59N3NaO4 +:680.4398,found 680.4400.
实施例40：
化合物O7的制备(方法同化合物U11的制备)
mp 152-153℃；[ɑ]24 D+58°(c 0.35,CHCl3)；IR(KBr):3315,2928,2864,1687,1603,1548,1459cm-1.1H NMR(400MHz,CDCl3)δ7.42(s,1H),7.23–7.19(m,2H),7.06(d,J＝8.1Hz,2H),6.72(t,J＝5.2Hz,1H),6.06(t,J＝5.6Hz,1H),5.98(t,J＝2.3Hz,1H),5.45–5.40(m,1H),5.16(d,J＝2.2Hz,1H),3.37(ddt,J＝33.7,15.2,6.1Hz,3H),3.19(dt,J＝12.1,5.4Hz,1H),2.67–2.56(m,2H),2.28(s,3H),2.10(d,J＝15.2Hz,1H),2.04–1.97(m,1H),1.92(dd,J＝10.3,3.1Hz,2H),1.74(d,J＝13.4Hz,1H),1.70–1.65(m,1H),1.60(td,J＝11.1,8.2,3.7Hz,3H),1.55–1.45(m,2H),1.44–1.37(m,3H),1.26(d,J＝7.5Hz,4H),1.22–1.18(m,1H),1.15(s,3H),1.11(s,3H),1.04(s,3H),0.89–0.85(m,9H),0.78(s,3H).13C NMR(100MHz,CDCl3)δ207.5,179.9,157.1,144.2,142.0,136.6,132.7,129.6,129.6,123.9,123.0,120.4,120.4,54.2,46.8,46.7,46.5,46.0,45.4,42.2,41.9,41.1,39.6,39.3,36.9,34.2,33.1,33.0,31.8,30.8,28.4,27.4,25.8,23.8,23.6,23.6,22.9,20.9,20.2,16.7,15.1.HRMS(ESI)calculated for C41H59N3NaO3 +:664.4449,found 664.4445.
实施例41：
化合物O8的制备(方法同化合物U4的制备)
mp 80-82℃；[ɑ]24 D+74°(c 0.33,CHCl3)；IR(KBr):3348,2946,2869,1715,1685,1650cm-1.
1H NMR(400MHz,CDCl3)δ8.94(t,J＝5.8Hz,1H),6.44(t,J＝4.8Hz,1H),5.98(t,J＝2.3Hz,1H),5.43–5.38(m,1H),5.15(d,J＝2.2Hz,1H),3.67(s,3H),3.54–3.46(m,2H),3.38(tt,J＝8.9,4.3Hz,1H),3.20–3.12(m,1H),2.61(d,J＝15.1Hz,2H),2.12(d,J＝15.1Hz,1H),2.01–1.93(m,3H),1.77–1.66(m,4H),1.63–1.58(m,3H),1.57–1.52(m,3H),1.49–1.39(m,4H),1.36–1.22(m,4H),1.19(d,J＝4.3Hz,1H),1.16(s,3H),1.12(s,3H),1.05(s,3H),0.93–0.88(m,9H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.5,178.6,173.8,170.0,144.7,142.1,123.8,122.6,54.2,52.4,46.9,46.7,46.4,46.0,45.5,42.2,42.0,40.6,39.4,39.2,36.9,34.3,33.2,32.9,31.9,30.9,28.4,27.5,26.2,25.8,23.7,23.7,23.7,22.9,20.3,20.3,20.2,16.7,15.1.HRMS(ESI)calculated for C39H58N2NaO5 +:657.4238,found 657.4241.
实施例42：
化合物O9的制备(方法同化合物U11的制备)
mp 156-158℃；[ɑ]24 D+63°(c 0.35,CHCl3)；IR(KBr):3340,3089,2944,2869,1691,1615,1553,1510,1463cm-1.1H NMR(400MHz,CDCl3)δ7.98(s,1H),7.40(d,J＝8.5Hz,2H),7.09(d,J＝8.5Hz,2H),6.70(t,J＝5.1Hz,1H),6.29(s,1H),5.98(s,1H),5.43(d,J＝3.8Hz,1H),5.15(s,1H),3.44(td,J＝15.2,14.2,6.0Hz,2H),3.32(q,J＝6.3,5.8Hz,1H),3.21(dt,J＝11.9,5.1Hz,1H),2.60(t,J＝12.3Hz,2H),2.10(d,J＝15.5Hz,1H),2.04–1.90(m,4H),1.76–1.65(m,2H),1.52(d,J＝34.3Hz,5H),1.45–1.37(m,3H),1.26(d,J＝10.7Hz,3H),1.19(s,1H),1.16(s,3H),1.11(s,3H),1.03(s,3H),0.86(s,6H),0.78(s,6H).13C NMR(100MHz,CDCl3)δ207.4,180.4,156.7,144.1,144.0,141.9,138.5,124.0,123.1,122.0,121.8,121.8,119.9,119.9,54.2,46.8,46.6,46.6,46.0,45.4,42.2,42.0,40.9,39.4,39.3,36.9,34.1,33.0,33.0,31.8,30.8,28.3,27.4,25.8,23.9,23.6,23.5,22.8,20.2,16.7,15.0.HRMS(ESI)calculated for C41H56F3N3NaO4 +:734.4115,found 734.4114.
实施例43：
化合物O10的制备(方法同化合物U20的制备)
mp 73-75℃；[ɑ]24 D+84°(c 0.33,CHCl3)；IR(KBr):3305,2929,2859,1715,1685,1649cm-1.
1H NMR(400MHz,CDCl3)δ6.58(t,J＝4.9Hz,1H),6.48(t,J＝5.3Hz,1H),5.98(t,J＝2.3Hz,1H),5.44(t,J＝3.6Hz,1H),5.16(d,J＝2.3Hz,1H),3.41(tq,J＝13.0,4.2Hz,2H),3.26(ddt,J＝20.4,13.3,3.6Hz,2H),2.60(t,J＝12.9Hz,2H),2.18–2.10(m,3H),2.03–1.95(m,3H),1.76(d,J＝13.4Hz,1H),1.70(d,J＝8.9Hz,1H),1.61(ddd,J＝14.6,11.0,7.5Hz,5H),1.55–1.50(m,2H),1.48–1.43(m,2H),1.39(dd,J＝9.4,5.3Hz,2H),1.33(d,J＝3.2Hz,1H),1.28(ddd,J＝11.5,7.5,4.2Hz,10H),1.21(d,J＝3.2Hz,1H),1.17(s,3H),1.12(s,3H),1.05(s,3H),0.90(d,J＝2.9Hz,9H),0.86(s,3H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.0,174.4,144.6,142.0,123.9,122.8,54.18,46.87,46.73,46.50,46.05,45.42,42.27,42.07,40.62,40.09,39.35,36.9,36.9,34.3,33.1,32.9,31.8,31.8,30.8,29.4,29.2,28.3,27.4,25.9,25.8,23.8,23.7,23.7,22.9,22.8,20.2,16.6,15.1,14.2.HRMS(ESI)calculated for C31H51NNaO2 +:492.3812,found 492.3815.
实施例44：
化合物O11的制备(方法同化合物U20的制备)
mp 162-164℃；[ɑ]24 D+48°(c 0.40,CHCl3)；IR(KBr):3326,3064,2943,2868,1647,1593cm-1.
1H NMR(400MHz,CDCl3)δ7.90(t,J＝4.2Hz,1H),7.73–7.69(m,2H),7.57–7.52(m,2H),6.50(t,J＝5.7Hz,1H),5.98(t,J＝2.3Hz,1H),5.42(t,J＝3.6Hz,1H),5.15(t,J＝2.2Hz,1H),3.61–3.50(m,3H),3.39(ddd,J＝11.3,7.9,4.2Hz,1H),2.60(dd,J＝12.2,8.7Hz,2H),2.10(d,J＝15.1Hz,1H),2.06–1.98(m,1H),1.90(ddd,J＝14.4,11.2,5.4Hz,2H),1.81–1.71(m,2H),1.67–1.59(m,3H),1.53(dd,J＝13.9,4.1Hz,1H),1.49–1.40(m,3H),1.39–1.31(m,3H),1.25–1.17(m,3H),1.16(s,3H),1.11(s,3H),1.03(s,3H),0.88(d,J＝9.0Hz,6H),0.84(s,3H),0.72(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.1,166.8,144.5,141.9,132.8,131.8,131.8,128.9,128.9,126.3,123.9,123.0,54.1,46.9,46.7,46.6,46.0,45.3,42.5,42.3,42.1,39.6,39.3,36.8,34.2,33.1,32.9,31.8,30.8,28.3,27.3,25.7,23.9,23.6,23.6,22.9,20.2,16.7,15.2.HRMS(ESI)calculated forC31H51NNaO2 +:492.3812,found 492.3815.
实施例45：
化合物O12的制备(方法同化合物U4的制备)
mp 135-137℃；[ɑ]24 D+32°(c 0.27,CHCl3)；IR(KBr):3346,2947,2867,1683,1636,1605,1530,1509,1461cm-1.1H NMR(400MHz,CDCl3)δ11.40(s,1H),7.54(ddd,J＝7.0,5.4,2.9Hz,3H),7.01–6.93(m,2H),6.42(t,J＝5.8Hz,1H),5.98(t,J＝2.3Hz,1H),5.44(t,J＝3.6Hz,1H),5.15(d,J＝2.2Hz,1H),3.51–3.43(m,1H),3.39–3.28(m,3H),2.65–2.51(m,2H),2.11(d,J＝15.1Hz,1H),2.07–1.94(m,3H),1.79(d,J＝13.5Hz,1H),1.75–1.64(m,6H),1.56(dd,J＝13.7,4.2Hz,1H),1.52–1.44(m,2H),1.41–1.35(m,5H),1.32–1.24(m,3H),1.23–1.21(m,1H),1.18(s,3H),1.10(s,3H),0.98(s,3H),0.91(d,J＝4.3Hz,6H),0.87(s,3H),0.77(s,3H).13C NMR(100MHz,CDCl3)δ207.3,181.9,173.8,167.9,160.4,144.6,141.9,134.7,123.9,123.1,121.7,121.6,115.6,115.4,54.1,46.9,46.8,46.7,46.0,45.3,43.2,42.4,42.4,39.4,39.0,36.9,34.1,33.0,32.7,31.8,30.8,28.3,27.4,27.3,25.7,23.9,23.7,23.6,22.8,20.1,18.6,18.4,16.7,15.1.HRMS(ESI)calculated forC31H51NNaO2 +:492.3812,found 492.3815.
实施例46：
化合物O13的制备(方法同化合物U20的制备)
mp 88-90℃；[ɑ]24 D+57°(c 0.35,CHCl3)；IR(KBr):3321,2931,1715,1687,1641cm-1.1H NMR(400MHz,CDCl3)δ6.62(d,J＝4.6Hz,1H),6.55(d,J＝5.1Hz,1H),5.99(d,J＝2.3Hz,1H),5.45(d,J＝3.7Hz,1H),5.16(d,J＝2.3Hz,1H),3.47–3.40(m,2H),3.33–3.24(m,2H),2.60(dd,J＝18.0,12.5Hz,2H),2.12(d,J＝15.1Hz,1H),2.01–1.97(m,2H),1.89(dt,J＝9.0,4.0Hz,1H),1.73(d,J＝13.7Hz,1H),1.68(dd,J＝7.2,2.7Hz,1H),1.66–1.60(m,3H),1.59–1.54(m,3H),1.51(d,J＝9.8Hz,2H),1.49–1.43(m,4H),1.42–1.30(m,4H),1.25–1.20(m,2H),1.18(s,3H),1.12(s,3H),1.05(s,3H),0.93–0.89(m,9H),0.86(t,J＝7.5Hz,6H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.5,180.1,177.0,144.6,142.0,123.9,122.9,54.12,51.4,46.9,46.8,46.5,46.1,45.4,42.3,42.1,40.7,40.3,39.4,36.9,34.3,33.1,32.7,31.8,30.8,28.3,27.4,25.8,25.7,25.0,23.9,23.7,23.6,22.9,20.2,16.7,15.1,12.3,11.9.HRMS(ESI)calculated for C31H51NNaO2 +:492.3812,found492.3815.
实施例47：
化合物O14的制备(方法同化合物U11的制备)
mp 163-164℃；[ɑ]21.5 D＝+38°(c 0.18,CHCl3)；IR(KBr):3382,3066,2947,2864,1645，1595,1531,1447cm-1.1H NMR(400MHz,CDCl3)δ7.87(s,1H),7.35(d,J＝8.6Hz,2H),7.28(d,J＝9.7Hz,2H),6.71(t,J＝5.1Hz,1H),6.35(d,J＝6.6Hz,1H),6.00(d,J＝2.4Hz,1H),5.43(d,J＝3.4Hz,1H),5.18(s,1H),3.39(dtd,J＝33.2,13.0,6.6Hz,3H),3.20(dq,J＝12.6,7.5,6.6Hz,1H),2.68–2.56(m,2H),2.15–2.00(m,2H),1.92(dt,J＝8.5,4.2Hz,2H),1.78–1.65(m,2H),1.59(q,J＝8.7,6.6Hz,3H),1.53–1.42(m,3H),1.40(d,J＝9.8Hz,2H),1.33(d,J＝2.7Hz,1H),1.27(d,J＝10.4Hz,3H),1.21(s,1H),1.17(s,3H),1.13(s,3H),1.05(s,3H),0.88(d,J＝6.7Hz,6H),0.84(s,3H),0.78(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.3,156.6,144.1,141.9,138.8,131.9,131.9,124.0,123.2,120.7,120.7,114.9,54.2,46.8,46.6,46.6,46.0,45.4,42.2,42.0,41.1,39.3,39.3,36.9,34.2,33.0,31.8,30.8,29.8,28.4,27.4,25.8,23.9,23.6,23.6,22.9,20.2,16.7,15.1.HRMS(ESI)calculated for C40H56BrN3NaO3 +:728.3397,found 728.3398.
实施例48：
化合物O15的制备(方法同化合物U4的制备)
mp 160-161℃；[ɑ]21.5 D＝+40°(c 0.67,CHCl3)；IR(KBr):3342,3059,2945,2866,1670,1594,1533,1448cm-1.1H NMR(400MHz,CDCl3)δ8.14(t,J＝4.3Hz,1H),7.39(dt,J＝6.5,2.1Hz,2H),6.91(tt,J＝8.5,2.4Hz,1H),6.51(t,J＝5.7Hz,1H),5.97(t,J＝2.3Hz,1H),5.44(t,J＝3.6Hz,1H),5.15(d,J＝2.2Hz,1H),3.56(ddt,J＝24.3,10.3,5.7Hz,3H),3.45–3.36(m,1H),2.69–2.57(m,2H),2.14–2.07(m,1H),2.02(dd,J＝13.9,3.8Hz,1H),1.95–1.83(m,2H),1.80–1.74(m,1H),1.61(t,J＝3.6Hz,3H),1.57–1.49(m,2H),1.48–1.41(m,2H),1.41–1.33(m,3H),1.28–1.18(m,4H),1.17(s,3H),1.11(s,3H),1.03(s,3H),0.89(d,J＝7.1Hz,6H),0.84(s,3H),0.73(s,3H).13C NMR(100MHz,CDCl3)δ207.3,181.2,165.3,164.3,161.9,144.8,141.9,137.6,123.9,123.0,110.6,110.4,106.8,54.2,46.9,46.7,46.6,46.0,45.3,42.7,42.3,42.2,39.5,39.3,36.8,34.2,33.1,32.9,31.8,30.8,28.4,27.4,25.7,23.9,23.6,23.6,22.9,20.2,16.7,15.0.HRMS(ESI)calculated forC40H54F2N2NaO3 +:671.3995,found 671.3993.
实施例49：
化合物O16的制备(方法同化合物U4的制备)
mp 163-164℃；[ɑ]21.5 D＝+47°(c 0.79,CHCl3)；IR(KBr):3356,3065,2947,2864,1647,1594,1533,1448cm-1.1H NMR(400MHz,CDCl3)δ8.10(d,J＝4.4Hz,1H),7.97(d,J＝2.1Hz,1H),7.67(dd,J＝8.3,2.1Hz,1H),7.48(d,J＝8.3Hz,1H),6.52(t,J＝5.7Hz,1H),5.97(t,J＝2.3Hz,1H),5.43(s,1H),5.15(s,1H),3.63–3.49(m,3H),3.45–3.37(m,1H),2.67–2.53(m,2H),2.13–1.98(m,2H),1.94–1.82(m,2H),1.71(s,1H),1.68–1.60(m,3H),1.54(dd,J＝13.8,4.3Hz,1H),1.50–1.33(m,6H),1.24(d,J＝2.4Hz,1H),1.22–1.14(m,6H),1.10(s,3H),1.03(s,3H),0.89(d,J＝7.7Hz,6H),0.83(s,3H),0.71(s,3H).13C NMR(100MHz,CDCl3)δ207.3,181.2,165.5,144.5,141.9,135.9,134.0,133.1,130.6,129.7,126.3,123.9,123.0,54.2,46.9,46.7,46.6,46.0,45.3,42.6,42.3,42.1,39.5,39.3,36.8,34.2,33.1,32.9,31.8,30.8,28.3,27.3,25.7,23.9,23.6,23.6,22.9,20.2,16.7,15.0.HRMS(ESI)calculated for C40H54Cl2N2NaO3 +:703.3404,found 703.3401.
实施例50：
化合物O17的制备(方法同化合物U4的制备)
mp 159-160℃；[ɑ]21.5 D＝+33°(c 0.41,CHCl3)；IR(KBr):3354,3077,2945,2865,1701,1594,1530,1447cm-1.1H NMR(400MHz,CDCl3)δ7.85(dd,J＝9.2,6.5Hz,1H),7.44(dt,J＝10.8,4.5Hz,1H),7.23(dd,J＝10.3,5.6Hz,1H),6.40(t,J＝5.1Hz,1H),5.98(t,J＝2.4Hz,1H),5.47–5.36(m,1H),5.15(d,J＝2.3Hz,1H),3.71–3.49(m,3H),3.31(tt,J＝12.0,5.3Hz,1H),2.59(d,J＝14.9Hz,2H),2.11(d,J＝15.1Hz,1H),1.96(dtd,J＝26.8,11.4,9.2,3.5Hz,3H),1.80–1.59(m,5H),1.56–1.36(m,7H),1.25(t,J＝5.7Hz,2H),1.16(s,4H),1.12(s,3H),1.04(s,3H),0.94–0.84(m,9H),0.76(s,3H).13C NMR(100MHz,CDCl3)δ207.3,179.7,162.2,156.1,154.6,144.7,142.0,123.9,122.8,119.1,119.0,118.8,118.5,54.2,46.9,46.8,46.5,46.1,45.4,42.3,42.1,41.1,39.8,39.3,36.9,34.2,33.1,32.8,31.8,30.9,28.4,27.4,25.7,23.8,23.6,23.6,22.9,20.2,16.6,15.0.HRMS(ESI)calculated for C40H53ClF2N2NaO3 +:705.3605,found 705.3606.
实施例51：
化合物O18的制备(方法同化合物U4的制备)
mp 144-145℃；[ɑ]21.5 D＝+40°(c 0.51,CHCl3)；IR(KBr):3354,3077,2945,2865,1648,1595,1527,1449cm-1.1H NMR(400MHz,CDCl3)δ7.39(d,J＝4.5Hz,1H),7.17(qd,J＝9.1,4.9Hz,1H),6.87(tq,J＝9.0,3.4,2.8Hz,1H),6.45(t,J＝5.3Hz,1H),5.98(t,J＝2.3Hz,1H),5.44(t,J＝3.6Hz,1H),5.16(d,J＝2.3Hz,1H),3.63–3.50(m,3H),3.37(ddd,J＝9.5,7.5,3.8Hz,1H),2.67–2.53(m,2H),2.12(d,J＝15.0Hz,1H),1.98(hept,J＝3.9,3.2Hz,3H),1.75(s,1H),1.71–1.66(m,1H),1.61–1.46(m,7H),1.41(d,J＝9.2Hz,1H),1.37–1.31(m,2H),1.25(s,2H),1.21(d,J＝4.1Hz,1H),1.17(s,3H),1.12(s,3H),1.05(s,3H),0.92–0.87(m,9H),0.82(s,3H).13C NMR(100MHz,CDCl3)δ207.4,180.5,160.1,149.0,146.6,146.1,144.7,142.0,123.9,123.0,118.4,111.8,111.5,54.2,46.9,46.8,46.5,46.1,45.4,42.3,42.2,41.7,39.5,39.4,36.9,34.2,33.1,32.6,31.7,30.8,28.4,27.3,25.7,23.9,23.7,23.5,22.9,20.2,16.6,15.1.HRMS(ESI)calculated for C40H53F3N2NaO3 +:689.3900,found 689.3902.
实施例52：
化合物O19的制备(方法同化合物U4的制备)
mp 162-163℃；[ɑ]21.5 D+37°(c 0.56,CHCl3)；IR(KBr):3370,3069,2947,2864,1659,1595,1526,1445cm-1.1H NMR(400MHz,CDCl3)δ8.07(t,J＝4.1Hz,1H),7.92(d,J＝1.7Hz,2H),7.76(d,J＝1.9Hz,1H),6.48(t,J＝5.7Hz,1H),5.98(t,J＝2.3Hz,1H),5.45(d,J＝3.7Hz,1H),5.16(d,J＝2.4Hz,1H),3.65–3.48(m,3H),3.42(dt,J＝14.8,5.4Hz,1H),2.69–2.52(m,2H),2.14–2.00(m,2H),1.93(ddt,J＝22.2,15.3,4.6Hz,2H),1.75(t,J＝13.3Hz,1H),1.66(dd,J＝11.0,6.3Hz,3H),1.56(dd,J＝13.7,4.2Hz,1H),1.48(ddd,J＝22.2,11.5,5.4Hz,3H),1.35(q,J＝9.8,9.3Hz,3H),1.23(dt,J＝11.0,5.2Hz,4H),1.17(s,3H),1.11(s,3H),1.04(s,3H),0.90(d,J＝4.9Hz,6H),0.84(s,3H),0.71(s,3H).13C NMR(100MHz,CDCl3)δ207.4,181.3,165.0,144.5,141.9,137.5,136.8,129.3,129.3,123.9,123.3,123.3,123.0,54.2,46.9,46.7,46.7,46.0,45.4,42.8,42.3,42.1,39.5,39.3,36.8,34.2,33.1,33.0,31.8,30.9,28.4,27.4,25.7,24.0,23.6,23.6,22.9,20.2,16.7,15.1.HRMS(ESI)calculated for C40H54Br2N2NaO3 +:791.2393,found 791.2395.
实施例53：
化合物O20的制备(方法同化合物U4的制备)
mp 160-161℃；[ɑ]21.5 D＝+24°(c 0.43,CHCl3)；IR(KBr):3349,3069,2948,2866,1706,1595,1530,1446cm-1.1H NMR(400MHz,CDCl3)δ8.29(d,J＝4.0Hz,1H),8.19(s,1H),8.06(s,1H),7.86(s,1H),6.48(t,J＝5.7Hz,1H),5.99(q,J＝2.7Hz,1H),5.45(d,J＝3.6Hz,1H),5.16(d,J＝2.5Hz,1H),3.62–3.41(m,4H),2.61(dd,J＝15.3,11.1Hz,2H),2.09(dd,J＝15.5,12.2Hz,1H),1.99(dt,J＝11.5,3.6Hz,1H),1.92(ddd,J＝14.7,8.9,3.6Hz,1H),1.76(t,J＝13.5Hz,1H),1.67(dt,J＝10.9,4.3Hz,4H),1.56(dd,J＝13.7,4.2Hz,1H),1.52–1.45(m,2H),1.44(t,J＝4.2Hz,1H),1.38(d,J＝3.2Hz,2H),1.29(d,J＝6.8Hz,1H),1.26(d,J＝4.0Hz,2H),1.22–1.17(m,5H),1.11(s,3H),1.05(d,J＝9.9Hz,3H),0.92–0.88(m,6H),0.84(s,3H),0.72(s,3H).13C NMR(100MHz,CDCl3)δ207.3,181.7,164.8,144.5,141.9,136.9,133.9,131.1,131.1,123.9,123.2,123.1,123.0,123.0,54.2,46.9,46.7,46.7,46.1,45.3,43.2,42.4,42.2,39.4,39.3,36.8,34.2,33.1,32.9,31.8,30.8,28.4,27.4,25.7,24.0,23.6,23.6,22.9,20.2,16.7,15.0.HRMS(ESI)calculated forC41H54BrF3N2NaO3 +:781.3162,found 781.3160.
实施例54：
化合物13的制备(方法同化合物2的制备)
mp 140-142℃；[ɑ]24 D+123°(c 0.36,CHCl3)；IR(KBr):3515,3356,2971,2935,1699,1653cm-1.1H NMR(400MHz,CDCl3)δ6.56(s,1H),5.70(s,1H),4.93(d,J＝6.1Hz,1H),3.31(dqt,J＝32.8,10.2,6.0Hz,5H),2.82–2.74(m,1H),2.32(s,1H),2.21–2.14(m,1H),2.03(dt,J＝13.7,6.8Hz,1H),1.93–1.76(m,3H),1.62(td,J＝15.2,14.5,9.7Hz,6H),1.42(s,9H),1.37(d,J＝8.4Hz,6H),1.31(d,J＝5.7Hz,1H),1.18(d,J＝14.7Hz,1H),1.12(d,J＝4.3Hz,9H),1.00(s,4H),0.97–0.91(m,1H),0.80(s,6H),0.69(d,J＝11.4Hz,1H).13C NMR(100MHz,DMSO-d 6)δ199.0,175.4,169.5,155.7,127.6,77.6,76.6,61.2,54.1,47.6,44.8,42.9,42.9,40.8,40.2,38.9,38.8,38.5,37.3,36.7,32.2,31.4,30.4,28.7,28.4,28.2,28.2,28.2,28.2,27.0,26.1,26.0,23.0,18.3,17.2,16.2,16.0.HRMS(ESI)calculated for C37H60N2NaO5 +:635.4394,found 635.4395.
实施例55：
化合物14的制备(方法同化合物3的制备)
mp 137-139℃；[ɑ]24 D+90°(c 1.8,CHCl3)；IR(KBr):3364,2975,2871,1703,1655cm-1.1H NMR(400MHz,CDCl3)δ6.68(t,J＝4.9Hz,1H),5.72(s,1H),5.07(t,J＝5.8Hz,1H),3.39–3.24(m,4H),2.93(ddd,J＝13.6,7.1,4.0Hz,1H),2.60(ddd,J＝15.8,11.2,7.1Hz,1H),2.40(s,1H),2.33(ddd,J＝15.8,6.5,4.0Hz,1H),2.19(dd,J＝13.5,3.9Hz,1H),2.07–1.99(m,2H),1.84(dd,J＝15.0,6.7Hz,3H),1.68–1.59(m,2H),1.58–1.47(m,3H),1.45(d,J＝2.8Hz,1H),1.40(s,9H),1.37(s,2H),1.35(s,3H),1.29–1.26(m,1H),1.24(s,3H),1.21–1.16(m,1H),1.13(s,3H),1.09(d,J＝9.0Hz,6H),1.04(s,3H),0.99(dt,J＝4.3,2.0Hz,1H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ217.4,199.4,176.8,169.7,157.4,128.6,79.9,61.1,55.5,48.1,47.9,45.3,43.6,43.4,41.7,41.3,40.5,39.9,37.6,36.8,34.3,32.2,32.0,31.5,29.6,28.7,28.5,28.5,28.5,26.6,26.5,26.5,23.4,21.5,18.9,18.6,15.7.HRMS(ESI)calculated for C37H58N2NaO5 +:633.4238,found 633.4244.
实施例56：
化合物15的制备(方法同化合物4的制备)
mp 141-142℃；[ɑ]24 D+144°(c 0.59,CHCl3)；IR(KBr):3373,2978,2931,1690,1656cm-1.1H NMR(400MHz,CDCl3)δ6.67(s,1H),5.99(s,1H),5.75(s,1H),5.23(s,1H),5.06(t,J＝5.9Hz,1H),3.73(d,J＝15.3Hz,1H),3.39–3.24(m,4H),2.43(s,1H),2.21(dd,J＝13.5,4.0Hz,1H),2.11(d,J＝15.8Hz,1H),2.04–2.00(m,1H),1.91–1.79(m,3H),1.71–1.56(m,2H),1.49(p,J＝4.7Hz,3H),1.38(d,J＝13.3Hz,16H),1.23–1.18(m,1H),1.15–1.09(m,12H),1.06(s,3H),1.03–0.99(m,1H),0.80(d,J＝4.7Hz,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,176.8,169.9,157.4,142.0,128.6,124.3,79.9,59.3,54.5,48.0,47.3,46.2,45.1,43.6,43.4,41.7,41.4,40.4,37.7,36.8,32.0,31.9,31.6,29.6,28.7,28.5,28.5,28.47,28.4,26.6,26.5,23.4,22.8,19.5,18.4,15.2.HRMS(ESI)calculated forC38H58N2NaO5 +:645.4238,found 645.4239.
实施例57：
化合物16的制备(方法同化合物5的制备)
实施例58：
化合物G1的制备(方法同化合物U11的制备)
mp 163-164℃；[ɑ]24 D+111°(c 0.48,CHCl3)；IR(KBr):3319,3073,2953,2930,1654,1616,1521,1469cm-1.1H NMR(400MHz,CDCl3)δ8.80(s,1H),7.60(d,J＝8.3Hz,2H),7.44(d,J＝43.9Hz,3H),7.03(s,1H),6.00(t,J＝2.4Hz,1H),5.69(s,1H),5.22(d,J＝2.3Hz,1H),3.92(d,J＝95.9Hz,2H),3.70(d,J＝15.4Hz,1H),3.49(q,J＝5.4Hz,2H),2.44(s,1H),2.21(s,1H),2.11(d,J＝15.5Hz,1H),2.03(d,J＝13.7Hz,1H),1.83(ddt,J＝17.9,13.5,7.5Hz,3H),1.72–1.61(m,2H),1.54–1.39(m,4H),1.34(d,J＝11.2Hz,5H),1.27–1.17(m,2H),1.15–1.06(m,15H),1.05–1.00(m,1H),0.77(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.9,181.6,178.0,170.4,141.9,140.7,128.4,126.8,126.8,124.3,124.3,123.9,123.9,122.6,59.4,54.4,48.5,47.3,46.2,45.2,44.7,43.8,43.5,41.7,40.8,37.6,36.8,32.0,31.9,31.3,29.5,28.8,28.4,26.6,26.5,23.3,22.8,19.5,18.3,15.2.HRMS(ESI)calculated for C41H54F3N3NaO3S+:748.3730,found 748.3727.
实施例59：
化合物G2的制备(方法同化合物U11的制备)
mp 144-146℃；[ɑ]24 D+109°(c 0.60,CHCl3)；IR(KBr):3300,3060,2951,2921,1683,1652,1600,1530,1497cm-1.1H NMR(400MHz,CDCl3)δ8.40–8.10(m,1H),7.41(t,J＝7.7Hz,2H),7.29(t,J＝7.4Hz,1H),7.22(d,J＝7.7Hz,2H),7.02(t,J＝4.9Hz,1H),6.77(s,1H),5.99(t,J＝2.4Hz,1H),5.76(s,1H),5.23(d,J＝2.3Hz,1H),4.04(d,J＝13.1Hz,1H),3.75(dd,J＝14.9,7.4Hz,2H),3.43(dq,J＝9.5,4.5Hz,2H),2.46(s,1H),2.11(dd,J＝18.0,14.4Hz,2H),2.03–1.98(m,1H),1.93–1.86(m,2H),1.86–1.78(m,1H),1.73–1.65(m,1H),1.61(t,J＝13.8Hz,1H),1.54–1.39(m,4H),1.37(s,3H),1.33(d,J＝5.1Hz,2H),1.26–1.18(m,2H),1.16–1.11(m,9H),1.08(d,J＝9.0Hz,6H),1.03–0.99(m,1H),0.78(s,3H).13CNMR(100MHz,CDCl3)δ206.9,200.0,181.5,177.4,170.1,141.9,136.2,130.2,130.2,128.5,127.5,125.3,125.3,124.3,59.4,54.5,48.3,47.3,46.2,45.1,44.7,43.7,43.4,41.6,41.1,37.6,36.8,32.0,31.9,31.6,29.5,28.8,28.4,26.6,26.5,23.3,22.8,19.5,18.4,15.3.HRMS(ESI)calculated for C40H55N3NaO3S+:680.3856,found 680.3855.
实施例60：
化合物G3的制备(方法同化合物U11的制备)
mp 145-147℃；[ɑ]24 D+126°(c 0.46,CHCl3)；IR(KBr):3312,2952,2929,1683,1653,1510,1464cm-1.1H NMR(400MHz,CDCl3)δ8.03(s,1H),7.13(d,J＝8.3Hz,2H),7.04(t,J＝4.8Hz,1H),6.95–6.90(m,2H),6.46(s,1H),5.99(t,J＝2.4Hz,1H),5.77(s,1H),5.22(t,J＝2.2Hz,1H),4.01(d,J＝9.3Hz,1H),3.79(s,3H),3.73(d,J＝15.4Hz,2H),3.41(p,J＝4.6Hz,2H),2.46(s,1H),2.11(td,J＝11.8,10.7,6.1Hz,2H),2.01(dd,J＝13.7,4.3Hz,1H),1.95–1.89(m,2H),1.86–1.79(m,1H),1.72–1.59(m,2H),1.48(ddd,J＝26.0,12.7,9.5Hz,4H),1.36(d,J＝14.7Hz,5H),1.21(d,J＝14.8Hz,2H),1.12(t,J＝9.8Hz,12H),1.07(s,3H),1.04–0.99(m,1H),0.79(s,3H).
13C NMR(100MHz,CDCl3)δ206.9,200.0,182.0,177.3,170.0,159.1,142.0,128.5,128.5,127.7,127.7,124.3,115.4,115.4,59.4,55.7,54.5,48.3,47.3,46.2,45.1,44.3,43.7,43.5,41.6,41.2,37.7,36.8,32.0,31.9,31.5,29.6,28.7,28.4,26.6,26.5,23.3,22.8,19.5,18.4,15.2.
实施例61：
化合物G4的制备(方法同化合物U11的制备)
mp 148-149℃；[ɑ]24 D+121°(c 0.48,CHCl3)；IR(KBr):3353,2952,2931,1656,1537,1510,1464cm-1.1H NMR(400MHz,CDCl3)δ7.48(s,1H),7.32(d,J＝4.2Hz,1H),7.22–7.18(m,2H),6.82–6.77(m,2H),6.00(d,J＝2.4Hz,1H),5.78(d,J＝6.3Hz,2H),5.21(d,J＝2.4Hz,1H),3.74(s,3H),3.66(d,J＝15.5Hz,1H),3.47–3.30(m,4H),2.41(s,1H),2.23(s,1H),2.14(dd,J＝13.6,3.7Hz,1H),2.05(t,J＝4.6Hz,1H),1.97–1.87(m,2H),1.82(dt,J＝13.8,6.8Hz,1H),1.68(dd,J＝13.3,6.2Hz,2H),1.47(dtd,J＝24.4,8.1,3.1Hz,4H),1.37(d,J＝5.7Hz,5H),1.25–1.16(m,2H),1.15–1.10(m,12H),1.07(s,3H),1.03–0.98(m,1H),0.77(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.8,177.3,170.5,158.1,156.4,142.0,131.6,128.4,128.4,124.2,123.5,114.5,114.5,59.3,55.6,54.5,48.4,47.3,46.2,45.2,43.7,43.5,42.1,41.8,39.6,37.6,36.8,32.0,31.9,31.4,29.6,28.7,28.4,26.7,26.6,23.3,22.8,19.5,18.4,15.3.HRMS(ESI)calculated for C41H57N3NaO5 +:694.4190,found694.4186.
实施例62：
化合物G5的制备(方法同化合物U11的制备)
mp 161-163℃；[ɑ]24 D+133°(c 0.45，CHCl3)；IR(KBr)：3353，2954，2927，1657，1603，1514，1554，1403cm-1。1H NMR(400MHz,CDCl3)δ7.70(s,1H),7.32(t,J＝4.4Hz,1H),7.18(d,J＝8.1Hz,2H),7.03(d,J＝8.1Hz,2H),6.00(q,J＝3.8,3.1Hz,2H),5.75(s,1H),5.21(d,J＝2.4Hz,1H),3.64(d,J＝15.3Hz,1H),3.39(dtd,J＝22.6,12.6,9.8,5.0Hz,4H),2.40(s,1H),2.25(s,3H),2.14(dd,J＝13.5,3.7Hz,1H),2.08–1.99(m,2H),1.96–1.87(m,2H),1.80(td,J＝13.7,4.5Hz,1H),1.71–1.60(m,2H),1.56–1.40(m,4H),1.37(d,J＝8.7Hz,5H),1.26–1.16(m,2H),1.14–1.06(m,15H),1.03–0.98(m,1H),0.76(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.8,177.4,170.5,157.7,142.0,136.3,133.0,129.7,129.7,128.4,124.2,120.8,120.8,59.3,54.5,48.4,47.3,46.2,45.2,43.7,43.5,41.9,41.8,39.6,37.6,36.8,32.0,31.9,31.4,29.6,28.7,28.4,26.7,26.5,23.2,22.8,20.9,19.5,18.3,15.2.HRMS(ESI)calculated for C37H62N2NaO4 +:621.4602,found 621.4600.
实施例63：
化合物G6的制备(方法同化合物U11的制备)
mp 156-158℃；[ɑ]24 D+119°(c 0.51,CHCl3)；IR(KBr):3361,2954,2931,1686,1658,1553,1509,1469cm-1.1H NMR(400MHz,CDCl3)δ8.15(s,1H),7.37(d,J＝8.5Hz,2H),7.20(d,J＝4.8Hz,1H),7.05(d,J＝8.5Hz,2H),6.22(s,1H),6.01(d,J＝2.3Hz,1H),5.73(s,1H),5.22(d,J＝2.6Hz,1H),3.67(d,J＝15.4Hz,1H),3.44(dt,J＝10.1,4.6Hz,4H),2.39(s,1H),2.15–1.97(m,3H),1.95–1.85(m,2H),1.79(td,J＝13.7,4.5Hz,1H),1.71–1.61(m,2H),1.52–1.37(m,6H),1.34(s,3H),1.20(dd,J＝20.0,6.9Hz,2H),1.16–1.10(m,9H),1.07(d,J＝6.9Hz,6H),1.03–0.99(m,1H),0.74(s,3H).13C NMR(100MHz,CDCl3)δ206.9,200.0,177.9,171.0,157.1,144.1,141.9,138.3,128.3,124.3,121.8,121.8,120.3,120.3,119.3,59.4,54.5,48.4,47.3,46.3,45.2,43.8,43.5,41.9,41.3,39.7,37.6,36.8,32.0,31.9,31.3,29.5,28.6,28.43,26.7,26.5,23.3,22.8,19.5,18.2,15.2.
HRMS(ESI)calculated for C41H54F3N3NaO5 +:748.3908,found 748.3911.
实施例64：
化合物G7的制备(方法同化合物U4的制备)
mp 97-99℃；[ɑ]24 D+112°(c 0.21,CHCl3)；IR(KBr):3355,2953,2929,1713,1656,1533cm-1.
1H NMR(400MHz,CDCl3)δ9.12(t,J＝5.9Hz,1H),6.81(t,J＝4.5Hz,1H),6.01(d,J＝2.5Hz,1H),5.76(s,1H),5.25(d,J＝2.4Hz,1H),3.74(d,J＝15.4Hz,1H),3.69(s,3H),3.51–3.46(m,2H),3.41(dq,J＝9.9,5.0,4.5Hz,2H),2.45(s,1H),2.25–2.19(m,1H),2.13(d,J＝15.3Hz,1H),2.08–2.01(m,1H),1.85(dt,J＝13.9,6.3Hz,3H),1.73–1.65(m,4H),1.58(d,J＝4.0Hz,2H),1.49(ddd,J＝18.3,11.2,4.6Hz,4H),1.38(d,J＝5.3Hz,5H),1.24(s,2H),1.15(d,J＝6.0Hz,9H),1.09(d,J＝7.5Hz,6H),1.04–0.99(m,1H),0.81(s,3H).13CNMR(100MHz,CDCl3)δ207.0,199.3,176.5,173.9,171.0,169.9,142.1,128.7,124.3,59.4,54.5,52.5,48.0,47.3,46.3,45.2,43.6,43.5,41.8,41.8,39.6,37.7,36.9,32.0,32.0,31.6,29.7,28.7,28.4,26.7,26.6,26.1,23.4,22.9,20.5,20.5,19.6,18.4,15.3.HRMS(ESI)calculated for C39H56N2NaO6 +:671.4031,found 671.4029.
实施例65：
化合物G8的制备(方法同化合物U4的制备)
mp 141-143℃；[ɑ]24 D+101°(c 0.23,CHCl3)；IR(KBr):3354,2952,2929,1656,1606,1530,1509,1454cm-1.1H NMR(400MHz,CDCl3)δ10.81(s,1H),7.64–7.56(m,3H),6.99(t,J＝8.7Hz,2H),6.77(t,J＝4.8Hz,1H),6.03(t,J＝2.4Hz,1H),5.64(s,1H),5.26(d,J＝2.3Hz,1H),3.72(d,J＝15.3Hz,1H),3.54–3.34(m,4H),2.51(s,1H),2.17(d,J＝15.3Hz,1H),2.06(dd,J＝13.6,4.6Hz,2H),2.02–1.96(m,1H),1.84(dd,J＝14.5,10.0Hz,1H),1.78–1.70(m,3H),1.54(tt,J＝7.1,3.7Hz,4H),1.48–1.44(m,2H),1.40(s,5H),1.37–1.31(m,2H),1.25(d,J＝4.2Hz,2H),1.19(s,3H),1.15(d,J＝4.4Hz,9H),1.10(s,3H),1.07–1.03(m,1H),0.81(s,3H).13C NMR(100MHz,CDCl3)δ206.8,200.5,177.6,173.2,171.8,168.8,158.2,141.8,134.5,128.1,124.4,121.9,121.8,115.7,115.5,59.6,54.5,48.6,47.4,46.3,45.4,43.7,43.7,42.1,41.4,41.1,37.6,36.9,32.1,31.9,31.3,29.8,29.1,28.7,28.4,26.7,26.5,23.5,22.9,19.5,18.4,17.8,16.2,15.3.HRMS(ESI)calculatedfor C44H58FN3NaO5 +:750.4253,found 750.4259.
实施例66：
化合物G9的制备(方法同化合物U20的制备)
mp 110-112℃；[ɑ]24 D+100°(c 0.40,CHCl3)；IR(KBr):3343,2953,2928,1657,1643cm-1.1H NMR(400MHz,CDCl3)δ6.89(d,J＝4.1Hz,1H),6.42(d,J＝4.9Hz,1H),5.99(t,J＝2.4Hz,1H),5.73(s,1H),5.24(d,J＝2.4Hz,1H),3.73(d,J＝15.3Hz,1H),3.38(q,J＝11.5,8.3Hz,4H),2.45(s,1H),2.22–2.15(m,3H),2.15–2.09(m,1H),2.02(dd,J＝13.7,4.4Hz,1H),1.86(tt,J＝13.7,6.7Hz,3H),1.69(dd,J＝8.7,4.1Hz,1H),1.60(d,J＝13.2Hz,2H),1.53–1.44(m,3H),1.38(s,7H),1.26(dt,J＝12.7,4.2Hz,10H),1.14(d,J＝7.2Hz,9H),1.09(d,J＝12.2Hz,6H),1.04–1.00(m,1H),0.85(t,J＝6.8Hz,3H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,177.3,175.2,169.9,142.0,128.6,124.3,59.4,54.5,48.2,47.3,46.3,45.2,43.7,43.5,41.7,41.2,40.2,37.7,36.8,36.8,32.0,32.0,31.8,31.6,29.6,29.4,29.1,28.8,28.4,26.7,26.6,25.9,23.4,22.8,22.7,19.5,18.4,15.2,14.2.HRMS(ESI)calculated for C41H64N2NaO4 +:671.4758,found 671.4760.
实施例67：
化合物G10的制备(方法同化合物U20的制备)
mp 143-145℃；[ɑ]24 D+132°(c 0.29,CHCl3)；IR(KBr):3347,2951,2928,1655,1591,1532,1481cm-1.1HNMR(400MHz,CDCl3)δ7.72–7.67(m,2H),7.58–7.52(m,3H),6.73(t,J＝5.2Hz,1H),6.01(d,J＝2.4Hz,1H),5.68(s,1H),5.26(d,J＝2.3Hz,1H),3.76(d,J＝15.3Hz,1H),3.65–3.47(m,4H),2.44(s,1H),2.16–2.05(m,2H),1.97(dd,J＝13.6,4.4Hz,1H),1.91–1.83(m,2H),1.76(dd,J＝13.6,4.4Hz,1H),1.72–1.65(m,1H),1.61(d,J＝13.6Hz,1H),1.50(t,J＝5.5Hz,2H),1.46–1.38(m,3H),1.35(s,3H),1.31(d,J＝10.6Hz,1H),1.26–1.19(m,2H),1.16–1.07(m,15H),1.01–0.96(m,1H),0.60(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,178.3,169.9,167.3,142.0,132.7,132.0,132.0,128.8,128.8,128.7,126.5,124.3,59.4,54.5,48.0,47.3,46.3,45.2,43.8,43.4,42.1,41.7,39.7,37.7,36.9,31.9,31.8,31.6,29.5,28.5,28.4,26.6,26.5,23.4,22.8,19.5,18.3,15.3.HRMS(ESI)calculated for C40H53BrN2NaO4 +:727.3081,found 727.3076.
实施例68：
化合物G11的制备(方法同化合物U20的制备)
mp 139-141℃；[ɑ]24 D+131°(c 0.59,CHCl3)；IR(KBr):3354,2952,2929,1654,1579,1488,1468cm-1.1HNMR(400MHz,CDCl3)δ7.84–7.78(m,2H),7.43(p,J＝7.2Hz,4H),6.86(d,J＝4.4Hz,1H),6.01(d,J＝2.4Hz,1H),5.69(s,1H),5.25(d,J＝2.3Hz,1H),3.75(d,J＝15.3Hz,1H),3.62(q,J＝9.7,8.6Hz,3H),3.52–3.45(m,1H),2.43(s,1H),2.16–2.09(m,2H),2.01(dt,J＝13.9,6.9Hz,1H),1.94–1.85(m,2H),1.79(dd,J＝13.7,4.3Hz,1H),1.71–1.64(m,1H),1.58(t,J＝13.6Hz,1H),1.54–1.44(m,3H),1.43–1.37(m,2H),1.33(d,J＝8.8Hz,4H),1.29–1.19(m,2H),1.14(d,J＝8.1Hz,6H),1.12–1.06(m,9H),1.00–0.95(m,1H),0.63(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,178.0,169.9,168.5,142.0,133.8,131.8,128.7,128.7,128.6,127.1,127.1,124.3,59.4,54.5,48.0,47.3,46.3,45.1,43.74,43.4,41.7,41.6,40.1,37.6,36.8,31.9,31.9,31.6,29.6,28.5,28.4,26.6,26.5,23.4,22.8,19.5,18.3,15.3.
HRMS(ESI)calculated for C40H54N2NaO4 +:649.3976,found 649.3978.
实施例69：
化合物G12的制备(方法同化合物U20的制备)
mp 139-141℃；[ɑ]24 D+124°(c 0.63,CHCl3)；IR(KBr):3333,2961,2931,1656,1530cm-1.1H NMR(400MHz,CDCl3)δ7.06(d,J＝4.6Hz,1H),6.52(t,J＝5.1Hz,1H),5.99(d,J＝2.4Hz,1H),5.75(s,1H),5.24(d,J＝2.4Hz,1H),3.73(d,J＝15.3Hz,1H),3.39(h,J＝5.3Hz,4H),2.44(s,1H),2.21(dd,J＝13.4,4.1Hz,1H),2.11(d,J＝15.5Hz,1H),2.02(dd,J＝13.6,4.4Hz,1H),1.88(ddq,J＝20.1,9.1,5.2,4.5Hz,4H),1.69(dd,J＝9.2,4.2Hz,1H),1.63–1.43(m,9H),1.38(s,6H),1.24–1.18(m,1H),1.14(s,6H),1.12(s,3H),1.10(s,3H),1.07(s,3H),1.04–0.99(m,1H),0.85(t,J＝7.4Hz,6H),0.80(s,3H).13C NMR(100MHz,CDCl3)δ207.00,199.3,177.9,177.3,169.9,142.0,128.7,124.3,59.4,54.5,51.3,48.1,47.3,46.2,45.1,43.6,43.5,41.9,41.7,40.1,37.7,36.8,32.0,32.0,31.6,29.6,28.7,28.4,26.6,26.7,25.8,25.8,23.4,22.8,19.52,18.4,15.2,12.3,12.3.HRMS(ESI)calculated for C39H60N2NaO4 +:643.4445,found 643.4441.
实施例70：
化合物G13的制备(方法同化合物U20的制备)
mp 139-140℃；[ɑ]24 D+159°(c 0.84,CHCl3)；IR(KBr):3348,3073,2953,2930,1655,1604,1536,1503,1456cm-1.1H NMR(400MHz,CDCl3)δ7.86–7.80(m,2H),7.59(d,J＝4.5Hz,1H),7.08(t,J＝8.6Hz,2H),6.88(d,J＝5.4Hz,1H),6.00(t,J＝2.4Hz,1H),5.66(s,1H),5.25(d,J＝2.3Hz,1H),3.73(d,J＝15.3Hz,1H),3.63–3.47(m,4H),2.42(s,1H),2.14–2.06(m,2H),1.99(td,J＝13.7,4.6Hz,1H),1.92–1.84(m,2H),1.77(td,J＝13.6,4.4Hz,1H),1.69–1.56(m,2H),1.53–1.37(m,5H),1.34(s,3H),1.31(s,1H),1.28–1.17(m,2H),1.13(d,J＝7.5Hz,6H),1.11–1.05(m,9H),1.01–0.95(m,1H),0.62(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,178.2,169.9,167.3,163.7,142.0,130.0,129.6,129.5,128.6,124.3,115.8,115.6,59.4,54.5,48.1,47.3,46.2,45.1,43.8,43.4,41.9,41.7,39.9,37.6,36.8,31.9,31.8,31.5,29.5,28.5,28.4,26.6,26.5,23.4,22.8,19.5,18.3,15.2.HRMS(ESI)calculated for C40H53FN2NaO4 +:667.3882,found 667.3886.
实施例71：
化合物G14的制备(方法同化合物U4的制备)
mp 160-161℃；[ɑ]21.5 D＝+84°(c 0.55,CHCl3)；IR(KBr):3356,3086,2930,2868,1737,1657,1594,1533,1462cm-1.1H NMR(400MHz,CDCl3)δ7.80(d,J＝4.3Hz,1H),7.45–7.31(m,2H),6.92(tt,J＝8.6,2.3Hz,1H),6.75(d,J＝4.7Hz,1H),6.01(d,J＝2.4Hz,1H),5.63(s,1H),5.25(d,J＝2.4Hz,1H),3.74(d,J＝15.4Hz,1H),3.66–3.47(m,4H),2.43(s,1H),2.16–2.07(m,2H),2.04–1.95(m,2H),1.91–1.84(m,2H),1.78(dd,J＝13.6,4.5Hz,1H),1.71–1.59(m,2H),1.49(s,2H),1.44(dd,J＝14.0,3.8Hz,2H),1.37(d,J＝12.1Hz,5H),1.30(dd,J＝14.3,3.0Hz,1H),1.22(ddd,J＝15.5,9.0,3.8Hz,2H),1.15–1.11(m,7H),1.09(d,J＝9.5Hz,6H),1.03–0.98(m,1H),0.68(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.4,178.4,169.8,165.9,164.3,161.9,142.0,137.3,128.6,124.4,110.7,110.4,107.1,59.4,54.5,48.2,47.3,46.3,45.1,43.8,43.4,42.1,41.7,39.8,37.6,36.8,31.9,31.9,31.6,29.6,28.6,28.4,26.6,26.5,23.4,22.8,19.5,18.3,15.2.HRMS(ESI)calculated for C40H52F2N2NaO4 +:685.3787,found 685.3789.
实施例72：
化合物G15的制备(方法同化合物U4的制备)
mp 175-176℃；[ɑ]21.5 D＝+78°(c 0.34,CHCl3)；IR(KBr):3365,3071,2928,2867,1734,1655,1531,1466cm-1.1H NMR(400MHz,CDCl3)δ7.96(d,J＝2.0Hz,1H),7.63(dd,J＝8.3,2.1Hz,1H),7.54(t,J＝8.5Hz,2H),6.52(t,J＝5.1Hz,1H),6.02(t,J＝2.4Hz,1H),5.66(s,1H),5.27(d,J＝2.3Hz,1H),3.76(d,J＝15.3Hz,1H),3.67–3.50(m,4H),2.44(s,1H),2.16–2.06(m,2H),1.99(dd,J＝13.6,4.4Hz,1H),1.89–1.82(m,2H),1.81–1.74(m,1H),1.71(s,3H),1.62(t,J＝13.7Hz,1H),1.52(dt,J＝11.2,5.7Hz,2H),1.46(dd,J＝12.9,3.3Hz,2H),1.41–1.39(m,1H),1.36(s,3H),1.27–1.21(m,2H),1.16(s,3H),1.14(s,3H),1.12(s,3H),1.10(s,3H),1.09(s,3H),0.65(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,178.5,169.7,166.0,142.0,136.2,133.7,133.3,130.9,129.8,128.7,126.0,124.4,59.4,54.5,48.1,47.3,46.3,45.1,43.8,43.4,42.4,41.7,39.7,37.7,36.9,31.9,31.9,31.7,29.6,28.6,28.4,26.6,26.5,23.5,22.9,19.5,18.3,15.3.HRMS(ESI)calculated for C40H52Cl2N2NaO4 +:717.3196,found 717.3192.
实施例73：
化合物G16的制备(方法同化合物U4的制备)
mp 162-163℃；[ɑ]21.5 D＝+109°(c 0.19,CHCl3)；IR(KBr):3366,3070,2929,2867,1734,1656,1530,1447cm-1.1H NMR(400MHz,CDCl3)δ7.91–7.80(m,1H),7.35(d,J＝11.7Hz,1H),7.28(s,1H),6.47(d,J＝5.0Hz,1H),6.02(s,1H),5.67(s,1H),5.27(s,1H),3.75(d,J＝15.3Hz,1H),3.64(ddd,J＝22.9,11.9,7.2Hz,3H),3.46(dd,J＝12.4,5.9Hz,1H),2.44(s,1H),2.12(dd,J＝14.0,8.4Hz,2H),2.00(dd,J＝13.7,4.3Hz,1H),1.88(d,J＝13.0Hz,3H),1.64(d,J＝12.7Hz,3H),1.52(q,J＝7.6,7.1Hz,2H),1.48–1.41(m,2H),1.38(d,J＝7.6Hz,4H),1.27–1.18(m,2H),1.15(d,J＝7.4Hz,6H),1.13–1.05(m,9H),1.01(d,J＝14.9Hz,1H),0.70(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.3,177.3,169.8,162.7,157.0,153.7,142.0,128.6,124.4,119.1,119.0,118.8,118.7,59.4,54.5,48.0,47.3,46.3,45.1,43.8,43.4,41.8,41.3,40.1,37.6,36.8,31.9,31.9,31.6,29.6,28.6,28.4,26.6,26.5,23.4,22.9,19.5,18.3,15.2.HRMS(ESI)calculated for C40H51ClF2N2NaO4 +:719.3398,found 719.3401.
实施例74：
化合物G17的制备(方法同化合物U4的制备)
mp 185-186℃；[ɑ]21.5 D＝+68°(c 0.44,CHCl3)；IR(KBr):3353,3072,2927,2867,1655,1554,1531,1454cm-1.1H NMR(400MHz,CDCl3)δ7.90(d,J＝1.7Hz,2H),7.77(d,J＝1.7Hz,1H),7.65(d,J＝4.3Hz,1H),6.58(t,J＝5.2Hz,1H),6.01(t,J＝2.4Hz,1H),5.69(s,1H),5.26(d,J＝2.3Hz,1H),3.75(d,J＝15.3Hz,1H),3.58(dtt,J＝16.7,10.5,5.6Hz,4H),2.44(s,1H),2.18–2.10(m,2H),2.02(dd,J＝12.8,8.3Hz,1H),1.90–1.84(m,2H),1.79(d,J＝15.6Hz,2H),1.66(d,J＝13.6Hz,2H),1.52(dt,J＝11.0,5.5Hz,2H),1.49–1.42(m,2H),1.41–1.39(m,1H),1.37(s,3H),1.30(dd,J＝14.2,3.3Hz,1H),1.26–1.22(m,1H),1.18–1.06(m,15H),1.04–0.99(m,1H),0.70(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.4,178.4,169.8,165.5,142.0,137.2,137.1,129.3,129.3,128.7,124.4,123.4,123.4,59.4,54.5,48.1,47.3,46.3,45.1,43.7,43.5,42.1,41.7,39.9,37.7,36.9,31.9,31.9,31.7,29.6,28.6,28.4,26.6,26.5,23.4,22.8,19.5,18.4,15.3.HRMS(ESI)calculated forC40H52Br2N2NaO4 +:805.2186,found 805.2188.
实施例75：
化合物G18的制备(方法同化合物U4的制备)
mp 128-129℃；[ɑ]21.5 D＝+80°(c 0.39,CHCl3)；IR(KBr):3367,3081,2954,2928,1657,1582,1532,1445cm-1.1H NMR(400MHz,CDCl3)δ8.16(s,1H),8.05(s,1H),7.87(s,1H),7.77(s,1H),6.49(d,J＝5.7Hz,1H),6.02(d,J＝2.4Hz,1H),5.67(s,1H),5.27(d,J＝2.5Hz,1H),3.75(d,J＝15.3Hz,1H),3.61(dt,J＝11.5,6.7Hz,4H),2.44(s,1H),2.17–2.10(m,2H),2.05–1.98(m,1H),1.92–1.86(m,1H),1.82(s,1H),1.73–1.66(m,4H),1.53(dt,J＝11.1,5.4Hz,2H),1.45(dd,J＝14.3,3.9Hz,2H),1.39(s,1H),1.37(s,3H),1.29(dd,J＝13.6,2.8Hz,1H),1.25(s,1H),1.17–1.06(m,15H),1.02(d,J＝12.4Hz,1H),0.69(s,3H).13CNMR(100MHz,CDCl3)δ207.0,199.3,178.6,169.6,165.3,142.0,136.6,133.7,131.4,131.4,128.7,124.4,123.3,123.1,123.1,59.4,54.5,48.2,47.3,46.3,45.1,43.8,43.47,42.5,41.8,39.8,37.7,36.9,32.0,31.9,31.7,29.6,28.6,28.4,26.6,26.5,23.5,22.9,19.5,18.4,15.3.HRMS(ESI)calculated for C41H52BrF3N2NaO4 +:795.2955,found795.2954.
实施例76：
化合物G19的制备(方法同化合物U4的制备)
mp 148-150℃；[ɑ]21.5 D＝+73°(c 0.28,CHCl3)；IR(KBr):3367,3030,2955,2928,1657,1581,1532,1444cm-1.1H NMR(400MHz,CDCl3)δ7.20(dd,J＝9.0,4.9Hz,2H),6.90(tt,J＝8.9,2.7Hz,1H),6.56(s,1H),6.01(t,J＝2.4Hz,1H),5.63(s,1H),5.25(d,J＝2.3Hz,1H),3.73(d,J＝15.3Hz,1H),3.66–3.57(m,3H),3.54–3.46(m,1H),2.44(s,1H),2.17–2.09(m,2H),2.07–1.99(m,1H),1.84(d,J＝14.5Hz,2H),1.71(s,3H),1.58(s,1H),1.55–1.47(m,3H),1.44(dd,J＝13.2,5.1Hz,2H),1.38(d,J＝5.5Hz,4H),1.24(d,J＝4.6Hz,1H),1.16–1.11(m,12H),1.08(s,3H),1.03(dt,J＝10.9,2.6Hz,1H),0.79(s,3H).13C NMR(100MHz,CDCl3)δ207.0,199.4,177.9,169.8,160.7,146.1,142.0,128.6,124.4,119.1,119.0,118.8,112.0,111.8,59.4,54.5,48.1,47.3,46.3,45.1,43.8,43.5,41.7,41.6,40.1,37.6,36.8,32.0,31.9,31.6,29.5,28.6,28.4,26.6,26.5,23.4,22.9,19.5,18.3,15.2.HRMS(ESI)calculated for C40H51F3N2NaO4 +:703.3693,found 703.3692.
实施例77：
五环三萜衍生物及其盐的体外癌细胞抑制作用
采用四甲基偶氮唑蓝(MTT)比色法检测五环三萜衍生物对癌细胞的抑制作用。
MTT比色法实验步骤：将处于对数生长期的癌细胞按照每毫升5×104细胞数的密度接种至96孔细胞培养板中，调零孔为不含细胞的正常培养基。12小时后更换含不同浓度梯度异土五环三萜衍生物的培养基，调零孔更换正常培养基，每个浓度梯度设置5个复孔，置于37℃，5％CO2培养箱中培养。24小时后显微镜下观察细胞状态及生长变化。48小时后每孔加入四甲基偶氮唑蓝(凯基生物，5mg/mL)溶液,继续在37℃，5％CO2培养箱中培养，4小时后吸走培养基，每孔加入DMSO 100μL，使用酶标仪在570纳米波长下测量吸光度值，使用Graphpad软件进行数据统计分析，计算半数有效浓度(IC50，单位：μM)。抑制效果见下表4-6所示。
表4齐墩果酸衍生物肿瘤细胞MTT测试
表5熊果酸衍生物肿瘤细胞MTT测试结果
表6甘草次酸衍生物肿瘤细胞MTT测试结果
其中，4T1,MCF-7,231,B16,A375,LLC,A549,HepG2,PLC,PANC-1分别表示小鼠黑色素瘤细胞、小鼠高转移黑色素瘤细胞、人宫颈癌细胞、人非小细胞肺癌细胞、人胰腺癌细胞、人高转移肝癌细胞、人肝癌细胞、人结肠癌细胞、人肾癌细胞、人乳腺癌细胞。
通过上表可知：所筛选的化合物对受试细胞均有一定的抑制作用。
实施例78
五环三萜衍生物的体内抗肿瘤作用
试验对象：本试验选用动物品系为BALB/c小鼠，雌性，18～22g，SPF级别。
试验接种内容：B16细胞皮下荷瘤。
方法为小鼠皮下荷瘤法，将培养好的肿瘤细胞逐一接种到小鼠背部腋下处。待种瘤部位观察到明显瘤体后重新分组，保证瘤体大小以及体重均匀分布于各组之中，模型对照组小鼠每天给予0.1mL生理盐水，待测药品的给药剂量为5mg/kg。均采用腹腔注射给药治疗。每天记录一次小鼠体重和肿瘤大小(V＝ab2/2，a为肿瘤长径，b为肿瘤短径)，给药两周之后解剖小鼠，固定心、肝、脾、肺、肾和肿瘤组织。结果如表7所示。
表7三萜类化合物对肿瘤的抑制作用
| 组别 | 小鼠平均体重变化(g) | 抑瘤率(％) |
| 生理盐水组 | 2.88±0.62 | 0 |
| 化合物O6组 | 1.43±0.48 | 66.45±4.21 |
| 化合物O12组 | 1.78±0.41 | 72.29±2.93 |
| 化合物O13组 | 1.58±0.31 | 62.29±2.93 |
| 化合物U13组 | 1.23±0.48 | 58.45±4.21 |
| 化合物U17组 | 1.58±0.61 | 62.79±2.93 |
| 化合物U25组 | 1.51±0.21 | 69.82±2.93 |
| 化合物G4组 | 1.53±0.42 | 56.45±3.21 |
| 化合物G6组 | 1.81±0.31 | 60.79±2.43 |
| 化合物G12组 | 1.21±0.27 | 44.82±2.73 |
通过表7可知：所筛选的化合物均对B16实体瘤均有一定的抑制作用，所筛选的化合物未使荷瘤小鼠体重降低。
实施例79
五环三萜衍生物的体内抗肿瘤作用
试验对象：本试验选用动物品系为BALB/c小鼠，雌性，18～22g，SPF级别。
试验接种内容：LLC细胞皮下荷瘤。
方法为小鼠皮下荷瘤法，将培养好的肿瘤细胞逐一接种到小鼠背部腋下处。待种瘤部位观察到明显瘤体后重新分组，保证瘤体大小以及体重均匀分布于各组之中，模型对照组小鼠每天给予0.1mL生理盐水，待测药品的给药剂量为5mg/kg。均采用腹腔注射给药治疗。每天记录一次小鼠体重和肿瘤大小(V＝ab2/2，a为肿瘤长径，b为肿瘤短径)，给药两周之后解剖小鼠，固定心、肝、脾、肺、肾和肿瘤组织。结果如表8所示。
表8三萜类化合物对肿瘤的抑制作用
通过表8可知：所筛选的化合物均对LLC实体瘤均有一定的抑制作用，所筛选的化合物未使荷瘤小鼠体重降低。
实施例80
五环三萜衍生物的体内抗肿瘤作用
试验对象：本试验选用动物品系为BALB/c Nude Mice小鼠，雌性，18～22g，SPF级别。
试验接种内容：A375细胞皮下荷瘤。
方法为小鼠皮下荷瘤法，将培养好的肿瘤细胞逐一接种到小鼠背部腋下处。待种瘤部位观察到明显瘤体后重新分组，保证瘤体大小以及体重均匀分布于各组之中，模型对照组小鼠每天给予0.1mL生理盐水，待测药品的给药剂量为5mg/kg。均采用腹腔注射给药治疗。每天记录一次小鼠体重和肿瘤大小(V＝ab2/2，a为肿瘤长径，b为肿瘤短径)，给药两周之后解剖小鼠，固定心、肝、脾、肺、肾和肿瘤组织。结果如表9所示。
表9三萜类化合物对肿瘤的抑制作用
| 组别 | 小鼠平均体重变化(g) | 抑瘤率(％) |
| 生理盐水组 | 2.76±0.57 | 0 |
| 化合物O6组 | 1.18±0.52 | 70.86±3.17 |
| 化合物O12组 | 1.28±0.33 | 66.37±2.80 |
| 化合物O13组 | 1.37±0.47 | 67.34±2.88 |
| 化合物U13组 | 1.54±0.48 | 56.45±4.21 |
| 化合物U17组 | 1.42±0.41 | 70.29±2.95 |
| 化合物U25组 | 1.62±0.31 | 62.23±2.53 |
| 化合物G4组 | 1.29±0.68 | 58.85±4.11 |
| 化合物G6组 | 1.71±0.31 | 53.79±2.13 |
| 化合物G12组 | 1.53±0.57 | 68.82±2.63 |
通过上可知：所筛选的化合物均对A375实体瘤均有一定的抑制作用，所筛选的化合物未使荷瘤小鼠体重降低。
Claims (10)
1.一种如式(I)所示的五环三萜衍生物，
式(I)中，
R3为氢或羰基；
R4为氢或甲基；
R5为氢或甲基；
R6选自氢、甲基、-C(O)-N(Ra)2或其中Ra选自氢、烷基、环烷基或-(CH2)m-NH-Rc；Rb选自氢、烷基、酰基烷基、酰基环烷基、酰基羟基、酰基氨基、酰基芳基、烯基烷基、烯基酯基、烯基氨基、烯基环烷基、烯基羟基；m为1～6；Rc选自酰基烷基、酰基芳基、磺酰基氨基芳基、酰基烷基酯基、酰基烷基酯基芳基、酰胺基芳基、酰胺基；
R7选自氢、甲基、-C(O)-N(Rd)2或其中Rd选自氢、烷基、环烷基或-(CH2)n-NH-Rf，Re选自氢、烷基、酰基烷基、酰基烯基、酰基环烷基、酰基环烷基烯基、酰基烯基烷基、酰基烯基酯基、酰基烯基羟基、酰基烯基三氟甲基；n为1～6；Rf选自酰基烷基、酰基芳基、酰基取代芳基、酰胺基芳基、酰胺基取代芳基、磺酰基氨基芳基、磺酰胺基取代芳基、酰基烷基酰胺芳基、酰基烷基炔基、酰基烯基、酰基烯基烷基、酰基烯基环烷基、酰基烯基氨基、烯基烯基芳基、酰基烯基酯基。
2.如权利要求1所述的五环三萜衍生物，其具有式(Ia)；
R7优选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R7a，其中，R7a选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-烷基-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，-NH-芳基，-C(O)-NH-(CH2)-NH-S(O)-NH-芳基。
3.如权利要求1所述的五环三萜衍生物，其具有式(Ib)；
R7选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R7a，其中，R7a选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-CH2-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，、-NH-芳基、-C(O)-NH-(CH2)-NH-S(O)-NH-芳基；Re选自碳原子数1～5的-CH＝CH-烷基，碳原子数5～8的-CH＝CH-环烷基，-CH＝CH-CH2-三氟甲基，-CH＝CH-(CH2)-二甲胺基，-CH＝CH-酯基。
4.如权利要求1所述的五环三萜衍生物，其具有式(Ic)；
R6选自如下基团：-C(O)-NH-CH3，-C(O)-NH-(CH2)2-NH-(Boc)，-C(O)-NH-(CH2)2-NH-C(O)-R6a，其中，R6a选自碳原子数1～8的烷基，碳原子数为5～8的环烷基，碳原子数为2～7的烷基炔基，碳原子数为1～3的烷基酯基，取代芳基，烷基-C(O)-NH-芳基，-CH＝CH-烷基，-CH＝CH-CH2-二甲胺基，-CH＝CH-酯基，-CH＝C-(Ph)2，-CH＝CH-芳基，-NH-芳基，-C(O)-NH-(CH2)-NH-S(O)-NH-芳基；Re选自碳原子数1～5的-CH＝CH-烷基，-CH＝CH-烷基羟基，碳原子数5～8的-CH＝CH-环烷基，-CH＝CH-CH2-三氟甲基，-CH＝CH-(CH2)-二甲胺基，-CH＝CH-酯基。
5.根据权利要求1所述的五环三萜衍生物，衍生物的结构式为：
不同R8对应的化合物分别为化合物U4-U26，化合物U4-U26中R8的结构式为：
或者，结构式为：不同R9对应的化合物分别为化合物O2-O20，化合物O2-O20中R9的结构式为：
或者，结构式为：不同R10对应的化合物分别为化合物G1-G19，化合物G1-G19中R10的结构式为：
6.一种权利要求1所述五环三萜衍生物的制备方法，制备路线为：
7.一种权利要求5所述五环三萜衍生物的制备方法，制备路线分别为：
路线一：
路线二：
路线三：
8.如权利要求1～5任一所述的五环三萜衍生物在制备治疗癌症药物中或在制备有益于癌症功能性食品中的应用。
9.一种治疗癌症的药物组合物，其特征在于：含有作为活性成分的至少一种权利要求1所述的五环三萜衍生物。
10.根据权利要求9所述的治疗癌症的药物组合物，其特征在于：含有作为活性成分的至少一种式O2～式O20、式U4～式U26和式G1～式G19的化合物。
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| CN111704646A (zh) * | 2020-06-23 | 2020-09-25 | 中国药科大学 | 甾体类化合物及其制备方法和用途 |
| CN113197905A (zh) * | 2021-04-23 | 2021-08-03 | 浙江大学 | 三萜类化合物在制备神经母细胞瘤治疗药物中的应用 |
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| CN108003174A (zh) * | 2017-12-18 | 2018-05-08 | 南开大学 | 一种倍半萜衍生物的晶型及其制备方法与用途 |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111704646A (zh) * | 2020-06-23 | 2020-09-25 | 中国药科大学 | 甾体类化合物及其制备方法和用途 |
| CN111704646B (zh) * | 2020-06-23 | 2021-09-28 | 中国药科大学 | 甾体类化合物及其制备方法和用途 |
| CN113197905A (zh) * | 2021-04-23 | 2021-08-03 | 浙江大学 | 三萜类化合物在制备神经母细胞瘤治疗药物中的应用 |
| CN113197905B (zh) * | 2021-04-23 | 2022-04-19 | 浙江大学 | 三萜类化合物在制备神经母细胞瘤治疗药物中的应用 |
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