齐墩果烷型氮糖苷化合物及其在制备治疗抗糖尿病药物中的应用
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专利汇可以提供齐墩果烷型氮糖苷化合物及其在制备治疗抗糖尿病药物中的应用专利检索，专利查询，专利分析的服务。并且本 发明 公开了一类齐墩果烷型氮糖苷化合物及其在制备 治疗 抗糖尿病药物中的应用，该化合物的结构式为式中R代表糖基，其是以 齐墩果酸 C28‑ 氨 基正己酸甲酯为起始原料，将其3位羟基转化为氨基后引入了不同的糖单元制备而成。该类化合物在抗糖尿病方面具有应用价值，药理活性测试显示对 蛋白质 酪氨酸 磷酸 酯酶1B具有很好的抑制活性，说明此类齐墩果烷型氮糖苷化合物可以作为一种新型的抗糖尿病药物而加以研究利用。，下面是齐墩果烷型氮糖苷化合物及其在制备治疗抗糖尿病药物中的应用专利的具体信息内容。
1.齐墩果烷型氮糖苷化合物，其特征在于该化合物的结构式如下所示：
所述的R选自β-D-吡喃葡萄糖基、α-D-吡喃葡萄糖基、β-D-吡喃葡萄糖醛酸基、α-D-吡喃葡萄糖醛酸基、β-D-吡喃半乳糖基、α-D-吡喃半乳糖基、β-D-吡喃甘露糖基、α-D-吡喃甘露糖基、β-D-吡喃甘露糖醛酸基、α-D-吡喃甘露糖醛酸基、β-D-吡喃木糖基、α-D-吡喃木糖基、β-L-吡喃鼠李糖基、α-L-吡喃鼠李糖基、β-L-吡喃阿拉伯糖基、α-L-吡喃阿拉伯糖基、β-D-吡喃岩藻糖基、α-D-吡喃岩藻糖基、β-D-吡喃乳糖基、α-D-吡喃乳糖基、β-D-唾液酸糖基、α-D-唾液酸糖基中任意一种。
2.权利要求1所述的齐墩果烷型氮糖苷化合物在制备治疗糖尿病的药物中的应用。
齐墩果烷型氮糖苷化合物及其在制备治疗抗糖尿病药物中的
应用
技术领域
[0001] 本发明属于化学药物技术领域，具体涉及齐墩果烷型氮糖苷化合物及其在制备治疗抗糖尿病药物中的应用。
背景技术
[0002] II型糖尿病作为一种内分泌紊乱性代谢类疾病，已经成为继肿瘤、心血管病变之后第三大严重威胁人类健康的慢性疾病。世界卫生组织(WHO)报道，2015年，在全世界范围内，直接死于II型糖尿病的人数已经达到160万，如果不采取有效地措施，预计到2030年，死于II型糖尿病的总人数会翻倍。蛋白酪氨酸磷酸酯酶1B(protein tyrosinephosphatase 1B,PTP1B)具有重要的细胞生物学功能，已成为公认的抗II型糖尿病药物的重要新作用靶标。目前，以PTP1B为靶点的用于治疗II型糖尿病的PTP1B抑制剂(如Trodusquemine和Ertiprotafib)已经进入临床研究阶段。但是随着对PTP1B抑制剂的开发不断深入，发现大多数高效、高选择性的小分子PTP1B抑制剂，由于化合物本身容易电离、细胞渗透性和生物利用度不是很理想，导致难以开发成为有治疗价值的抗II型糖尿病药物。因此，寻找高效、高选择性和药学性质良好的新型PTP1B抑制剂具有重要的研究意义和应用前景。
[0003] 天然产物结构的多样性和新颖性是新药先导化合物的重要源泉，对天然活性化合物进行化学合成和改性研究又是实现创新药物研究的关键环节和重要课题。研究表明齐墩果烷类化合物作为一类新型的PTP1B抑制剂具有显著的抗II型糖尿病活性，目前已成为抗II型糖尿病药物研究领域的热点之一。抑制蛋白酪氨酸磷酸酯酶1B的活性是目前针对齐墩果酸抗糖尿病的结构修饰的主要策略，其结构修饰主要对C-3、A环、C环和C-28位的修饰。
[0004] 现有技术对齐墩果酸进行修饰筛选PTP1B抑制剂的报道较多，而关于齐墩果酸氮糖基化合物进行的PTP1B抑制活性的研究尚未见报道。
发明内容
[0005] 本发明的目的是提供一类新的齐墩果烷型氮糖苷化合物，并为该化合物提供一种新用途。
[0006] 针对上述目的，本发明所采用的齐墩果烷型氮糖苷化合物的结构式如下所示：
[0007]
[0008] 其中，R选自D-葡萄糖基、D-葡萄糖醛酸基、D-半乳糖基、D-甘露糖基、D-甘露糖醛酸基、D-木糖基、L-鼠李糖基、L-阿拉伯糖基、D-岩藻糖基、D-乳糖基、D-唾液酸糖基中任意一种，优选β-D-吡喃葡萄糖基、α-D-吡喃葡萄糖基、β-D-吡喃葡萄糖醛酸基、α-D-吡喃葡萄糖醛酸基、β-D-吡喃半乳糖基、α-D-吡喃半乳糖基、β-D-吡喃甘露糖基、α-D-吡喃甘露糖基、β-D-吡喃甘露糖醛酸基、α-D-吡喃甘露糖醛酸基、β-D-吡喃木糖基、α-D-木糖基、β-L-吡喃鼠李糖基、α-L-吡喃鼠李糖基、β-L-吡喃阿拉伯糖基、α-L-吡喃阿拉伯糖基、β-D-吡喃岩藻糖基、α-D-吡喃岩藻糖基、β-D-吡喃乳糖基、α-D-吡喃乳糖基、β-D-唾液酸糖基、α-D-唾液酸糖基中任意一种。
[0009] 本发明齐墩果烷型氮糖苷化合物的合成路线和具体合成方法如下：
[0010]
[0011] 1、合成化合物24
[0013] 2、合成化合物25
[0014] 以甲醇和吡啶体积比12～13:1的混合液为溶剂，将化合物24与甲氧胺基盐酸盐按摩尔比为1:1.5～2，室温搅拌反应30min。反应完毕后，减压蒸除溶剂，浓缩物溶解于二氯甲烷中，依次用1mol/L盐酸、饱和食盐水洗涤，无水硫酸钠干燥，过滤，浓缩，得到化合物25。
[0015] 3、合成化合物26
[0016] 以乙醇与二氧六环体积比1:2.5～3的混合液为溶剂，将化合物25与氰基硼氢化钠按摩尔比为1:3～3.5，在0℃下搅拌反应3h。反应完毕后，减压蒸除溶剂，浓缩物溶解于二氯甲烷中，无水硫酸钠干燥，过滤，浓缩，硅胶柱层析，得到化合物26。
[0017] 4、合成齐墩果烷型氮糖苷化合物
[0018] 以二甲基甲酰胺与乙酸体积比3:1的混合液为溶剂，将化合物26与糖类化合物(即RH)按摩尔比为1:1.1～1.3，60℃搅拌反应48h。反应结束后，减压浓缩，硅胶柱层析，得到齐墩果烷型氮糖苷化合物。
[0019] 本发明齐墩果烷型氮糖苷化合物在制备治疗抗糖尿病药物中的用途，其按常规药用制剂，与药学上可接受的载体按照各种制剂的常规制备工艺制成，可以是片剂、颗粒剂、胶囊剂。
[0020] 本发明以齐墩果酸C28-氨基正己酸甲酯为母体，将其3位羟基转化为氨基后引入不同的糖单元制备齐墩果烷型氮糖苷化合物。经药理活性检测，此类化合物对蛋白质酪氨酸磷酸酯酶1B显示出很好的抑制活性，可以用于制备治疗糖尿病的药物。
具体实施方式
[0021] 下面结合实施例对本发明进一步详细说明，但本发明的保护范围不仅限于这些实施例。
[0022] 实施例1
[0023] 制备齐墩果烷型氮糖苷化合物1～22
[0024] 1、合成化合物24
[0025] 将5g(8.57mmol)化合物23溶解于50mL干燥二氯甲烷，室温搅拌下加入6.44g(17.14mmol)吡啶重铬酸盐(PDC)，保持室温继续搅拌反应4h。反应完毕后，过滤，减压蒸除溶剂，浓缩物经硅胶柱层析(乙酸乙酯/石油醚＝1:4，V/V)精制得到白色固体4.6g，即化合物24，产率92.3％，结构表征数据为：1H NMR(600MHz,DMSO-d6)δ:7.23(t,J＝5.5Hz,1H,N-H),5.20(t,J＝3.2Hz,1H,H-12),3.57(s,3H,H-37),3.03(m,1H,H-31-1),2.93(m,1H,H-31-2),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-
1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:215.0(C-3),180.3(C-28),175.8(C-36),145.4(C-13),123.9(C-12),
56.9,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,
33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理论值C37H60NO4[M+H]+582.4517,实测值582.4563.
1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:215.0(C-3),180.3(C-28),175.8(C-36),145.4(C-13),123.9(C-12),
56.9,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,
33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理论值C37H60NO4[M+H]+582.4517,实测值582.4563.
[0026] 2、合成化合物25
[0027] 将4g(6.88mmol)化合物24溶解于15mL甲醇和1.2mL吡啶的混合溶剂中。室温搅拌下加入917mg(10.98mmol)甲氧胺基盐酸盐，保持室温继续搅拌反应30min。反应完毕后，减压蒸除溶剂，浓缩物溶解于二氯甲烷中，依次用1mol/L盐酸、饱和食盐水洗涤，无水硫酸钠干燥，过滤，浓缩，得到3.82g化合物25，产率91％，结构表征数据为：1H NMR(600MHz,DMSO-d6)δ:7.24(t,J＝5.5Hz,1H,N-H),5.21(t,J＝3.2Hz,1H,H-12),3.93(s,3H,OCH3),3.57(s,3H,H-37),3.03(m,1H,H-31-1),2.93(m,1H,H-31-2),2.78(dd,J＝13.7,4.1Hz,1H,H-18),
2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,
0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.3(C-28),175.8(C-
36),162.4(C-3),145.4(C-13),123.9(C-12),61.9,56.9,52.0,47.7,47.5,42.9,42.6,
40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,30.1,28.5,27.7,27.0,+
26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理论值C38H63N2O4[M+H]
611.4782,实测值611.4751.
2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,
0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.3(C-28),175.8(C-
36),162.4(C-3),145.4(C-13),123.9(C-12),61.9,56.9,52.0,47.7,47.5,42.9,42.6,
40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,30.1,28.5,27.7,27.0,+
26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理论值C38H63N2O4[M+H]
611.4782,实测值611.4751.
[0028] 3、合成化合物26
[0029] 将3.50g(5.73mmol)化合物25溶解于8mL乙醇和21mL二氧六环的混合溶剂中，0℃下加入1.19g(18.94mmol)氰基硼氢化钠，保持0℃继续搅拌反应3h。反应完毕后，减压蒸除溶剂，浓缩物溶解于二氯甲烷中，无水硫酸钠干燥，过滤，浓缩，硅胶柱层析(乙酸乙酯/石油醚＝1:1，V/V)精制得到2.28g化合物26，产率65％，结构表征数据为：1H NMR(600MHz,DMSO-d6)δ:7.24(t,J＝5.5Hz,1H,N-H),5.21(t,J＝3.2Hz,1H,H-12),3.67(s,3H,OCH3),3.57(s,3H,H-37),3.03(m,1H,H-31-1),2.93(m,1H,H-31-2),2.78(dd,J＝13.7,4.1Hz,1H,H-18),
2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-
16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:
180.3(C-28),175.8(C-36),145.4(C-13),123.9(C-12),66.5(C-3),65.2,56.9,52.0,
47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,
30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理+
论值C38H65N2O4[M+H]613.4939,实测值613.4971.
2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-
16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:
180.3(C-28),175.8(C-36),145.4(C-13),123.9(C-12),66.5(C-3),65.2,56.9,52.0,
47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,
30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):m/z理+
论值C38H65N2O4[M+H]613.4939,实测值613.4971.
[0030] 4、合成化合物1
[0031] 将100mg(0.16mmol)化合物26与34mg(0.192mmol)β-D-葡萄糖溶解于2.5mL DMF和HOAc体积比为3:1的混合溶剂中，60℃搅拌反应48h。反应结束后，减压浓缩，硅胶柱层析，得到白色泡沫状固体化合物1。
[0032] 上述步骤4中，用等摩尔α-D-葡萄糖、β-D-葡萄糖醛酸、α-D-葡萄糖醛酸、β-D-半乳糖、α-D-半乳糖、β-D-甘露糖、α-D-甘露糖、β-D-甘露糖醛酸、α-D-甘露糖醛酸、β-D-木糖、α-D-木糖、β-L-鼠李糖、α-L-鼠李糖、β-L-阿拉伯糖、α-L-阿拉伯糖、β-D-岩藻糖、α-D-岩藻糖、β-D-乳糖、α-D-乳糖、β-D-唾液酸、α-D-唾液酸分别替换β-D-葡萄糖，其他步骤与实施例1相同，依次得到化合物2～22。
[0033] 表1化合物1～22的取代基和产率
[0034]
[0035] 化合物 R 产率1 β-D-吡喃葡萄糖基 35％
2 α-D-吡喃葡萄糖基 31％
3 β-D-吡喃葡萄糖醛酸基 38％
4 α-D-吡喃葡萄糖醛酸基 35％
5 β-D-吡喃半乳糖基 45％
6 α-D-吡喃半乳糖基 33％
7 β-D-吡喃甘露糖基 39％
8 α-D-吡喃甘露糖基 30％
9 β-D-吡喃甘露糖醛酸基 29％
10 α-D-吡喃甘露糖醛酸基 27％
11 β-D-吡喃木糖基 43％
12 α-D-吡喃木糖基 35％
13 β-L-吡喃鼠李糖基 37％
14 α-L-吡喃鼠李糖基 29％
15 β-L-吡喃阿拉伯糖基 29％
16 α-L-吡喃阿拉伯糖基 27％
17 β-D-吡喃岩藻糖基 33％
18 α-D-吡喃岩藻糖基 29％
19 β-D-吡喃乳糖基 36％
20 α-D-吡喃乳糖基 29％
21 β-D-唾液酸糖基 28％
22 α-D-唾液酸糖基 24％
2 α-D-吡喃葡萄糖基 31％
3 β-D-吡喃葡萄糖醛酸基 38％
4 α-D-吡喃葡萄糖醛酸基 35％
5 β-D-吡喃半乳糖基 45％
6 α-D-吡喃半乳糖基 33％
7 β-D-吡喃甘露糖基 39％
8 α-D-吡喃甘露糖基 30％
9 β-D-吡喃甘露糖醛酸基 29％
10 α-D-吡喃甘露糖醛酸基 27％
11 β-D-吡喃木糖基 43％
12 α-D-吡喃木糖基 35％
13 β-L-吡喃鼠李糖基 37％
14 α-L-吡喃鼠李糖基 29％
15 β-L-吡喃阿拉伯糖基 29％
16 α-L-吡喃阿拉伯糖基 27％
17 β-D-吡喃岩藻糖基 33％
18 α-D-吡喃岩藻糖基 29％
19 β-D-吡喃乳糖基 36％
20 α-D-吡喃乳糖基 29％
21 β-D-唾液酸糖基 28％
22 α-D-唾液酸糖基 24％
[0036] 化合物1的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.24(t,J＝5.5Hz,1H,N-H),5.21(t,J＝3.2Hz,1H,H-12),4.09(d,J＝8.8Hz,1H),3.67(s,3H,OCH3),3.61(s,3H,OCH3),
3.59(t,J＝9.0Hz,1H),3.44(br s,1H),3.37(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),
2.93(m,1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,
1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,
0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.8(C-36),145.4(C-13),123.9(C-12),94.7,81.3,77.6,71.2,68.9,66.5(C-3),65.2,61.9,
56.9,56.3,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5483.
3.59(t,J＝9.0Hz,1H),3.44(br s,1H),3.37(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),
2.93(m,1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,
1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,
0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.8(C-36),145.4(C-13),123.9(C-12),94.7,81.3,77.6,71.2,68.9,66.5(C-3),65.2,61.9,
56.9,56.3,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5483.
[0037] 化合物2的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.24(t,J＝5.5Hz,1H,N-H),5.19(br s,1H,H-12),4.07(d,J＝8.7Hz,1H),3.67(s,3H,OCH3),3.59(t,J＝9.1Hz,1H),
3.57(s,3H,OCH3),3.44(br s,1H),3.37(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),2.93(m,
1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,
13
0.85,0.75,0.66(s,3H,CH3×7)；C NMR(150MHz,CD3OD)δ:180.3(C-28),175.8(C-36),
145.4(C-13),123.9(C-12),94.9,81.3,77.6,71.3,68.9,66.5(C-3),65.2,61.7,56.7,
56.5,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,
33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS+
(ESI):m/z理论值C44H75N2O9[M+H]775.5467,实测值775.5441.
3.57(s,3H,OCH3),3.44(br s,1H),3.37(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),2.93(m,
1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,
13
0.85,0.75,0.66(s,3H,CH3×7)；C NMR(150MHz,CD3OD)δ:180.3(C-28),175.8(C-36),
145.4(C-13),123.9(C-12),94.9,81.3,77.6,71.3,68.9,66.5(C-3),65.2,61.7,56.7,
56.5,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,
33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS+
(ESI):m/z理论值C44H75N2O9[M+H]775.5467,实测值775.5441.
[0038] 化合物3的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.26(t,J＝5.6Hz,1H,N-H),5.21(br s,1H,H-12),4.63(d,J＝8.0Hz,1H),3.63(s,3H,OCH3),3.59(t,J＝8.8Hz,1H),
3.58(s,3H,OCH3),3.44(br s,1H),3.33(m,1H),3.01(m,1H,H-31-1),2.93(m,1H,H-31-2),
2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,
7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,
0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.5(C-28),176.1(C-6),175.8(C-36),
145.4(C-13),123.9(C-12),94.9,81.3,77.6,71.3,68.9,66.5(C-3),65.2,56.9,56.3,
52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,
31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):
+
m/z理论值C44H73N2O10[M+H]789.5260,实测值789.5273.
3.58(s,3H,OCH3),3.44(br s,1H),3.33(m,1H),3.01(m,1H,H-31-1),2.93(m,1H,H-31-2),
2.84(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,
7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,
0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.5(C-28),176.1(C-6),175.8(C-36),
145.4(C-13),123.9(C-12),94.9,81.3,77.6,71.3,68.9,66.5(C-3),65.2,56.9,56.3,
52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,
31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.0,15.7；HR-MS(ESI):
+
m/z理论值C44H73N2O10[M+H]789.5260,实测值789.5273.
[0039] 化合物4的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.26(t,J＝5.6Hz,1H,N-H),5.20(br s,1H,H-12),4.65(d,J＝7.8Hz,1H),3.67(s,3H,OCH3),3.60(s,3H,OCH3),3.59(t,J＝8.8Hz,1H),3.44(br s,1H),3.33(m,1H),3.02(m,1H,H-31-1),2.95(m,1H,H-31-2),
2.85(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,
7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,
0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.5(C-28),176.3(C-6),175.8(C-36),
145.3(C-13),123.7(C-12),94.7,81.3,77.6,71.3,68.9,66.9(C-3),65.2,56.9,56.5,
52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,
31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.3,15.7；HR-MS(ESI):
m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5244.
2.85(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),2.27(t,J＝7.7,
7.4Hz,2H,H-35-1,H-35-2),1.87-1.91(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,
0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.5(C-28),176.3(C-6),175.8(C-36),
145.3(C-13),123.7(C-12),94.7,81.3,77.6,71.3,68.9,66.9(C-3),65.2,56.9,56.5,
52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,
31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.3,15.7；HR-MS(ESI):
m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5244.
[0040] 化合物5的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.5Hz,1H,N-H),5.21(t,J＝3.6Hz,1H,H-12),4.19(d,J＝8.5Hz,1H),3.65(s,3H,OCH3),3.59(t,J＝9.3Hz,
1H),3.59(s,3H,OCH3),3.44(br s,1H),3.24-3.29(m,2H),3.18(m,1H),3.03(m,1H,H-31-
1),2.93(m,1H,H-31-2),2.88(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝
3.6Hz,1H),2.27(t,J＝7.7,7.3Hz,2H,H-35-1,H-35-2),1.89(m,1H,H-16-1),1.07,0.97,
0.88,0.86,0.83,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.9(C-28),175.9(C-36),144.9(C-13),123.5(C-12),95.1,81.7,77.6,71.2,68.3,66.3(C-3),65.2,61.9,
56.7,56.3,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.5,24.1,19.3,17.6,17.0,15.9；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5497.
1H),3.59(s,3H,OCH3),3.44(br s,1H),3.24-3.29(m,2H),3.18(m,1H),3.03(m,1H,H-31-
1),2.93(m,1H,H-31-2),2.88(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.55(t,J＝
3.6Hz,1H),2.27(t,J＝7.7,7.3Hz,2H,H-35-1,H-35-2),1.89(m,1H,H-16-1),1.07,0.97,
0.88,0.86,0.83,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.9(C-28),175.9(C-36),144.9(C-13),123.5(C-12),95.1,81.7,77.6,71.2,68.3,66.3(C-3),65.2,61.9,
56.7,56.3,52.0,47.7,47.5,42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.5,27.7,27.0,26.5,25.7,24.5,24.1,19.3,17.6,17.0,15.9；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5497.
[0041] 化合物6的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.5Hz,1H,N-H),5.21(t,J＝3.6Hz,1H,H-12),4.19(d,J＝8.7Hz,1H),3.65(s,3H,OCH3),3.57(t,J＝9.6Hz,
1H),3.57(s,3H,OCH3),3.43(br s,1H),3.31(m,2H),3.18(m,1H),3.03(m,1H,H-31-1),
2.93(m,1H,H-31-2),2.88(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.57(t,J＝3.6Hz,
1H),2.27(t,J＝7.5,7.1Hz,2H,H-35-1,H-35-2),1.92(m,1H,H-16-1),1.07,0.97,0.89,
0.86,0.83,0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.6(C-28),175.9(C-
36),144.6(C-13),123.7(C-12),95.3,81.7,77.6,71.2,68.3,66.5(C-3),65.2,61.9,
56.7,56.3,52.0,47.7,47.3,42.9,42.5,40.7,40.3,40.2,39.5,37.7,35.1,34.7,34.3,
33.9,33.5,31.6,30.1,28.3,27.7,27.0,26.5,25.7,24.5,24.3,19.3,17.6,17.0,15.1；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5453.
1H),3.57(s,3H,OCH3),3.43(br s,1H),3.31(m,2H),3.18(m,1H),3.03(m,1H,H-31-1),
2.93(m,1H,H-31-2),2.88(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.57(t,J＝3.6Hz,
1H),2.27(t,J＝7.5,7.1Hz,2H,H-35-1,H-35-2),1.92(m,1H,H-16-1),1.07,0.97,0.89,
0.86,0.83,0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.6(C-28),175.9(C-
36),144.6(C-13),123.7(C-12),95.3,81.7,77.6,71.2,68.3,66.5(C-3),65.2,61.9,
56.7,56.3,52.0,47.7,47.3,42.9,42.5,40.7,40.3,40.2,39.5,37.7,35.1,34.7,34.3,
33.9,33.5,31.6,30.1,28.3,27.7,27.0,26.5,25.7,24.5,24.3,19.3,17.6,17.0,15.1；
HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5453.
[0042] 化合物7的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.25(t,J＝5.7Hz,1H,N-H),5.27(t,J＝3.4Hz,1H,H-12),4.13(d,J＝7.8Hz,1H),3.67(s,3H,OCH3),3.62(s,3H,OCH3),
3.59(t,J＝9.0Hz,1H),3.43(m,1H),3.36(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),2.93(m,1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.3Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),
2.25(m,2H,H-35-1,H-35-2),1.88(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.8(C-36),145.3(C-13),123.9(C-12),94.7,81.0,77.6,71.2,68.9,66.5(C-3),65.2,61.7,56.9,56.3,52.0,47.7,47.5,
42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.7,31.6,30.1,28.5,
27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.3,16.7；HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5440.
3.59(t,J＝9.0Hz,1H),3.43(m,1H),3.36(m,2H),3.15(m,1H),3.03(m,1H,H-31-1),2.93(m,1H,H-31-2),2.84(m,1H),2.78(dd,J＝13.7,4.3Hz,1H,H-18),2.55(t,J＝3.6Hz,1H),
2.25(m,2H,H-35-1,H-35-2),1.88(m,1H,H-16-1),1.08,0.97,0.88,0.86,0.85,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.8(C-36),145.3(C-13),123.9(C-12),94.7,81.0,77.6,71.2,68.9,66.5(C-3),65.2,61.7,56.9,56.3,52.0,47.7,47.5,
42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.7,31.6,30.1,28.5,
27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.9,17.3,16.7；HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5440.
[0043] 化合物8的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.24(t,J＝5.5Hz,1H,N-H),5.19(br s,1H,H-12),4.07(d,J＝8.7Hz,1H),3.67(s,3H,OCH3),3.61(s,3H,OCH3),3.53(t,J＝9.3Hz,1H),3.44(br s,1H),3.32(m,1H),3.15-3.19(m,2H),3.05(m,1H,H-31-1),2.95(m,1H,H-31-2),2.84(m,1H),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.53(t,J＝3.6Hz,1H),
2.29(m,2H,H-35-1,H-35-2),1.87-1.90(m,1H,H-16-1),1.05,0.95,0.89,0.86,0.83,
0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.9(C-36),145.1(C-
13),124.1(C-12),95.3,81.5,77.9,71.3,68.9,67.5(C-3),65.2,61.7,56.7,56.5,52.0,
47.9,47.5,42.9,42.6,40.7,40.6,40.1,39.3,37.7,35.1,34.7,34.3,33.9,33.6,31.6,
30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.3,17.0,16.3；HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5479.
2.29(m,2H,H-35-1,H-35-2),1.87-1.90(m,1H,H-16-1),1.05,0.95,0.89,0.86,0.83,
0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),175.9(C-36),145.1(C-
13),124.1(C-12),95.3,81.5,77.9,71.3,68.9,67.5(C-3),65.2,61.7,56.7,56.5,52.0,
47.9,47.5,42.9,42.6,40.7,40.6,40.1,39.3,37.7,35.1,34.7,34.3,33.9,33.6,31.6,
30.1,28.5,27.7,27.0,26.5,25.7,24.6,24.0,19.3,17.3,17.0,16.3；HR-MS(ESI):m/z理论值C44H75N2O9[M+H]+775.5467,实测值775.5479.
[0044] 化合物9的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.23(t,J＝5.6Hz,1H,N-H),5.23(s,1H,H-12),4.73(d,J＝7.9Hz,1H),3.65(s,3H,OCH3),3.59(s,3H,OCH3),3.56(t,J＝
9.3Hz,1H),3.44(br s,1H),3.35(m,1H),3.01(m,1H,H-31-1),2.91(m,1H,H-31-2),2.85(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.56(t,J＝3.7Hz,1H),2.27(t,J＝7.6Hz,2H,H-35),1.88(m,1H,H-16-1),1.06,0.97,0.89,0.87,0.85,0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),176.3(C-6),175.6(C-36),145.3(C-13),123.7(C-
12),95.3,81.3,77.6,71.3,68.9,66.7(C-3),65.2,56.7,56.3,52.0,47.7,47.5,42.9,
42.6,40.7,40.6,40.2,39.9,37.7,35.1,34.7,34.5,33.9,33.6,31.6,30.1,28.5,27.9,
27.1,26.5,25.7,24.6,24.0,19.3,17.9,17.3,15.9；HR-MS(ESI):m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5287.
9.3Hz,1H),3.44(br s,1H),3.35(m,1H),3.01(m,1H,H-31-1),2.91(m,1H,H-31-2),2.85(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.56(t,J＝3.7Hz,1H),2.27(t,J＝7.6Hz,2H,H-35),1.88(m,1H,H-16-1),1.06,0.97,0.89,0.87,0.85,0.75,0.67(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:180.1(C-28),176.3(C-6),175.6(C-36),145.3(C-13),123.7(C-
12),95.3,81.3,77.6,71.3,68.9,66.7(C-3),65.2,56.7,56.3,52.0,47.7,47.5,42.9,
42.6,40.7,40.6,40.2,39.9,37.7,35.1,34.7,34.5,33.9,33.6,31.6,30.1,28.5,27.9,
27.1,26.5,25.7,24.6,24.0,19.3,17.9,17.3,15.9；HR-MS(ESI):m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5287.
[0045] 化合物10的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.23(t,J＝5.3Hz,1H,N-H),5.21(s,1H,H-12),4.61(d,J＝7.8Hz,1H),3.67(s,3H,OCH3),3.63(s,3H,OCH3),3.59(t,J＝9.6Hz,1H),3.44(m,1H),3.31(m,1H),3.02(m,1H,H-31-1),2.97(m,1H,H-31-2),2.86(m,1H),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.57(t,J＝3.7Hz,1H),2.27(t,J＝7.5Hz,2H,H-35-1,H-35-2),1.87(m,1H,H-16-1),1.07,0.96,0.88,0.86,0.83,0.75,0.66(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.7(C-28),176.1(C-6),175.6(C-36),145.3(C-13),123.6(C-12),95.3,81.5,78.1,71.3,68.7,66.7(C-3),65.3,56.9,56.5,52.0,47.7,47.5,
42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,30.1,28.5,
27.7,27.0,26.5,25.7,24.3,24.0,19.3,18.3,17.6,15.9；HR-MS(ESI):m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5251.
42.9,42.6,40.7,40.6,40.2,39.8,37.7,35.1,34.7,34.3,33.9,33.6,31.6,30.1,28.5,
27.7,27.0,26.5,25.7,24.3,24.0,19.3,18.3,17.6,15.9；HR-MS(ESI):m/z理论值C44H73N2O10[M+H]+789.5260,实测值789.5251.
[0046] 化合物11的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.23(t,J＝5.1Hz,1H,N-H),5.23(t,J＝3.6Hz,1H,H-12),4.73(d,J＝8.0Hz,1H),3.67(s,3H,OCH3),3.61(t,J＝9.6Hz,1H),3.56(s,3H,OCH3),3.49(m,1H),3.15(m,1H),3.01(m,1H,H-31-1),2.95(m,1H,H-31-2),2.87(m,1H),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.56(t,J＝3.6Hz,1H),2.27(t,J＝7.5Hz,2H,H-35),1.89(m,1H,H-16),1.07,0.97,0.87,0.86,0.83,0.75,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.3(C-28),175.5(C-36),144.6(C-13),123.5(C-12),
96.7,77.0,71.2,68.6,68.1(C-3),65.2,56.9,56.3,52.1,47.6,47.3,42.9,42.5,40.7,
40.6,40.2,39.3,37.7,35.1,34.5,34.3,33.9,33.6,31.7,30.3,28.5,27.9,27.3,26.5,
25.3,24.6,24.1,19.3,17.5,17.1,16.3；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+
745.5361,实测值745.5393.
96.7,77.0,71.2,68.6,68.1(C-3),65.2,56.9,56.3,52.1,47.6,47.3,42.9,42.5,40.7,
40.6,40.2,39.3,37.7,35.1,34.5,34.3,33.9,33.6,31.7,30.3,28.5,27.9,27.3,26.5,
25.3,24.6,24.1,19.3,17.5,17.1,16.3；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+
745.5361,实测值745.5393.
[0047] 化合物12的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.24(t,J＝5.3Hz,1H,N-H),5.23(t,J＝3.6Hz,1H,H-12),4.69(d,J＝7.9Hz,1H),3.67(s,3H,OCH3),3.60(t,J＝9.3Hz,1H),3.57(s,3H,OCH3),3.47(m,1H),3.15(m,1H),3.03(m,1H,H-31-1),2.95(m,1H,H-31-2),2.89(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.57(t,J＝3.6Hz,1H),2.27(t,J＝7.3Hz,2H,H-35),1.87(m,1H,H-16),1.06,0.97,0.87,0.85,0.83,0.75,0.61(s,3H,CH3
13
×7)；C NMR(150MHz,CD3OD)δ:179.3(C-28),175.3(C-36),144.6(C-13),123.4(C-12),
96.3,77.3,71.2,68.9,68.3(C-3),65.1,56.7,56.3,52.3,47.3,47.1,42.8,42.5,40.7,
40.6,40.2,39.3,37.7,35.1,34.5,34.3,33.9,33.6,31.7,30.5,28.6,27.9,27.4,26.5,
25.3,24.6,24.3,19.3,17.5,17.1,16.5；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+
745.5361,实测值745.5343.
13
×7)；C NMR(150MHz,CD3OD)δ:179.3(C-28),175.3(C-36),144.6(C-13),123.4(C-12),
96.3,77.3,71.2,68.9,68.3(C-3),65.1,56.7,56.3,52.3,47.3,47.1,42.8,42.5,40.7,
40.6,40.2,39.3,37.7,35.1,34.5,34.3,33.9,33.6,31.7,30.5,28.6,27.9,27.4,26.5,
25.3,24.6,24.3,19.3,17.5,17.1,16.5；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+
745.5361,实测值745.5343.
[0048] 化合物13的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.20(t,J＝5.1Hz,1H,N-H),5.24(t,J＝3.6Hz,1H,H-12),5.05(d,J＝1.9Hz,1H),3.96(dd,J＝3.8,1.4Hz,1H),3.75-3.78(m,2H),3.67(s,3H,OCH3),3.59(s,3H,OCH3),3.39(t,J＝9.6Hz,1H),3.15(m,
1H),3.01(m,1H,H-31-1),2.95(m,1H,H-31-2),2.87(m,1H),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.56(t,J＝3.6Hz,1H),2.27(t,J＝7.5Hz,2H,H-35),1.89(m,1H,H-16),1.24(d,J＝
6.4Hz,3H),1.05,0.96,0.87,0.85,0.83,0.74,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.9(C-28),174.5(C-36),144.7(C-13),124.3(C-12),100.7,76.7,71.3,66.6,
68.3(C-3),65.1,56.6,56.1,52.1,47.6,47.3,42.7,42.5,40.9,40.6,40.2,39.3,37.9,
35.3,34.5,34.3,33.9,33.6,31.7,30.6,28.5,27.9,27.3,26.5,25.5,24.7,24.3,19.3,
17.7,17.1,16.0；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5563.[0049] 化合物14的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.3Hz,1H,N-H),5.24(t,J＝3.7Hz,1H,H-12),5.06(d,J＝2.0Hz,1H),3.96(dd,J＝3.8,1.6Hz,1H),3.76(m,2H),3.67(s,3H,OCH3),3.61(s,3H,OCH3),3.35(t,J＝9.6Hz,1H),3.16(m,1H),3.03(m,
1H,H-31-1),2.96(m,1H,H-31-2),2.87(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.59(t,J＝3.6Hz,1H),2.28(t,J＝7.5Hz,2H,H-35),1.90(m,1H,H-16),1.23(d,J＝6.5Hz,3H),
1.05,0.97,0.87,0.85,0.81,0.74,0.65(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.3(C-28),174.3(C-36),144.5(C-13),124.5(C-12),100.4,76.8,71.3,66.7,68.1(C-3),
65.3,56.7,56.1,52.1,47.9,47.3,42.7,42.5,40.9,40.7,40.2,39.4,37.9,35.5,34.5,
34.1,33.9,33.3,31.7,30.6,28.7,27.9,27.3,26.7,25.3,24.7,24.5,19.6,17.7,17.3,
16.1；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5541.
1H),3.01(m,1H,H-31-1),2.95(m,1H,H-31-2),2.87(m,1H),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.56(t,J＝3.6Hz,1H),2.27(t,J＝7.5Hz,2H,H-35),1.89(m,1H,H-16),1.24(d,J＝
6.4Hz,3H),1.05,0.96,0.87,0.85,0.83,0.74,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.9(C-28),174.5(C-36),144.7(C-13),124.3(C-12),100.7,76.7,71.3,66.6,
68.3(C-3),65.1,56.6,56.1,52.1,47.6,47.3,42.7,42.5,40.9,40.6,40.2,39.3,37.9,
35.3,34.5,34.3,33.9,33.6,31.7,30.6,28.5,27.9,27.3,26.5,25.5,24.7,24.3,19.3,
17.7,17.1,16.0；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5563.[0049] 化合物14的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.3Hz,1H,N-H),5.24(t,J＝3.7Hz,1H,H-12),5.06(d,J＝2.0Hz,1H),3.96(dd,J＝3.8,1.6Hz,1H),3.76(m,2H),3.67(s,3H,OCH3),3.61(s,3H,OCH3),3.35(t,J＝9.6Hz,1H),3.16(m,1H),3.03(m,
1H,H-31-1),2.96(m,1H,H-31-2),2.87(m,1H),2.78(dd,J＝13.7,4.1Hz,1H,H-18),2.59(t,J＝3.6Hz,1H),2.28(t,J＝7.5Hz,2H,H-35),1.90(m,1H,H-16),1.23(d,J＝6.5Hz,3H),
1.05,0.97,0.87,0.85,0.81,0.74,0.65(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.3(C-28),174.3(C-36),144.5(C-13),124.5(C-12),100.4,76.8,71.3,66.7,68.1(C-3),
65.3,56.7,56.1,52.1,47.9,47.3,42.7,42.5,40.9,40.7,40.2,39.4,37.9,35.5,34.5,
34.1,33.9,33.3,31.7,30.6,28.7,27.9,27.3,26.7,25.3,24.7,24.5,19.6,17.7,17.3,
16.1；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5541.
[0050] 化合物15的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.3Hz,1H,N-H),5.27(t,J＝3.6Hz,1H,H-12),4.55(d,J＝5.0Hz,1H),3.85(dd,J＝11.6,6.0Hz,1H),3.78(m,2H),3.71(dd,J＝7.2,3.8Hz,1H),3.66(s,3H,OCH3),3.63(s,3H,OCH3),3.48(dd,J＝11.6,2.8Hz,1H),3.15(m,1H),3.03(m,1H,H-31-1),2.97(m,1H,H-31-2),2.85(m,1H),
2.79(dd,J＝13.7,3.7Hz,1H,H-18),2.61(t,J＝3.6Hz,1H),2.27(t,J＝7.7Hz,2H,H-35),
1.93(m,1H,H-16),1.06,0.99,0.87,0.86,0.81,0.75,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.8(C-28),174.1(C-36),144.3(C-13),123.7(C-12),102.0,77.8,
73.3,68.7,68.1(C-3),64.5,56.7,56.3,52.1,47.6,47.3,42.6,42.3,40.9,40.5,40.2,
39.4,37.7,35.5,34.5,34.1,33.9,33.1,31.7,30.5,28.7,27.9,27.3,26.8,25.3,24.9,
24.5,19.3,17.5,17.3,16.0；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+745.5361,实测值
745.5383.
2.79(dd,J＝13.7,3.7Hz,1H,H-18),2.61(t,J＝3.6Hz,1H),2.27(t,J＝7.7Hz,2H,H-35),
1.93(m,1H,H-16),1.06,0.99,0.87,0.86,0.81,0.75,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.8(C-28),174.1(C-36),144.3(C-13),123.7(C-12),102.0,77.8,
73.3,68.7,68.1(C-3),64.5,56.7,56.3,52.1,47.6,47.3,42.6,42.3,40.9,40.5,40.2,
39.4,37.7,35.5,34.5,34.1,33.9,33.1,31.7,30.5,28.7,27.9,27.3,26.8,25.3,24.9,
24.5,19.3,17.5,17.3,16.0；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+745.5361,实测值
745.5383.
[0051] 化合物16的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.20(t,J＝5.6Hz,1H,N-H),5.27(t,J＝3.7Hz,1H,H-12),4.53(d,J＝4.9Hz,1H),3.89(dd,J＝11.6,6.2Hz,1H),3.79(m,2H),3.75(dd,J＝7.2,3.4Hz,1H),3.64(s,3H,OCH3),3.59(s,3H,OCH3),3.47(dd,J＝11.6,2.7Hz,1H),3.16(m,1H),3.01(m,1H,H-31-1),2.97(m,1H,H-31-2),2.85(m,1H),
2.79(dd,J＝13.7,3.7Hz,1H,H-18),2.63(t,J＝3.7Hz,1H),2.27(t,J＝7.7Hz,2H,H-35),
1.94(m,1H,H-16),1.06,0.97,0.87,0.85,0.81,0.76,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.3(C-28),174.5(C-36),144.6(C-13),123.5(C-12),101.9,77.8,
72.3,68.7,68.1(C-3),64.9,56.7,56.7,52.1,47.6,47.3,42.7,42.4,40.9,40.5,40.2,
39.5,37.9,35.7,34.5,34.1,33.7,33.1,31.7,30.5,28.7,27.9,27.5,26.9,25.3,24.7,
24.3,19.6,17.9,17.3,16.3；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+745.5361,实测值
745.5346.
2.79(dd,J＝13.7,3.7Hz,1H,H-18),2.63(t,J＝3.7Hz,1H),2.27(t,J＝7.7Hz,2H,H-35),
1.94(m,1H,H-16),1.06,0.97,0.87,0.85,0.81,0.76,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:179.3(C-28),174.5(C-36),144.6(C-13),123.5(C-12),101.9,77.8,
72.3,68.7,68.1(C-3),64.9,56.7,56.7,52.1,47.6,47.3,42.7,42.4,40.9,40.5,40.2,
39.5,37.9,35.7,34.5,34.1,33.7,33.1,31.7,30.5,28.7,27.9,27.5,26.9,25.3,24.7,
24.3,19.6,17.9,17.3,16.3；HR-MS(ESI):m/z理论值C43H73N2O8[M+H]+745.5361,实测值
745.5346.
[0052] 化合物17的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.21(t,J＝5.3Hz,1H,N-H),5.27(t,J＝3.6Hz,1H,H-12),4.07(d,J＝7.8Hz,1H,H-1'),3.66(s,3H,OCH3),3.59(s,3H,OCH3),3.45(dd,J＝12.8,5.9Hz,1H),3.38(t,J＝4.1,4.6Hz,1H),3.24-3.27(m,1H),
3.15-3.19(m,1H,H),3.08(dd,J＝11.9,4.1Hz),2.99(m,1H,H-31-1),2.94(m,1H,H-31-2),
2.79(dd,J＝12.4,3.3Hz,1H,H-18),2.27(t,J＝7.3Hz,2H,H-35),1.93(m,1H,H-16),1.01,
0.97,0.87,0.86,0.83,0.75,0.61(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.9(C-28),
175.3(C-36),145.1(C-13),123.7(C-12),102.7(C-1'),75.3,73.1,72.4,71.6,66.1(C-
3),57.4,51.9,47.7,47.5,42.9,42.6,40.7,40.6,39.6,39.1,38.3,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.9,28.5,27.7,26.7,26.5,26.1,25.7,24.6,24.3,24.0,19.5,+
18.5,17.3,16.9,16.1；HR-MS(ESI):m/z理论值C44H75N2O8[M+H] 759.5518,实测值
759.5543.
3.15-3.19(m,1H,H),3.08(dd,J＝11.9,4.1Hz),2.99(m,1H,H-31-1),2.94(m,1H,H-31-2),
2.79(dd,J＝12.4,3.3Hz,1H,H-18),2.27(t,J＝7.3Hz,2H,H-35),1.93(m,1H,H-16),1.01,
0.97,0.87,0.86,0.83,0.75,0.61(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.9(C-28),
175.3(C-36),145.1(C-13),123.7(C-12),102.7(C-1'),75.3,73.1,72.4,71.6,66.1(C-
3),57.4,51.9,47.7,47.5,42.9,42.6,40.7,40.6,39.6,39.1,38.3,35.1,34.7,34.3,
33.9,33.6,31.6,30.1,28.9,28.5,27.7,26.7,26.5,26.1,25.7,24.6,24.3,24.0,19.5,+
18.5,17.3,16.9,16.1；HR-MS(ESI):m/z理论值C44H75N2O8[M+H] 759.5518,实测值
759.5543.
[0053] 化合物18的结构表征数据为：1H NMR(600MHz,CD3OD)δ:7.23(t,J＝5.4Hz,1H,N-H),5.27(t,J＝3.7Hz,1H,H-12),4.07(d,J＝7.9Hz,1H,H-1'),3.66(s,3H,OCH3),3.57(s,3H,OCH3),3.45(dd,J＝12.8,5.6Hz,1H),3.38(t,J＝4.5Hz,1H),3.26(m,1H),3.19(m,1H,H),3.08(dd,J＝11.9,4.4Hz),2.99(m,1H,H-31-1),2.94(m,1H,H-31-2),2.78(dd,J＝
12.4,3.7Hz,1H,H-18),2.27(t,J＝7.3Hz,2H,H-35),1.95(m,1H,H-16),1.01,0.95,0.87,
0.85,0.79,0.75,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.6(C-28),175.5(C-
36),145.3(C-13),123.4(C-12),102.1(C-1'),75.3,73.1,72.4,71.6,66.3(C-3),57.5,
51.9,47.7,47.5,42.9,42.7,40.5,40.3,39.6,39.1,38.3,35.1,34.7,34.3,33.8,33.5,
31.6,30.1,28.7,28.5,27.5,26.7,26.5,26.1,25.7,24.6,24.1,24.0,19.7,18.5,17.6,
16.9,16.0；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5539.[0054] 化合物19的结构表征数据为：1H NMR(600MHz,DMSO-d6):δ7.23(t,J＝5.7Hz,1H,N-H),5.23(br s,1H,H-12),5.12(d,J＝4.1Hz,1H),5.06(d,J＝5.5Hz,1H),4.81(d,J＝
5.0Hz,1H),4.65-4.68(m,2H),4.53(d,J＝4.6Hz,1H),4.47(t-like,J＝6.3,5.9Hz,1H),
4.19-4.22(m,2H),3.72(dd,J＝11.0,5.5Hz,1H),3.66(s,3H,OCH3),3.60(s,3H,OCH3),
3.45-3.51(m,5H),3.24-3.31(m,4H),2.92-3.06(m,4H),2.78(dd,J＝13.7,5.0Hz,1H,H-
18),2.29(t,J＝7.5Hz,2H,H-35),1.05,0.97,0.88,0.86,0.83,0.75,0.63(s,3H,CH3×7)
13
；C NMR(150MHz,CD3OD):δ178.5(C-28),174.7(C-36),144.7(C-13),123.4(C-12),104.7(C-1'),103.5(C-1”),79.3,75.6,75.1,74.6,73.9,73.6,71.3,69.2,68.3(C-3),61.2,
60.7,56.8,55.7,50.7,46.4,46.2,41.6,41.3,39.5,39.3,39.1,38.7,36.6,33.8,33.5,
33.0,32.7,32.3,30.3,28.9,27.2,26.4,25.9,25.1,24.4,23.3,22.7,22.7,17.9,16.7,+
15.9,15.7,14.3；HR-MS(ESI):m/z理论值C50H85N2O14[M+H]937.5995,实测值937.5941.[0055] 化合物20的结构表征数据为：1H NMR(600MHz,DMSO-d6):δ7.23(t,J＝5.5Hz,1H,N-H),5.21(br s,1H,H-12),5.14(d,J＝4.5Hz,1H),5.03(d,J＝5.3Hz,1H),4.83(d,J＝
5.1Hz,1H),4.66(m,2H),4.55(d,J＝4.8Hz,1H),4.49(t,J＝6.1Hz,1H),4.20(m,2H),3.72(dd,J＝11.0,5.6Hz,1H),3.66(s,3H,OCH3),3.60(s,3H,OCH3),3.45-3.51(m,5H),3.24-
3.31(m,4H),3.02(m,4H),2.78(dd,J＝13.7,4.6Hz,1H,H-18),2.29(t,J＝7.5Hz,2H,H-
35),1.03,0.97,0.88,0.86,0.81,0.75,0.61(s,3H,CH3×7)；13C NMR(150MHz,CD3OD):δ
178.9(C-28),174.3(C-36),144.3(C-13),122.5(C-12),105.1(C-1'),103.9(C-1”),79.4,
75.9,75.3,74.9,73.9,73.7,71.2,69.1,68.6(C-3),61.2,60.7,56.8,55.7,50.7,46.4,
46.2,41.6,41.3,39.4,39.3,39.1,38.5,36.6,33.8,33.4,33.0,32.6,32.3,30.3,28.8,
27.2,26.4,25.7,25.1,24.4,23.3,22.7,22.6,17.9,16.7,15.7,15.0,14.6；HR-MS(ESI):
m/z理论值C50H85N2O14[M+H]+937.5995,实测值937.5963.
12.4,3.7Hz,1H,H-18),2.27(t,J＝7.3Hz,2H,H-35),1.95(m,1H,H-16),1.01,0.95,0.87,
0.85,0.79,0.75,0.63(s,3H,CH3×7)；13C NMR(150MHz,CD3OD)δ:178.6(C-28),175.5(C-
36),145.3(C-13),123.4(C-12),102.1(C-1'),75.3,73.1,72.4,71.6,66.3(C-3),57.5,
51.9,47.7,47.5,42.9,42.7,40.5,40.3,39.6,39.1,38.3,35.1,34.7,34.3,33.8,33.5,
31.6,30.1,28.7,28.5,27.5,26.7,26.5,26.1,25.7,24.6,24.1,24.0,19.7,18.5,17.6,
16.9,16.0；HR-MS(ESI):m/z理论值C44H75N2O8[M+H]+759.5518,实测值759.5539.[0054] 化合物19的结构表征数据为：1H NMR(600MHz,DMSO-d6):δ7.23(t,J＝5.7Hz,1H,N-H),5.23(br s,1H,H-12),5.12(d,J＝4.1Hz,1H),5.06(d,J＝5.5Hz,1H),4.81(d,J＝
5.0Hz,1H),4.65-4.68(m,2H),4.53(d,J＝4.6Hz,1H),4.47(t-like,J＝6.3,5.9Hz,1H),
4.19-4.22(m,2H),3.72(dd,J＝11.0,5.5Hz,1H),3.66(s,3H,OCH3),3.60(s,3H,OCH3),
3.45-3.51(m,5H),3.24-3.31(m,4H),2.92-3.06(m,4H),2.78(dd,J＝13.7,5.0Hz,1H,H-
18),2.29(t,J＝7.5Hz,2H,H-35),1.05,0.97,0.88,0.86,0.83,0.75,0.63(s,3H,CH3×7)
13
；C NMR(150MHz,CD3OD):δ178.5(C-28),174.7(C-36),144.7(C-13),123.4(C-12),104.7(C-1'),103.5(C-1”),79.3,75.6,75.1,74.6,73.9,73.6,71.3,69.2,68.3(C-3),61.2,
60.7,56.8,55.7,50.7,46.4,46.2,41.6,41.3,39.5,39.3,39.1,38.7,36.6,33.8,33.5,
33.0,32.7,32.3,30.3,28.9,27.2,26.4,25.9,25.1,24.4,23.3,22.7,22.7,17.9,16.7,+
15.9,15.7,14.3；HR-MS(ESI):m/z理论值C50H85N2O14[M+H]937.5995,实测值937.5941.[0055] 化合物20的结构表征数据为：1H NMR(600MHz,DMSO-d6):δ7.23(t,J＝5.5Hz,1H,N-H),5.21(br s,1H,H-12),5.14(d,J＝4.5Hz,1H),5.03(d,J＝5.3Hz,1H),4.83(d,J＝
5.1Hz,1H),4.66(m,2H),4.55(d,J＝4.8Hz,1H),4.49(t,J＝6.1Hz,1H),4.20(m,2H),3.72(dd,J＝11.0,5.6Hz,1H),3.66(s,3H,OCH3),3.60(s,3H,OCH3),3.45-3.51(m,5H),3.24-
3.31(m,4H),3.02(m,4H),2.78(dd,J＝13.7,4.6Hz,1H,H-18),2.29(t,J＝7.5Hz,2H,H-
35),1.03,0.97,0.88,0.86,0.81,0.75,0.61(s,3H,CH3×7)；13C NMR(150MHz,CD3OD):δ
178.9(C-28),174.3(C-36),144.3(C-13),122.5(C-12),105.1(C-1'),103.9(C-1”),79.4,
75.9,75.3,74.9,73.9,73.7,71.2,69.1,68.6(C-3),61.2,60.7,56.8,55.7,50.7,46.4,
46.2,41.6,41.3,39.4,39.3,39.1,38.5,36.6,33.8,33.4,33.0,32.6,32.3,30.3,28.8,
27.2,26.4,25.7,25.1,24.4,23.3,22.7,22.6,17.9,16.7,15.7,15.0,14.6；HR-MS(ESI):
m/z理论值C50H85N2O14[M+H]+937.5995,实测值937.5963.
[0056] 化合物21的结构表征数据为：1H NMR(600MHz,CD3OD):δ5.34(t,J＝3.6Hz,1H,H-12),3.89(m,1H),3.86(t,J＝3.4Hz,1H),3.83(t,J＝2.3Hz,1H),3.80(s,3H,COOCH3),3.73(t,J＝10.0Hz,1H),3.65(s,3H,COOCH3),3.60(s,3H,OCH3),3.63(m,3H),3.47(dd,J＝9.3,
1.9Hz,1H),3.38(dd,J＝10.5,1.8Hz,1H),3.21(m,1H,H-31-1),3.08(m,1H,H-31-2),3.04(m,1H,H-3),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.78(dd,J＝12.8,4.6Hz,1H,H-3′eq),
2.32(t,J＝7.3Hz,2H,H-35),2.00(s,3H,NAc),1.16,1.05,0.95,0.94,0.90,0.78,0.73(s,
3H,CH3×7)；13C NMR(150MHz,CDCl3):δ179.3,174.5,174.1,170.7,144.3(C-13),122.7(C-
12),97.6(C-2'),73.7,71.5,68.9,67.6(C-3),67.4,63.7,55.9,52.5,46.4,46.2,41.6,
41.3,40.8,39.3,39.2,38.3,36.5,33.9,33.4,33.2,32.5,32.2,30.3,29.5,28.8,28.1,
27.2,26.5,25.1,24.5,24.3,23.2,22.6,21.3,18.6,16.7,15.7,14.5；HR-MS(ESI):m/z理论值C49H82N3O12[M+H]+904.5893,实测值904.5865.
1.9Hz,1H),3.38(dd,J＝10.5,1.8Hz,1H),3.21(m,1H,H-31-1),3.08(m,1H,H-31-2),3.04(m,1H,H-3),2.78(dd,J＝13.7,3.7Hz,1H,H-18),2.78(dd,J＝12.8,4.6Hz,1H,H-3′eq),
2.32(t,J＝7.3Hz,2H,H-35),2.00(s,3H,NAc),1.16,1.05,0.95,0.94,0.90,0.78,0.73(s,
3H,CH3×7)；13C NMR(150MHz,CDCl3):δ179.3,174.5,174.1,170.7,144.3(C-13),122.7(C-
12),97.6(C-2'),73.7,71.5,68.9,67.6(C-3),67.4,63.7,55.9,52.5,46.4,46.2,41.6,
41.3,40.8,39.3,39.2,38.3,36.5,33.9,33.4,33.2,32.5,32.2,30.3,29.5,28.8,28.1,
27.2,26.5,25.1,24.5,24.3,23.2,22.6,21.3,18.6,16.7,15.7,14.5；HR-MS(ESI):m/z理论值C49H82N3O12[M+H]+904.5893,实测值904.5865.
[0057] 化合物22的结构表征数据为：1H NMR(600MHz,CD3OD):δ5.33(t,J＝3.3Hz,1H,H-12),3.92(m,1H),3.86(t,J＝3.6Hz,1H),3.83(t,J＝2.1Hz,1H),3.77(s,3H,COOCH3),3.73(t,J＝10.0Hz,1H),3.66(s,3H,COOCH3),3.63(s,3H,OCH3),3.63(m,3H),3.47(dd,J＝9.3,
2.1Hz,1H),3.38(dd,J＝10.5,2.3Hz,1H),3.21(m,1H,H-31-1),3.12(m,1H,H-31-2),3.06(m,1H,H-3),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.76(dd,J＝12.8,4.6Hz,1H),2.31(t,J＝7.3Hz,2H,H-35),2.01(s,3H,NAc),1.16,1.07,0.97,0.94,0.91,0.77,0.73(s,3H,CH3×
7)；13C NMR(150MHz,CDCl3):δ179.7,174.3,174.1,170.5,144.5(C-13),122.9(C-12),97.7(C-2'),73.9,71.5,68.7,67.5,67.3(C-3),63.7,55.9,52.7,46.3,46.2,41.7,41.3,40.6,
39.3,39.2,38.5,36.5,33.9,33.4,33.3,32.5,32.1,30.3,29.5,28.9,28.1,27.3,26.5,
25.3,24.5,24.3,23.2,22.6,21.5,18.6,16.5,15.7,14.7；HR-MS(ESI):m/z理论值C49H82N3O12[M+H]+904.5893,实测值904.5878.
2.1Hz,1H),3.38(dd,J＝10.5,2.3Hz,1H),3.21(m,1H,H-31-1),3.12(m,1H,H-31-2),3.06(m,1H,H-3),2.77(dd,J＝13.7,3.7Hz,1H,H-18),2.76(dd,J＝12.8,4.6Hz,1H),2.31(t,J＝7.3Hz,2H,H-35),2.01(s,3H,NAc),1.16,1.07,0.97,0.94,0.91,0.77,0.73(s,3H,CH3×
7)；13C NMR(150MHz,CDCl3):δ179.7,174.3,174.1,170.5,144.5(C-13),122.9(C-12),97.7(C-2'),73.9,71.5,68.7,67.5,67.3(C-3),63.7,55.9,52.7,46.3,46.2,41.7,41.3,40.6,
39.3,39.2,38.5,36.5,33.9,33.4,33.3,32.5,32.1,30.3,29.5,28.9,28.1,27.3,26.5,
25.3,24.5,24.3,23.2,22.6,21.5,18.6,16.5,15.7,14.7；HR-MS(ESI):m/z理论值C49H82N3O12[M+H]+904.5893,实测值904.5878.
[0058] 实施例2
[0059] 本发明齐墩果烷型氮糖苷化合物在制备治疗抗糖尿病药物中的应用
[0060] 发明人分别将上述实施例合成的化合物1～22作为受试化合物，测试其对蛋白质酪氨酸磷酸酯酶1B(PTP1B)的抑制活性，具体试验情况如下：
[0061] 200μL反应体系中含PTP1B(重组表达)、缓冲液(25mM HEPES,50mM氯化钠,2.5mM EDTA,0.1％BSA,pH 7.2)和上述的齐墩果烷型氮糖苷化合物，同时设立空白对照(不含酶和上述的齐墩果烷型氮糖苷化合物)和阴性对照(不含上述的齐墩果烷型氮糖苷化合物)，37℃反应10min，加入蛋白质酪氨酸磷酸酶底物PNPP，37℃再反应30min，加入2M Na2CO3终止反应，405nm测定OD值。根据OD值计算抑制率，抑制率＝[1-(OD样品-OD空白)/(OD阴性-OD空白)]×100％。初筛时每个样品单浓度设双复孔，抑制率大于70％的样品测定IC50值，每个样品梯度稀释六个浓度，每个浓度设双复孔。根据抑制率，应用Xlfit软件中的4Parameter Logistic Model计算IC50。试验结果见表2。
[0062] 表2化合物1～22体外PTP1B的抑制活性
[0063]
[0064] 由表2的活性结果可见，本发明的齐墩果烷型氮糖苷化合物对蛋白质酪氨酸磷酸酯酶1B表现出了很好的抑制活性，效果明显优于阳性对照正钒酸钠，可用于制备治疗糖尿病的药物。
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