Diterpene alkaloid glycoside derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of synthetic chemistry and pharmacy, and provides a diterpenoid alkaloid glycoside derivative and a preparation method and application thereof, and the diterpenoid alkaloid glycoside derivative or pharmaceutically acceptable salt thereof has good analgesic activity. The analgesic medicine prepared by taking the compound as an active ingredient has the advantages of quick response, strong medicine effect and long duration time; more importantly, the diterpenoid alkaloid glycoside derivative or the pharmaceutically acceptable salt thereof can also significantly reduce the original toxic and side effects of diterpenoid alkaloid, and shows good safety.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the field of synthetic chemistry and pharmaceutical technology, in particular to a diterpene alkaloid glycoside derivative and a preparation method and application thereof. BACKGROUND

[0002] Traditional Chinese medicine Fuzi is the processed product of lateral roots of Aconitum carmichaelii Debx. of Ranunculaceae, which has the effects of restoring yang and saving from danger, dispelling cold and relieving pain, and is widely used in China, Japan and Southeast Asia (Acta Pharmaceutica Sinica, 1983, (05): 394-400). The main active components of Fuzi are various C 19 - diterpene alkaloids, which generally have anti-inflammatory, analgesic and antiarrhythmic activities (Chinese Journal of Experimental Traditional Medical Formulae, 2010, 16(11): 210-213).

[0003] The group of Shi Jianguo of Chinese Academy of Medical Sciences has conducted in-depth and systematic research on the chemical components of traditional Chinese medicine Fuzi, and found several C 19 - diterpene alkaloid glycosides in the water-soluble fraction (Chin. Chem. Lett., 2017, 28(08): 1705-1710; Acta Pharm. Sin. B., 2018, 8(03): 409-419). The structural characteristics of these diterpene alkaloid glycosides are that in addition to having C 19 - diterpene alkaloid nucleus, the C14 position is connected with an arabinosyl group. Among them, the compounds aconicarmichoside F and aconicarmichoside I with significant analgesic activity have analgesic inhibition rates of 63.3% (0.3 mg / kg) and 63.8% (0.3 mg / kg) in acetic acid writhing test, which are comparable to the positive drug morphine (inhibition rate 65.5%, 0.3 mg / kg), and do not show the addiction and corresponding toxic side effects of morphine analgesics. However, the corresponding compounds have low content in Fuzi water decoction, limited sources, and unclear structure-activity relationship.

[0004]

[0005] In summary, the chemical synthesis method is expected to efficiently prepare diterpene alkaloid glycoside derivatives with new structures, which is of great significance for solving the source problem and discovering new non-addictive analgesics. SUMMARY

[0006] The purpose of the present disclosure is to overcome the shortcomings of the prior art and provide a diterpene alkaloid glycoside derivative and a preparation method and application thereof.

[0007] The purpose of the present disclosure is achieved by the following technical solutions:

[0008] In one aspect, there is provided a diterpenoid alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof. The structure of the diterpenoid alkaloid glycoside derivative is shown in Formula I:

[0009]

[0010] wherein R1-R6 are each independently selected from a hydrogen atom, a hydroxyl group, an alkoxy group, an acyloxy group, or a siloxy group; and R7 is selected from an arabinopyranosyl group, an arabinofuranosyl group, a glucopyranosyl group, a mannopyranosyl group, a xylopyranosyl group, a ribopyranosyl group, or a galactopyranosyl group.

[0011] In some embodiments, the alkoxy group is selected from a methoxy group, a methoxymethoxy group, or a benzyloxy group.

[0012] In some embodiments, the acyloxy group is selected from a formyloxy group, an acetyloxy group, a benzoyloxy group, a trifluoroacetyloxy group, a methoxycarbonyloxy group, or a tert-butoxymethylcarbonyloxy group.

[0013] In some embodiments, the siloxy group is selected from a tert-butyldimethylsiloxy group, a trimethylsiloxy group, a triethylsiloxy group, a triisopropylsiloxy group, or a tert-butyldiphenylsiloxy group.

[0014] In another aspect, there is provided a method for preparing the diterpenoid alkaloid glycoside derivative as described in any one of the above embodiments.

[0015] The method comprises:

[0016] S1. subjecting a diterpenoid alkaloid product to a functional group modification reaction to obtain an intermediate; wherein the functional group modification reaction comprises at least one of a hydroxyl group protection reaction and an ester group hydrolysis reaction; and the structure of the intermediate is shown in Formula II:

[0017]

[0018] S2. subjecting the intermediate to a glycosylation reaction with a glycosyl donor to obtain a glycosylated product;

[0019] S3. subjecting the glycosylated product to a protecting group removal reaction to obtain the diterpenoid alkaloid glycoside derivative.

[0020] It should be understood that the diterpenoid alkaloid product can be a natural product or a product further prepared from a natural product, which can be selected by a person skilled in the art according to actual needs, and the disclosure embodiments do not limit this.

[0021] In some embodiments, the method for preparing the pharmaceutically acceptable salt comprises:

[0022] subjecting the diterpenoid alkaloid glycoside derivative to a reaction with an acid reagent to obtain the pharmaceutically acceptable salt.

[0023] In some examples, the acid reagent is selected from HC1, HBr, H2SO4, CF3COOH, or CH3SO3H.

[0024] In some embodiments, the diterpene alkaloid product comprises a diterpene alkaloid natural product.

[0025] In some embodiments, the diterpene alkaloid natural product has a structure as shown in Formula III or Formula IV:

[0026]

[0027] It should be understood that, in the case where the diterpene alkaloid natural product has a structure as shown in Formula III, the diterpene alkaloid natural product can be referred to as diannine.

[0028] It should also be understood that, in the case where the diterpene alkaloid natural product has a structure as shown in Formula IV, the diterpene alkaloid natural product can be referred to as grassine.

[0029] In some embodiments, the diterpene alkaloid product has a structure as shown in Formula V or Formula VI:

[0030]

[0031] It should be understood that, in the case where the diterpene alkaloid product has a structure as shown in Formula V, the diterpene alkaloid product is a product prepared from the diannine.

[0032] It should also be understood that, in the case where the diterpene alkaloid product has a structure as shown in Formula VI, the diterpene alkaloid product is a product obtained by hydrolysis of the grassine.

[0033] In some examples, the protecting reagent employed in the hydroxyl protection reaction comprises one of benzyl bromide, chloromethyl methyl ether, trimethylchlorosilane, triethylchlorosilane, triisopropylchlorosilane, tert-butyldimethylchlorosilane, trimethylsilyl trifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate, triisopropylsilyl trifluoromethanesulfonate, and tert-butyldimethylsilyl trifluoromethanesulfonate.

[0034] In some examples, the base employed in the hydroxyl protection reaction comprises one of sodium hydride, triethylamine, imidazole, pyridine, 4-dimethylaminopyridine, 2,6-dimethylpyridine, and diisopropylethylamine.

[0035] In some examples, the solvent employed in the hydroxyl protection reaction comprises at least one of dichloromethane, 1,2-dichloroethane, tetrahydrofuran, and toluene.

[0036] In some examples, the base used in the ester hydrolysis reaction includes one of lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium carbonate, potassium carbonate, sodium tert-butoxide, and potassium tert-butoxide.

[0037] In some examples, the solvent used in the ester hydrolysis reaction includes one of water and alcohol solvents.

[0038] For example, the alcohol solvent includes at least one of methanol, ethanol, isopropanol, and tert-butanol.

[0039] In some embodiments, the glycosyl donor is selected from arabinopyranose donors, arabinofuranose donors, glucose donors, mannose donors, xylose donors, ribose donors, or galactose donors.

[0040] In some examples, the glycosylation reaction is carried out in the presence of a dehydrating agent and a catalyst.

[0041] For example, the molar ratio of the intermediate to the catalyst is 1:0.01 to 0.5.

[0042] For example, the catalyst includes one of Ph3PAuOTf and Ph3PAuNTf2, such as Ph3PAuNTf2.

[0043] For example, the dehydrating agent includes Molecular sieves One of molecular sieves and magnesium sulfate.

[0044] In some examples, the organic solvent used in the glycosylation reaction includes one of dichloromethane, 1,2-dichloroethane, trichloromethane, tetrahydrofuran, toluene, and diethyl ether, such as dichloromethane.

[0045] In some examples, the protecting group removal reaction uses a removing agent including an acid, a base, and a fluoride.

[0046] For example, the acid includes one of hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, and trifluoroacetic acid.

[0047] For example, the alkali includes one of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium carbonate, potassium carbonate, sodium tert-butoxide, and potassium tert-butoxide.

[0048] For example, the fluoride includes one of tetrabutylammonium fluoride, potassium fluoride, cesium fluoride, and TAS-F.

[0049] In other examples, the protecting group removal reaction uses one of the following removing reagents: ZnBr2 / n-PrSH, BF3·Et2O / Me2S, and AlCl3 / NaI.

[0050] In some examples, the solvent used in the protecting group removal reaction includes one of water, dichloromethane, tetrahydrofuran, ethyl acetate, acetone, and an alcohol solvent.

[0051] For example, the alcohol solvent includes at least one of methanol, ethanol, isopropanol, and tert-butanol.

[0052] In another aspect, a pharmaceutical composition is provided. The pharmaceutical composition includes the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof according to any one of the above embodiments, and a pharmaceutically acceptable carrier.

[0053] In yet another aspect, use of the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof according to any one of the above embodiments, or the method according to any one of the above embodiments, or the pharmaceutical composition according to any one of the above embodiments, in the preparation of an analgesic drug is provided.

[0054] It should be noted that the focus of the present disclosure is not only on the analgesic activity of the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof, which is equivalent to or even better than that of a diterpene alkaloid, but also on the significantly reduced side effects of the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof, as compared to a diterpene alkaloid.

[0055] In detail, a diterpene alkaloid produces side effects at a very low dosage (for example, mice died at a dosage of 0.24 mg / kg of diouine; for another example, mice showed adverse reactions such as respiratory depression, movement disorder, and rigidity at a dosage of 0.6 mg / kg of grass peacockine), whereas the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof provided by the present disclosure still has no side effects at a dosage of 8 mg / kg.

[0056] The present disclosure has the following beneficial effects:

[0057] The present disclosure provides a diterpene alkaloid glycoside derivative, a preparation method and use thereof. The diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof has good analgesic activity, and an analgesic drug prepared by taking the diterpene alkaloid glycoside derivative as an active ingredient has the advantages of fast onset, strong efficacy, and long duration. More importantly, the diterpene alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof can also significantly reduce the side effects of a diterpene alkaloid originally, and show good safety. BRIEF DESCRIPTION OF DRAWINGS

[0058] In order to more clearly illustrate the technical solutions in the present disclosure, the following will briefly introduce the drawings needed to be used in some embodiments of the present disclosure. Obviously, the drawings described in the following description are only some drawings of the embodiments of the present disclosure, and other drawings can also be obtained by those skilled in the art according to these drawings. In addition, the drawings in the following description can be regarded as schematic diagrams, and are not limited to the actual process of the method involved in the embodiments of the present disclosure.

[0059] Figure 1 The test results of analgesic activity of each compound in Embodiment 2 of the present disclosure are shown in the following table.

[0060] Figure 2 The test results of acute inflammatory pain of formalin are shown in the following table.

[0061] Figure 3 The test results of visceral pain in writhing are shown in the following table. DETAILED DESCRIPTION

[0062] The technical solutions in some embodiments of the present disclosure will be described clearly and completely below. Obviously, the described embodiments are only some of the embodiments of the present disclosure, but not all the embodiments. Based on the embodiments provided in the present disclosure, all other embodiments obtained by those skilled in the art belong to the scope of protection of the present disclosure.

[0063] Synthesis of diterpene alkaloid glycoside derivatives

[0064]

[0065] Dianthine (compound 1, 70 mg, 1.0 eq, 0.106 mmol) was dissolved in dry DCM (2.5 mL) under argon protection, and Et3N (88 μL, 6.0 eq, 0.637 mmol) and TBSOTf (73 μL, 3.0 eq, 0.318 mmol) were added successively at -78 °C, and the reaction was continued at -78 °C for 1 h. After TLC monitoring, the reaction was quenched by adding aqueous NH4Cl solution, extracted with DCM three times, and the organic phase was combined and washed with water and saturated brine, dried over MgSO4, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (petroleum ether / EtOAc = 4 / 1, v / v) to obtain white solid 2 (69.8 mg, 85%). 1H NMR (400 MHz, CDC13) δ 8.03 - 7.97 (m, 2H), 6.94 - 6.88 (m, 2H), 4.86 (d, J = 5.2 Hz, 1H), 4.04 (d, J = 6.4 Hz, 1H), 3.85 (s, 3H), 3.81 (s, 1H), 3.71 (dd, J = 12.4, 5.6 Hz, 1H), 3.61 (d, J = 8.4 Hz, 1H), 3.51 (s, 3H), 3.39 - 3.32 (m, 2H), 3.23 (s, 3H), 3.22 (s, 3H), 3.18 (s, 3H), 3.04 - 2.95 (m, 3H), 2.94 - 2.89 (m, 1H), 2.86 (s, 1H), 2.83 - 2.74 (m, 2H), 2.59 - 2.36 (m, 4H), 2.17 (dd, J = 15.2, 6.2 Hz, 2H), 2.09 - 2.00 (m, 3H), 1.34 (s, 3H), 1.07 (t, J = 7.0 Hz, 3H), 0.88 (s, 9H), 0.06 (s, 3H), 0.03 (s, 3H); 13 C NMR (100 MHz, CDC13) δ 169.9, 166.2, 163.5, 131.8 (x 2), 122.8, 113.8 (x 2), 85.7, 83.8, 83.5, 82.7, 78.6, 74.9, 71.7, 68.8, 61.9, 58.8, 58.4, 58.3, 56.5, 55.6, 50.1, 49.8, 49.1, 46.6, 46.4, 45.5, 44.1, 40.7, 39.6, 36.3, 36.1, 26.1 (x 3), 21.7, 18.2, 13.4, -3.7, -4.9; IR (neat): v max = 2930, 2252, 1714, 1607, 1256, 1089, 906, 771, 725, 647 cm -1 ; Optical rotation: [a]25D= +30.1 (c 0.87, CHC13). HRMS (ESI): m / z calcd for C 41 H 63 NO 11 Si (M + H) + 774.4243, found 774.4241.

[0066]

[0067] Compound 2 (70 mg, 1.0 eq, 0.090 mmol) was dissolved in 5% NaOH methanol (2 mL) solution and reacted at 40 °C for 2 h. After the reaction was complete as monitored by TLC, the reaction was quenched by adding ammonium chloride aqueous solution at 0 °C. The mixture was extracted three times with DCM, and the combined organic phases were washed with water and saturated brine. The mixture was dried over Mg2SO4 and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 7 / 1, v / v) to give white solid 3 (50.3 mg, 93%). 1 H NMR (400MHz, CDCl3) δ4.19(d,J=6.8Hz,1H),4.01–3.97(m,1H),3.91(s,1H),3.86(d,J=8.0Hz,1H),3.69(dd,J=12.4,5. 2Hz,1H),3.49–3.42(m,1H),3.42–3.38(m,4H),3.35(d,J=8.0Hz,1H),3.31(s,3H),3.28(s,1H),3.25(s,3H),3.21(s,3H ),3.09(s,1H),2.97(dd,J=11.2,6.4Hz,1H),2.82(d,J=10.8Hz,1H),2.57–2.42(m,3H),2.40–2.24(m,4H),2.23–2.16( m,2H),2.16–2.08(m,1H),2.05(s,1H),1.93–1.77(m,2H),1.06(t,J=7.2Hz,3H),0.88(s,9H),0.05(s,3H),0.03(s,3H); 13 C NMR (100MHz, CDCl3) δ84.6,83.4,83.0,79.8,76.9,73.0,72.3,69.2,62.6,58.6,57.8,57.8,56.5,53.0, 50.9,49.9,49.4,47.0,46.9,44.4,42.0,40.1,36.1,35.5,26.1(×3),18.2,13.7,–3.7,–4.9; IR(neat):ν max =3449,2927,1256,1089,991,936,867,835,773,732cm -1 ;Optical rotation:[α]25D=+25.8(c 0.40,CHC13);HRMS(ESI):m / z calcd.ForC 31 H 55 NO8Si(M+H) + 598.3770, found 598.3765.

[0068]

[0069] Compound 3 (25 mg, 1.0 eq, 0.042 mmol), arabinopyranose donor 4 (81 mg, 3.0 eq, 0.125 mmol), Ph3PAuNTf2 (15.5 mg, 0.5 eq, 0.021 mmol) and MS (200 mg) was dissolved in dry DCM (2 mL) and reacted at room temperature for 16 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / EtOAc = 1 / 1, v / v) to obtain white solid 5 (30.1 mg, 69%). 1 H NMR (400 MHz, CDC13) δ 8.10 (d, J = 7.2 Hz, 2H), 7.99 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.64 - 7.57 (m, 1H), 7.53 (t, J = 7.2 Hz, 1H), 7.50 - 7.44 (m, 3H), 7.38 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 5.83 - 5.76 (m, 1H), 5.71 - 5.62 (m, 2H), 4.73 (d, J = 6.8 Hz, 1H), 4.38 (dd, J = 13.2, 2.8 Hz, 1H), 3.96 - 3.86 (m, 3H), 3.82 (d, J = 5.2 Hz, 1H), 3.77 (d, J = 8.0 Hz, 1H), 3.66 (dd, J = 12.0, 5.2 Hz, 1H), 3.32 (d, J = 8.0 Hz, 1H), 3.28 (s, 3H), 3.21 (s, 3H), 3.19 (s, 3H), 3.16 (s, 3H), 2.94 (dd, J = 10.8, 6.4 Hz, 1H), 2.88 (s, 1H), 2.83 - 2.75 (m, 2H), 2.63 (dd, J = 14.8, 4.8 Hz, 1H), 2.52 - 2.34 (m, 4H), 2.20 - 2.09 (m, 3H), 2.08 - 1.99 (m, 2H), 1.95 (s, 1H), 1.94 - 1.85 (m, 1H), 1.81 - 1.72 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H), 0.87 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H); 13C NMR (100 MHz, CDC13) δ 166.4, 165.9, 165.8, 133.6 (x 2), 133.5, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.3, 129.1, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.3, 88.6, 83.2, 83.1, 83.0, 75.3, 73.3, 72.2, 70.9, 70.8, 69.0, 68.7, 63.8, 61.7, 58.5, 58.4, 57.8, 56.5, 53.9, 50.1, 49.6, 49.1, 46.9, 46.5, 44.1, 42.7, 41.7, 37.1, 36.0, 26.1 (x 3), 18.2, 13.6, -3.7, -4.9; IR (neat): v max = 3551, 2926, 1725, 1451, 1259, 1090, 835, 755, 709 cm -1 ; Optical rotation: [a]25D= +85.4 (c 0.50, CHC13); HRMS (ESI): m / z calcd. For C 57 H 75 NO 15 Si (M+H) + 1042.4979, found 1042.4975.

[0070]

[0071] Compound 5 (20 mg, 1.0 eq, 0.019 mmol) was dissolved in normal MeOH (1.5 mL), KOH (54 mg, 50.0 eq, 0.959 mmol) was added, and the reaction was stirred in a 40 °C oil bath for 12 h. After TLC monitoring the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 5 / 1, v / v) to give a white solid. The product was dissolved in EA (2 mL), and HCl (7 μL, 4 M in EA, 1.5 eq, 0.029 mmol) was added at room temperature to generate a white precipitate, and the supernatant was decanted. The white precipitate was washed with EA twice, concentrated, and pumped on oil to give white solid 6 (12.8 mg, 87%). 1H NMR (400 MHz, CDC13) δ 4.40 (d, J = 6.8 Hz, 1H), 4.33 (d, J = 6.4 Hz, 1H), 4.27 (d, J = 3.2 Hz, 1H), 4.08 (d, J = 4.8 Hz, 1H), 3.96 - 3.90 (m, 2H), 3.76 (d, J = 9.2 Hz, 1H), 3.69 - 3.60 (m, 3H), 3.54 (s, 1H), 3.49 - 3.45 (m, 1H), 3.44 (s, 4H), 3.40 - 3.31 (m, 11H), 3.29 - 3.18 (m, 3H), 2.67 - 2.53 (m, 2H), 2.45 (d, J = 6.4 Hz, 1H), 2.40 - 2.32 (m, 1H), 2.30 - 2.14 (m, 4H), 1.69 (dd, J = 14.8, 4.8 Hz, 1H), 1.59 - 1.50 (m, 1H), 1.38 (t, J = 7.4 Hz, 3H), 0.92 (s, 9H), 0.19 (s, 3H), 0.16 (s, 3H); 13 CNMR (10 MHz, D20) δ 102.3, 84.9, 82.3, 81.9, 79.4, 76.1, 75.2, 74.3, 72.3, 70.7, 70.6, 68.1, 66.0, 64.6, 58.9, 58.7, 57.9, 55.4, 53.3, 50.4, 49.8, 49.7, 44.8, 43.2, 42.1, 41.8, 39.4, 35.4, 29.6, 25.4 (x 3), 17.2, 10.3, -5.0, -5.8; IR (neat): v max = 3368, 2930, 1677, 1446, 1203, 1133, 1061, 1002, 952, 836, 777 cm -1 ; Optical rotation: [a]25D= -4.7 (c 0.19, MeOH); HRMS (ESI): m / z calcd for C 36 H 63 NO 12 Si (M+H) + 730.4192, found 730.4190.

[0072]

[0073] Compound 3 (25 mg, 1.0 eq, 0.042 mmol), arabinofuranose donor 7 (81 mg, 3.0 eq, 0.125 mmol), Ph3PAuNTf2(15.5 mg, 0.5 eq, 0.021 mmol) and MS (200 mg) was dissolved in dry DCM (2 mL) and reacted at room temperature for 16 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / EtOAc = 1.5 / 1, v / v) to obtain white solid 8 (26.5 mg, 61%). 1 HNMR (400 MHz, CDC13) δ 8.09 (d, J = 7.2 Hz, 2H), 8.07 - 8.00 (m, 4H), 7.64 - 7.56 (m, 2H), 7.51 - 7.44 (m, 3H), 7.42 (t, J = 7.8 Hz, 2H), 7.32 (t, J = 7.8 Hz, 2H), 5.57 - 5.50 (m, 2H), 5.36 (s, 1H), 4.98 - 4.93 (m, 1H), 4.84 (dd, J = 12.0, 3.2 Hz, 1H), 4.64 (dd, J = 12.0, 6.0 Hz, 1H), 4.17 (d, J = 6.8 Hz, 1H), 4.00 (s, 1H), 3.92 (d, J = 5.2 Hz, 1H), 3.84 (d, J = 8.0 Hz, 1H), 3.71 (dd, J = 12.4, 5.6 Hz, 1H), 3.39 - 3.35 (m, 4H), 3.32 - 3.23 (m, 7H), 3.22 (s, 3H), 2.99 (dd, J = 10.8, 6.4 Hz, 1H), 2.90 (s, 1H), 2.84 - 2.78 (m, 2H), 2.74 (dd, J = 14.6, 4.6 Hz, 1H), 2.53 - 2.40 (m, 4H), 2.25 - 2.18 (m, 1H), 2.18 - 2.12 (m, 3H), 2.05 - 2.03 (m, 1H), 2.02 - 1.87 (m, 3H), 1.07 (t, J = 7.0 Hz, 3H), 0.89 (s, 9H), 0.04 (s, 6H); 13C NMR (100 MHz, CDC13) δ 166.4, 166.0, 165.8, 133.9, 133.8, 133.2, 130.2 (x 2), 130.1 (x 2), 129.9 (x 2), 129.8, 129.0, 128.9, 128.8 (x 2), 128.7 (x 2), 128.52 (x 2), 107.03, 88.0, 83.6, 83.3, 82.9, 82.7, 81.8, 77.8, 75.7, 74.2, 72.2, 69.0, 64.2, 61.9, 58.8, 58.5, 58.1, 56.5, 53.6, 50.1, 49.6, 49.2, 46.9, 46.6, 44.1, 43.3, 41.7, 37.5, 36.1, 26.1 (x 3), 18.3, 13.6, -3.7, -4.9; IR (neat): v max = 2927, 2250, 1720, 1452, 1353, 1265, 1094, 905, 726, 710, 648 cm -1 ; Optical rotation: [a]25D= +9.8 (c 0.37, CHC13); HRMS (ESI): m / z calcd. For C 57 H 75 NO 15 Si (M+H) + 1042.4979, found 1042.4976.

[0074]

[0075] Compound 8 (15 mg, 1.0 eq, 0.014 mmol) was dissolved in normal MeOH (1.5 mL), KOH (40 mg, 50.0 eq, 0.720 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring the reaction was complete, the reaction was quenched with aqueous NH4C1 at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 5 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1 mL), CF3COOH (1.3 μL, 1.2 eq, 0.017 mmol) was added at room temperature, and after stirring at room temperature for 10 min, the product was concentrated and pumped to give white solid 9 (10.0 mg, 82%). 1H NMR (400 MHz, D20) δ 5.11 (s, 1H), 4.30 (d, J = 6.8 Hz, 1H), 4.28 - 4.24 (m, 1H), 4.20 - 4.16 (m, 1H), 4.14 (dd, J = 2.8, 1.2 Hz, 1H), 3.99 (d, J = 5.2 Hz, 1H), 3.90 (dd, J = 5.6, 2.8 Hz, 1H), 3.79 - 3.74 (m, 2H), 3.72 - 3.69 (m, 2H), 3.65 - 3.61 (m, 1H), 3.54 (s, 1H), 3.42 (s, 4H), 3.37 (s, 3H), 3.36 (s, 3H), 3.36 (s, 3H), 3.33 (s, 1H), 3.28 - 3.20 (m, 3H), 2.62 - 2.54 (m, 1H), 2.54 - 2.49 (m, 1H), 2.46 (d, J = 6.8 Hz, 1H), 2.41 - 2.32 (m, 1H), 2.32 - 2.11 (m, 4H), 1.68 (dd, J = 14.4, 4.8 Hz, 1H), 1.58 - 1.50 (m, 1H), 1.38 (t, J = 7.2 Hz, 3H), 0.92 (s, 9H), 0.19 (s, 3H), 0.16 (s, 3H); 13 C NMR (100 MHz, D20) δ 166.1, 119.3 (q, J = 290.0 Hz), 109.2, 87.5, 85.4, 84.8, 83.3, 79.7, 78.3, 77.2, 73.6, 72.6, 72.5, 67.6, 67.5, 64.2, 61.7, 61.6, 60.7, 58.4, 56.7, 53.3, 52.7, 52.6, 46.9, 46.2, 44.8, 42.2, 37.9, 36.7, 32.6, 28.3 (x 3), 20.1, 13.2, -2.0, -2.8; IR (neat): v max = 3350, 2929, 1673, 1463, 1349, 1183, 1098, 1055, 990, 836, 570, 510 cm -1 ; Optical rotation: [a]25D= -16.9 (c 0.18, MeOH); HRMS (ESI): m / z calcd for C 36 H 63 NO 12 Si (M+H) + 730.4192, found 730.4195.

[0076]

[0077] Dienolide (Compound 1, 300 mg, 1.0 eq, 0.455 mmol) was dissolved in dry DCE (10 mL) under argon protection, DIPEA (475 μL, 6.0 eq, 2.728 mmol) and MOMCI (104 μL, 3.0 eq, 1.364 mmol) were added successively at 0 °C, the reaction was placed in 60 °C oil bath for 12 h. TLC monitoring reaction was complete, the reaction was quenched by adding aqueous NH4CI solution, extracted with DCM three times, the combined organic phase was washed with water and saturated brine, dried over MgS04, concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 40 / 1, v / v) to give white solid 10 (240 mg, 75%). 1 H NMR (400 MHz, CDC13) δ 8.03 - 7.98 (m, 2H), 6.93 - 6.88 (m, 2H), 4.86 (d, J = 5.2 Hz, 1H), 4.69 - 4.64 (m, 2H), 4.05 (d, J = 6.4 Hz, 1H), 3.86 (s, 3H), 3.80 (s, 1H), 3.78 (d, J = 8.8 Hz, 1H), 3.57 (dd, J = 12.0, 6.0 Hz, 1H), 3.51 (s, 3H), 3.39 (s, 3H), 3.38 - 3.32 (m, 1H), 3.28 (s, 1H), 3.26 (s, 3H), 3.24 (s, 3H), 3.19 (s, 3H), 3.07 - 2.95 (m, 3H), 2.94 - 2.87 (m, 2H), 2.84 - 2.77 (m, 1H), 2.75 - 2.70 (m, 1H), 2.60 - 2.51 (m, 1H), 2.49 - 2.42 (m, 2H), 2.42 - 2.35 (m, 2H), 2.22 (d, J = 6.4 Hz, 1H), 2.17 - 2.12 (m, 1H), 2.08 - 2.03 (m, 2H), 1.34 (s, 3H), 1.08 (t, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 170.0, 166.3, 163.6, 131.9 (x 2), 122.8, 113.9 (x 2), 96.6, 85.6, 83.8, 83.5, 82.7, 78.6, 75.3, 75.0, 71.8, 61.6, 58.9, 58.4, 58.3, 56.5, 55.7, 55.6, 50.0, 49.6, 49.2, 47.4, 46.7, 45.4, 43.5, 40.7, 39.5, 36.0, 33.5, 21.8, 13.6; IR (neat): v max=2932,2820,1715,1606,1512,1460,1256,1168,1088,1027,915,801,770,730cm -1 ;Opticalrotation:[α]25D=+50.4(c 0.37,CHC13);HRMS(ESI):m / z calcd.For C 37 H 53 NO 12 (M+H) + 704.3641, found 704.3638.

[0078]

[0079] Compound 10 (240 mg, 1.0 eq, 0.341 mmol) was dissolved in 5% NaOH methanol (9 mL) solution and reacted at 40 °C for 4 h. After the reaction was complete as monitored by TLC, the reaction was quenched by adding ammonium chloride aqueous solution at 0 °C. The mixture was extracted three times with DCM, and the combined organic phases were washed with water and saturated brine. The mixture was dried over MgSO4 and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 25 / 1, v / v) to give a white solid 11 (169 mg, 94%). 1 H NMR (400MHz, CDCl3) δ4.70–4.65(m,2H),4.20(d,J=6.8Hz,1H),4.04(d,J=8.4Hz,1H),4.01–3.96(m, 1H),3.93(d,J=3.6Hz,1H),3.54(dd,J=11.6,5.0Hz,1H),3.45(s,1H),3.43–3.35(m,7H),3.31(s,3H) ,3.28–3.21(m,8H),3.13(s,1H),3.01(dd,J=10.4,7.2Hz,1H),2.74(d,J=10.8Hz,1H),2.57–2.43(m, 3H),2.41–2.25(m,6H),2.21(d,J=6.8Hz,1H),2.06(s,1H),1.93–1.80(m,2H),1.08(t,J=7.0Hz,3H); 13C NMR (100 MHz, CDC13) δ 96.6, 84.6, 83.3, 82.9, 79.8, 76.9, 75.8, 72.9, 72.4, 62.4, 58.6, 57.9, 57.7, 56.6, 55.6, 52.7, 50.8, 49.9, 49.4, 47.7, 47.2, 43.8, 42.0, 39.9, 35.9, 33.0, 13.9; IR (neat): v max = 3450, 2926, 1669, 1450, 1371, 1261, 1090, 1030, 912, 802, 731 cm -1 ; Optical rotation: [a]25D= +47.2 (c 0.25, CHC13); HRMS (ESI): m / z calcd. For C 27 H 45 NO9 (M + H) + 528.3167, found 528.3165.

[0080]

[0081] Compound 11 (70 mg, 1.0 eq, 0.132 mmol), arabinopyranose donor 4 (257 mg, 3.0 eq, 0.398 mmol), Ph3PAuNTf2(49 mg, 0.5 eq, 0.066 mmol) and DMAP (0.5 eq, 0.066 mmol) were dissolved in dry DCM (5 mL) under argon protection, and the reaction was stirred at room temperature for 24 h. The reaction solution was filtered with celite, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain white solid 12 (59.3 mg, 46%). Compound 11 (70 mg, 1.0 eq, 0.132 mmol), arabinopyranose donor 4 (257 mg, 3.0 eq, 0.398 mmol), Ph3PAuNTf2(49 mg, 0.5 eq, 0.066 mmol) and DMAP (0.5 eq, 0.066 mmol) were dissolved in dry DCM (5 mL) under argon protection, and the reaction was stirred at room temperature for 24 h. The reaction solution was filtered with celite, and the filtrate was concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain white solid 12 (59.3 mg, 46%). 1H NMR (400 MHz, CDC13) δ 8.10 (d, J = 7.2 Hz, 2H), 7.98 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.63 - 7.58 (m, 1H), 7.53 (t, J = 7.0 Hz, 1H), 7.50 - 7.45 (m, 3H), 7.38 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 5.83 - 5.74 (m, 1H), 5.73 - 5.63 (m, 2H), 4.73 (d, J = 6.8 Hz, 1H), 4.65 (s, 2H), 4.38 (dd, J = 13.2, 2.8 Hz, 1H), 3.98 - 3.87 (m, 4H), 3.82 (d, J = 5.2 Hz, 1H), 3.56 - 3.48 (m, 1H), 3.37 (s, 3H), 3.29 (s, 3H), 3.24 - 3.16 (m, 10H), 3.00 - 2.93 (m, 1H), 2.91 (s, 1H), 2.84 (s, 1H), 2.74 - 2.63 (m, 2H), 2.53 - 2.38 (m, 4H), 2.35 (d, J = 11.2 Hz, 1H), 2.22 - 2.12 (m, 3H), 2.05 - 2.00 (m, 2H), 1.96 (s, 1H), 1.89 (t, J = 13.6 Hz, 1H), 1.81 - 1.75 (m, 1H), 1.06 (t, J = 7.0 Hz, 3H); 13 C NMR (150 MHz, CDC13) δ 166.4, 165.9, 165.8, 133.6 (x 2), 133.5, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.3, 129.0, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.4, 96.5, 88.6, 83.1, 82.9, 75.5, 75.3, 73.2, 72.1, 70.9, 70.8, 68.7, 63.9, 61.4, 58.5 (x 2), 57.8, 56.5, 55.6, 53.6 (x 2), 50.0, 49.5, 49.1, 47.6, 46.8, 43.5, 42.6, 41.7, 36.8, 22.8, 13.7; IR (neat): v max = 3547, 2925, 1724, 1602, 1451, 1260, 1178, 1089, 1027, 907, 803, 709 cm -1 ; Optical rotation: [a]25D= +83.3 (c 0.57, CHC13); HRMS (ESI): m / z calcd for C53 H 65 NO 16 (M+H) + 972.4376, found 972.4373.

[0082]

[0083] Compound 12 (25 mg, 1.0 eq, 0.026 mmol) was dissolved in normal MeOH (2 mL), KOH (72 mg, 50.0 eq, 1.286 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring of the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 8 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1 mL), CF3COOH (2.4 μL, 1.2 eq, 0.031 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 min, concentrated, and pumped to give white solid 13 (15.5 mg, 78%). 1 H NMR (400 MHz, D2O) δ 4.39 (d, J = 7.2 Hz, 1H), 4.31 (d, J = 6.0 Hz, 1H), 4.09 - 4.04 (m, 2H), 3.95 - 3.89 (m, 2H), 3.68 - 3.60 (m, 4H), 3.60 - 3.51 (m, 3H), 3.51 - 3.45 (m, 2H), 3.44 (s, 3H), 3.43 (s, 3H), 3.41 - 3.37 (m, 1H), 3.36 (s, 3H), 3.35 (s, 3H), 3.34 - 3.33 (m, 1H), 3.32 (s, 3H), 3.31 - 3.23 (m, 3H), 2.63 - 2.53 (m, 2H), 2.44 - 2.32 (m, 3H), 2.30 - 2.14 (m, 3H), 1.69 (dd, J = 14.6, 5.0 Hz, 1H), 1.55 - 1.47 (m, 1H), 1.35 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, D20) δ 163.8 (q, J = 35.0 Hz), 117.2 (q, J = 290.0 Hz), 103.2, 96.1, 85.8, 83.1, 82.6, 79.9, 77.3, 76.2, 76.1, 75.0, 73.2, 71.5, 69.0, 66.9, 65.8, 59.8, 59.7, 58.8, 56.7, 55.7, 54.2, 51.3, 50.6, 50.0, 45.6, 43.6, 43.2, 43.0, 40.2, 36.4, 26.8, 10.8; IR (neat): v max = 3325, 2923, 2853, 1674, 1447, 1376, 1099, 1059, 918 cm -1 ; Optical rotation: [a]25D= -8.4 (c 0.32, MeOH); HRMS (ESI): m / z calcd for C 32 H 53 NO 13 (M+H) + 660.3590; found 660.3594.

[0084]

[0085] Compound 12 (30 mg, 1.0 eq, 0.031 mmol), ZnBr2(42 mg, 6.0 eq, 0.185 mmol) were dissolved in dry DCM (2 mL) under argon protection, n-PrSH (34 μL, 12.0 eq, 0.370 mmol) was added dropwise with stirring, and the reaction was allowed to proceed at room temperature for 12 h. After the reaction was monitored to be complete by TLC, the reaction was quenched by the addition of water at 0 °C, and extracted with DCM three times. The combined organic phase was washed with water and saturated brine, dried over MgS04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 40 / 1, v / v) to give 14 as a white solid (19.2 mg, 67%). 1H NMR (400 MHz, CDC13) δ 8.10 (d, J = 7.2 Hz, 2H), 7.98 (d, J = 7.6 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.64 - 7.51 (m, 2H), 7.51 - 7.44 (m, 3H), 7.39 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 5.81 - 5.75 (m, 1H), 5.71 - 5.62 (m, 2H), 4.73 (d, J = 6.8 Hz, 1H), 4.38 (dd, J = 13.0, 2.6 Hz, 1H), 3.96 - 3.81 (m, 4H), 3.73 - 3.65 (m, 2H), 3.62 - 3.55 (m, 1H), 3.30 (s, 3H), 3.27 (s, 3H), 3.26 - 3.22 (m, 1H), 3.20 (s, 3H), 3.17 (s, 3H), 3.07 - 3.00 (m, 1H), 2.89 - 2.80 (m, 2H), 2.52 - 2.37 (m, 5H), 2.34 - 2.20 (m, 2H), 2.19 - 2.11 (m, 2H), 2.05 - 1.98 (m, 1H), 1.96 (s, 1H), 1.93 - 1.86 (m, 2H), 1.85 - 1.78 (m, 1H), 1.68 - 1.61 (m, 1H), 1.07 (t, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 166.4, 165.9, 165.8, 133.7, 133.7, 133.6, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.3, 129.0, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.3, 88.6, 82.9, 82.7, 82.6, 77.8, 75.3, 73.3, 72.3, 70.9, 70.7, 68.7, 63.8, 61.6, 59.3 (x 2), 58.5, 57.7, 56.0, 53.0, 50.5, 49.1, 48.9, 43.3 (x 2), 42.9, 41.9, 36.4, 22.8, 13.6; IR (neat): v max = 3498, 2926, 1723, 1602, 1451, 1260, 1088, 1026, 908, 802, 709, 647 cm -1 ; Optical rotation: [a]25D= +86.8 (c 0.39, CHC13). HRMS (ESI): m / z calcd for C 51 H 61 NO15 (M+H) + 928.4114, found 928.4111.

[0086]

[0087] Compound 14 (15 mg, 1.0 eq, 0.016 mmol) was dissolved in normal MeOH (1.5 mL), KOH (45 mg, 50.0 eq, 0.808 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring of the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 6 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1 mL), CF3COOH (1.5 μL, 1.2 eq, 0.019 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 min, concentrated, and pumped to give white solid 15 (10.4 mg, 88%). 1 H NMR (400 MHz, D2O) δ 4.39 (d, J = 7.2 Hz, 1H), 4.30 (d, J = 6.8 Hz, 1H), 4.21 (d, J = 4.8 Hz, 1H), 4.07 (d, J = 4.8 Hz, 1H), 3.95 - 3.89 (m, 2H), 3.76 - 3.66 (m, 1H), 3.66 - 3.62 (m, 2H), 3.61 - 3.57 (m, 2H), 3.56 - 3.50 (m, 3H), 3.49 - 3.46 (m, 1H), 3.43 (s, 3H), 3.36 (s, 3H), 3.33 (s, 6H), 3.31 - 3.27 (m, 1H), 3.26 - 3.22 (m, 2H), 2.63 - 2.52 (m, 2H), 2.41 (d, J = 6.4 Hz, 1H), 2.39 - 2.31 (m, 1H), 2.30 - 2.27 (m, 1H), 2.27 - 2.14 (m, 3H), 1.69 (dd, J = 14.4, 4.8 Hz, 1H), 1.62 (dt, J = 16.4, 4.4 Hz, 1H), 1.35 (t, J = 7.2 Hz, 3H); 13CNMR (100 MHz, D20) δ 164.0 (q, J = 36.0 Hz), 117.4 (q, J = 289.9 Hz), 103.4, 86.0, 83.3, 82.8, 80.5, 78.1, 76.3, 75.3, 73.4, 71.7, 69.2, 67.1, 65.8, 63.6, 60.0, 59.9, 59.0, 56.0, 54.3, 51.6, 50.8, 50.2, 45.8, 43.9, 43.7, 43.2, 40.4, 36.6, 30.0, 10.92; IR (neat): v 3356, 3169, 2922, 2852, 1661, 1632, 1403, 1200, 1099, 1010 cm max 3356, 3169, 2922, 2852, 1661, 1632, 1403, 1200, 1099, 1010 cm -1 ; Optical rotation: [a]25D= -6.4 (c 0.33, MeOH); HRMS (ESI): m / z calcd for C 30 H 49 NO 12 (M+H) + 616.3328, found 616.3330.

[0088]

[0089] Compound 11 (65 mg, 1.0 eq, 0.123 mmol), arabinofuranose donor 7 (238 mg, 3.0 eq, 0.370 mmol), Ph3PAuNTf2(46 mg, 0.5 eq, 0.062 mmol) and MS (500 mg) was dissolved in dry DCM (5 mL) and reacted at room temperature for 24 h. The reaction was filtered through celite and the filtrate was concentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 50 / 1, v / v) to give 16 as a white solid (73.0 mg, 61%). 1H NMR (400 MHz, CDC13) δ 8.10 - 8.02 (m, 4H), 7.99 (d, J = 7.6 Hz, 2H), 7.64 - 7.57 (m, 2H), 7.55 - 7.46 (m, 3H), 7.40 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.8 Hz, 2H), 5.61 (d, J = 4.4 Hz, 1H), 5.46 (s, 1H), 5.35 (s, 1H), 4.89 - 4.82 (m, 2H), 4.75 - 4.69 (m, 2H), 4.65 (dd, J = 12.8, 6.0 Hz, 1H), 4.26 (d, J = 6.4 Hz, 1H), 4.17 - 4.09 (m, 2H), 4.00 (d, J = 5.2 Hz, 1H), 3.53 - 3.47 (m, 3H), 3.43 - 3.39 (m, 9H), 3.36 (s, 4H), 3.32 (s, 6H), 3.06 (s, 1H), 2.58 - 2.49 (m, 1H), 2.47 - 2.30 (m, 4H), 2.29 - 2.15 (m, 4H), 2.07 - 1.97 (m, 2H), 1.68 (s, 1H), 1.41 (t, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 166.4, 166.3, 166.0, 134.0, 133.9, 133.3, 130.2 (x 2), 130.1 (x 2), 130.0, 129.9 (x 2), 129.8, 128.9, 128.8 (x 2), 128.7 (x 2), 128.6 (x 2), 106.0, 96.2, 84.9, 83.0, 82.1, 81.4, 81.3, 79.8, 77.3, 76.6, 75.4, 75.0, 74.2, 66.1, 63.8, 59.3, 59.0, 58.5, 56.5, 55.7, 53.5, 50.9, 50.4, 50.3, 46.7, 43.7, 43.3, 43.2, 40.6, 36.0, 22.8, 14.3; IR (neat): v max = 3501, 2929, 1721, 1602, 1452, 1352, 1267, 1193, 1103, 1060, 1027, 966, 911, 712 cm -1 ; Optical rotation: [a]25D= +12.7 (c 0.22, CHC13); HRMS (ESI): m / z calcd for C 53 H 65 NO 16 (M+H) +972.4376; found 972.4376.

[0090]

[0091] Compound 16 (10 mg, 1.0 eq, 0.010 mmol) was dissolved in normal MeOH (1 mL), KOH (29 mg, 50.0 eq, 0.514 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 15 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1 mL), CF3COOH (0.9 μL, 1.2 eq, 0.012 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 min, concentrated, and pumped to give white solid 17 (6.4 mg, 88%). 1 H NMR (400 MHz, D2O) δ 5.11 (s, 1H), 4.28 (d, J = 6.8 Hz, 1H), 4.20 - 4.13 (m, 2H), 4.08 (d, J = 4.4 Hz, 1H), 3.99 (d, J = 5.2 Hz, 1H), 3.90 (dd, J = 5.2, 2.8 Hz, 1H), 3.82 - 3.76 (m, 1H), 3.76 - 3.70 (m, 1H), 3.69 - 3.61 (m, 2H), 3.60 - 3.54 (m, 2H), 3.54 - 3.45 (m, 3H), 3.44 (s, 3H), 3.42 (s, 3H), 3.37 (s, 3H), 3.36 (s, 3H), 3.33 (s, 4H), 3.30 - 3.25 (m, 3H), 2.60 - 2.47 (m, 2H), 2.45 - 2.33 (m, 3H), 2.32 - 2.13 (m, 3H), 1.69 (dd, J = 14.4, 5.0 Hz, 1H), 1.56 - 1.48 (m, 1H), 1.35 (t, J = 7.4 Hz, 3H). 13 C NMR (100 MHz, D2O) δ 119.3 (q, J = 289.8 Hz), 109.2, 98.2, 87.5, 85.3, 84.8, 84.6, 83.3, 82.1, 79.7, 79.4, 78.3, 78.3, 77.0, 68.0, 64.2, 61.8, 61.6, 60.7, 58.7, 57.8, 56.7, 53.4, 52.7, 52.2, 47.0, 45.7, 45.3, 44.7, 42.4, 38.2, 28.9, 12.8; IR (neat): v max= 3362, 2923, 1675, 1466, 1349, 1181, 1133, 1101, 1056, 739, 615, 570 cm -1 ; Optical rotation: [a]25D= -18.9 (c 0.19, MeOH); HRMS (ESI): m / z calcd for C 32 H 53 NO 13 (M+H) + 660.3590, found 660.3592.

[0092]

[0093] Compound 16 (30 mg, 1.0 eq, 0.031 mmol), ZnBr2(42 mg, 6.0 eq, 0.185 mmol) were dissolved in dry DCM (2 mL) under argon protection, n-PrSH (34 μL, 12.0 eq, 0.370 mmol) was added dropwise with stirring, and the reaction was allowed to proceed at room temperature for 12 h. After TLC monitoring showed that the reaction was complete, the reaction was quenched by the addition of water at 0 °C, and the mixture was extracted with DCM three times. The combined organic phase was washed with water and saturated brine, dried over MgS04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 40 / 1, v / v) to give 18 as a white solid (20.9 mg, 73%). 1 H NMR (400 MHz, CDC13) δ 8.09 - 7.98 (m, 6H), 7.64 - 7.57 (m, 2H), 7.53 - 7.46 (m, 3H), 7.42 (t, J = 7.8 Hz, 2H), 7.34 (t, J = 7.8 Hz, 2H), 5.61 (d, J = 4.0 Hz, 1H), 5.49 - 5.43 (m, 1H), 5.35 (s, 1H), 4.90 - 4.82 (m, 2H), 4.68 - 4.62 (m, 1H), 4.29 - 4.22 (m, 2H), 4.12 (s, 1H), 4.00 (d, J = 5.2 Hz, 1H), 3.65 (d, J = 11.6 Hz, 1H), 3.58 (d, J = 8.0 Hz, 1H), 3.51 - 3.45 (m, 3H), 3.41 (s, 3H), 3.40 (s, 3H), 3.37 (s, 3H), 3.31 (s, 3H), 3.29 - 3.23 (m, 3H), 3.03 (s, 1H), 2.49 - 2.39 (m, 3H), 2.37 - 2.30 (m, 2H), 2.25 - 2.17 (m, 4H), 2.06 - 1.97 (m, 2H), 1.74 - 1.68 (m, 1H), 1.41 (t, J = 7.2 Hz, 3H);13 C NMR (100 MHz, CDC13) δ 166.4, 166.3, 165.9, 134.1, 134.0, 133.3, 130.2, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.7, 128.9, 128.8 (x 4), 128.6 (x 2), 106.2, 85.3, 83.0, 82.6, 81.5, 81.4, 79.9, 77.3, 76.9, 75.1, 74.3, 70.1, 65.1, 63.9, 59.4, 59.2, 58.5, 55.4, 53.5, 51.0, 50.7, 50.0, 47.0, 43.8, 43.6, 43.5, 40.6, 36.0, 22.8, 14.3; IR (neat): v = 3487, 3364, 2921, 2850, 1718, 1662, 1452, 1351, 1267, 1191, 1101, 1057, 908, 712, 649, 616 cm max ; Optical rotation: [a]25D= +2.8 (c 0.22, CHC13); HRMS (ESI): m / z calcd for C -1 H 51 H 61 NO 15 (M+H) + 928.4114, found 928.4112.

[0094]

[0095] Compound 18 (10 mg, 1.0 eq, 0.011 mmol) was dissolved in normal MeOH (1 mL), KOH (30 mg, 50.0 eq, 0.538 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous sodium chloride solution, dried over Na2SO4, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 12 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1 mL), CF3COOH (1.0 μL, 1.2 eq, 0.013 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give a white solid 19 (5.7 mg, 73%). 1H NMR (400 MHz, D20) δ 5.10 (s, 1H), 4.26 (d, J = 6.8 Hz, 1H), 4.21 (d, J = 3.6 Hz, 1H), 4.19 - 4.09 (m, 2H), 3.98 (d, J = 4.8 Hz, 1H), 3.89 (dd, J = 5.0, 2.6 Hz, 1H), 3.81 - 3.76 (m, 1H), 3.72 - 3.66 (m, 1H), 3.59 - 3.53 (m, 3H), 3.51 - 3.43 (m, 2H), 3.41 (s, 3H), 3.36 (s, 3H), 3.33 (s, 7H), 3.29 - 3.22 (m, 3H), 2.60 - 2.46 (m, 2H), 2.44 - 2.32 (m, 2H), 2.31 - 2.13 (m, 4H), 1.72 - 1.58 (m, 2H), 1.34 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, D20) δ 162.7 (q, J = 35.4 Hz), 116.1 (q, J = 289.8 Hz), 106.0, 84.3, 82.1, 81.6, 81.3, 80.1, 79.3, 76.8, 76.5, 75.1, 73.9, 69.2, 64.5, 61.0, 58.6, 58.4, 57.5, 54.7, 53.4, 50.3, 49.5, 48.9, 43.8, 42.6, 42.4, 41.5, 39.3, 35.1, 28.7, 9.6; IR (neat): v max = 3385, 2925, 2849, 1678, 1444, 1349, 1191, 1133, 1057, 839, 740 cm -1 ; Optical rotation: [a]25D= -14.3 (c 0.23, MeOH); HRMS (ESI): m / z calcd for C 30 H 49 NO 12 (M+H) + 616.3328, found 616.3330.

[0096]

[0097] Compound 20 (12 mg, 1.0 eq, 0.026 mmol), arabinopyranose donor (50 mg, 3.0 eq, 0.077 mmol), Ph3PAuNTf2(9.5 mg, 0.5 eq, 0.013 mmol) and TBAF (0.1 mL, 0.5 M in THF, 0.05 eq, 0.05 mmol) were added to a vial and stirred at 60 °C for 24 h. The reaction mixture was purified by HPLC (0.1% formic acid in water / acetonitrile) to give compound 21 (5 mg, 40% yield). MS (150 mg) was dissolved in dry DCM (1.5 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with diatomaceous earth, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 120 / 1, v / v) to give a white solid 21 (11.7 mg, 50%). 1 HNMR (400MHz, CDCl3) δ8.10(d,J=7.6Hz,2H),7.98(d,J=7.2Hz,2H),7.88(d,J=7.2Hz,2H),7.61(t,J=7.4Hz,1H),7.54(t,J=7.4Hz,1H),7.51 –7.45(m,3H),7.39(t,J=7.8Hz,2H),7.32(t,J=7.8Hz,2H),5.82–5.73(m,1H),5.72–5.64(m,2H),4.73(d,J=6.8Hz,1H),4.38(dd,J=13.2,2.8 Hz,1H),3.98–3.81(m,4H),3.66(d,J=8.4Hz,1H),3.30(s,3H),3.29–3 .28(m,1H),3.27(s,4H),3.25–3.14(m,7H),3.09–2.93(m,2H),2.68–2. 48(m,2H),2.43(t,J=15.2,8.8Hz,2H),2.22(t,J=7.6Hz,2H),2.14(t, J=5.8Hz,2H),2.08–1.96(m,4H),1.71–1.60(m,4H),1.32–1.30(m,3H). 13 C NMR (100MHz, CDCl3) δ167.0,165.8,165.7,134.1,133.8,133.7,130.1(×4),130. 0(×2),129.5,128.9(×2),128.8(×4),128.6(×2),102.3,87.8,82.3,81.5,80.6, 78.0,74.8,73.5,71.2,70.4,68.5,63.9,62.1,59.3,59.0,58.4,58.0,55.9,53. 5,50.8,49.1,47.7,43.4,42.0,40.3,38.1,36.8,26.9,21.9,10.3.;IR(neat):ν max =3358,2924,1724,1451,1260,1089,1027,908,709,645cm -1; Optical rotation: [a]25D= +71.3 (c 0.17, CHC13); HRMS (ESI): m / z calcd. For C 51 H 61 NO 14 (M+H) + 912.4165, found 912.4168.

[0098]

[0099] Compound 21 (10 mg, 1.0 eq, 0.011 mmol) was dissolved in normal MeOH (1 mL), KOH (31 mg, 50.0 eq, 0.548 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol six times, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 9 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1 mL), CF3COOH (1.0 μL, 1.2 eq, 0.013 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give an oily solid 22 (6.4 mg, 82%). 1 H NMR (400 MHz, D20) δ 4.40 (d, J = 7.2 Hz, 1H), 4.27 (d, J = 6.8 Hz, 1H), 4.08 (d, J = 4.8 Hz, 1H), 3.96 - 3.89 (m, 2H), 3.69 - 3.64 (m, 3H), 3.64 - 3.60 (m, 1H), 3.57 - 3.53 (m, 1H), 3.47 (d, J = 8.8 Hz, 1H), 3.44 (s, 3H), 3.40 - 3.36 (m, 1H), 3.35 (s, 3H), 3.35 (s, 3H), 3.33 (s, 2H), 3.30 (s, 3H), 3.25 (s, 1H), 3.22 - 3.12 (m, 1H), 3.00 (d, J = 12.4 Hz, 1H), 2.63 - 2.51 (m, 2H), 2.45 (d, J = 6.8 Hz, 1H), 2.40 - 2.32 (m, 1H), 2.30 - 2.18 (m, 3H), 2.02 - 1.90 (m, 2H), 1.70 - 1.56 (m, 2H), 1.44 - 1.39 (m, 1H), 1.36 (t, J = 7.0 Hz, 3H); 13CNMR (100 MHz, D20) δ 117.2 (q, J = 289.8 Hz), 103.2, 85.9, 83.2, 82.3, 81.1, 79.2, 76.1, 75.0, 73.2, 71.5, 69.0, 66.9, 63.3, 59.8, 59.7, 58.8, 58.2, 55.9, 53.8, 51.2, 50.0, 45.5, 42.9, 42.5, 40.0, 38.4, 37.0, 27.6, 21.7, 10.6; IR (neat): v max 3350, 2924, 2836, 1659, 1449, 1203, 1109, 1016, 857 cm -1 ; Optical rotation: [a]25D= -5.7 (c 0.07, MeOH); HRMS (ESI): m / z calcd. For C 30 H 49 NO 11 (M+H) + 600.3378, found 600.3380.

[0100]

[0101] Compound 20 (12 mg, 1.0 eq, 0.026 mmol), arabinofuranose donor 7 (50 mg, 3.0 eq, 0.077 mmol), Ph3PAuNTf2(9.5 mg, 0.5 eq, 0.013 mmol) and DMAP (2.5 mg, 0.2 eq, 0.013 mmol) were dissolved in dry DCM (1.5 mL) under argon protection, and the reaction was stirred at room temperature for 12 h. The reaction solution was filtered with celite, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 110 / 1, v / v) to obtain white solid 23 (11.2 mg, 48%). Compound 20 (12 mg, 1.0 eq, 0.026 mmol), arabinofuranose donor 7 (50 mg, 3.0 eq, 0.077 mmol), Ph3PAuNTf2(9.5 mg, 0.5 eq, 0.013 mmol) and DMAP (2.5 mg, 0.2 eq, 0.013 mmol) were dissolved in dry DCM (1.5 mL) under argon protection, and the reaction was stirred at room temperature for 12 h. The reaction solution was filtered with celite, and the filtrate was concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 110 / 1, v / v) to obtain white solid 23 (11.2 mg, 48%). 1HNMR (400 MHz, Chloroform-d) δ 8.08 - 8.03 (m, 4H), 8.02 - 7.99 (m, 2H), 7.64 - 7.58 (m, 2H), 7.56 - 7.51 (m, 1H), 7.50 - 7.46 (m, 2H), 7.44 - 7.40 (m, 2H), 7.34 (t, J = 7.8 Hz, 2H), 5.61 (dd, J = 5.2, 2.0 Hz, 1H), 5.45 (d, J = 2.0 Hz, 1H), 5.34 (s, 1H), 4.89 - 4.82 (m, 2H), 4.69 - 4.62 (m, 1H), 4.21 (d, J = 6.8 Hz, 1H), 4.09 (s, 1H), 4.01 (d, J = 5.2 Hz, 1H), 3.67 (d, J = 8.0 Hz, 1H), 3.45 - 3.43 (m, 1H), 3.40 (s, 3H), 3.39 (s, 3H), 3.37 - 3.35 (m, 1H), 3.34 (s, 3H), 3.32 (s, 3H), 3.30 (d, J = 3.6 Hz, 1H), 3.27 (s, 1H), 3.26 - 3.22 (m, 1H), 3.20 - 3.17 (m, 1H), 3.17 - 3.12 (m, 2H), 3.00 (s, 1H), 2.44 - 2.38 (m, 4H), 2.27 - 2.18 (m, 1H), 2.17 - 2.09 (m, 2H), 2.07 - 1.94 (m, 3H), 1.78 - 1.68 (m, 1H), 1.61 (dd, J = 14.0, 4.4 Hz, 1H), 1.39 (t, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 166.3 (x 2), 165.9, 134.1, 134.0, 133.4, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.7, 128.8, 128.7 (x 4), 128.6, 128.5 (x 2), 106.1, 85.3, 83.1, 82.7, 81.4 (x 2), 80.7, 78.1, 77.3, 75.0, 74.1, 63.8, 62.6, 59.4, 59.2, 58.5, 58.1, 55.9, 53.3, 50.8, 49.3, 46.8, 43.6, 42.3, 40.4, 38.2, 37.1, 27.0, 21.8, 10.4; IR (neat): v max = 3519, 2924, 2244, 1721, 1602, 1451, 1265, 1094, 1026, 908, 710 cm -1; Optical rotation: [a]25D= +17.7 (c 0.32, CHCI3). HRMS (ESI): m / z calcd for C 51 H 61 NO 14 (M+H) + : 912.4165; found: 912.4163.

[0102]

[0103] Compound 23 (11 mg, 1.0 eq, 0.012 mmol) was dissolved in normal MeOH (1 mL), KOH (34 mg, 50.0 eq, 0.603 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring the reaction was complete, the reaction was quenched with aqueous NH4CI at 0 °C, extracted with n-butanol five times, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 8 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1 mL), CF3COOH (1.1 μL, 1.2 eq, 0.014 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give an oily solid 24 (6.2 mg, 71%). 1 H NMR (400 MHz, D20) δ 5.11 (s, 1H), 4.23 (d, J = 6.8 Hz, 1H), 4.20 - 4.13 (m, 2H), 3.99 (d, J = 4.8 Hz, 1H), 3.90 (dd, J = 5.0, 2.6 Hz, 1H), 3.83 - 3.76 (m, 1H), 3.74 - 3.67 (m, 1H), 3.65 (d, J = 9.2 Hz, 1H), 3.54 (s, 1H), 3.51 - 3.44 (m, 2H), 3.42 (s, 3H), 3.38 (s, 1H), 3.36 (s, 3H), 3.35 (s, 3H), 3.33 (s, 1H), 3.30 (s, 3H), 3.25 (s, 1H), 3.21 - 3.13 (m, 1H), 2.99 (d, J = 12.4 Hz, 1H), 2.55 (dd, J = 15.2, 8.8 Hz, 1H), 2.50 - 2.43 (m, 2H), 2.41 - 2.33 (m, 1H), 2.33 - 2.27 (m, 1H), 2.26 - 2.18 (m, 2H), 2.00 - 1.89 (m, 2H), 1.69 - 1.56 (m, 2H), 1.45 - 1.39 (m, 1H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, D20) δ 119.3 (q, J = 289.8 Hz), 109.2, 87.4, 85.4, 84.8, 84.3, 83.3, 83.2, 81.4, 79.7, 78.3, 76.9, 65.4, 64.2, 61.7, 61.6, 60.6, 60.3, 57.9, 56.4, 53.3, 52.1, 46.8, 44.6 (x 2), 42.2, 40.4, 38.8, 29.7, 23.8, 12.6; IR (neat): v max = 3353, 3204, 2921, 2851, 1661, 1631, 1467, 1260, 1201, 1085, 800, 720 cm -1 ; Optical rotation: [a]25D= -19.1 (c 0.11, MeOH); HRMS (ESI): m / z calcd for C 30 H 49 NO 11 (M+H) + 600.3378, found 600.3380.

[0104]

[0105] Compound 20 (30 mg, 1.0 eq, 0.064 mmol), ribose donor 25 (124 mg, 3.0 eq, 0.192 mmol), Ph3PAuNTf2(23.7 mg, 0.5 eq, 0.032 mmol) and MS (300 mg) was dissolved in dry DCM (3.0 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain 26 (41 mg, 70%) as a white solid. 1H NMR (400 MHz, Chloroform-d) δ 8.08 - 8.04 (m, 2H), 8.00 - 7.96 (m, 2H), 7.94 - 7.90 (m, 2H), 7.59 - 7.53 (m, 3H), 7.44 - 7.39 (m, 4H), 7.39 - 7.35 (m, 2H), 5.77 - 5.70 (m, 2H), 5.42 (d, J = 2.0 Hz, 1H), 4.81 - 4.76 (m, 1H), 4.73 - 4.67 (m, 1H), 4.66 - 4.61 (m, 1H), 4.17 (d, J = 6.8 Hz, 1H), 4.01 (s, 1H), 3.98 (d, J = 5.2 Hz, 1H), 3.65 (d, J = 8.0 Hz, 1H), 3.42 (s, 3H), 3.41 - 3.39 (m, 1H), 3.37 (s, 3H), 3.36 - 3.33 (m, 1H), 3.32 (s, 3H), 3.31 (s, 3H), 3.30 - 3.28 (m, 1H), 3.25 (s, 1H), 3.19 (t, J = 8.4 Hz, 2H), 3.14 - 3.08 (m, 3H), 2.41 - 2.34 (m, 4H), 2.26 - 2.17 (m, 1H), 2.14 (s, 1H), 2.12 - 2.06 (m, 1H), 2.02 - 1.94 (m, 2H), 1.75 - 1.67 (m, 2H), 1.58 (dd, J = 14.4, 4.4 Hz, 1H), 1.39 (t, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 166.3, 165.9, 165.6, 134.0, 133.9, 133.5, 130.0 (x 2), 129.9 (x 2), 129.9 (x 2), 129.6, 128.9, 128.8, 128.7 (x 4), 128.7 (x 2), 106.4, 85.6, 82.6, 81.4, 80.7, 80.2, 78.1, 76.0, 74.9, 73.9, 72.9, 65.3, 62.4, 59.3, 59.1, 58.4, 58.1, 55.8, 53.4, 50.7, 49.2, 46.7, 43.4, 42.2, 40.2, 38.1, 36.8, 26.9, 21.8, 10.3; IR (neat): v max = 3516, 3067, 2934, 2831, 1723, 1602, 1453, 1349, 1267, 1188, 1104, 1057, 798, 752, 710 cm -1Optical rotation: [a]25D= +7.0 (c 1.13, CHCl3); HRMS (ESI): m / z calcd for C 51 H 61 NO 14 (M+H) + : 912.4165; found: 912.4163.

[0106]

[0107] Compound 26 (25 mg, 1.0 eq, 0.027 mmol) was dissolved in normal MeOH (2 mL), KOH (76.9 mg, 50.0 eq, 1.371 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 20 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1 mL), CF3COOH (2.5 μL, 1.2 eq, 0.033 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give an oily solid 27 (13.1 mg, 71%). 1 H NMR (400 MHz, D20) δ 5.09 (s, 1H), 4.34 (dd, J = 7.0, 4.6 Hz, 1H), 4.26 (d, J = 6.8 Hz, 1H), 4.16 - 4.12 (m, 1H), 4.10 - 4.02 (m, 1H), 3.99 (d, J = 5.2 Hz, 1H), 3.88 - 3.81 (m, 1H), 3.75 - 3.70 (m, 1H), 3.68 (d, J = 9.2 Hz, 1H), 3.57 (s, 1H), 3.52 (d, J = 8.8 Hz, 1H), 3.47 (s, 3H), 3.45 - 3.40 (m, 2H), 3.39 (s, 3H), 3.38 (s, 3H), 3.37 - 3.35 (m, 1H), 3.34 (s, 3H), 3.28 (s, 1H), 3.24 - 3.16 (m, 1H), 3.02 (d, J = 12.4 Hz, 1H), 2.57 - 2.45 (m, 3H), 2.42 - 2.35 (m, 1H), 2.31 - 2.19 (m, 3H), 2.03 - 1.94 (m, 2H), 1.70 - 1.59 (m, 2H), 1.48 - 1.41 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H); 13C NMR (150 MHz, D20) δ 119.14 (q, J = 317.9 Hz), 106.1, 82.9, 82.8, 82.5, 81.3, 80.2, 78.3, 75.1, 74.6, 73.8, 70.0, 62.3, 61.6, 59.2, 58.7, 57.6, 57.3, 54.9, 53.3, 50.3, 49.0, 43.5, 41.5, 41.3, 39.2, 37.4, 36.0, 26.6, 20.7, 9.6; IR (neat): v max = 3370, 3204, 3053, 2933, 1676, 1442, 1417, 1348, 1188, 1132, 1109, 1055, 940, 792, 722 cm -1 ; Optical rotation: [a]25D= -10.5 (c 0.22, MeOH); HRMS (ESI): m / z calcd for C 30 H 49 NO 11 (M+H) + 600.3378, found 600.3375.

[0108]

[0109] Compound 20 (30 mg, 1.0 eq, 0.064 mmol), xylose donor 28 (124 mg, 3.0 eq, 0.192 mmol), Ph3PAuNTf2(23.7 mg, 0.5 eq, 0.032 mmol) and MS (300 mg) was dissolved in dry DCM (3.0 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain white solid 29 (32 mg, 55%). 1H NMR (600 MHz, CDC13) δ 8.00 - 7.96 (m, 2H), 7.96 - 7.92 (m, 4H), 7.58 - 7.54 (m, 2H), 7.51 - 7.47 (m, 1H), 7.43 - 7.37 (m, 4H), 7.36 - 7.33 (m, 2H), 5.92 (t, J = 8.7 Hz, 1H), 5.51 - 5.43 (m, 2H), 4.73 (d, J = 6.6 Hz, 1H), 4.51 (dd, J = 12.0, 5.4 Hz, 1H), 3.99 (d, J = 6.6 Hz, 1H), 3.97 (s, 1H), 3.82 (d, J = 5.4 Hz, 1H), 3.71 - 3.65 (m, 2H), 3.46 (s, 3H), 3.44 - 3.38 (m, 2H), 3.35 - 3.33 (m, 1H), 3.32 (s, 3H), 3.31 - 3.30 (m, 1H), 3.29 (s, 3H), 3.28 (s, 3H), 3.25 (s, 1H), 3.20 (t, J = 7.8 Hz, 1H), 3.16 (s, 1H), 3.16 - 3.12 (m, 1H), 3.08 (d, J = 8.4 Hz, 1H), 3.06 - 3.02 (m, 1H), 2.42 - 2.31 (m, 3H), 2.20 - 2.15 (m, 1H), 2.11 - 2.03 (m, 3H), 2.00 - 1.92 (m, 2H), 1.75 (td, J = 15.0, 4.8 Hz, 1H), 1.62 - 1.59 (m, 1H), 1.40 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, CDC13) δ 166.9, 165.8, 165.7, 134.1, 133.8, 133.7, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.0, 128.9, 128.8, 128.7 (x 4), 128.6 (x 2), 102.8, 88.6, 82.6, 81.5, 80.5, 78.0, 74.8, 73.5, 72.3, 71.1, 69.8, 62.9, 62.0, 59.7, 59.4, 58.4, 58.0, 55.9, 53.4, 50.7, 49.1, 47.9, 43.4, 42.0, 40.3, 38.1, 36.9, 26.9, 21.9, 10.3. IR (neat): v max = 3519, 3067, 2931, 1725, 1453, 1350, 1260, 1189, 1098, 1060, 797, 712 cm -1; Optical rotation: [a]25D= -3.8 (c 0.32, CHCl3); HRMS (ESI): m / z calcd. For C 51 H 61 NO 14 (M+H) + : 912.4165; found: 912.4162.

[0110]

[0111] Compound 29 (25 mg, 1.0 eq, 0.027 mmol) was dissolved in normal MeOH (2 mL), KOH (76.9 mg, 50.0 eq, 1.371 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 20 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1 mL), CF3COOH (2.5 μL, 1.2 eq, 0.033 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give oily solid 30 (14.1 mg, 72%). 1 H NMR (400 MHz, D20) δ 4.48 (d, J = 7.6 Hz, 1H), 4.30 (d, J = 6.8 Hz, 1H), 4.11 (d, J = 5.8 Hz, 1H), 4.00 (dd, J = 11.6, 5.2 Hz, 1H), 3.70 - 3.61 (m, 2H), 3.57 (s, 1H), 3.50 (d, J = 8.8 Hz, 1H), 3.49 - 3.47 (m, 1H), 3.46 (s, 3H), 3.46 - 3.43 (m, 1H), 3.42 - 3.39 (m, 2H), 3.38 (s, 3H), 3.38 (s, 3H), 3.37 - 3.34 (m, 2H), 3.33 (s, 3H), 3.27 (s, 1H), 3.20 (dd, J = 13.2, 7.2 Hz, 1H), 3.03 (d, J = 12.4 Hz, 1H), 2.65 - 2.55 (m, 2H), 2.48 (d, J = 6.8 Hz, 1H), 2.42 - 2.35 (m, 1H), 2.30 - 2.21 (m, 3H), 2.03 - 1.92 (m, 2H), 1.73 - 1.59 (m, 2H), 1.48 - 1.41 (m, 1H), 1.39 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, D20) δ 102.3, 85.0, 82.1, 81.4, 80.1, 78.3, 75.6, 75.0, 74.0, 72.7, 69.0, 65.2, 62.4, 58.8, 58.7, 57.8, 57.2, 54.9, 52.8, 50.3, 49.1, 44.5, 42.0, 41.6, 39.0, 37.4, 36.0, 26.6, 20.7, 9.6; IR (neat): v max = 3289, 3050, 2939, 2830, 1667, 1445, 1402, 1165, 1081, 1043, 986 cm -1 ; Optical rotation: [a]25D= -7.0 (c 0.50, MeOH); HRMS (ESI): m / z calcd for C 30 H 49 NO 11 (M+H) + 600.3378, found 6000.3379.

[0112]

[0113] Compound 31 (Chem. Pharm. Bull., 2002, 50, 1310) (600 mg, 1.0 eq, 1.334 mmol), arabinopyranose donor 4 (2.6 g, 3.0 eq, 4.004 mmol), Ph3PAuNTf2(493 mg, 0.5 eq, 0.667 mmol) and MS (6.0 g) was dissolved in dry DCM (60 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 90 / 1, v / v) to obtain white solid 32 (477.3 mg, 40%). 1H NMR(400MHz,CDCl3)δ8.13–8.07(m,2H),8.03–7.96(m,2H),7.92–7.85(m,2H),7.65–7.52(m,3H),7.48(dt,J=7.4,3.6Hz,4H),7.41(t,J=7.8Hz,2H),7.31(t,J=7.8Hz,2H),6.41(d,J=10.4Hz,1H),6.21(d,J=10.0Hz,1H),5.78(dd,J=8.8,6.8Hz,1H),5.71–5.63(m,2H),4.77(d,J=6.8Hz,1H),4.39(dd,J=13.2,2.8Hz,1H),4.01–3.90(m,4H),3.88–3.75(m,2H),3.30(s,3H),3.26(s,6H),3.24(s,6H),3.19(t,J=7.8Hz,1H),2.93(d,J=6.4Hz,1H),2.82(s,1H),2.65(d,J=10.8Hz,1H),2.51(s,1H),2.50–2.41(m,2H),2.43–2.32(m,2H),2.29–2.16(m,3H),2.15(s,1H),2.06(d,J=12.2Hz,1H),1.54(dd,J=14.2,5.0Hz,1H),0.98(t,J=7.0Hz,3H); 13 C NMR(100MHz,CDCl3)δ200.9,166.7,165.9,165.7,147.7,133.9,133.7,133.6,132.0,130.1(×2),130.0(×2),129.9(×2),129.5,129.1,129.0,128.7(×2),128.6(×2),128.6(×2),102.3,88.6,83.0,81.9,75.2,74.3,72.3,71.0,70.6,68.6,63.8,60.7,59.2,58.8,58.1,53.6,51.7,51.1,49.7,48.8(×2),48.0,43.7,39.0,38.2,13.1;IR(neat):ν max =3531,2927,1722,1672,1451,1259,1176,1091,1026,820,707cm -1 ;Optical rotation:[α]25D=+151.3(c 0.31,CHC13);HRMS(ESI):m / z calcd.For C50 H 55 NO 14 (M+H) + 894.3695, found 894.3690.

[0114]

[0115] Compound 32 (25 mg, 1.0 eq, 0.028 mmol) was dissolved in normal MeOH (2 mL), KOH (78 mg, 50.0 eq, 1.398 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring of the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol three times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 20 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.5 mL), CF3COOH (2.5 μL, 1.2 eq, 0.034 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give white solid 33 (17.9 mg, 92%). 1 H NMR (400 MHz, D2O) δ 6.89 (d, J = 10.0 Hz, 1H), 6.46 (d, J = 10.4 Hz, 1H), 4.45 (d, J = 6.4 Hz, 2H), 4.17 (d, J = 4.8 Hz, 1H), 4.08 - 3.92 (m, 4H), 3.74 - 3.66 (m, 3H), 3.56 (d, J = 13.6 Hz, 1H), 3.51 (t, J = 8.2 Hz, 1H), 3.46 (s, 3H), 3.43 (s, 3H), 3.42 - 3.38 (m, 2H), 3.34 (s, 3H), 3.32 (s, 1H), 3.24 (d, J = 7.2 Hz, 1H), 3.20 (d, J = 13.2 Hz, 1H), 2.71 - 2.62 (m, 2H), 2.59 (s, 1H), 2.53 - 2.45 (m, 1H), 2.37 - 2.27 (m, 2H), 1.76 (dd, J = 14.6, 5.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, D20) δ 198.5, 163.0 (q, J = 35.3 Hz), 147.8, 133.0, 116.3 (q, J = 289.9 Hz), 102.3, 84.7, 81.9, 80.0, 75.3, 73.8, 72.3, 70.6, 70.5, 68.0, 65.9, 61.9, 58.9, 58.8, 57.8, 54.2, 51.4, 50.4, 49.6, 48.3, 46.0, 44.3, 41.7, 37.4, 36.8, 8.8. IR (neat): v max = 3355, 2919, 2850, 1977, 1671, 1453, 1199, 1079, 1012, 800, 721 cm -1 ; Optical rotation: [a]25D= +23.1 (c 0.13, MeOH); HRMS (ESI): m / z calcd. For C 29 H 43 NO 11 (M+H) + 582.2909, found 582.2910.

[0116]

[0117] Compound 32 (50 mg, 1.0 eq, 0.056 mmol) was dissolved in dry MeOH (4 mL) under argon protection, CeCl3-7H2O (83 mg, 4.0 eq, 0.224 mmol) and NaBH4(5.3 mg, 2.5 eq, 0.140 mmol) were added successively at 0 °C, the reaction was placed in 0 °C room temperature for 30 min. After the reaction was monitored by LC-MS, KOH (157 mg, 50.0 eq, 2.796 mmol) was added to the reaction, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After the reaction was monitored by TLC, NH4CI aqueous solution was added to quench the reaction at 0 °C, n-butanol was extracted three times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 8 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (2.0 mL), CF3COOH (5.1 μL, 1.2 eq, 0.067 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give white solid 34 (14.4 mg, 37%). 1H NMR (400 MHz, D20) δ 6.05 (dd, J = 10.4, 2.0 Hz, 1H), 5.53 (dd, J = 10.4, 2.4 Hz, 1H), 4.44 - 4.40 (m, 2H), 4.34 (d, J = 7.2 Hz, 1H), 4.10 (d, J = 4.8 Hz, 1H), 3.94 - 3.89 (m, 2H), 3.86 (d, J = 9.6 Hz, 1H), 3.70 - 3.60 (m, 4H), 3.52 (d, J = 9.6 Hz, 1H), 3.47 - 3.42 (m, 1H), 3.41 (s, 3H), 3.37 (s, 3H), 3.34 (s, 3H), 3.33 - 3.23 (m, 2H), 3.11 - 3.03 (m, 2H), 2.69 (d, J = 6.8 Hz, 1H), 2.65 - 2.51 (m, 2H), 2.41 (s, 1H), 2.31 - 2.21 (m, 2H), 2.18 - 2.09 (m, 1H), 1.64 (dd, J = 14.6, 5.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, D20) δ 162.9 (q, J = 35.4 Hz), 136.0, 124.9, 116.2 (q, J = 289.5 Hz), 102.1, 84.6, 82.0, 80.7, 75.3, 73.8, 73.0, 72.2, 70.4, 67.9, 67.4, 65.8, 64.3, 58.8, 58.7, 57.6, 53.5, 51.1, 48.7, 47.7, 44.4, 44.3, 42.7, 41.6, 37.2, 36.5, 9.0. IR (neat): v max = 3138, 3046, 1678, 1407, 1201, 1102, 1080, 801, 782, 719 cm -1 ; Optical rotation: [a]25D= -28.2 (c 0.39, MeOH); HRMS (ESI): m / z calcd for C 29 H 45 NO 11 (M+H) + 584.3065, found 584.3070.

[0118]

[0119] Compound 32 (50 mg, 1.0 eq, 0.056 mmol) was dissolved in normal EtOH (4 mL), Pd / C (10 mg, 10% w / w) was added, the reaction was stirred at room temperature under H2for 1.5 h. After TLC monitoring the reaction was complete, the reaction was filtered with celite, concentrated to get the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to get 35 as a white solid (35.1 mg, 70%). 1 H NMR (400 MHz, CDC13) δ 8.12 - 8.08 (m, 2H), 8.02 - 7.98 (m, 2H), 7.91 - 7.86 (m, 2H), 7.63 - 7.53 (m, 2H), 7.48 (t, J = 7.6 Hz, 3H), 7.40 (t, J = 7.8 Hz, 2H), 7.31 (t, J = 7.8 Hz, 2H), 5.80 - 5.74 (m, 1H), 5.71 - 5.64 (m, 2H), 4.76 (d, J = 6.8 Hz, 1H), 4.38 (dd, J = 13.2, 2.8 Hz, 1H), 4.01 - 3.84 (m, 5H), 3.45 (d, J = 7.6 Hz, 1H), 3.29 (s, 3H), 3.24 (s, 3H), 3.17 (s, 4H), 2.82 (d, J = 6.4 Hz, 1H), 2.73 (s, 1H), 2.66 - 2.53 (m, 2H), 2.41 - 2.24 (m, 6H), 2.22 - 2.15 (m, 2H), 2.14 - 2.00 (m, 2H), 1.99 - 1.92 (m, 2H), 1.49 - 1.42 (m, 1H), 1.39 (dd, J = 13.6, 3.2 Hz, 1H), 0.99 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDC13) δ 218.0, 166.6, 165.9, 165.7, 133.8, 133.6, 133.5, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.2, 129.1, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.3, 88.6, 83.0, 82.6, 75.9, 75.2, 74.4, 71.0, 70.6, 68.7, 64.7, 63.7, 59.2, 58.7, 58.0, 53.2 (x 2), 52.5, 48.5, 48.3, 45.9, 44.4, 43.8, 41.0, 38.9, 38.4, 25.2, 13.4; IR (neat): v max=3538,2925,1719,1601,1451,1259,1092,1026,908,802,709,646cm -1 ;Optical rotation:[α]25D=+56.7(c 0.73,CHC13);HRMS(ESI):m / z calcd.ForC 50 H 57 NO 14 (M+H) + 896.3852, found 896.3856.

[0120]

[0121] Compound 35 (15 mg, 1.0 eq, 0.017 mmol) was dissolved in ordinary MeOH (1.5 mL), and KOH (47 mg, 50.0 eq, 0.8371 mmol) was added. The reaction was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete as monitored by TLC, the reaction was quenched by adding NH4Cl aqueous solution at 0 °C. The mixture was extracted three times with n-butanol, backwashed with water and saturated sodium chloride aqueous solution, dried over Na2SO4, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 25 / 1, v / v) to obtain a white solid. The obtained product was dissolved in MeOH (1.0 mL), and CF3COOH (1.5 μL, 1.2 eq, 0.020 mmol) was added at room temperature. After stirring at room temperature for 10 min, the mixture was concentrated and pumped to obtain white solid 36 (8.5 mg, 73%). 1 H NMR(400MHz,D2O)δ4.43(d,J=6.8Hz,2H),4.11(d,J=3.6Hz,1H),4.06(d,J=8.8Hz,1H ),3.98–3.92(m,2H),3.72–3.63(m,3H),3.59(d,J=9.2Hz,1H),3.47(t,J=8.2Hz,1H), 3.44(s,3H),3.40(s,4H),3.38–3.31(m,3H),3.27(s,3H),3.25(s,2H),2.71–2.55(m ,4H),2.39–2.15(m,4H),2.06–1.85(m,2H),1.60–1.51(m,1H),1.34(t,J=7.2Hz,3H). 13C NMR (100 MHz, D20) δ 217.98, 162.9 (q, J = 35.4 Hz), 116.3 (q, J = 289.8 Hz), 102.3, 84.8, 81.8, 80.4, 75.2, 74.7, 73.9, 72.3, 70.6, 68.0, 66.5, 65.9, 59.1, 58.9, 57.7, 53.5, 52.2, 51.6, 50.9, 45.9, 44.5, 41.9, 41.6, 40.4, 36.9, 36.6, 22.9, 8.8; IR (neat): v max = 3371, 2925, 1721, 1672, 1447, 1241, 1175, 1081, 833, 799, 720, 647 cm -1 ; Optical rotation: [a]25D= -44.3 (c 0.51, MeOH); HRMS (ESI): m / z calcd for C 29 H 45 NO 11 (M+H) + 584.3065, found 584.3066.

[0122]

[0123] Compound 35 (30 mg, 1.0 eq, 0.033 mmol) was dissolved in dry MeOH (2.5 mL) under argon protection, NaBH4(3 mg, 2.5 eq, 0.084 mmol) was added at 0 °C, the reaction was allowed to react at room temperature for 1 h. After LC-MS monitoring the reaction was complete, KOH (56 mg, 30.0 eq, 1.004 mmol) was added to the reaction, the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring the reaction was complete, NH4CI aqueous solution was added at 0 °C to quench the reaction, n-butanol was extracted four times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 20 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.0 mL), CF3COOH (3.0 μί, 1.2 eq, 0.040 mmol) was added at room temperature, concentrated and pumped to give oil solid 37 (16.2 mg, 69%) after stirring at room temperature for 10 min. 1H NMR (400 MHz, D20) δ 6.05 (dd, J = 10.4, 2.0 Hz, 1H), 5.53 (dd, J = 10.4, 2.4 Hz, 1H), 4.44 - 4.40 (m, 2H), 4.34 (d, J = 7.2 Hz, 1H), 4.10 (d, J = 4.8 Hz, 1H), 3.94 - 3.89 (m, 2H), 3.86 (d, J = 9.6 Hz, 1H), 3.70 - 3.60 (m, 4H), 3.52 (d, J = 9.6 Hz, 1H), 3.47 - 3.42 (m, 1H), 3.41 (s, 3H), 3.37 (s, 3H), 3.34 (s, 3H), 3.33 - 3.23 (m, 2H), 3.11 - 3.03 (m, 2H), 2.69 (d, J = 6.8 Hz, 1H), 2.65 - 2.51 (m, 2H), 2.41 (s, 1H), 2.31 - 2.21 (m, 2H), 2.18 - 2.09 (m, 1H), 1.64 (dd, J = 14.6, 5.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, D20) δ 162.9 (q, J = 35.4 Hz), 136.0, 124.9, 116.2 (q, J = 289.5 Hz), 102.1, 84.6, 82.0, 80.7, 75.3, 73.8, 73.0, 72.2, 70.4, 67.9, 67.4, 65.8, 64.3, 58.8, 58.7, 57.6, 53.5, 51.1, 48.7, 47.7, 44.4, 44.3, 42.7, 41.6, 37.2, 36.5, 9.0; IR (neat): v max = 3138, 3046, 1678, 1407, 1201, 1102, 1080, 801, 782, 719 cm -1 ; Optical rotation: [a]25D= -28.2 (c 0.39, MeOH); HRMS (ESI): m / z calcd for C 29 H 45 NO 11 (M+H) + 584.3065, found 584.3070.

[0124]

[0125] Compound 31 (600 mg, 1.0 eq, 1.334 mmol), arabinofuranose donor 7 (2.6 g, 3.0 eq, 4.004 mmol), Ph3PAuNTf2(493 mg, 0.5 eq, 0.667 mmol) and MS (6.0 g) was dissolved in dry DCM (60 mL) and the reaction was stirred at room temperature for 12 h. The reaction was filtered through celite and the filtrate was concentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 80 / 1, v / v) to give 38 as a white solid (644.4 mg, 54%). 1 H NMR (400 MHz, CDC13) δ 8.10 - 8.05 (m, 3H), 8.05 - 7.99 (m, 3H), 7.63 - 7.57 (m, 2H), 7.52 - 7.45 (m, 3H), 7.41 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.6 Hz, 2H), 6.44 (d, J = 10.4 Hz, 1H), 6.23 (d, J = 10.4 Hz, 1H), 5.59 (d, J = 5.2 Hz, 1H), 5.49 (d, J = 1.6 Hz, 1H), 5.38 (s, 1H), 4.95 - 4.89 (m, 1H), 4.85 (dd, J = 12.0, 3.2 Hz, 1H), 4.65 (dd, J = 12.0, 5.6 Hz, 1H), 4.21 (d, J = 6.4 Hz, 1H), 4.10 (s, 1H), 4.05 (d, J = 5.2 Hz, 1H), 3.90 - 3.82 (m, 2H), 3.39 (s, 3H), 3.33 (s, 3H), 3.28 (s, 3H), 3.26 - 3.21 (m, 1H), 3.04 (d, J = 6.4 Hz, 1H), 2.77 (s, 1H), 2.70 (d, J = 10.8 Hz, 1H), 2.56 - 2.50 (m, 2H), 2.50 - 2.44 (m, 2H), 2.44 - 2.37 (m, 2H), 2.33 - 2.25 (m, 2H), 2.24 - 2.17 (m, 2H), 1.58 (dd, J = 14.2, 4.6 Hz, 1H), 1.00 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDC13) δ 200.8, 166.3, 166.0, 165.9, 147.6, 133.9, 133.8, 133.2, 132.0, 130.1 (x 4), 129.8 (x 2), 129.7, 128.9, 128.8, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 106.5, 86.9, 83.5, 82.8, 81.9, 81.6, 77.6, 75.5, 75.0, 72.3, 63.9, 60.9, 59.3, 59.1, 58.2, 53.4, 51.6, 51.1, 49.7, 48.9, 48.8, 47.7, 44.1, 39.3, 38.2, 13.0; IR (neat): v max = 3506, 2930, 2822, 1719, 1672, 1601, 1451, 1263, 1177, 1095, 1026, 803, 809 cm -1 ; Optical rotation: [a]25D= +38.7 (c 0.77, CHC13); HRMS (ESI): m / z calcd for C 50 H 55 NO 14 (M+H) + 894.3695, found: 894.3692.

[0126]

[0127] Compound 38 (45 mg, 1.0 eq, 0.050 mmol) was dissolved in normal MeOH (3 mL), KOH (141 mg, 50.0 eq, 2.517 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4C1 at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl solution, dried over Na2S04, and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 14 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.5 mL), CF3COOH (4.6 μL, 1.2 eq, 0.060 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give white solid 39 (23.8 mg, 68%). 1H NMR (400 MHz, D20) δ 6.87 (d, J = 10.4 Hz, 1H), 6.45 (d, J = 10.4 Hz, 1H), 5.15 (s, 1H), 4.39 (d, J = 6.8 Hz, 1H), 4.21 - 4.18 (m, 1H), 4.17 (dd, J = 2.6, 1.0 Hz, 1H), 4.07 (d, J = 4.8 Hz, 1H), 4.06 - 3.95 (m, 2H), 3.91 (dd, J = 5.0, 2.6 Hz, 1H), 3.83 - 3.77 (m, 1H), 3.74 - 3.68 (m, 1H), 3.54 (d, J = 13.2 Hz, 1H), 3.49 (t, J = 7.8 Hz, 1H), 3.42 (s, 3H), 3.42 (s, 3H), 3.40 - 3.35 (m, 2H), 3.33 (s, 3H), 3.31 (s, 1H), 3.23 (d, J = 6.8 Hz, 1H), 3.17 (d, J = 13.2 Hz, 1H), 2.66 - 2.54 (m, 3H), 2.52 - 2.43 (m, 1H), 2.39 - 2.24 (m, 2H), 1.72 (dd, J = 14.8, 5.6 Hz, 1H), 1.31 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, D20) δ 198.5, 162.9, 147.9 (q, J = 35.4 Hz), 132.93, 116.3 (q, J = 289.8 Hz), 106.3, 84.77, 82.0, 81.6, 80.2, 79.9, 76.8, 75.5, 73.7, 70.6, 62.0, 61.3, 58.9, 58.6, 57.5, 54.7, 51.4, 50.4, 49.6, 48.3, 46.0, 43.6, 41.3, 37.6, 36.7, 8.8; IR (neat): v max = 3371, 2925, 1977, 1673, 1411, 1295, 1198, 1094, 1030, 834, 799, 625 cm -1 ; Optical rotation: [a]25D= +2.8 (c 0.57, MeOH); HRMS (ESI): m / z calcd for C 29 H 43 NO 11 (M+H) + 582.2909, found 582.2910.

[0128]

[0129] Compound 38 (50 mg, 1.0 eq, 0.056 mmol) was dissolved in dry MeOH (2 mL) under argon protection, CeCl3·7H2O (83 mg, 4.0 eq, 0.224 mmol) and NaBH4(5.3 mg, 2.5 eq, 0.140 mmol) were added successively at 0 °C, the reaction was placed in 0 °C room temperature for 30 min. After the reaction was monitored by LC-MS to be completed, KOH (157 mg, 50.0 eq, 2.796 mmol) was added to the reaction, and the reaction was placed in a 40 °C oil bath and stirred for 6 h. After the reaction was monitored by TLC to be completed, NH4Cl aqueous solution was added at 0 °C to quench the reaction, n-butanol was extracted three times, washed with water and saturated aqueous sodium chloride solution, dried over Na2SO4, concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 12 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (2.0 mL), CF3COOH (5.1 μL, 1.2 eq, 0.067 mmol) was added at room temperature, and after stirring at room temperature for 10 min, concentration and oil pump pumping could give white solid 40 (21.9 mg, 56%). 1 H NMR (400 MHz, D2O) δ 6.05 (dd, J = 10.4, 2.0 Hz, 1H), 5.53 (dd, J = 10.4, 2.4 Hz, 1H), 4.44 - 4.40 (m, 2H), 4.34 (d, J = 7.2 Hz, 1H), 4.10 (d, J = 4.8 Hz, 1H), 3.94 - 3.89 (m, 2H), 3.86 (d, J = 9.6 Hz, 1H), 3.70 - 3.60 (m, 4H), 3.52 (d, J = 9.6 Hz, 1H), 3.47 - 3.42 (m, 1H), 3.41 (s, 3H), 3.37 (s, 3H), 3.34 (s, 3H), 3.33 - 3.23 (m, 2H), 3.11 - 3.03 (m, 2H), 2.69 (d, J = 6.8 Hz, 1H), 2.65 - 2.51 (m, 2H), 2.41 (s, 1H), 2.31 - 2.21 (m, 2H), 2.18 - 2.09 (m, 1H), 1.64 (dd, J = 14.6, 5.4 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, D20) δ 162.9 (q, J = 35.4 Hz), 136.0, 124.9, 116.2 (q, J = 289.5 Hz), 102.1, 84.6, 82.0, 80.7, 75.3, 73.8, 73.0, 72.2, 70.4, 67.9, 67.4, 65.8, 64.3, 58.8, 58.7, 57.6, 53.5, 51.1, 48.7, 47.7, 44.4, 44.3, 42.7, 41.6, 37.2, 36.5, 9.0; IR (neat): v 3138, 3046, 1678, 1407, 1201, 1102, 1080, 801, 782, 719 cm max ; Optical rotation: [a]25D= -28.2 (c 0.39, MeOH); HRMS (ESI): m / z calcd for C -1 H 29 H 45 NO 11 (M+H) + : 584.3065; found: 584.3070.

[0130]

[0131] Compound 31 (250 mg, 1.0 eq, 0.557 mmol) was dissolved in normal EtOH (10 mL), Pd / C (25 mg, 10% w / w) was added, after H2 was exchanged, the reaction was reacted at room temperature for 12 h. After TLC monitoring the reaction was complete, the reaction was filtered with celite, concentrated to get the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 40 / 1, v / v) to get white solid 41 (233.6 mg, 93%). 1H NMR (400MHz, CDCl3) δ4.20(d,J=6.4Hz,1H),4.03(d,J=5.2Hz,1H),3.94–3.86(m,2H),3.47(d,J=8.0Hz,1H),3. 42(s,3H),3.33(s,3H),3.30–3.24(m,1H),3.19(s,3H),3.18–3.05(m,1H),2.93(d,J=6.8Hz,1H),2.91–2.87(m ,1H),2.69–2.57(m,2H),2.49–2.33(m,6H),2.32–2.17(m,3H),2.11(d,J=13.6Hz,1H),2.07–2.03(m,1H),1.97 (td,J=13.8,5.6Hz,1H),1.47(ddd,J=13.6,7.4,2.8Hz,1H),1.36(dd,J=14.4,4.8Hz,1H),1.00(t,J=7.0Hz,3H; 13 C NMR (100MHz, CDCl3) δ218.1,82.9,82.4,79.4,76.6,75.9,75.0,65.5,59.2,58.2,58.0, 53.3,53.1,52.1,49.2,48.6,45.6,44.8,43.9,40.8,38.8,38.0,25.3,13.4.IR(neat):ν max =3456,2928,2884,2247,1713,1450,1232,1191,1094,1017,909,804,727cm -1 ;Optical rotation:[α]25D=–26.2(c 0.87,CHC13);HRMS(ESI):m / z calcd.For C 24 H 37 NO7(M+H) + 452.2643, found 452.2639.

[0132]

[0133] Under argon protection, compounds 41 (200 mg, 1.0 eq, 0.443 mmol), arabinofuranose donor 7 (573 mg, 2.0 eq, 0.886 mmol), Ph3PAuNTf2 (164 mg, 0.5 eq, 0.221 mmol) and... MS (1.5 g) was dissolved in dry DCM (15 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (petroleum ether / EtOAc = 1 / 1, v / v) to obtain white solid 42 (242.1 mg, 61%). 1 H NMR (400 MHz, CDC13) δ 8.11 - 7.99 (m, 6 H), 7.63 - 7.57 (m, 2 H), 7.54 - 7.49 (m, 1 H), 7.47 (t, J = 7.8 Hz, 2 H), 7.41 (t, J = 7.8 Hz, 2 H), 7.32 (t, J = 7.8 Hz, 2 H), 5.58 (dd, J = 5.0, 1.0 Hz, 1 H), 5.49 (d, J = 1.2 Hz, 1 H), 5.38 (s, 1 H), 4.94 - 4.89 (m, 1 H), 4.85 (dd, J = 12.0, 3.2 Hz, 1 H), 4.65 (dd, J = 12.0, 5.6 Hz, 1 H), 4.20 (d, J = 6.8 Hz, 1 H), 4.08 (s, 1 H), 4.00 (d, J = 5.2 Hz, 1 H), 3.92 (d, J = 8.0 Hz, 1 H), 3.48 (d, J = 8.0 Hz, 1 H), 3.37 (s, 3 H), 3.33 (s, 3 H), 3.25 - 3.21 (m, 1 H), 3.21 (s, 3 H), 2.94 (d, J = 6.4 Hz, 1 H), 2.70 - 2.58 (m, 3 H), 2.51 - 2.45 (m, 1 H), 2.44 - 2.33 (m, 5 H), 2.32 - 2.20 (m, 3 H), 2.19 - 2.11 (m, 1 H), 2.08 - 1.94 (m, 2 H), 1.55 - 1.47 (m, 1 H), 1.43 (dd, J = 14.0, 4.4 Hz, 1 H), 1.00 (t, J = 7.2 Hz, 3 H). 13 C NMR (100 MHz, CDC13) δ 218.0, 166.4, 166.0, 165.9, 133.9, 133.8, 133.2, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.8, 128.9, 128.8, 128.7 (x 2), 128.7 (x 2), 128.5 (x 2), 106.5, 87.1, 83.5, 82.9, 82.6, 81.6, 77.6, 75.9, 75.5, 75.1, 64.9, 64.0, 59.3 59.0, 58.1, 53.3, 53.2, 52.3, 48.5, 48.1, 45.9, 44.5, 44.3, 41.0, 38.8 (x 2), 25.2, 13.3. IR (neat): v max= 3513, 2929, 1719, 1601, 1451, 1264, 1177, 1096, 1026, 966, 710 cm -1 ; Optical rotation: [a]25D= -16.3 (c 0.27, CHC13); HRMS (ESI): m / z calcd. For C 50 H 57 NO 14 (M+H) + : 896.3852; found: 896.3855.

[0134]

[0135] Compound 42 (25 mg, 1.0 eq, 0.028 mmol) was dissolved in normal MeOH (1 mL), KOH (47 mg, 30.0 eq, 0.8371 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 4 h. After TLC monitoring the reaction was complete, the reaction was quenched with aqueous NH4CI at 0 °C, extracted with n-butanol three times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 20 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.0 mL), CF3COOH (2.5 μL, 1.2 eq, 0.033 mmol) was added at room temperature, and after stirring at room temperature for 10 min, the product was concentrated and pumped to give white solid 43 (16.2 mg, 83%). 1 H NMR (400 MHz, D20) δ 5.13 (s, 1H), 4.38 (d, J = 6.4 Hz, 1H), 4.20 - 4.13 (m, 2H), 4.06 (d, J = 9.2 Hz, 1H), 4.01 (d, J = 4.8 Hz, 1H), 3.90 (t, J = 5.0, 2.6 Hz, 1H), 3.83 - 3.76 (m, 1H), 3.74 - 3.67 (m, 1H), 3.58 (d, J = 8.8 Hz, 1H), 3.48 - 3.41 (m, 2H), 3.40 (s, 3H), 3.38 (s, 3H), 3.36 - 3.29 (m, 3H), 3.28 - 3.23 (m, 5H), 2.70 - 2.49 (m, 4H), 2.41 - 2.25 (m, 3H), 2.17 (t, J = 13.6 Hz, 1H), 2.07 - 1.82 (m, 2H), 1.52 (dd, J = 14.8, 5.2 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, D20) δ 218.0, 162.9 (q, J = 35.4 Hz), 116.3 (q, J = 289.8 Hz), 106.2, 84.5, 81.9, 81.7, 80.3 (x 2), 76.8, 75.4, 74.8, 73.8, 66.6, 61.3, 59.2, 58.6, 57.5, 53.9, 52.2, 51.6, 50.9, 45.9, 43.8, 41.7, 41.5, 40.5, 36.9, 36.5, 23.0, 8.8; IR (neat): v max = 3373, 2926, 1721, 1671, 1422, 1293, 1198, 1178, 1095, 1039, 834, 800, 720 cm -1 ; Optical rotation: [a]25D= -13.2 (c 0.28, MeOH); HRMS (ESI): m / z calcd for C 29 H 45 NO 11 (M+H) + : 584.3065; found: 584.3066.

[0136]

[0137] Compound 42 (50 mg, 1.0 eq, 0.056 mmol) was dissolved in dry MeOH (4.0 mL) under argon protection, NaBH4(5.3 mg, 2.5 eq, 0.139 mmol) was added at 0 °C, the reaction was allowed to react at room temperature for 2 h. After LC-MS monitoring the reaction was complete, KOH (94 mg, 30.0 eq, 1.674 mmol) was added to the reaction, the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring the reaction was complete, NH4CI aqueous solution was added at 0 °C to quench the reaction, n-butanol was extracted three times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 12 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.5 mL), CF3COOH (5.0 μί, 1.2 eq, 0.067 mmol) was added at room temperature, concentrated and pumped to give white solid 44 (28.4 mg, 76%) after stirring at room temperature for 10 min. 1HNMR (400 MHz, D20) δ 5.10 (s, 1H), 4.28 (d, J = 7.2 Hz, 1H), 4.19 - 4.12 (m, 2H), 3.97 (s, 1H), 3.96 (d, J = 2.8 Hz, 1H), 3.89 (dd, J = 5.0, 2.6 Hz, 1H), 3.80 - 3.73 (m, 2H), 3.72 - 3.65 (m, 1H), 3.56 (d, J = 9.6 Hz, 1H), 3.50 (d, J = 13.2 Hz, 1H), 3.44 - 3.39 (m, 2H), 3.38 (s, 3H), 3.37 (s, 3H), 3.33 (s, 3H), 3.22 (dd, J = 12.8, 7.2 Hz, 1H), 3.16 (s, 1H), 3.02 (d, J = 13.6 Hz, 1H), 2.55 (dd, J = 15.6, 8.8 Hz, 1H), 2.46 - 2.40 (m, 2H), 2.31 (s, 1H), 2.23 (dd, J = 15.4, 6.6 Hz, 1H), 2.13 - 1.95 (m, 4H), 1.50 - 1.40 (m, 3H), 1.37 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, D20) δ 162.9 (q, J = 35.2 Hz), 116.2 (q, J = 289.8 Hz), 106.1, 84.6, 82.2, 81.5, 81.2, 80.0, 76.7, 75.4, 73.3, 72.0, 70.0, 67.0, 61.2, 58.6, 58.4, 57.3, 54.5, 52.4, 48.2, 45.7, 44.5, 44.0, 43.4, 41.1, 41.0, 36.2, 28.1, 26.0, 9.2; IR (neat): v max = 3358, 2923, 2851, 1673, 1411, 1294, 1200, 1129, 1097, 1045, 834, 800, 720 cm -1 ; Optical rotation: [a]25D= -14.6 (c 0.26, MeOH); HRMS (ESI): m / z calcd for C 29 H 47 NO 11 (M+H) + 586.3222. found 586.3226.

[0138]

[0139] Compound 31 (200 mg, 1.0 eq, 0.445 mmol) was dissolved in dry THF (10.0 mL) under argon, Triton B (789 μL, 40% in MeOH, 4.0 eq, 1.780 mmol) and TBHP (3.6 mL, 5 M in decane, 40.0 eq, 17.80 mmol) were added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with EA three times, washed with aqueous NaHC03, water and saturated aqueous NaCl, dried over MgS04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 90 / 1, v / v) to give 45 (170 mg, 82%) as a white solid. 1 HNMR (400 MHz, CDC13) δ 4.17 (d, J = 6.4 Hz, 1H), 4.12 (d, J = 3.6 Hz, 1H), 3.89 (s, 1H), 3.86 (d, J = 8.4 Hz, 1H), 3.74 (d, J = 8.4 Hz, 1H), 3.44 (s, 3H), 3.42 (d, J = 4.4 Hz, 1H), 3.33 (s, 3H), 3.32 - 3.23 (m, 3H), 3.22 (s, 3H), 3.02 (s, 1H), 2.89 (d, J = 6.8 Hz, 1H), 2.79 (d, J = 10.8 Hz, 1H), 2.73 (s, 1H), 2.52 - 2.24 (m, 8H), 2.11 (s, 1H), 1.58 (dd, J = 14.2, 4.2 Hz, 1H), 0.99 (t, J = 7.2 Hz, 3H). 13 C NMR (100 MHz, CDC13) δ 209.0, 83.1, 81.4, 79.3, 76.7, 74.7, 72.7, 61.5, 59.2, 58.3, 58.2, 56.5, 55.8, 55.1, 53.3, 51.8, 49.2, 48.8, 48.1, 43.6, 41.3, 38.0, 37.2, 13.3; IR (neat): v max = 3459, 2963, 2930, 2250, 1706, 1451, 1260, 1195, 1086, 1018, 908, 870, 799, 727 cm -1 ; Optical rotation: [a]25D= +24.2 (c 0.93, CHC13); HRMS (ESI): m / z calcd for C 24 H 35 NO8 (M + H) + 466.2435, found 466.2431.

[0140]

[0141] Compound 45 (100 mg, 1.0 eq, 0.215 mmol), arabinopyranose donor 4 (417 mg, 3.0 eq, 0.644 mmol), Ph3PAuNTf2 (79 mg, 0.5 eq, 0.107 mmol) and MS (1.4 g) was dissolved in dry DCM (14 mL) and the reaction was stirred at room temperature for 12 h. The reaction was filtered through celite and the filtrate was concentrated under reduced pressure to give a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 120 / 1, v / v) to give 46 as a white solid (127 mg, 65%). 1 H NMR (400 MHz, CDC13) δ 8.13 - 8.08 (m, 2H), 8.02 - 7.97 (m, 2H), 7.91 - 7.85 (m, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.51 - 7.45 (m, 3H), 7.40 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 5.82 - 5.76 (m, 1H), 5.72 - 5.65 (m, 2H), 4.76 (d, J = 6.8 Hz, 1H), 4.39 (dd, J = 13.2, 2.8 Hz, 1H), 4.00 (s, 1H), 3.98 - 3.90 (m, 3H), 3.81 (d, J = 8.4 Hz, 1H), 3.72 (d, J = 8.4 Hz, 1H), 3.41 (d, J = 3.6 Hz, 1H), 3.33 (s, 3H), 3.31 - 3.27 (m, 1H), 3.25 - 3.22 (m, 1H), 3.22 (s, 3H), 3.19 (s, 3H), 2.86 (s, 1H), 2.81 - 2.69 (m, 3H), 2.46 - 2.30 (m, 5H), 2.29 - 2.21 (m, 3H), 2.06 (s, 1H), 1.62 (dd, J = 14.0, 4.4 Hz, 1H), 0.99 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDC13) δ 209.0, 166.8, 165.8, 165.7, 133.9, 133.7, 133.6, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.1, 129.0, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.5, 88.7, 83.2, 81.6, 75.2, 74.1, 72.7, 71.0, 70.7, 68.7, 63.9, 60.7, 59.2, 58.8, 58.1, 56.5, 55.6, 55.2, 53.8, 51.7, 48.7, 48.4 (x 2), 43.7, 409, 38.6, 37.3, 13.2; IR (neat): v max = 3530, 2929, 1722, 1601, 1451, 1259, 1090, 1027, 870, 802, 709 cm -1 ; Optical rotation: [a]25D= +92.4 (c 0.67, CHC13); HRMS (ESI): m / z calcd for C 50 H 55 NO 15 (M+H) + 910.3644, found 910.3644.

[0142]

[0143] Compound 46 (60 mg, 1.0 eq, 0.066 mmol) was dissolved in dry mixed solvent (6.0 mL, THF:MeOH = 1:2) under argon protection, SmI2(19.8 mL, 0.1 M in THF, 30.0 eq, 1.978 mmol) was added dropwise at 0 °C, and the reaction was stirred at room temperature for 30 min. After TLC monitoring that the reaction was completed, NH4Cl aqueous solution was added at 0 °C to quench the reaction, and EA was extracted three times, and water and saturated aqueous sodium chloride solution were washed, dried over MgSO4, and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 120 / 1, v / v) to obtain white solid 47 (42.2 mg, 70%). 1H NMR (400 MHz, CDC13) δ 8.12 - 8.07 (m, 2H), 8.03 - 7.98 (m, 2H), 7.88 (dd, J = 8.2, 1.1 Hz, 2H), 7.63 - 7.51 (m, 2H), 7.51 - 7.44 (m, 3H), 7.40 (t, J = 7.8 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 5.78 (dd, J = 9.2, 6.8 Hz, 1H), 5.71 - 5.64 (m, 2H), 4.79 - 4.72 (m, 2H), 4.37 (dd, J = 13.2, 3.2 Hz, 1H), 4.19 (d, J = 8.4 Hz, 1H), 3.98 - 3.87 (m, 5H), 3.83 (d, J = 9.6 Hz, 1H), 3.74 - 3.66 (m, 1H), 3.31 (s, 3H), 3.30 (s, 3H), 3.22 (s, 3H), 3.18 - 3.11 (m, 2H), 2.84 (d, J = 14.4 Hz, 1H), 2.77 - 2.72 (m, 2H), 2.69 - 2.60 (m, 1H), 2.48 (s, 1H), 2.45 - 2.29 (m, 4H), 2.23 - 2.06 (m, 4H), 1.95 - 1.88 (m, 2H), 1.47 (dd, J = 14.6, 5.4 Hz, 1H), 1.01 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDC13) δ 166.6, 165.9, 165.7, 133.7, 133.6, 133.5, 130.1 (x 2), 130.0 (x 2), 129.9 (x 2), 129.6, 129.2, 129.1, 128.7 (x 2), 128.6 (x 2), 128.5 (x 2), 102.4, 89.0, 83.4, 82.9, 81.5, 80.7, 75.3, 74.0, 71.0, 70.7, 69.2, 68.7, 63.8, 62.4, 59.3, 58.7, 57.8, 52.2, 51.8, 50.5, 48.6, 48.5, 43.7, 42.5, 39.0, 37.2, 36.1, 35.2, 13.4; IR (neat): v max = 3447, 2928, 1723, 1451, 1259, 1091, 1026, 909, 859, 802, 731, 709 cm -1 ; Optical rotation: [a]25D= +80.6 (c 0.77, CHC13); HRMS (ESI): m / z calcd for C 50 H 59 NO 15(M+H) + 914.3958, found 914.3953.

[0144]

[0145] Compound 47 (30 mg, 1.0 eq, 0.033 mmol) was dissolved in normal MeOH (2.0 mL), KOH (55 mg, 30.0 eq, 0.9847 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4Cl at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCl, dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 12 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.0 mL), CF3COOH (3.0 μL, 1.2 eq, 0.039 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 min, concentrated, and pumped to give white solid 48 (16.7 mg, 71%). 1 H NMR (400 MHz, D2O) δ 4.44 (d, J = 6.8 Hz, 1H), 4.32 (d, J = 7.2 Hz, 1H), 4.17 - 4.15 (m, 1H), 4.13 (d, J = 5.2 Hz, 1H), 4.06 - 4.01 (m, 2H), 3.98 - 3.92 (m, 2H), 3.75 - 3.64 (m, 4H), 3.48 - 3.45 (m, 1H), 3.44 (s, 6H), 3.39 (s, 3H), 3.34 (s, 3H), 3.31 - 3.23 (m, 1H), 3.18 (s, 1H), 2.88 - 2.78 (m, 2H), 2.63 (dd, J = 15.6, 9.2 Hz, 1H), 2.53 (dd, J = 7.0, 5.4 Hz, 1H), 2.36 (s, 1H), 2.31 - 2.21 (m, 2H), 2.13 - 2.01 (m, 2H), 1.56 (dd, J = 14.8, 6.0 Hz, 1H), 1.37 (t, J = 7.0 Hz, 3H); 13 C NMR (150 MHz, D2O) δ 102.2, 84.6, 82.1, 80.40, 75.8, 75.2, 73.5, 72.2, 70.4, 69.3, 67.9, 65.8, 65.7, 65.2, 58.8, 58.7, 57.5, 53.4, 52.6 (x2), 50.8, 44.5, 43.1, 41.6, 38.6, 35.7, 35.3, 34.5, 9.1; IR (neat): v max= 3347, 2924, 1672, 1447, 1200, 1101, 1066, 800, 721, 647 cm -1 ; Optical rotation: [a]25D= -2.5 (c 0.28, MeOH); HRMS (ESI): m / z calcd. For C 29 H 47 NO 12 (M+H) + 602.3172, found 602.3175.

[0146]

[0147] Compound 45 (120 mg, 1.0 eq, 0.258 mmol), arabinofuranose donor 7 (500 mg, 3.0 eq, 0.773 mmol), Ph3PAuNTf2 (95 mg, 0.5 eq, 0.129 mmol) and MS (1.5 g) was dissolved in dry DCM (15 mL) and reacted at room temperature for 12 h. The reaction solution was filtered with celite and the filtrate was concentrated under reduced pressure to obtain a crude product, which was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to obtain white solid 49 (140.7 mg, 60%). 1H NMR (600 MHz, CDC13) δ 8.08 (d, J = 7.8 Hz, 2H), 8.05 (d, J = 7.8 Hz, 2H), 8.02 (d, J = 7.8 Hz, 2H), 7.63 - 7.58 (m, 2H), 7.52 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.8 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 5.59 (d, J = 4.2 Hz, 1H), 5.51 (s, 1H), 5.39 (s, 1H), 4.95 - 4.91 (m, 1H), 4.88 - 4.83 (m, 1H), 4.66 (dd, J = 12.0, 6.0 Hz, 1H), 4.17 (d, J = 6.6 Hz, 1H), 4.11 (s, 1H), 4.08 (d, J = 4.8 Hz, 1H), 3.87 (d, J = 9.0 Hz, 1H), 3.75 (d, J = 9.0 Hz, 1H), 3.45 - 3.42 (m, 1H), 3.37 (s, 3H), 3.35 (s, 3H), 3.33 - 3.30 (m, 1H), 3.28 - 3.25 (m, 1H), 3.24 (s, 3H), 2.90 (d, J = 6.0 Hz, 1H), 2.78 (dd, J = 19.4, 12.0 Hz, 3H), 2.56 - 2.53 (m, 1H), 2.49 - 2.44 (m, 2H), 2.43 - 2.32 (m, 4H), 2.28 (dd, J = 15.0, 7.2 Hz, 1H), 2.13 (s, 1H), 1.66 (dd, J = 15.0, 3.9 Hz, 1H), 0.99 (t, J = 6.9 Hz, 3H); 13 C NMR (150 MHz, CDC13) δ 209.0, 166.4, 166.0, 165.9, 134.0, 133.8, 133.3, 130.1 (x 4), 129.9 (x 2), 129.8, 128.9, 128.8 (x 3), 128.7 (x 2), 128.5 (x 2), 106.6, 87.0, 83.7, 82.8, 81.6 (x 2), 77.6, 75.6, 74.8, 72.8, 64.0, 60.9, 59.3, 59.1, 58.3, 56.5, 55.6, 55.2, 53.6, 51.8, 48.7, 48.4, 48.1, 44.2, 41.1, 39.0, 37.4, 13.3; IR (neat): v max 3511, 2929, 2822, 1719, 1601, 1451, 1262, 1097, 1026, 909, 870, 802, 710 cm -1; Optical rotation: [a]25D= +1.7 (c 0.7, CHC13); HRMS (ESI): m / z calcd. For C 50 H 55 NO 15 (M+H) + 910.3644, found 910.3640.

[0148]

[0149] Compound 49 (60 mg, 1.0 eq, 0.066 mmol) was dissolved in dry mixed solvent (6.0 mL, THF:MeOH = 1:2) under argon protection, SmI2(19.8 mL, 0.1 M in THF, 30.0 eq, 1.978 mmol) was added dropwise at 0 °C, and the reaction was stirred at room temperature for 1.5 h. After TLC monitoring the reaction was complete, the reaction was quenched by adding aqueous NH4Cl solution at 0 °C, extracted with EA for three times, washed with water and saturated aqueous NaCl solution, dried over MgSO4, concentrated to get the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 100 / 1, v / v) to give white solid 50 (42.2 mg, 70%). 1H NMR (600 MHz, CDC13) δ 8.09 (d, J = 7.2 Hz, 2H), 8.04 (d, J = 7.2 Hz, 2H), 8.01 (d, J = 7.8 Hz, 2H), 7.63 - 7.56 (m, 2H), 7.51 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.41 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 5.56 (d, J = 4.2 Hz, 1H), 5.50 (s, 1H), 5.38 (s, 1H), 4.93 (s, 1H), 4.83 (d, J = 12.0 Hz, 1H), 4.79 (s, 1H), 4.64 (dd, J = 11.7, 5.7 Hz, 1H), 4.25 (d, J = 8.4 Hz, 1H), 4.19 (d, J = 6.0 Hz, 1H), 4.06 - 4.00 (m, 2H), 3.92 (s, 1H), 3.86 (d, J = 9.0 Hz, 1H), 3.77 - 3.70 (m, 1H), 3.37 (s, 3H), 3.36 (s, 3H), 3.32 (s, 3H), 3.23 - 3.16 (m, 2H), 2.89 - 2.84 (m, 2H), 2.78 - 2.72 (m, 1H), 2.68 (s, 1H), 2.51 (s, 1H), 2.47 - 2.35 (m, 5H), 2.26 - 2.12 (m, 3H), 2.01 (s, 1H), 1.93 (d, J = 14.4 Hz, 1H), 1.52 (dd, J = 14.4, 4.8 Hz, 1H), 1.02 (t, J = 6.9 Hz, 3H); 13 C NMR (150 MHz, CDC13) δ 166.4, 165.9 (x 2), 133.9, 133.8, 133.2, 130.1 (x 2), 130.1 (x 2), 129.9 (x 2), 129.8, 129.0, 128.9, 128.8 (x 2), 128.7 (x 2), 128.5 (x 2), 106.7, 87.6, 84.0, 83.0, 82.8, 81.6 (x 2), 80.7, 77.8, 75.6, 74.8, 69.3, 64.1, 62.6, 59.3, 59.0, 57.9, 52.0, 51.8, 50.6, 48.6, 48.4, 44.2, 42.6, 39.2, 37.6, 36.2, 35.2, 13.4; IR (neat): v max = 3357, 2922, 2851, 1659, 1632, 1468, 1423, 1100, 704 cm -1Optical rotation: [a]25D= -150.0 (c 0.02, CHCI3); HRMS (ESI): m / z calcd for C 50 H 59 NO 15 (M+H) + 914.3958, found 914.3958.

[0150]

[0151] Compound 50 (35 mg, 1.0 eq, 0.038 mmol) was dissolved in normal MeOH (2.5 mL), KOH (64 mg, 30.0 eq, 1.149 mmol) was added, and the reaction was placed in a 40 °C oil bath and stirred for 12 h. After TLC monitoring that the reaction was complete, the reaction was quenched with aqueous NH4CI at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCI solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 10 / 1, v / v) to give a white solid. The product was dissolved in MeOH (1.0 mL), CF3COOH (3.4 μL, 1.2 eq, 0.046 mmol) was added at room temperature, and after stirring at room temperature for 10 min, the product was concentrated and pumped to give white solid 51 (27 mg, 82%). 1 H NMR (400 MHz, D20) δ 5.15 (s, 1H), 4.27 (d, J = 6.8 Hz, 1H), 4.23 - 4.14 (m, 3H), 4.07 - 4.00 (m, 3H), 3.92 (dd, J = 4.8, 2.4 Hz, 1H), 3.83 - 3.77 (m, 1H), 3.73 (s, 1H), 3.72 - 3.68 (m, 1H), 3.43 (d, J = 6.3 Hz, 4H), 3.41 (s, 3H), 3.39 (s, 3H), 3.33 (s, 3H), 3.25 (dd, J = 12.4, 7.2 Hz, 1H), 3.18 (s, 1H), 2.88 - 2.80 (m, 2H), 2.58 (dd, J = 15.4, 9.0 Hz, 1H), 2.46 (dd, J = 7.0, 5.4 Hz, 1H), 2.38 (s, 1H), 2.33 - 2.20 (m, 2H), 2.11 - 2.00 (m, 2H), 1.53 (dd, J = 15.2, 6.0 Hz, 1H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, D20) δ 162.9 (q, J = 35.4 Hz), 116.3 (q, J = 289.8 Hz), 106.3, 84.7, 82.3, 81.7, 80.4, 80.1, 76.7, 75.9, 75.4, 73.5, 69.4, 65.8, 65.4, 61.3, 58.9, 58.5, 57.3, 53.9, 52.8, 52.7, 50.8, 44.0, 43.2, 41.2, 38.7, 35.9, 35.2, 34.5, 9.2; IR (neat): v max 3358, 2923, 1673, 1418, 1200, 1123, 1099, 835, 800, 721 cm -1 ; Optical rotation: [a]25D= -21.7 (c 0.30, MeOH); HRMS (ESI): m / z calcd for C 29 H 47 NO 12 (M+H) + : 602.3172; found: 602.3172.

[0152]

[0153] Compound 32 (490 mg, 1.0 eq, 0.548 mmol) was dissolved in normal MeOH (10.0 mL), H202(560 μL, 30% in H20, 10.0 eq, 5.481 mmol) and LiOH-H20 (46 mg, 2.0 eq, 1.096 mmol) were added, and the reaction was placed at room temperature for 12 h. After TLC monitoring the reaction was complete, hydrochloric acid (1.6 mL, 2.0 M, 6.0 eq, 3.289 mmol) was added at 0 °C to quench the reaction, n-butanol was extracted four times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 7 / 1, v / v) to give white solid 52 (243 mg, 70%). 1H NMR (400 MHz, MeOD) δ 5.12 (d, J = 3.6 Hz, 1H), 4.55 (d, J = 7.2 Hz, 1H), 4.48 (d, J = 6.4 Hz, 1H), 4.18 - 4.11 (m, 3H), 4.09 - 4.02 (m, 2H), 4.01 - 3.97 (m, 1H), 3.92 (dd, J = 12.2, 3.8 Hz, 1H), 3.85 (s, 2H), 3.71 - 3.58 (m, 4H), 3.56 - 3.51 (m, 1H), 3.48 (s, 3H), 3.43 (s, 3H), 3.27 (s, 3H), 3.23 (d, J = 7.2 Hz, 1H), 2.98 - 2.84 (m, 2H), 2.76 - 2.70 (m, 1H), 2.67 - 2.57 (m, 2H), 2.57 - 2.50 (m, 1H), 2.39 (dd, J = 15.4, 7.2 Hz, 1H), 2.19 - 2.09 (m, 1H), 1.70 - 1.60 (m, 1H), 1.48 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, MeOD) δ 207.1, 102.7, 85.2, 84.4, 83.7, 83.2, 82.3, 76.9, 75.4, 74.3, 72.0, 71.4, 69.1, 66.4, 64.7, 62.5, 60.3, 59.5, 59.5, 58.7, 58.0, 54.5, 45.0, 44.2, 43.5, 40.5, 36.6, 34.2, 9.3; IR (neat): v max = 3335, 2942, 1732, 1644, 1446, 1083, 1066, 1012, 830, 784 cm -1 ; Optical rotation: [a]25D= -17.5 (c 0.87, MeOH); HRMS (ESI): m / z calcd for C 29 H 44 NO 12 + (M) + 598.2858, found 598.2859.

[0154]

[0155] Compound 52 (150 mg, 1.0 eq, 0.237 mmol) was dissolved in mixed solvent (8.0 mL, THF:AcOH = 2:1), activated Zn powder (309 mg, 20.0 eq, 4.732 mmol) was added, and the reaction was placed at room temperature for 20 min. After TLC monitoring reaction was completed, the reaction was quenched with aqueous sodium bicarbonate solution at 0 °C, n-butanol was extracted seven times, washed with water and saturated aqueous sodium chloride solution, dried over Na2SO4, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 15 / 1, v / v) to give white solid 53 (93 mg, 66%). 1 H NMR (400 MHz, MeOD / CDCl3) δ 4.27 (d, J = 7.2 Hz, 1H), 4.22-4.16 (m, 2H), 4.00-3.87 (m, 4H), 3.81 (s, 1H), 3.65-3.59 (m, 1H), 3.57-3.49 (m, 2H), 3.46 (s, 1H), 3.43 (s, 3H), 3.34 (s, 3H), 3.18 (s, 3H), 2.94 (d, J = 6.4 Hz, 1H), 2.83 (s, 1H), 2.79-2.70 (m, 3H), 2.53-2.36 (m, 4H), 2.36-2.22 (m, 2H), 2.18-2.07 (m, 2H), 2.02 (s, 1H), 1.94-1.88 (m, 1H), 1.05 (t, J = 7.2 Hz, 3H); 13 C NMR (150 MHz, MeOD / CDCl3) δ 217.3, 103.1, 86.2, 84.0, 83.1, 76.5, 75.9, 74.5, 73.8, 71.6, 71.5, 68.8, 66.7, 64.1, 59.6, 59.4, 58.2, 54.4, 53.7, 52.8, 50.1, 49.8, 48.5, 46.1, 45.0, 43.9, 40.4, 37.3, 12.9; IR (neat): v max = 3337, 2917, 1723, 1454, 1395, 1100, 1011, 867, 716, 646 cm -1 ; Optical rotation: [a]25D= -48.7 (c 0.57, CHCl3:MeOH = 1:1); HRMS (ESI): m / z calcd for C 29 H 45 NO 12 (M+H) + 600.3015, found 600.3019.

[0156]

[0157] Compound 53 (25 mg, 1.0 eq, 0.042 mmol) was dissolved in dry MeOH (2.0 mL) under argon, NaBH4(4 mg, 2.5 eq, 0.1042 mmol) was added, and the reaction was stirred at room temperature for 1 h. After TLC monitoring of the reaction completion, the reaction was quenched with aqueous NH4CI solution at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCI solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 8 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1.0 mL), CF3COOH (3.7 μL, 1.2 eq, 0.050 mmol) was added at room temperature, and after stirring at room temperature for 10 min, it was concentrated and pumped to give white solid 54 (17.9 mg, 60%). 1 H NMR (400 MHz, D20) δ 4.40 (d, J = 6.8 Hz, 1H), 4.31 (d, J = 6.4 Hz, 1H), 4.25 - 4.21 (m, 1H), 4.07 (d, J = 4.8 Hz, 1H), 4.06 - 4.03 (m, 1H), 3.95 - 3.90 (m, 2H), 3.69 - 3.58 (m, 5H), 3.58 - 3.49 (m, 2H), 3.43 (s, 3H), 3.37 (s, 3H), 3.36 - 3.30 (m, 5H), 3.29 - 3.23 (m, 2H), 2.65 - 2.51 (m, 2H), 2.38 (d, J = 6.4 Hz, 1H), 2.35 - 2.28 (m, 2H), 2.28 - 2.13 (m, 2H), 1.93 - 1.79 (m, 3H), 1.36 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, D20) δ 162.9 (q, J = 35.4 Hz), 116.3 (q, J = 289.8 Hz), 102.3, 84.9, 82.1, 81.8, 77.1, 75.2, 74.2, 72.3, 70.6, 69.9, 69.5, 68.1, 66.0, 65.0, 58.9, 58.8, 57.9, 53.4, 50.2, 49.7, 48.9, 44.7, 43.2, 42.7, 42.1, 39.1, 35.9, 35.4, 9.8; IR (neat): v max = 3134, 2923, 1673, 1399, 1257, 1200, 1175, 1100, 1007, 836, 800, 720 cm -1Optical rotation: [a]25D= -2.88 (c 0.59, MeOH); HRMS (ESI): m / z calcd for C 29 H 47 NO 12 (M+H) + 602.3172, found 602.3174.

[0158]

[0159] Compound 38 (300 mg, 1.0 eq, 0.336 mmol) was dissolved in normal MeOH (6.0 mL), H202(343 μL, 30% in H20, 10.0 eq, 3.336 mmol) and LiOH H20 (28 mg, 2.0 eq, 0.671 mmol) were added, and the reaction was placed at room temperature for 12 h. After TLC monitoring the reaction was complete, hydrochloric acid (1.0 mL, 2.0 M, 6.0 eq, 2.013 mmol) was added at 0 °C to quench the reaction, n-butanol was extracted four times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 8 / 1, v / v) to give white solid 55 (142.6 mg, 67%). 1 H NMR (400 MHz, MeOD) δ 5.11 (s, 1H), 4.52 (d, J = 7.2 Hz, 1H), 4.23 - 4.18 (m, 1H), 4.15 (d, J = 13.2 Hz, 2H), 4.08 - 4.05 (m, 2H), 4.05 - 4.02 (m, 1H), 4.00 - 3.97 (m, 1H), 3.89 (s, 1H), 3.87 - 3.84 (m, 1H), 3.76 - 3.61 (m, 4H), 3.58 - 3.53 (m, 1H), 3.47 (s, 3H), 3.44 (s, 4H), 3.27 (s, 3H), 3.24 - 3.22 (m, 1H), 2.97 - 2.84 (m, 2H), 2.74 (s, 1H), 2.70 - 2.59 (m, 2H), 2.47 (t, J = 5.6 Hz, 1H), 2.38 (dd, J = 15.6, 6.4 Hz, 1H), 2.14 (t, J = 13.2 Hz, 1H), 1.66 (dd, J = 14.4, 4.8 Hz, 1H), 1.47 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, MeOD) δ 207.2, 108.9, 87.3, 84.5, 84.4, 83.6, 83.4, 82.3, 81.9, 78.7, 77.1, 75.3, 71.5, 64.7, 63.1, 62.6, 60.2, 59.6, 59.5, 58.6, 58.2, 54.5, 45.5, 44.2, 43.3, 40.5, 36.6, 34.3, 9.4; IR (neat): v max = 3320, 2941, 2075, 1732, 1646, 1446, 1391, 1086, 1039, 991, 964 cm -1 ; Optical rotation: [a]25D= -45.5 (c 1.17, MeOH); HRMS (ESI): m / z calcd for C 29 H 44 NO 12 + (M) + 598.2858, found 598.2859.

[0160]

[0161] Compound 55 (140 mg, 1.0 eq, 0.221 mmol) was dissolved in mixed solvent (6.0 mL, THF:AcOH = 2:1), activated Zn powder (287 mg, 20.0 eq, 4.416 mmol) was added, and the reaction was placed at room temperature for 20 min. After TLC monitoring reaction was completed, the reaction was quenched by adding aqueous sodium bicarbonate solution at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous sodium chloride solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 12 / 1, v / v) to give 56 (87.4 mg, 66%) as a white solid. 1H NMR (400 MHz, MeOD) δ 5.04 (s, 1H), 4.25 - 4.17 (m, 2H), 4.04 (dd, J = 2.8, 1.2 Hz, 1H), 3.99 (d, J = 8.0 Hz, 1H), 3.93 (d, J = 4.8 Hz, 2H), 3.86 (t, J = 4.6, 3.0 Hz, 1H), 3.76 - 3.63 (m, 2H), 3.46 (s, 1H), 3.44 (s, 3H), 3.38 (s, 3H), 3.36 - 3.34 (m, 1H), 3.20 (s, 3H), 3.02 (d, J = 6.8 Hz, 1H), 2.90 (s, 1H), 2.84 (dd, J = 13.6, 4.4 Hz, 1H), 2.77 - 2.70 (m, 2H), 2.62 - 2.51 (m, 1H), 2.49 - 2.35 (m, 3H), 2.34 - 2.25 (m, 3H), 2.18 - 2.10 (m, 1H), 2.06 (s, 1H), 1.91 (dd, J = 14.2, 5.0 Hz, 1H), 1.07 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, MeOD) δ 217.8, 109.2, 86.9, 85.9, 85.0, 83.8, 82.2, 78.5, 77.1, 76.9, 75.1, 72.3, 64.9, 63.0, 59.6, 59.4, 58.3, 55.0, 54.7, 53.5, 50.8, 50.3, 48.9, 47.3, 45.7, 44.6, 41.1, 38.2, 13.0; IR (neat): v max = 3357, 2920, 2849, 1644, 1419, 1097, 1015, 596, 438 cm -1 ; Optical rotation: [a]25D= -56.5 (c 0.20, MeOH); HRMS (ESI): m / z calcd for C 29 H 45 NO 12 (M+H) + 600.3015, found 600.3015.

[0162]

[0163] Compound 56 (65 mg, 1.0 eq, 0.108 mmol) was dissolved in dry MeOH (4.0 mL) under argon, NaBH4(10 mg, 2.5 eq, 0.2710 mmol) was added, and the reaction was stirred at room temperature for 1 h. After TLC monitoring of the reaction completion, the reaction was quenched with aqueous NH4CI solution at 0 °C, extracted with n-butanol four times, washed with water and saturated aqueous NaCI solution, dried over Na2S04, and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (DCM / MeOH = 10 / 1, v / v) to give a white solid. The obtained product was dissolved in MeOH (1.0 mL) respectively, CF3COOH was added at room temperature, and stirred at room temperature for 10 min. After concentration and oil pump, white solid 57 (31.0 mg, 40%) and 58 (6.2 mg, 8%) were obtained. Compound 57: 1 H NMR (600 MHz, D20) δ 5.08 (s, 1H), 4.24 (d, J = 6.0 Hz, 1H), 4.20 (d, J = 3.0 Hz, 1H), 4.16 - 4.13 (m, 1H), 4.12 (s, 1H), 4.02 (s, 1H), 3.96 (d, J = 4.2 Hz, 1H), 3.89 - 3.86 (m, 1H), 3.79 - 3.73 (m, 1H), 3.67 (dd, J = 12.0, 5.4 Hz, 1H), 3.61 - 3.55 (m, 2H), 3.55 - 3.52 (m, 1H), 3.46 (t, J = 7.8 Hz, 1H), 3.39 (s, 3H), 3.35 (s, 3H), 3.34 - 3.32 (m, 1H), 3.31 (s, 3H), 3.29 - 3.25 (m, 1H), 3.25 - 3.21 (m, 2H), 2.54 (t, J = 15.0, 9.0 Hz, 1H), 2.46 (t, J = 6.0 Hz, 1H), 2.36 (d, J = 6.0 Hz, 1H), 2.33 - 2.28 (m, 2H), 2.26 (dd, J = 15.0, 7.2 Hz, 1H), 2.13 (t, J = 13.8 Hz, 1H), 1.89 - 1.76 (m, 3H), 1.34 (t, J = 7.2 Hz, 3H); 13 CNMR (100 MHz, D20) δ 162.7 (q, J = 35.6 Hz), 116.1 (q, J = 289.6 Hz), 106.2, 84.4, 82.1, 81.8, 81.6, 80.2, 77.0, 76.6, 75.2, 73.9, 69.8, 69.3, 64.8, 61.1, 58.7, 58.5, 57.6, 53.7, 50.0, 49.5, 48.8, 43.9, 43.0, 42.6, 41.5, 39.2, 35.6, 35.2, 9.7; IR (neat): vmax = 3347, 2925, 1673, 1421, 1199, 1100, 837, 800, 720 cm -1 ; Optical rotation: [a]25D= -21.2 (c 1.00, MeOH); HRMS (ESI): m / z calcd. For C 29 H 47 NO 12 (M+H) + 602.3172, found 602.3171. Compound 58: 1 H NMR (400 MHz, D20) δ 5.10 (s, 1H), 4.22 (d, J = 6.8 Hz, 1H), 4.19 - 4.09 (m, 3H), 4.04 - 3.95 (m, 3H), 3.91 - 3.87 (m, 1H), 3.81 - 3.75 (m, 1H), 3.72 - 3.66 (m, 2H), 3.47 - 3.41 (m, 2H), 3.39 (s, 3H), 3.36 (s, 3H), 3.34 - 3.31 (m, 2H), 3.28 (s, 3H), 3.27 - 3.20 (m, 2H), 2.57 (d, J = 6.8 Hz, 1H), 2.55 - 2.40 (m, 2H), 2.39 - 2.24 (m, 3H), 2.19 - 2.06 (m, 1H), 2.04 - 1.92 (m, 1H), 1.91 - 1.75 (m, 2H), 1.35 (t, J = 7.0 Hz, 3H); 13 CNMR (100 MHz, D20) δ 162.5 (q, J = 35.3 Hz), 115.8 (q, J = 289.7 Hz), 105.8, 84.1, 81.8, 81.3, 80.6, 79.7, 76.3, 74.9, 73.1, 73.0, 69.5, 68.2, 62.5, 60.8, 58.1, 57.9, 57.1, 55.9, 53.1, 49.4, 48.9, 43.5, 42.7, 41.7, 40.7, 39.1, 36.0, 35.3, 9.1; IR (neat): v max = 3358, 2923, 1674, 1424, 1200, 1129, 835, 800, 720 cm -1 ; Optical rotation: [a]25D= -14.5 (c 0.20, MeOH); HRMS (ESI): m / z calcd. For C 29 H 47 NO 12 (M+H) +602.3172, found 602.3172.

[0164] The compounds involved in this example as shown in the following table were used for analgesic activity test and safety evaluation.

[0165]

[0166]

[0167] It should be noted that, among the compounds as shown in the above table, except for compound 1, the rest of the compounds belong to the category of diterpene alkaloid glycoside derivatives or pharmaceutically acceptable salts thereof provided by the present disclosure.

[0168] Example 2 Analgesic activity test and safety evaluation

[0169] 1. CFA-induced chronic inflammatory pain model

[0170] 1.1 Experimental method

[0171] Male ICR mice with a body weight of 25±1 g were randomly divided into 30 groups, 3 mice in each group. Before the experiment, the baseline mechanical withdrawal threshold of the left hind foot of the mice under mechanical stimulation was determined using an electronic von Frey pain tester (the mechanical withdrawal threshold at each time point was the average of three tests with an interval of 20 s). Then 20 μL of CFA was injected into the left hind foot using a microsyringe to induce chronic pain. One day after the injection of CFA, the mechanical withdrawal threshold of the left hind foot was determined again. The test compound solution (240 μg / kg) was administered subcutaneously, and the control group was administered the same volume of normal saline subcutaneously. Then the mechanical withdrawal threshold was determined at 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, and 5 h after administration, respectively.

[0172] 1.2. Experimental results

[0173] The experimental results were analyzed using Graphpad Prism 8 software, and the results are shown in Figure 1 . Among them, it should be noted that, Figure 1 compound 1 and compound 59 in

[0174]

[0175] It can be seen that most of the diterpenoid alkaloid glycoside derivatives exhibit analgesic activity close to that of the positive control drug, sinomontanin (i.e., compound 59). Among them, the analgesic activity of compounds 17, 24, 37, 55, and 57 is comparable to that of sinomontanin. Upon observation of the graph, the synthesized diterpenoid alkaloid glycoside derivatives have the advantages of fast onset, strong efficacy, and long duration.

[0176] 2 Acute inflammatory pain model of formalin

[0177] 2.1 Experimental method

[0178] Male ICR mice weighing 25±1 g were randomly divided into two groups, with 5-6 mice in each group. 60 min before the experiment, the test compound (240 μg / kg) was injected subcutaneously, and the control group was given the same volume of normal saline. Subsequently, 20 μL of 5% formalin solution was injected subcutaneously into the left hind foot of the mouse using a microsyringe, and the total amount of time that the mouse licks, bites, and flails the affected foot was recorded by a stopwatch to quantify the nociceptive behavior induced by formalin injection. The recording period is divided into two stages: the first stage is 0-10 min after formalin injection, representing acute pain caused by chemical nociceptive stimulation; the second stage is 10-30 min after formalin injection, representing inflammatory pain caused by central sensitization.

[0179] 2.2 Experimental results

[0180] The experimental results were analyzed using Graphpad Prism 8 software, and the results are shown in Figure 2 Compound 24 can effectively relieve phase II inflammatory pain caused by central sensitization in the acute inflammatory pain model induced by injection of 20 μL of 5% formalin into the hind foot.

[0181] 3 Visceral pain model of writhing

[0182] 3.1 Experimental method

[0183] Male ICR mice weighing 25±1 g were randomly divided into three groups, with 12 mice in each group. 60 min in advance, the test compound (240 μg / kg) was injected subcutaneously, and the control group was given the same volume of normal saline. Subsequently, a freshly prepared ice acetic acid solution (1%, 0.1 mL / 10 g) was injected intraperitoneally to stimulate peritoneal-induced visceral pain, causing the mouse to writh. Each mouse was placed individually, and the number of writhes of the mouse 5-20 min after injection of the ice acetic acid solution was recorded, with one complete writhing being recorded as the mouse's head being raised, the arch of the foot being extended, and the reset stretching.

[0184] 3.2 Experimental results

[0185] The experimental results were analyzed using Graphpad Prism 8 software, and the results are shown in Figure 3Compound 24 can effectively relieve visceral pain caused by intraperitoneal injection of 1% acetic acid, and the analgesic effect is better than that of the positive control drug, lappaconitine (compound 59)

[0186] 4. Safety evaluation

[0187] The synthesized diterpene alkaloid glycoside derivatives or pharmaceutically acceptable salts thereof (i.e., the remaining compounds in the above table except for compound 1) were subjected to safety evaluation, with diouanine (i.e., compound 1) and lappaconitine (i.e., compound 59) as positive control drugs. The results showed that, when administered via tail vein, diouanine caused death of mice at a dose of 0.24 mg / kg, and lappaconitine caused adverse reactions such as respiratory depression, movement disorder, rigidity, and the like at a dose of 0.6 mg / kg, and its LD50was 1.3 mg / kg. Under the same administration mode, the synthesized diterpene alkaloid glycoside derivatives 4, 17, 24, and 26 had no side effects at a dose of 8 mg / kg; the optimal compound 24 still showed normal performance when administered via tail vein at a dose of 80 mg / kg. 50 The results showed that the synthesized diterpene alkaloid glycoside derivatives or pharmaceutically acceptable salts thereof can significantly reduce the original toxic side effects of diterpene alkaloids, and exhibit good safety.

[0188] The results showed that the synthesized diterpene alkaloid glycoside derivatives or pharmaceutically acceptable salts thereof can significantly reduce the original toxic side effects of diterpene alkaloids, and exhibit good safety.

[0189] The above description is merely preferred embodiments of the present disclosure, and it should be understood that the present disclosure is not limited to the forms disclosed herein, and should not be considered as excluding other embodiments, but can be used in various other combinations, modifications, and environments, and can be modified within the scope of the concepts described herein, by the above teachings or related art or knowledge. Any modification and change made by those skilled in the art without departing from the spirit and scope of the present disclosure shall fall within the protection scope of the claims of the present disclosure.

Claims

1. A diterpenoid alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof, characterized in that, The structure of the diterpene alkaloid glycoside derivative is shown in Formula I: In the formula, R1 to R6 are each independently selected from hydrogen atom, hydroxyl group, alkoxy group, acyloxy group or siloxy group; R7 is selected from arabinopyranosyl, arabinofuranosyl, glucosyl, mannosyl, xylose, ribosyl or galactosyl.

2. The diterpenoid alkaloid glycoside derivative or its pharmaceutically acceptable salt according to claim 1, characterized in that, The alkoxy group is selected from methoxy, methoxymethoxy, or benzyloxy.

3. The diterpenoid alkaloid glycoside derivative or its pharmaceutically acceptable salt according to claim 1, characterized in that, The acyloxy group is selected from formyloxy, acetoxy, benzoyloxy, trifluoroacetoxy, methoxyformyloxy, or tert-butoxyformyloxy. And / or, the siloxy group is selected from tert-butyldimethylsiloxy, trimethylsiloxy, triethylsiloxy, triisopropylsiloxy, or tert-butyldiphenylsiloxy.

4. A method for preparing diterpenoid alkaloid glycoside derivatives as described in any one of claims 1 to 3, characterized in that, include: S1. A functional group modification reaction is performed on the diterpene alkaloid product to obtain an intermediate; wherein the functional group modification reaction includes at least one of a hydroxyl protection reaction and an ester hydrolysis reaction; the structure of the intermediate is shown in Formula II: S2. The intermediate is subjected to a glycosylation reaction with a glycosyl donor to obtain a glycosylated product; S3. Perform a protecting group removal reaction on the glycosylated product to obtain the diterpenoid alkaloid glycoside derivative.

5. The method according to claim 4, characterized in that, The diterpenoid alkaloid products include natural diterpenoid alkaloid products.

6. The method according to claim 5, characterized in that, The structures of the diterpenoid alkaloid natural products are shown in Formula III or Formula IV:

7. The method according to claim 4, characterized in that, The structure of the diterpenoid alkaloid product is shown in formula V or formula VI:

8. The method according to claim 4, characterized in that, The glycosyl donor is selected from arabinopyranose donor, arabinofuranose donor, glucose donor, mannose donor, xylose donor, ribose donor, or galactose donor.

9. A pharmaceutical composition, characterized in that, It comprises a diterpenoid alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof as described in any one of claims 1 to 3, and a pharmaceutically acceptable carrier.

10. The use of a diterpenoid alkaloid glycoside derivative or a pharmaceutically acceptable salt thereof as described in any one of claims 1 to 3, or the method as described in any one of claims 4 to 8, or the pharmaceutical composition as described in claim 9, in the preparation of an analgesic.

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