CN1542016A - Chemosynthesis of glucuronide oleanane type double sugar chains triterpenoid saponin - Google Patents

Chemosynthesis of glucuronide oleanane type double sugar chains triterpenoid saponin Download PDF

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CN1542016A
CN1542016A CNA2003101085210A CN200310108521A CN1542016A CN 1542016 A CN1542016 A CN 1542016A CN A2003101085210 A CNA2003101085210 A CN A2003101085210A CN 200310108521 A CN200310108521 A CN 200310108521A CN 1542016 A CN1542016 A CN 1542016A
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glycosyl
benzoyl
synthetic method
hydroxyl
glucosidesization
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CN1295246C (en
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飚 俞
俞飚
彭文杰
林峰
韩秀文
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention provides practical GOTCAB saponin synthesis process. The synthesis process includes the following steps: connecting site-28 glucose chain; connecting site-3 glycosyl; connecting rest site-3 glycosyl after protecting radical operation; making site-6' hydroxy group empty via protecting radical operation; selectively oxidizing site-6' primer hydroxy group into carboxylic acid; and finally eliminating all the protecting radicals under alkali condition.

Description

The chemosynthesis of glucuronide oleanane type double sugar chains triterpenoid saponin
Technical field
The present invention relates to the synthetic method of oleanane type pentacyclic triterpenoid saponin, relate in particular to glucuronide oleanane type double sugar chains triterpenoid saponin synthetic method.
Background technology
Glucuronide oleanane type double sugar chains triterpenoid saponin (glucuronide oleanane-typetriterpene carboxylic acid 3,28-O-bisdesmoside are called for short GOTCAB) is a class formation saponin as shown below.Be characterized in: (1) glucoside unit is the oleanane type pentacyclic triterpene; (2) 3-OH of triterpene and 28-COOH are all the glycosyl replacement; (3) 3 sugar chains link to each other with glucoside unit with β-D-glucuronide.During 1962-1997, in 20 section plants isolation identification 192 GOTCAB saponins [Tan, N.; Zhou, J.; Zhao, S.Phytochemistry 1999,52,153-192.].Thereafter, new structure is found at faster speed.Some GOTCAB saponins have been found has various biologies and physiologically active.And its chemosynthesis is not appeared in the newspapers as yet.In fact also very limited to the synthetic report of other triterpenoid saponin so far.Below with ginsenoside Ro (1) and from Aralia dasyphylla isolating saponin 2 be example report synthetic method to a kind of practicality of this class saponin.
GOTCAB general structure (glucoside unit is the oleanane type triterpene) R 1, R 2, R 3=H or glycosyl; R 4=glycosyl
Figure A20031010852100042
Ginsenoside Ro (1, English name Ginsenoside Ro or Chikusetsusaponin V; Chemical name: 28-O-β-D-glucopyranosyl oleanate 3-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucuronopyranoside) almost is present in all panax ginseng plants (Panax species), unique exception is not find [Tanaka, O. in pseudo-ginseng (Panaxnotoginseng); Kasai, R.Saponins of Ginseng and Related Plants.InProg.Chem.Org.Nat.Prod.; Herz, W.; Grisebach, H.; Kirby, G.W.; Tamm, Ch., Eds.; Springer-Verlag:Wien, New York, 1984; Vol.46, pp1-76.].Also there is ginsenoside Ro (1) in other various plants, as: (a) Fagus sylvatica[Romussi, G.; Bignardi, G.; Falsone .G.; Wendisch, D.Arch.Pharm.1987,320,153-8]. (b) Hericium erinaceus[Qian, F.; Du, S.; Xu, G.; Li, M.; Zeng, C.; Shu, Y.Zhongcaoyao, 1988,19,290-3]. (c) Polyscias scutellaria[Paphassarang, S.; Raynaud, J.; Lussignol, M.; Cabalion, P.J.Nat.Prod.1990,53,163-6]. (d) Hemsleya graciliflora[Kasai, R.; Tanaka, T.; Nie, R.L.; Miyakoshi, M.; Zhou, J.; Tanaka, O.Chem.Pharm.Bull.1990,38,1320-2]. (e) H.dolichocarpa[Shi, Y.; Yang, P.; Nie, R.Yunnan Zhiwu Yanjiu 1990,12,460-2]. (f) Wedelia calendulaceae[Govindachari, T.R.; Premila, M.S.Indian J.Chem., Sect.B 1991,30B, 466-8]. (g) Achyranthes fauriei[Ida, Y.; Katsumata, M.; Satoh, Y.; Shoji, J.Planta Med.1994,60,286-7]. (h) A.bidentata[Marouf, A.; Desbene, S.; Khanh, T.C.; Wagner, H.; Correia, M.; Chauffert, B.; Lacaille-Dubois, M.A.Pharmaceutical Biology 2001,39,263-267]. (i) Aralia armata[Fang, Z.; Lei, J.; Zeng, X.Zhiwu Xuebao 1995,37,74-80]. (j) A.cordata[Kawai, H.; Nishida, M.; Tashiro, Y.; Kuroganagi, M.; Ueno, A.; Satake, M.Chem.Pharm.Bull.1989,37,2318-21]. (k) Kochia indica[Mohamed, K.M.; Hasanean, H.H.; Ohtani, K.; Yamasaki, K.Bull.Pharm.Sci., Assiut Univ.1998,21,27-36]. ginsenoside Ro (1), a structure representative as GOTCAB does not have hemolytic [Nakamura, T. that other saponin has usually; Inoue, K.; Nojima, S.; Sankawa, U.; Shoji, J.; Kawasaki, T.; Shibata, S.J.Pharmacobio-Dyn.1979,2,374-382.], do not have cytotoxicity [Atopkina, L.N. yet; Malinovskaya, G.V.; Elyakov, G.B.; Uvarova, N.I.; Woerdenbag, H.J.; Koulman, A.; Pras, N.; Potier, P.Planta Med.1999,65,30-34.].But can significantly increase solvability [(a) Zhou, the X.-H. of other hydrophobic compound in water; Kasai, R.; Yoshikawa, M.; Kitagawa, I.; Tanaka, O.Chem.Pharm.Bull.1991,39,1250-2. (b) Patent JP 59162931/1984; Chem.Abstr.102,67394.].Ginsenoside Ro (1) has also shown significant anticoagulant active [(a) Matsuda, H. on cell and mouse model; Namba, K.; Fukuda, S.; Tani, T.; Kubo, M.Chem.Pharm.Bull.1986,34,2100-4. (b) Patent JP57163315/1982; Chem.Abstr.98:78132]., anti-inflammatory activity [(a) Lee, Y.-M.; Saito, H.; Takagi, K.; Shibata, S.; Shoji, J.; Kondo, N.Chem.Pharm.Bull.1977,25,1391-8. (b) Matsuda, H.; Samukawa, K.; Kubo, M.Planta Med.1990,56,19-23.], hepatitis virus resisting activity [Matsuda, H.; Samukawa, K.; Kubo, M.Planta Med.1991,57,523-6. (b) Kubo, M.; Matsuda, H.Patent JP 04005235/1992; Chem.Abstr.116:158902.] and other activity.
GOTCAB saponin (2) " 3-O-{ β-D-semi-lactosi (1 → 2)-[β-D-glucose (1 → 3)]-β-D-glucuronic acid }-Oleanolic Acid-28-O-β-D-glucose " is that Xiao equals to separate from the root bark of Aralia dasyphylla in 1999 and obtains [Xiao, K.; Yi, Y.H.; Wang, Z.Z.; Tang, H.E.; Li, Y.Q.; Lin, H.W.J.Nat.Prod.1999,62,1030-1032.], this kind of plant also can be used as tonic in hepatitis, the diabetes of being used for the treatment of among the people always, and its tender shoots can also eat.This molecule is implanted human cancer cell's cell strain (KB and Hela-S to two classes 3) 503nhibiting concentration be respectively 1.2 μ g/mL and 0.02 μ g/mL, 5 FU 5 fluorouracil that is better than using in the control experiment and cytosine arabinoside, they are respectively 0.93 (KB) to the 503nhibiting concentration of two class cell strains, 0.44 μ g/mL (Hela-S 3) and 0.81 (KB), 0.23 μ g/mL (Hela-S 3).
Summary of the invention
The problem to be solved in the present invention provides a kind of new synthetic method of glucuronide oleanane type double sugar chains triterpenoid saponin.
This patent provides the synthetic method of the new practicality of a kind of glucuronide oleanane type double sugar chains triterpenoid saponin (GOTCAB saponin), and this method comprises the steps:
(1) be that raw material connects 28 sugar chains earlier with the oleanane type triterpene; (2) connect 3 glycosyls again; (3) after the protecting group operation, connect 3 all the other glycosyls; (4) vacate 6 ' (3 first glycosyls 6) hydroxyl through protecting group operation; (5) 6 ' primary hydroxyl of selective oxidation becomes carboxylic acid; (6) remove all protecting groups under the last alkaline condition.
Specifically, recommend each step as follows:
The glucosidesization of (1) 28 carboxyl: the oleanane type triterpene can be directly and glycosyl bromine glycosides under alkaline condition, in the presence of phase-transfer catalyst, react, obtain the ester glucosides with very high productive rate, and need not protect 3-OH.Described alkali is recommended as mineral alkali (for example salt of wormwood, yellow soda ash, saleratus, sodium bicarbonate etc.) or organic bases such as DBU.Described phase-transfer catalyst is recommended as quarternary ammonium salt (as Bu 4NBr).Solvent is recommended as polar solvent (as DMF, DMSO).Temperature of reaction is recommended in 10-140 ℃.
The glucosidesization of (2) 3 hydroxyls: 2 hydroxyls of the glycosyl donor of use are with benzoyl class protecting group (as benzoyl Bz, as the neighbour-n-formyl sarcolysine base-benzoyl AZMB etc. changes) protection; 1 hydroxyl is with tribromo-acetyl imines ester or the activation of trifluoroacetyl imines ester; Promotor recommendation is used the Louis silk acid or the protonic acid of catalytic amount, as the trialkyl silyl triflate (as trimethylsilyl trifluoromethanesulfonate TMSOTf, the silica-based triflate TESOTf of triethyl, the silica-based triflate TBSOTf of tertiary butyl dimethyl) and trifluoromethanesulfonic acid (HOTf) etc.Described glycosyl donor is recommended as the oligosaccharyl of glucosyl group, mannose group, galactosyl, Arabic glycosyl, xylosyl etc. or their compositions.Solvent, temperature of reaction, amount ratio etc. are normal condition herein.
(3) other glycosylation reaction all recommends to use glycosyl tribromo-acetyl imines ester or trifluoroacetyl imines ester to give body; Promotor recommendation is used the Louis silk acid or the protonic acid of catalytic amount.
(4) recommend to use 6 ' primary hydroxyl of oxidation style selective oxidation of TEMPO mediation to become carboxylic acid.Recommendation is with Losantin (Ca (ClO) 2) or clorox (NaClO) be co-oxidants.Other condition is a normal condition.
(5) (as NaOMe, NaOH, LiOH etc.) removes protecting group and obtains target compound under the alkaline condition, its general structure for example:
Figure A20031010852100071
R1, R2, R3=H or glycosyl; The R4=glycosyl
Described glycosyl is recommended as the oligosaccharyl into glucosyl group, mannose group, galactosyl, Arabic glycosyl, xylosyl etc. or their compositions.
The raw material of described glucosidesization (raw material-glucosidesization that promptly connects glycosyl is given body) is recommended as different head position hydroxyl and is activated, and all the other hydroxyls are by the glycosyl of (as Bz, Ac, Bn etc.) protecting group protection.
Described oleanane type triterpene is recommended as Oleanolic Acid, and its structural formula for example
The benzoyl that replaces refers to the benzoyl that replaced by other any group on its phenyl, as RO-, and ROOC-(the R=alkyl is recommended as the alkyl of C1～C4), Cl, Br etc.
The alkyl of above-mentioned trialkyl silyl triflate is recommended as the alkyl of C1～C4.
Aforementioned protecting group is operating as normal condition.
We once carried out oleanane type triterpene 3 with following order, 38-disaccharide chain saponin synthetic: with protecting group earlier protection oleanane type triterpene 28 is carboxyl; Connect 3 glycosyls or part glycosyl; Remove 28 protecting groups; Connect 28 glycosyls; Deprotection obtains target molecule.[(a) Yu, B.; Xie, J.; Deng, S.; Hui, Y.J.Am.Chem.Soc.1999,121,12196-12197. (b) Sun, J.; Hah, X.; Yu, B.Carbohydr.Res.2003,338,827-833.] but present synthetic route step weak point, the overall yield height.
Embodiment
Embodiment 1
Ginsenoside Ro's (1) is synthetic
Synthetic route is as shown below:
Reagent and condition: (a) K 2CO 3, Bu 4NBr, CH 2Cl 2-H 2O, reflux, 90%. (b) TBSOTf (0.1 equiv), CH 2Cl 2, 4 MS, rt, 91%. (c) Bu 3P, THF-H 2O, 75%. (d) TBSOTf (0.4equiv), CH 2Cl 2, 4 MS, rt, 79%. (e) AcCl, MeOH-CH 2Cl 2, 0 ℃-rt, 89%. (f) TEMPO, Ca (ClO) 2, KBr, Bu 4NBr, CHCl 3-H 2O, 0 ℃, 89%. (g) NaOMe, MeOH-CH 2Cl 2, 72%.
Concrete experiment and data:
(1) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranosyl oleanolic ester (4): (195mg, 0.43mmol) with 2,3,4,6-four-O-benzoyl-alpha-D-glucose bromine glycosides (377mg, 1.3 equivalents) is dissolved in CH with Oleanolic Acid 2Cl 2(5.0mL) and the two-phase system formed of water (5.0.mL), and add K 2CO 3(151mg, 2.5 equivalents) and Bu 4NBr (56mg, 0.4 equivalent), reflux is finished until TLC demonstration reaction then.Reaction system CH 2Cl 2Dilution, water, the saturated NaCl aqueous solution are washed respectively then, and organic phase is used anhydrous Na after merging 2SO 4Dry.Be spin-dried for, with silicagel column separation and purification (toluene: ethyl acetate=25: 1), obtain spumescence solid 4 (398mg, productive rate 90%). 1H?NMR(300MHz，CDCl 3)δ8.04(d，J＝7.2Hz，2H)，7.97(d，J＝7.5Hz，2H)，7.90(d，J＝7.2Hz，2H)，7.83(d，J＝7.2Hz，2H)，7.59-7.28(m，12H)，5.99(t，J＝9.6Hz，1H)，5.96(d，J＝8.1Hz，1H)，5.78-5.69(m，2H)，5.28(s，1H)，4.56(dd，J＝3.0，12.3Hz，1H)，4.46(dd，J＝5.4，9.3Hz，1H)，4.26(m，1H)，3.14(m，1H)，2.79(m，1H)，0.97(s，3H)，0.94(s，3H)，0.86(s，3H)，0.83(s，3H)，0.76(s，3H)，0.74(s，3H)，0.45(s，3H)。
(2) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[4,6-Di-O-acetyl-2-O-(2-azidomethyl) benzoyl-3-O-benzoyl-β-D-glucopyranosyl] oleanolic ester (6): will be to body 5 (337mg, 1.2 equivalent) and acceptor 4 (416mg 0.40mmol) is dissolved in anhydrous CH 2Cl 2(5mL), and add 4 molecular sieves, in system, drip the TBSOTf (0.10 equivalent) of catalytic amount.Stir under the room temperature after 3 hours, with triethylamine cancellation reaction.After the filtration, be spin-dried for rapid column chromatography separation and purification (sherwood oil: ethyl acetate=2.5: 1), obtain spumescence solid 6 (556mg, 91%).[α] D：+66°(c0.81，CHCl 3)； 1HNMR(300MHz，CDCl 3)δ8.05-7.78(m，10H)，7.58-7.30(m，19H)，5.98(t，J＝9.3Hz，1H)，5.85(d，J＝8.4Hz，1H)，5.72(t，J＝9.0Hz，2H)，5.64(t，J＝9.8Hz，1H)，5.44(t，J＝9.3Hz，1H)，5.28(t，J＝9.3Hz，1H)，5.26(s，1H)，4.74(d，J＝8.1Hz，1H)，4.66(dd，J＝8.7，6.3Hz，2H)，4.54(m，1H)，4.46(m，1H)，4.36-4.12(m，3H)，3.82(m，1H)，3.8(m，1H)，2.78(m，1H)，2.10(s，3H)，1.93(s，3H)，0.92(s，3H)，0.84(s，3H)，0.81(s，3H)，0.72(s，3H)，0.64(s，6H，2?CH 3)，0.40(s，3H)； 13C?NMR(75MHz，CDCl 3)δ175.7，170.6，169.4，166.0，165.6，165.1，164.7，143.0，137.9，133.4，133.2，133.0，131.0，129.8，129.0，128.7，128.4，128.3，127.8，122.7，102.9，91.9，90.6，73.2，72.9，72.1，71.6，70.4，69.3，68.8，62.7，62.3，55.3，52.7，47.4，46.8，45.7，41.5，40.9，38.9，38.7，38.3，36.5，33.7，32.9，31.8，30.5，29.6，27.8，25.7，25.4，23.4，23.3，22.6，20.7，20.5，18.0，16.4，16.3，15.1。
(3) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[4,6-di-O-acetyl-3-O-benzoyl-β-D-glucopyranosyl] oleanolic ester (7): (530mg 0.343mmol) is dissolved among the 4mL THF, adds the water of 0.4mL with compound 6, add tributylphosphine (256 μ L, 3.0 equivalents) subsequently.Stir after 3 hours reaction system CH under the room temperature 2Cl 2Saturated NaHCO is used in dilution respectively 3And washing, organic phase is used anhydrous Na after merging 2SO 4Dry.Be spin-dried for, with rapid column chromatography separation and purification (sherwood oil: ethyl acetate=2.5: 1), obtain foamed solid 7 (357mg, productive rate 75%).[α] D＝+36.9°(c0.95，CHCl 3)；IR(thin?film)：3503，3341，3064，2949，1739，1653，1603，1585，1494，1453，1388，1368，1316，1269，1178，1107，1095，1027，990，853，802，710，687，618，599，495； 1HNMR(300MHz，CDCl 3)δ8.03(d，J＝6.9Hz，4H)，7.98(d，J＝7.1Hz，2H)，7.89(d，J＝7.1Hz，2H)，7.82(d，J＝7.1Hz，2H)，7.59-7.29(m，15H)，5.99(t，J＝9.9Hz，1H)，5.94(d，J＝8.4Hz，1H)，5.74(t，J＝9.6Hz，1H)，5.72(dd，J＝1.2，9.6Hz，1H)，5.38(t，J＝9.3Hz，1H)，5.28(s，1H)，5.22(t，J＝9.9Hz，1H)，4.56(d，J＝3.3，12.3Hz，1H)，4.52-4.45(m，2H)，4.34-4.23(m，2H)，4.10(dd，J＝2.1，12.0Hz，1H)，3.75(m，2H)，3.18(m，1H)，2.79(m，1H)，2.08(s，3H)，1.93(s，3H)，0.96(s，6H，2?CH 3)，0.85(s，3H)，0.83(s，3H)，0.78(s，3H)，0.77(s，3H)，0.44(s，3H)； 13C?NMR(75MHz，CDCl 3)δ175.7，170.6，169.5，166.3，166.0，165.6，165.1，164.7，143.0，133.4，133.3，133.0，129.9，129.8，129.7，129.3，129.7，128.4，128.3，122.6，105.0，91.9，90.4，75.1，73.1，72.9，71.6，70.4，69.3，68.5，62.7，62.4，55.4，47.4，46.8，45.7，41.5，40.9，38.9，38.3，36.6，33.7，32.9，31.8，30.5，28.2，27.7，25.7，25.6，23.4，23.3，22.6，20.7，20.5，18.0，16.6，16.4，15.1；HRMS-ESI(M+Na +)calcd?for?C 81H 92O 20Na?1407.6074，found?1407.6039。
(4) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 2)-4,6-di-O-acetyl-3-O-benzoyl-β-D-glucopyranosyl] oleanolic ester (9): (171mg 0.123mmol) and to body 8 (273mg, 3.0 equivalents), 4 molecular sieves is dissolved in the anhydrous CH of 2mL with acceptor 7 2Cl 2In.Under the argon shield, stirring at room, the CH of dropping TBSOTf in system 2Cl 2Solution (0.4 equivalent).Continue to stir after 3 hours, add triethylamine cancellation reaction.After the filtration, be spin-dried for, silica gel column chromatography gets white solid 9 (190mg, productive rate 79%).[α] D＝+43.8°(c1.04，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ8.25(d，J＝7.7Hz，4H)，7.99(d，J＝7.1Hz，2H)，7.92-7.80(m，7H)，7.72(t，J＝8.8Hz，4H)，7.66-7.18(m，28H)，6.00(t，J＝9.6Hz，1H)，5.96(d，J＝8.2Hz，1H)，5.78(dd，J＝8.4，9.6Hz，1H)，5.71(t，J＝9.6Hz，1H)，5.66(t，J＝9.3Hz，1H)，5.58(t，J＝9.4Hz，1H)，5.41(dd，J＝9.3，9.1Hz，1H)，5.39(t，J＝9.1Hz，1H)，5.26(s，1H)，5.12(t，J＝9.6Hz，1H)，5.02(d，J＝7.7Hz，1H)，4.67(dd，J＝3.6，12.1Hz，1H)，4.61-4.53(m，2H)，4.52-4.43(m，2H)，4.30-4.19(m，2H)，4.13-4.01(m，3H)，3.68(m，1H)，3.08(dd，J＝4.5，3.1Hz，1H)，2.79(m，1H)，2.05(s，3H)，1.76(s，3H)，1.09(s，3H)，0.97(s，3H)，0.86(s，3H)，0.84(s，3H)，0.76(s，3H)，0.69(s，3H)，0.43(s，3H)； 13C?NMR(75MHz，CDCl 3)δ175.7，170.6，169.5，166.2，165.7，165.1，164.8，143.1，133.6，133.5，133.3，133.2，133.0，129.8，129.6，129.2，128.9，128.7，128.3，122.7，103.3，100.6，91.9，90.9，75.3，72.9，72.0，71.1，70.4，70.1，69.4，68.9，63.4，62.8，62.4，55.4，47.4，46.8，45.7，41.5，41.0，39.1，38.9，38.4，36.5，33.7，33.0，31.7，30.5，29.7，27.8，25.8，25.5，23.5，23.3，22.6，20.7，20.4，18.0，16.4，16.3，15.2；HRMS-ESI(M+Na +)calcd?for?C 115H 118O 29Na?1985.7651，found1985.7643。
(5) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 2)-3-O-benzoyl-β-D-glucopyranosyl] oleanolic ester (10): (190mg, 96.7 μ mol) are dissolved in anhydrous methanol (20mL) and exsiccant CH with compound 9 2Cl 2(8mL) in the mixed solvent of Zu Chenging, under the ice bath, dripping acetyl chloride (0.6mL).Reaction system at room temperature stirs until the TLC demonstration and reacts completely, and then, adds triethylamine cancellation reaction.Behind the concentrating under reduced pressure, rapid column chromatography (sherwood oil: ethyl acetate=1: 1), obtain white foam 10 (89%).[α] D＝+51.1°(c1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ8.05-7.82(m，13H)，7.76-7.71(m，4H)，7.64-7.16(m，28H)，6.01(t，J＝9.6Hz，1H)，5.96(d，J＝8.0Hz，1H)，5.76(dd，J＝8.4，9.6Hz，1H)，5.71(t，J＝9.6Hz，1H)，5.67-5.61(m，2H)，5.53(t，J＝8.7Hz，1H)，5.27(s，1H)，5.18(t，J＝9.2Hz，1H)，5.13(d，J＝7.7Hz，1H)，4.68(dd，J＝3.7，11.8Hz，1H)，4.61-4.45(m，4H)，4.27(m，1H)，4.11(m，1H)，4.04(t，J＝8.1Hz，1H)，3.88(m，1H)，3.75-3.65(m，2H)，3.38(m，1H)，3.10(m，1H)，2.80(m，1H)，1.11(s，3H)，0.97(s，3H)，0.87(s，3H)，0.84(s，3H)，0.78(s，3H)，0.70(s，3H)，0.43(s，3H)； 13C?NMR(75MHz，CDCl 3)δ175.7，167.0，166.15，166.07，165.6，165.2，165.1，164.7，143.0，133.9，133.4，133.2，133.0，129.8，129.6，129.0，128.7，128.3，128.2，122.7，103.3，100.8，91.9，90.7，79.4，75.1，72.9，72.0，70.3，70.1，69.4，63.4，62.7，62.4，55.4，47.4，46.8，45.7，41.5，40.9，39.1，38.9，38.4，36.5，33.7，32.9，31.7，30.5，29.6，27.8，26.1，25.4，23.4，23.3，22.6，18.0，16.4，16.3，15.1；HRMS-ESI(M+Na +)calcd?forC 111H 114O 27Na?1901.7440，found?1901.7436。
(6) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl (1 → 2)-3-O-benzoyl-β-D-glucuronopyranosyl] oleanolic ester (11): (142mg, 75.5 μ mol) are dissolved in CHCl with compound 10 3(0.7mL) and NaHCO 3The mixing solutions formed of saturated solution (0.7mL) in, add Ca (ClO) then 2(22mg, 2.0 equivalents), KBr (1.8mg, 0.2 equivalent) and phase-transfer catalyst Bu 4NBr (1.7mg, 0.07 equivalent).Ice bath stirs down, and TEMPO (0.24mg, 0.02 equivalent) is joined in the reaction system.Ice bath stirred 4 hours down, the Na of dilute with water, and adding then 2SO 3The cancellation reaction.With acetic acid regulator solution pH=3～4, stir after 15 minutes, use twice of ethyl acetate extraction.Organic phase is washed with saturated common salt, and uses anhydrous Na 2SO 4Dry.Be spin-dried for, rapid column chromatography separation and purification (methylene chloride-methanol=30: 1) gets white solid 11 (127mg, 89%).[α] D＝+44.4°(c0.73，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ8.02-7.80(m，13H)，7.78-7.71(m，4H)，7.64-7.19(m，28H)，6.00(t，J＝9.6Hz，1H)，5.96(d，J＝7.7Hz，1H)，5.78-5.68(m，3H)，5.64(t，J＝9.5Hz，1H)，5.44(t，J＝8.4Hz，1H)，5.27(s，1H)，5.25-5.11(m，2H)，4.75-4.62(m，2H)，4.60-4.44(m，3H)，4.28(m，1H)，4.18-3.95(m，4H)，3.58-2.92(brs，1H)，3.12(m，1H)，2.79(m，1H)，1.26(s，3H)，1.00(s，3H)，0.86(s，3H)，0.84(s，3H)，0.71(s，3H)，0.68(s，3H)，0.42(s，3H)； 13C?NMR(75MHz，CDCl 3)δ175.6，166.1，165.6，165.2，165.1，164.7，142.9，133.4，133.0，129.8，129.6，128.6，128.3，128.2，122.7，102.9，100.5，91.9，91.0，72.9，72.0，70.3，69.9，69.3，63.4，62.7，55.3，47.3，46.8，45.7，41.5，40.9，38.9，38.8，38.3，36.4，33.7，32.9，31.7，30.5，29.6，27.8，25.4，23.4，22.6，18.0，16.4，16.2，15.1；HRESI-MS(M+Na +)?calcd?for?C 111H 112O 28Na?1915.7232，found?1915.7197。
(7) β-D-glucopyranoside-3-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucuronopyranosyloleanolic ester (1): with compound 11 (50mg, 26.4 μ mol) be dissolved in methyl alcohol-methylene dichloride (9mL) of 2: 1, in system, drip the methanol solution (0.5%) of the NaOMe of 0.4mL then.Stirred 24 hours under the room temperature, add acidic resins Dowex 50-X8 (H then +) the cancellation reaction, stirred 30 minutes.Filter, wash with methyl alcohol.Be spin-dried for the organic phase after the merging, and rapid column chromatography (methylene dichloride: methyl alcohol: water=2.5: 1: 0.1), solid 1 (18mg, 72%).[α] D＝+3°(c?0.35，MeOH)； 13C?NMR(100MHz，C 5D 5N)δ177.9，144.9，126.0，105.6，105.4，96.3，90.7，81.8，78.9，78.5，78.3，78.1，77.0，74.4，73.9，72.3，71.6，63.4，62.7，56.6，48.7，47.9，47.0，42.8，42.4，40.6，40.3，39.5，37.6，34.7，33.9，33.2，31.5，30.6，28.9，28.8，26.8，24.4，19.2，18.2，17.4，16.2；HRESI-MS(M+Na +)calcd?for?C 48H 76O 19Na?979.4873，found?979.4907。
Embodiment 2
Synthesizing of GOTCAB saponin 2
Synthetic route is as shown below:
Reagent and condition: (a) TBSOTf (0.1 equiv), CH 2Cl 2, 4 MS, rt, 89%. (b) Bu 3P, THF-H 2O, 90%. (c) TBSOTf (0.4 equiv), CH 2Cl 2, 4 MS, rt, 90%. (d) AcCl, MeOH-CH 2Cl 2, 0 ℃-rt, 88%. (f) TEMPO, Ca (ClO) 2, KBr, Bu 4NBr, CHCl 3-H 2O, 0 ℃, 85%. (g) NaOMe, MeOH-CH 2Cl 2, 78%.
Concrete experiment and data:
(1) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 3)-4,6-di-O-acetyl-2-O-(2-azidomethyl) benzoyl-β-D-glucopyranosyl] oleanolic ester (13): will (806mg 0.779mmol) be dissolved in anhydrous CH to body 12 (1.0g, 1.1 equivalents) and acceptor 4 2Cl 2In, and add 4 molecular sieves.Under the argon shield, in system, drip TBSOTf (0.1 equivalent).Stir under the room temperature after 3 hours, with triethylamine cancellation reaction.After the filtration, be spin-dried for, rapid column chromatography divides pure, obtains spumescence solid 13 (1.398g, 89%).[α] D＝+40.8°(c0.93，CHCl 3)；R f＝0.39(1.5∶1?petroleum?ether-EtOAc).IR(thin?film)：2952，2104，1737，1603，1585，1492，1452，1369，1316，1265，1178，1106，1093，1069，1027，977，709，687cm -1； 1HNMR(300MHz，CDCl 3)δ8.03(t，J＝6.9Hz，3H)，7.94(m，9H)，7.67(t，J＝8.0Hz，2H)，7.58-7.09(m，30H)，5.97(t，J＝9.8Hz，1H)，5.94(d，J＝8.2Hz，1H)，5.79-5.68(m，2H)，5.62(t，J＝9.6Hz，1H)，5.42(t，J＝8.5Hz，1H)，5.25(s，1H)，5.23(t，J＝7.7Hz，1H)，5.09(t，J＝9.5Hz，1H)，5.00(d，J＝7.7Hz，1H)，4.65(dd，J＝3.0，12.1Hz，1H)，4.60-4.40(m，5H)，4.29-4.20(m，1H)，4.19-4.09(m，4H)，4.02(d，J＝16.2Hz，1H)，3.51(m，1H)，2.89(dd，J＝4.1，11.0Hz，1H)，2.78(d，J＝9.9Hz，1H)，2.07(s，CH 3CO)，1.99(s，CH 3CO)，0.90，0.84，0.81，0.68，0.48，0.43，0.38(7s，7*CH 3)； 13CNMR(75MHz，CDCl 3)δ175.6，170.7，169.2，166.0，165.6，165.1，164.7，163.7，142.9，139.2，133.5，133.2，133.0，132.8，130.4，129.8，129.6，129.5，129.1，128.7，128.4，128.3，128.0，127.6，127.0，122.7，103.0，101.3，91.9，90.3，79.2，73.3，72.9，72.0，71.6，70.3，69.6，69.3，68.8，63.1，62.7，62.5，55.3，52.8，47.4，46.8，45.7，41.5，40.9，38.8，38.5，38.3，36.5，33.7，32.9，31.8，30.5，29.7，27.6，25.6，25.4，23.4，22.6，20.8，20.6，17.9，16.4，16.1，15.1；ESI-MS：m/z?2040.8(M+Na +)；Calcd?for?C 116H 119N 3O 29·H 2O：C，68.40；H，5.94；N，2.06.Found：C，68.07；H，5.69；N，1.60.
(2) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 3)-4,6-di-O-acetyl-β-D-glucopyranosyl] oleanolic ester (14): with compound 13 (1.20g, 0.596mmol) be dissolved among the 6mL THF, add the water of 0.27mL, add tributylphosphine (446 μ L, 3.0 equivalents) subsequently.Stir after 1 hour reaction system CH under the room temperature 2Cl 2Saturated NaHCO is used in dilution respectively 3And washing, organic phase is used anhydrous Na after merging 2SO 4Dry.Be spin-dried for, with rapid column chromatography separation and purification (sherwood oil: ethyl acetate=2: 1), obtain foamed solid 14 (995mg, productive rate 90%).[α] D＝+43.6°(c1.0，CHCl 3)；R f＝0.71(1∶1?petroleum?ether-EtOAc).IR(thin?film)：3066，2952，1737，1603，1585，1492，1453，1369，1317，1266，1178，1094，1069，1027，853，802，709，683，503cm -1； 1H?NMR(300MHz，CDCl 3)δ8.07-7.78(m，15H)，7.59-7.18(m，25H)，5.95(t，J＝9.6Hz，1H)，5.92(d，J＝8.2Hz，1H)，5.86(t，J＝9.6Hz，1H)，5.76-5.68(m，2H)，5.66(t，J＝9.7Hz，1H)，5.45(dd，J＝8.0，9.0Hz，1H)，5.25(s，1H)，5.20(t，J＝8.0Hz，1H)，4.83(t，J＝9.6Hz，1H)，4.60(dd，J＝2.8，12.2?Hz，1H)，4.52(dd，J＝2.9，12.4Hz，1H)，4.43(dd，J＝4.8，12.2Hz，2H)，4.28-4.16(m，2H)，4.15-3.97(m，3H)，3.76(t，J＝9.2Hz，1H)，3.49(m，1H)，3.31(t，J＝7.1Hz，1H)，3.00(dd，J＝4.4，11.5Hz，1H)，2.76(d，J＝11.0Hz，1H)，2.00(s，CH 3CO)，1.87(s，CH 3CO)，0.93，0.86，0.82，0.79，0.70，0.66，0.42(7s，7*CH 3)； 13CNMR(75MHz，CDCl 3)δ175.7，170.6，169.4，166.0，165.8，165.6，165.1，164.9，164.7，143.0，133.2，133.0，129.9，129.7，128.7，128.4，128.3，122.7，104.5，101.5，91.9，89.9，81.0，74.8，72.9，72.2，72.0，71.6，70.4，69.6，69.3，68.4，62.9，62.7，62.6，55.3，47.4，46.8，45.7，41.5，40.9，38.9，38.8，38.3，36.6，33.7，32.9，31.8，30.5，28.2，27.7，25.6，25.5，23.4，22.6，20.7，20.5，18.1，16.6，16.5，15.1；HRESI-MS(M+Na) +caclcd?for?C 108H 114O 28Na?1881.7389，obsd?1881.7356.
(3) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-{2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-(1 → 2)-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 3)]-4,6-di-O-acetyl-β-D-glucopyranosyl}olearolic ester (16): with acceptor 14 (381mg, 0.205mmol) and be dissolved in the anhydrous CH of 15mL for body 15 (472mg, 3.0 equivalents), 4 molecular sieves 2Cl 2In.Under the argon shield, stirring at room dripped the CH of TBSOTf after 1 hour in system 2Cl 2Solution (0.4 equivalent).Continue to stir after 3 hours, add triethylamine cancellation reaction.After the filtration, be spin-dried for silica gel column chromatography (sherwood oil: ethyl acetate=5: 1～2: 1), get white solid 16 (447mg, 90%).[α] D＝+85.1°(c1.13，CHCl 3)；R f＝0.33(3∶2?petroleum?ether-EtOAc). 1H?NMR(300MHz，CDCl 3)δ8.24(d，J＝7.4Hz，2H)，8.16(d，J＝7.4Hz，2H)，8.07(d，J＝7.4Hz，2H)，8.05-7.78(m，18H)，7.72-7.18(m，36H)，6.98(t，J＝9.6Hz，1H)，5.94(d，J＝8.2Hz，1H)，5.87(t，J＝9.9Hz，1H)，5.78-5.68(m，2H)，5.65-5.06(m，2H)，5.48-5.39(m，3H)，3.27(s，1H)，4.85(t，J＝9.5Hz，1H)，4.72(d，J＝7.4Hz，2H)，4.54(dd，J＝2.6，12.2Hz，1H)，4.48(dd，J＝4.8，12.2Hz，1H)，4.38(dd，J＝6.3，11.3Hz，1H)，4.29-4.19(m，4H)，4.18-3.98(m，5H)，3.79(m，2H)，3.35(m，1H)，2.98(dd，J＝4.4，11.5Hz，1H)，2.78(d，J＝11.6Hz，1H)，2.42(m，1H)，2.32(t，J＝7.0Hz，1H)，2.04(s，CH 3CO)，1.90(s，CH 3CO)，1.22，0.99，0.86，0.84，0.79，0.74，0.42(7s，7*CH 3)； 13C?NMR(75MHz，CDCl 3)δ175.6，170.6，169.3，166.0，165.6，165.5，165.0，164.7，142.9，134.7，134.7，133.5，133.3，133.0，130.2，129.8，128.6，128.3，122.8，103.5，100.1，91.9，90.7，80.0，72.9，72.4，71.3，70.9，70.6，70.4，69.6，69.3，68.6，67.8，62.7，60.6，55.6，47.5，46.8，45.8，41.6，41.0，39.2，39.0，38.6，36.6，33.7，33.0，31.8，30.6，29.7，27.9，25.8，25.5，23.4，22.7，20.8，18.1，16.5，15.2；HRESI-MS(M+Na +)caclcd?for?C 142H 140O 37Na2459.8966，obsd?2459.8973.
(4) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-{2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-(1 → 2)-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 3)]-β-D-glucopyranosyl}oleanolic ester (17): (390mg 0.16mmol) is dissolved in anhydrous methanol (15mL) and exsiccant CH with compound 15 2Cl 2(8mL) in the mixed solvent of Zu Chenging, under the ice bath, dripping acetyl chloride (0.4mL).Reaction system at room temperature stirs until the TLC demonstration and reacts completely, and then, adds triethylamine cancellation reaction.Behind the concentrating under reduced pressure, rapid column chromatography (sherwood oil: ethyl acetate=3: 2), obtain white foam shape solid (336mg, 88%).[α] D＝81.4°(c0.67，CHCl 3)；R f＝0.45(1∶1?petroleumether-EtOAc)； 1H?NMR(300MHz，CDCl 3)δ8.29-7.74(m，24H)，7.72-7.18(m，36H)，5.99(t，J＝9.6Hz，1H)，5.93(d，J＝8.2Hz，1H)，5.89(t，J＝9.0Hz，1H)，5.79-5.66(m，2H)，5.64-5.55(m，2H)，5.53-5.36(m，3H)，5.28(s，1H)，4.79(dd，J＝9.3，11.4Hz，1H)，4.69(dd，J＝7.5，11.4Hz，1H)，4.59-4.12(m，7H)，4.04(m，1H)，3.92-3.67(m，3H)，3.59(t，J＝8.3Hz，1H)，3.50(t，J＝9.6Hz，1H)，3.44(s，1H)，3.22(m，1H)，3.02(m，1H)，2.79(m，1H)，2.62(m，1H)，2.46(m，1H)，2.33(m，1H)，1.24，0.99，0.87，0.86，0.83，0.70，0.44(7s，7X?CH 3)； 13C?NMR(75MHz，CDCl 3)δ175.6，166.0，165.9，165.7，165.6，165.3，165.2，165.0，164.9，164.8，164.6，142.8，133.8，133.6，133.4，133.2，133.0，130.2，129.9，129.7，129.5，129.2，128.6，128.5，128.3，122.7103.5，100.4，99.8，91.8，90.1，85.8，74.7，72.9，72.1，71.9，71.7，71.0，70.8，70.4，69.5，69.3，69.0，67.6，63.1，62.7，61.8，60.4，55.5，47.4，46.8，45.7，41.5，40.9，39.2，38.9，38.5，36.5，33.7，32.9，31.8，30.5，27.8，26.2，25.4，25.4，23.4，22.7，18.1，16.4，15.1；ESI-MS：m/z?2375.5(M+Na +)；Calcd?for?C 138H 136O 35：C，70.40；H，5.82.Found：C，69.72；H.6.01.
(5) 2,3,4,6-Tetra-O-benzoyl-β-D-glucopyranoside-3-O-{methyl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl-(1 → 2)-[2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl}oleanolic ester (18): (107mg, 44.7 μ mol) are dissolved in CHCl with compound 17 3(0.7mL) and NaHCO 3The mixing solutions formed of saturated solution (0.7mL) in, add Ca (ClO) then 2(12mg, 2.0 equivalents), KBr (1.1mg, 0.2 equivalent) and phase-transfer catalyst Bu 4NBr (1.0mg, 0.07 equivalent).Ice bath stirs down, and TEMPO (0.139mg, 0.02 equivalent) is joined in the reaction system.Ice bath stirred 3 hours down, the Na of dilute with water, and adding then 2SO 3The cancellation reaction.With acetic acid regulator solution pH=3～4, stir after 15 minutes, use twice of ethyl acetate extraction.Organic phase is washed with saturated common salt, and uses anhydrous Na 2SO 4Dry.Be spin-dried for, rapid column chromatography separation and purification (methylene chloride-methanol=30: 1) gets white solid 17 (85%).[α] D＝+72.8°(c0.91，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ5.97(t，J＝9.6Hz，1H)，5.94(d，J＝8.5Hz，1H)，5.90(t，J＝9.8Hz，1H)，5.78-5.69(m，2H)，5.58(t，J＝8.4Hz，2H)，5.52-5.43(m，2H)，5.38(d，J＝3.6Hz，1H)，5.27(s，1H)，4.68(d，J＝7.7Hz，1H)，4.60(d，J＝8.0Hz.1H)，4.56(dd，J＝2.8，12.4Hz，1H)，4.45(d?d，J＝4.8，12.2Hz，1H)，4.42-4.30(m，2H)，4.28-4.16(m，2H)，4.03(dd，J＝7.7，11.0Hz，1H)，3.88-3.75(m，2H)，3.78(s，3H)，3.70(d，J＝9.6Hz，1H)，3.58(t，J＝8.6Hz，1H)，3.53(s，1H)，3.02(d?d，J＝4.2，15.7Hz，1H)，2.78(d，J＝9.0Hz，1H)，2.62(m，1H)，2.33(t，J＝6.9Hz，1H)，1.16，1.02，0.98，0.95，0.86，0.82，0.42(7s，7*CH 3)； 13C?NMR(75MHz，CDCl 3)δ175.7，168.5，166.1，165.6，165.4，164.9，164.8，142.9，133.5，133.3，133.0，129.8，129.5，129.3，128.6，128.4，122.8，103.8，100.4，100.0，91.9，90.3，85.3，74.8，72.9，72.2，71.9，71.0，70.4，69.9，69.3，69.1，67.6，62.7，62.1，60.6，55.5，52.5，47.5，46.8，45.8，41.5，41.0，39.3，38.9，36.5，33.7，33.0，31.8，30.6，29.7，27.8，25.5，23.4，22.7，18.1，16.4，15.2；ESI-MS：m/z2403.3(M+Na +)；Calcd?for?C 139H 136O 36：C，70.07；H，5.75.Found：C，69.79；H，6.09.
(14) 3-O-{ β-D-galactopyranosyl-(1 → 2)-[β-D-glucopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl}-oleanolic acid-28-O-β-D-glucopyranoside (2): compound 18 (50mg) is dissolved in methyl alcohol-methylene dichloride (9mL) of 2: 1, in system, drips the methanol solution (0.5%) of the NaOMe of 0.4mL then.Stirred 24 hours under the room temperature, add acidic resins Dowex 50-X8 (H then +) the cancellation reaction, stirred 30 minutes.Filter, wash with methyl alcohol.Be spin-dried for the organic phase after the merging, and rapid column chromatography, solid 2 (78%).[α] D＝17°(c0.39，MeOH)； 13C?NMR(100MHz，C 5D 5N-D 2O)δ178.8，145.3，124.4，105.7，104.6，104.4，96.5，92.3，86.8，79.6，79.5，78.7，78.6，78.4，77.8，75.8，75.5，74.5，74.0，72.9，72.0，71.7，70.9，64.7，63.3，62.9，57.0，49.0，48.4，47.44，43.2，42.8，40.9，40.7，39.5，37.9，35.0，34.3，34.1，33.5，31.8，30.8，29.3，29.0，27.2，24.8，24.7，24.4，19.5，18.5，17.7，16.5；HRESI-MS(M+Na +)calcd?forC 54H 86O 24Na?1141.5401，found?1141.5392.

Claims (8)

1. the synthetic method of the new practicality of a glucuronide oleanane type double sugar chains triterpenoid saponin (GOTCAB saponin) is characterized in that this method comprises the steps:
(1) be that raw material connects 28 sugar chains earlier with the oleanane type triterpene; (2) connect 3 glycosyls again; (3) after the protecting group operation, connect 3 all the other glycosyls; (4) vacate 6 ' hydroxyl through the protecting group operation; (5) 6 ' primary hydroxyl of selective oxidation becomes carboxylic acid; (6) remove all protecting groups under the last alkaline condition.
2. synthetic method as claimed in claim 1 is characterized in that each step is as follows:
The glucosidesization of (1) 28 carboxyl: the oleanane type triterpene can be directly and the bromine glucosides under alkaline condition, react, obtain the ester glucosides;
The glucosidesization of (2) 3 hydroxyls: 2 hydroxyls of the glycosyl donor of use are with the benzoyl protection of benzoyl or replacement, and 1 hydroxyl is with tribromo-acetyl imines ester or the activation of trifluoroacetyl imines ester, and promotor is used the Louis silk acid or the protonic acid of catalytic amount;
(3) other glucosidesization all uses tribromo-acetyl imines ester or trifluoroacetyl imines ester to give body;
(4) vacate 6 ' hydroxyl through the protecting group operation;
(5) 6 ' primary hydroxyl of oxidation becomes carboxylic acid.
(6) remove protecting group under the alkaline condition and obtain target compound, its general structure is as follows:
Figure A2003101085210002C1
R1, R2, R3=H or glycosyl; The R4=glycosyl
3. synthetic method as claimed in claim 1 or 2 is characterized in that described glycosyl is the oligosaccharyl of glucosyl group, mannose group, galactosyl, Arabic glycosyl, xylosyl etc. or their compositions.
4. synthetic method as claimed in claim 1 or 2 is characterized in that described oleanane type triterpene is an Oleanolic Acid.
5. synthetic method as claimed in claim 1 or 2 is characterized in that the raw material-glucosidesization of described glucosidesization is that different head position hydroxyl is activated the glycosyl of the protected base protection of all the other hydroxyls to body.
6. synthetic method as claimed in claim 5 is characterized in that described protecting group is Bz, Ac, Bn.
7. synthetic method as claimed in claim 2 is characterized in that the glucosidesization of 3 hydroxyls of described oleanane type triterpene is given the benzoyl protection of 2 hydroxyls of body with benzoyl (Bz) or replacement.Silk acid of described Louis or protonic acid are trialkyl silyl triflate and trifluoromethanesulfonic acid etc., and 1 hydroxyl of described glycosyl donor is with tribromo-acetyl imines ester or the activation of trifluoroacetyl imines ester.6 ' primary hydroxyl of oxidation becomes carboxylic acid to use the oxidation style selective oxidation of TEMPO mediation.
8. synthetic method as claimed in claim 2 is characterized in that the substituting group on the benzoyl of described replacement is RO-, ROOC-, Cl, Br, wherein R=alkyl; The alkyl of trialkyl silyl triflate is the alkyl of C1～C4.
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