TW201228666A - Methods for preparation of glycosphingolipids and uses thereof - Google Patents

Abstract

Methods for synthesis and preparation of alpha-glycosphingolipids are provided. Methods for synthesis of α -galactosyl ceramide, and pharmaceutically active analogs and variants thereof are provided. Novel alpha-glycosphingolipids are provided, wherein the compounds are immunogenic compounds which serve as ligands for NKT (natural killer T) cells.

Description

201228666, invention: TECHNICAL FIELD OF THE INVENTION The present invention relates to novel glycosphingolipid analogs and intermediate products useful in the manufacture thereof. In particular, the invention relates to novel methods for preparing glycosphingolipids. More specifically, the present invention relates to a method for synthesizing a novel α-binding glycosphingolipid compound and use thereof. [Prior Art] Studies have shown that sputum cells, a unique subset of lymphocytes, are characterized by a common expression of variant antigen receptors and purinergic receptors. Human νκτ cells (Va24-Jal8) are activated by a specific glycolipid antigen in a CDld-dependent manner. The CDld molecule heterodimer consists of a heavy polypeptide chain non-covalently linked to a 2-microglobulin and has substantial structural similarity to the first class of major histocompatibility complex (MHC) proteins. After activation, the cells exhibit unaffected antitumor activity against tumor cells via several mechanisms both in vitro and in vivo. Activated Va24 NKT cells produce high concentrations of fines, such as IFN-Tf, thereby bridging innate and adaptive via activation of other effector cells, including dendritic cells (DC) 'NK cells' and CD8 T cells. Immunity. NKTs play a regulator role in the immune system and are therefore an attractive target in terms of '='. Moreover, the most well-researched CDld-presenting antigen is a-galactosylamine guanamine (aGalCer, KRN-7000). It was initially of interest when the extract from the sponge, where it was confirmed, had a novel anti-tumor property. Kirin Beer Pharmaceutical Company (US Patent No. 5,847,716). This activity is later traced back to a family of ct-binding glycosphingolipids (GSLs), from which a(^alCer is structurally optimal. GSLs consist of a sugar moiety with alpha linkage to monoceramide) The ceramide is formed by a fatty acid and a long-chain test of the amine bond. Under the activation of aGalCer, the release of sputum cells promotes inflammation (ΤΜ) and immune regulation (Th2) cytokines. The production of TH1 cytokines is Think 3 201228666 y 廇 ▲, anti-virus 'and adjuvant activity related, * TH2 cytokines and endure this to suppress autoimmune diseases. aGalCer has its target for anti-cancer potential...5 test but in the first period Terminated. The non-specific nature of cytokine profile (expression pattern) induced by aGalCer, ΤΜ and Th2 舌 tongues are slightly less effective as therapeutic treatments. This turn has encouraged many groups to find increase, Th1 · Th2 cytokines - the choice of reaction, 3 substances. Wong et al. have synthesized a series of aromatic wei in the acid side chain, these molecules have the finer testin for Th1 response release spectrum

L table violation) (J. Am. Chem. Soc. 2006, 128, 9022-9023. US 2007 = 38871). Mouse live gamma experiments with aggressive lung cancer tumors (τα cell line) and breast cancer ^ (4T1 cell line) have shown that mice with lung cancer significantly prolonged survival compared to 5 fresh glycolipids. I have a cancer-free mouse in the 'Gao no treatment group, with a new glycolipid, growth rate of 75%, and the control a_GalCer treatment group of mice with 5〇% inhibition (Proc. Natl. Acad. Sd.USA 2007,104 , 10299-10304). Therefore, there is a need for an effective method for synthesizing an α-glycosphingolipid, such as an aGa丨Cer compound, to synthesize an _-lipid compound having an immunomodulatory effect. SUMMARY OF THE INVENTION The present invention provides a novel method for synthesizing galactose allergens, comprising 盥α_galactosyl-based nerves and active analogs thereof, such as C34-associated new compounds 0, 〇 〇Η η

Oh?h

C34 H(f c25h51 ΟΗΠ ξ oh 0^VS4h29

OH α-half-glucosyl-based ceramide, known in the art, in one embodiment, a compound represented by the structure of formula (1): 201228666

J29 (Ο ^ in Ri = 〇H 'NH2, NHC0R2; R2 = H or an alkyl group, a dilute group, or a terminal group, a substituted aryl group, a heteroaryl group, or a substituted heteroaryl group; χ = , Base, alkenyl; R3, RfH, OH; RS = aryl, substituted aryl, hetero, or substituted heteroaryl. In one embodiment of the invention, the compound of Formula 1 is obtained by a method The method comprises, among other things, the step of removing the phenylidene protecting group of the compound represented by the chemical formula (2) and hydrogenating: σ

14η29 OPG (2) wherein PG is a hydroxy protecting group. In another embodiment, the hydroxy protecting group can be a ruthenium group. In a specific embodiment of the invention, the compound of formula 2, ~(CH2)8'R3=H, R4=H' phenyloxy-phenyl, may be used by one

The PG0^ method is obtained, and the method comprises the step of, among other things, the formation of an amine bond of the chemical formula (3) and the compound of the formula (4).

PGO] NH2 OPG 〇^Τ^14Η29 (3)

OPG, in a specific embodiment, PG is awkward (4) 201228666

HO

And r. In a specific embodiment of the present invention, the compound of the formula (3), wherein the R is a benzoinyl group, can be obtained by a method comprising, among other things, the following step: reduction by the chemical formula (5) The azide group of the compound represented by the structure:

OPG (5) In a specific embodiment of the present invention, the compound of the formula 5, wherein the PG is a phenyl fluorenyl group, can be obtained by a method. The method comprises, among other things, the following steps: Structure represented by the compound

Wherein PG is a base protecting group and the LG group is leaving a group, and reacts with a compound represented by the chemical formula (7) structure.

H 〇 ^ PG OPG (7) wherein PG is via a protecting group ' to form an alpha glycosidic chain, thus obtaining a compound of formula (5). In another embodiment, the leaving group of formula (6) can be any of the following: 201228666

In a specific embodiment of the present invention, the compound of Chemical Formula 1 can be obtained by a method which comprises, among other things, removing the phenylidene protecting group of the compound represented by the chemical formula (8) and hydrogenating it. step:

OPG P. , PGO

Wherein PG is a hydroxy protecting group. In another embodiment, the PG can be, among others, a phenyl fluorenyl group. In a specific embodiment of the present invention, the compound of the formula (8) can be obtained by a method which comprises, among other things, the following steps: reacting a compound represented by the chemical formula (9) with a compound , the compound is represented by an alkanoic acid, an aromatic acid, an aromatic acid, a substituted aromatic acid, and a heterocyclic acid.

Wherein PG is a hydroxy protecting group. In a specific embodiment of the present invention, the compound (9) can be obtained by a method which comprises, among other things, the following steps: reduction of the azide of the compound represented by the chemical formula (10) (10) ) 201228666

OPG PGO

R3

—0卜x々5 HN opg K

The OPG compound (10) can be protected by one of the PG-based hydroxy groups. In one embodiment of the present invention, V Chuan"1, the method of the method of the formula (11) is substituted for, among other things, the following step: replacing the compound represented by the structure of the formula (11)

R

OPG (11) ', thus obtaining a compound of formula (8). I am stupid. In the second: 11 may be 'among other than 'another' or a compound may be by way of a specific embodiment, the step of the chemical formula (u): carried out by the chemical formula method, among other things, the following substitution The base portion of the compound represented by the structure of action

R3 HN opg R4

OPG, c14h: 29 (12) In another embodiment, it is carried out in the presence of sulfonium chloride. The substitution function can be carried out in the base of the present invention. It is known that the method comprises, in addition to the compound (12), the compound represented by the structure of the structure of the process of the first step of the hydrolysis of 201228666 (13).

OR

0PG (13) wherein R is a hydroxy protecting group, and in one embodiment, an R-based alkyl ester. In another specific embodiment, R is an acetate. In a specific embodiment of the present invention, the compound (13) can be obtained by a method comprising, among other things, the following steps: a compound represented by the chemical formula (4) and a chemical formula (14) The indole bond formation of the compound represented by the structure,

OR

0PG (14). In a specific embodiment of the present invention, the compound (14) can be obtained by a method comprising, among other things, a step of reducing an azide of a compound represented by the structure of the formula (15).

OR

N3 opg 〇N/"Y^C14H2g 0PG (15) In one embodiment of the invention, the compound (15) can be obtained by a method of 'the method includes', among other things, the following steps: (16) Structure represented by compound (16) 201228666 OR 〇PG PG〇

PGO

LG

I 〇v^OOU Y NH wherein PG is a hydroxy protecting group, LG is a leaving group, and an R group ester is reacted with a compound represented by the formula (7), wherein the pG system is protected by a group to form a glycoside Chain, thus obtaining a compound of formula (15). In another embodiment, the leaving group can be any of the following:

OH Η

, -hs-CHa ^-S-CH, in a specific embodiment of the present invention, the compound of the formula (17) is obtainable by a method comprising, among other things, the following steps: The PG is thereby obtained as a compound of the formula (17), which may be, among other things, a triptycium group.

N3 OPG l ^14^29 OPG (17) From the T-figure _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The spirit and the scope are made. In the case of the present invention, the present invention generally has the meaning of the technical content and the specific content of each terminology, and the description of the present invention. Force =: for the second two will be = door > can be used to wake up the target is not 'for example, using the body and / or quotes. Eyes 201228666 use does not affect - the scope and meaning of the word; the same system, regardless of whether It can be explained by means of awakening. It can be explained in the same way as the internal weight. Therefore, you can use ^ for any - or more vocabulary of discussion: t. δ and synonym elaborate or discuss without any special The description of t.- or more _ is not used. Any use of the terms discussed herein includes the vocabulary = example, and the present invention is not in the specification of the present invention.

Unless otherwise specified, A 'here all the techniques and the t t T thinking. ^ There are contradictory situations, which are subject to this document (including definitions). A new method of class II usually involves binding brain amines to the bile to form an amine group to form a guanamine group to complete the chemical formula. As an example of this synthesis, it is also possible to pass the following steps 201228666 methyl milk) - this methyl group, or isopropylidene. Toluene was selected as a solvent to synthesize a compound from αι to A3. The secondary reaction was not possible with toluene as the sole solvent. In order to overcome the low reactivity of the localization in toluene, a co-solvent of 1% by weight of toluene was used to improve the bathing degree of the oxides of the tobacco. After the aqueous experimental procedure was carried out, a crude A3 toluene solution was obtained, which was acid deprotected to provide a sugar acceptor A4. Deprotection of trityl groups can be carried out using various acids, such as hydrochloric acid, sulfuric acid, hydrogen bromide, trifluoroacetic acid, BFrOEt' nitric acid, acidic resins (such as Ambedite IR12®), and the like. Previously, various glycation methods have been applied to glycolipid synthesis, including vine fluoride, trichloroacetoimidate, glycosyl bromide and glycosyl iodide.

Tetrahedron 1998 ' 54 ' 3141-3150 ; J 〇rg Chem 2005, 70, 10260-10270; J Org Chem 2002 > 67 >4559-4564; Chem Commun 2007, 2336-2338. Glycosyl imine ethers were originally used in our synthesis to have excellent yields (89%) and rotational heterogeneity (α/|3 = 9/1). Since the imine ether is easily hydrolyzed and needs to be prepared, the use of this departure in large-scale synthesis may encounter storage and purification problems based on saccharification. Alternatively, using a Lewis acid' such as TMSOTf, Tf20, BF3.0Et2, TfOH, Me2SrTf2〇 as a catalyst, and using a molecular sieve to remove water, a thioglycoside can be achieved as a donor (d〇n〇r). (thio glycoside) A5. Compound A5 includes an azide group which contributes to saccharification' and the amine group of phytosphingosine is protected by decylamine or amine phthalate (t-butyl carbamate), see US5849716; US 2007/0238871; J. Am Chem. Soc 2004 '126, 13602-13603; J. Org. Chem. 2005, 70, 10260-10270; Tetrahedron 1998, 54, 3141-3150; Synthesis 2004 '847-850; Bioorg. Med. Chem. Lett 2006 ' 16 ' 2195-2199. 2-ΝΉ and 1-OH form intermolecular hydrogen bonds which hinder the nucleophile from attacking the activated glycoside' resulting in a low yield of saccharification. After saccharification between A4 and A5, column purification provides pure alpha-type and pure beta-form A6. 201228666 Azide-containing compound A6 can be reduced by using any of lithium aluminum hydride, sodium borohydride, borane complex, phosphine complex, enzyme reduction, hydrogenation, or transfer hydrogenation. The reduction of the phosphine complex, which produces the by-product phosphine oxide which is difficult to remove, and the reduction of the lithium hydride (LiAfflU) provides the hydrazine-purified amine A7. Compound A7 is attached to a variety of different prepared carboxylic acids (see Figure 3 for the preparation) to provide the corresponding guanamine compounds. The total deprotection of these compounds is achieved under the conditions of hydrogenolysis in the presence of catalyzed Pd(〇H) 2 and H 2 in a mixed solvent of MeOH and (3⁄4⁄4) to produce an analog of C34, compound A15. - 21. The reductive dehalogenation reaction of the aryl halide on the fluorenyl chain is carried out by a hydrogenation reaction of a compound containing a gas-sulfonic group and a odor-blue group. Therefore, in order to avoid a dehalogenation reaction, A6 is deprotected and reduced by the formation of water in the presence of catalyzed Pd(〇H)2 and h2. The resulting amine A22 is spliced to the appropriate acid under splicing conditions (see Figure 3 for preparation). After that, the analog A23-25 is produced (Fig. 2). For this process, there are many known reaction methods, especially guanidation. It is also possible to use sulfhydryl chloride, and anhydride or retinoic acid. It is used in the condensation reaction in the presence of a suitable condensing agent. Suitable condensing agents used in the reaction include dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3,didecylamino) Propyl)carbinimide (EDC)' and 2-(1-p-benzotriazol-1-yl)_1,1,3,3-carbazyl hexafluorophosphate Ester (HBTU) 'Hydroxy-p-triazole (H0Bt) or the like. In order to carry out the reaction rapidly, an organic base such as triethylamine is added, and the ratio is bite, methyl marlin's aniline, 4 · diterpene Amine, such as tetrahydrofuran, diethyl ether, phthalic acid, dioxane, ethyl acetate, etc. Solvents can be any inert solvent that does not interfere with the reaction. , acetone or the like. To prepare various different substituted benzene acids, use Wittig reaction can be seen in Figure 3. In the process, bromo-alkanoic acid and diphenyl in the presence of solvent Phosphine mixing. Usually the reaction is carried out in a suitable solvent, but when the reaction is not good, the reaction can be carried out without solvent to enhance the reaction. The solvent can be any inert solvent that does not interfere with the reaction, such as toluene, benzene , diglycol ether, dioxane sulphur or the like. 201228666 Another synthetic example, the compound represented by the formula (1) can also be synthesized by performing the respective actions at the galactose C6 (see Fig. 4). -5) Synthesis of C6" modified analogues Beginning with compound C1, as described in B. 2002, No. 4, p. 1267_127. The reduction of azide, followed by the amidation of different commercial aromatic acids, and complete deprotection, resulting in C5 C6 ( Figure 4, Flowchart 4). In addition, in order to avoid the exchanging of the f-protecting group from the compound C1, * synthesize the C6"-Wiki chain two-stage ageing substance, use (Fig. 5). Chlorine or 甲 醯 醯 并 并 并 在 在 在 在 在 ' ' ' ' ' ' ' ' ' 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如 例如Shihuang brewing, y. Nitrile should be substituted with azide to replace the corresponding toluene yellow base or A can provide 08. Staudinger of azide (St-ingeO reduction, amidation of various acids to produce C20-31. Use of the compound of the present invention The compound represented by the formula (1) exhibits the following physiological activities and can be used. It is an anti-cancer immunotherapeutic agent or as an anti-allergic disease. APC activation produces: IL-2 can be detected in A2〇cmd and dirty! 2 cell system, as APC and effector cells, such as Example 2: Like 9 plague tongue: measurable 1TM_γ and IM cell hormone secretion, as tested by 'sacred C57BL/6 mice (16w4d) and the spleen was taken out to the present invention The compound has a Th1 biased cytokine secretion profile (synaptic) and can be used for anti-tumor activity and immunostimulatory effects. The compound can be used as an anti-tumor immunotherapeutic agent, and these compounds can be used alone or combined with chemistry. Therapy or radiation therapy. The compound of the invention of the tumor immunostimulating agent can be administered at any time. The compound is usually formed into a diluted form of the preparation, and the acceptable carrier (liposome, or micelle) is used together. this

S 14 201228666 When applied, it can be administered orally or parenterally to humans or mammals. The use of the compound of the present invention by injection may be carried out in the form of a solution, a suspension, or a suitable solvent (10), intravenously, intramuscularly, subcutaneously or by suction. 2 If necessary, polysorbate may be added. Alcohol vinegar or polyethylene glycol, biliary α yeast as a stabilizer. When the compound is orally administered, it may be in the form of a tablet, a powder, a granule, or a dry syrup in a suitable additive. EXAMPLES The present invention is described in the context of a specific embodiment of the invention. The results of the apparatus 'green and its etc.' are provided below. The title, or subtitle, which is worthy of phonetic, can be used for real money for convenience, but it should not be used to formulate the theory or line of scales. The theory should not be correct and (4) should not be the scope of the invention. The following is a description of the synthesis method of the compound of the present invention and the compound in the synthesis process on the 35th, the target, the diagram. In the flow chart shown here, the following condensation THF is used: tetrahydrofuran DMF: Μ·dimethyl hydrazine Amine MS-4A : Molecular Sieve-4Α (dewatering agent) CH2C12 : Dioxane NMM : Mercapto Fulin HBTU : 〇-benzotris-A/; A/; iVW, - IV, TMSOTf : Sancha Decane trifluorodecane sulfonate Tf20 : dioxetine xanthate CDC13 : dl-gas NMR : NMR HRMS : high resolution mass spectrometer 201228666 ESI : electrospray free other abbreviations have the same as shown in the flow chart above Significance Synthesis Flowchart 1 (Fig. 1) These routes specifically show the preparation of compounds C34, A13, AM, A15, 'A18 'A19, A20 'A21' and can also be synthesized according to this method. ,3S,4R)-2-Azide-D-ribosyl-Eighteen-yard-1 2 4-triol (A1) 5

Dioxane methane (350 mL) was added to a 250 mL aqueous solution of sodium azide (64 3 g, 989 mm 〇1). The biphasic mixture was cooled to 5 in an ice bath. 〇, add trifluoromethanesulfonic anhydride (47 5 mL, 2 phantom, ^ temple temperature below 1 Ό t during 20 minutes. After lion 2 5 in the ice bath, (four), after 7 〇 匕 ^ ^ C 〇 3 The reaction mixture was quenched, the organic phase was separated, and water was extracted with CH2C12 (200). The organic phases were combined to provide a solution of the tris. , must be stored together with the solvent.] Coffee substance proline hydrochloride (high purity plant sphingosine hydrochloride ^J ^ * soil-丨, 3,4-octadecane triol) from the reasonable price phase H , appropriate yeast fermentation broth, · g, 141 丨 、, 碳酸 7 7. g g '211.9mmol) and 醇 (1 〇 L) to copper sulphate (〇 (15GmL). Cool in a salt ice bath Suspension 』 add 欢 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 550 The mixture was stirred at room temperature; 2 L) was overwhelmed with water (500 mL x 2). By with toluene (1 5 (2S3S4R^-?i?^ C7〇'8° 〇C) 200-250mmH^^ ' ') and nitrogen-D-ribosyl-octadecane-1,3,4-three The alcohol (Al) 201228666 ' (47.0g, 137111111〇1'97%) is a white solid. Teacher: 8700111-^]^ (CD3OD, 400 MHz) (5 3.85 (dd ' 11.6, 3.3 Hz, 1H) ' 3.69 (dd, 11.6, 7.9 Hz ' 1H), 3.50-3.55 (m, 1H), 3.43 3.47 (m, 2H), 1.22-1.60 (m, 26H), 0.83 (t, "/=6.4 Hz, 3H). 3C-NMR (CD3OD ' 100 MHz) 3 74.6, 71.5, 65.3, 61.2, 32.5, 31.7 ' 29.4, 29.4, 29.1, 25.4 ' 22.4, 13.1. HRMS (ESI) calculated for Ci8H37N303Na [M+Na]+: 366.2733, found: 366.2729. (2S,3S,4R)-2-Azide-3,4 Synthesis of 2-di-fluorenyl-benzoyl-d-ribosyl-octadecyl-1,3,4-triol (A4) N3 OBn h〇^VS4h29 OBn (2S,3 S,4R)-2- Azide-D-ribosyl-octadecane-1,3,4-triol mixture (47.0 g, 137 mmol) in benzene (1.0 L) was added to triethylamine (46 mL ' 332 mmol) And gasified triphenylsulfonyl group (42.0 g, 151 mmol). After 6 hours of 50-55 C was added, triethylamine (4.6 mL, 33 mmol) and triphenylsulfonium chloride (4.20 g ' 15.1 mmol) were added. Then, another 15 hours of mixing. Add water (1.0 L) and stir the mixture for 3 minutes. Wash the organic phase with water (1. 〇l, 500 mL) and concentrate to provide crude (2S, 3S, 4 R)-2-Azide-1-trityl ribosyl-octadeca-1,3,4-triol (A2) The analytical sample for NMR was purified by column chromatography. iH-NMR (CDC13, 400 MHz) (5 7.22-7.47 (m ' 15H), 3.62 (dd, "7=3.7,10.1 Hz, 2H), 3.53 (m'2H), 3.40 (dd, "/=6 , 10.1 Hz, lH), 2.35 (brs, 1H), 1.83 (brs, 1H) ' 1.20-1.52 (m, 26H), 0.87 (t, 6.8 Hz, 3H) °13C-NMR (CDC13 > 100 MHz) ^ 143.35 > 128.54^128.01 > 127.27,87.78,74.19,72.18 '63.48,62.3b 31.90,31.74, 29.67,29.64,29.60,29.55,29.34,25.59,22.67,14.10. Add three parts of sodium hydride (60% in mineral oil, during i〇 minutes)

21.9 g ' 548 mmol) to coarse (2S, 3S, 4R)-2- stacked gas-1_three awk base _D_ribosyl-octadecyl-1,3,4-triol (A2) A solution of toluene (750 mL) and DMF (75 mL). After stirring the mixture for 30 minutes, gas benzene (5 〇 5 17 201228666 mL '0.438 mmol) was added to the reaction mixture. The mixture was warmed to 50-60 ° C and stirred for 18 hours. The mixture was then cooled to 〇 °c and water (50 mL) was added dropwise. The organic phase was washed with saturated gas (500 mL >< 2) and water (500 mL >< 2). The organic phase was filtered through a pad of Celite pad and concentrated to give crude (2S,3S,4R)-2-azido-2,3-di-benzoyl-1-trityl-D. - Ribosyl-octadecyl-1,3,4-triol (A3). Add aqueous HC1 (33% '6.0 mL) to a solution of A3 in benzene/methanol (600 mL, 18). The mixture was warmed to 50-60 ° C and stirred for 20 hours. The reaction mixture was quenched with 1.0 N NaOH (55 mL). The residue was separated by toluene (5 〇〇 mL) and water (500 mL). The organic phase was concentrated, and the residue was purified by column chromatography (yield: 100 g, EtOAc 500 g, ethyl acetate / «-hexane = 1/1 〇) to afford (2S, 3S, 4R) Gas-2,3-di-benzyl-D-ribosyl-octadecyl-1,3,4-triol (A4) (27.5 g '52.5 mmo b 38%, after four steps) butter. 1H-NMR (CDC13 '200 MHz) <57.26-7.39 (m, 10H), 4.69 (d, "/= 1.4 Hz ' 2H), 4.59 (d, /=4.3 Hz, 2H), 3.59-3.94 (m '5H) '1.26-1.61 (m, 26H) '0.88 (t, / = 6.4 Hz, 3H). l3C-NMR (CDC13 ' 50MHz) (Π37.9,137.6,128.5,128.4, 128.1 '127.97 ' 127.81,127.10,80.38,78.96 ' 73.59 ' 72.49, 63.03,62.20,21.90,30.16,29.66,29.35,25.43,22.67 , 14.11. C.sub.32. 1-thiol-£)-galactoside-pyranose (A5)

Ph~V

OBn Compound A5 can be prepared according to the method described in Plettenburg, 0 et al J. c/zew. 2002, β ' 4559-4564. Data for compound A5: h-NMR (CDC13, 400 MHz) <5 7.58 (d' 8.1 Hz, 1H), 7_50 (m, 2H), 7.23-7.42 (m, 15H), 201228666 • d, 9.5 Hz' 1H), 4 35 (dd.i23, i5Hz 3.82 (Α93Ηζ' 1H), 3 6 hearts 3.39 and S' m), 2.28 (s, 3H). M 3.4 Hz, 1H)' i ^ nitrogen-3,4-mono-benzyl 3-i-〇 曱 - D-;,«〇+tl

N3 OBn _l,j,4 monodecyl alcohol (A6) OBn s fff bath 'Add San Dun yoghurt liver (17mL, 100mmo1) 5 ll3mm 〇l) (75 mL)

Ss-Tf. After mixing the reaction mixture for 30 minutes, a solution of 222.-gas was obtained, and it was stored in an ice bath for 3 small hands. This δ compound A4 (27.3 g, 52.2 mmol), A5 (347 g '62 6 ΓτΪ=Α f^(33 g)' and dried in vacuum for 1 hour, and added CH Π S 〇Me2S2~Tf2〇< ^ Μ ^. After half a 2 minutes, the mixture was diluted with triethylamine (22 dynamite) and the mixture was washed with dioxane (50 mL). Acacia (500 mL) and water (mL) were separated. Concentration was determined by column chromatography (crude weight = 153 g, 6 〇〇 g guar, vinegar π hexane = 1:15 to 1:12 to 1:〗 〇) Purification of the residue to provide 2__ is ^ j曰 di-Ο-benzyl-1-anthracene-(2,3«_benzyl_4,6-oxime-stupyl) lactose "Glycosides"-D-ribosyl-octadecane-3,4-triol (A6)- 19 201228666 g, 33.60 mmol, 64%) of white worms. mp: 59 ° C. iH- NMR (CDC13, 400MHz) 37.22-7.50 (m, 25H), 5.44 (s, 1H), 4.96 (d, "7=3.4 Hz, 1H), 4.85 (d, 11.9 Hz, 1H), 4.79 (d, /= 12.3 Hz, 1H), 4.73 (d, </= 12·3 Hz, 1H) ' 4.664.69 (m, 2H) ' 4.59 (d, *7 = 8.5 Hz, 1H), 4.56 (d, 12.8 Hz, 1H), 4.48 (d, J=ll_5Hz, 1H) 4.15 (d, J = 2.8 Hz, 1H), 4.06-4.12 (m, 1H), 3.98-4.04 (m, 3H), 3.86 (dd, */= 12.5, 1.5 Hz, 1H), 3.68-3.73 (m , 3H), 3.60 - 3.62 (m, 1H), 3.55 (s, 1H), 1.25-1.55 (m, 26H), 0.87 (t, J = 7.1 Hz, 3H). l3C-NMR (CDC13, 100 MHz) (5 138.75, 138.36, 138.01, 137.82, 128.85, 128.37, 128.34, 128.26, 128.22, 128.09, 127.90, 127.79, 127.75, 127.70, 127.66, 127.6, 127.50, 127.45, 126.33 '101.05, 99.13, 79.4, 78.95, 76.68, 75.80,75.44 ' 74.66 ' 73.77 ' 73.49,72.06,72.03,69.31,68.43,62.97,6U0, 31.91 ' 30.01,29.75 ' 29.69,29.67,29.65,29.63,29.60,29.35, 25.44,22.68,14.10. [啦+63.1 ( c 1.0, CHC13 ). HRMS (ESI) calcd for C59H75N308Na [M+Na]+: 976.5452, Found: 97.548. Synthesis of 3,4-diphenylfluorenyl-b (^^-~benzoyl-^-~phenylidene-CX-D-galactofuranoside)_2_(丨丨_(4_(4_fluorobenzene) Oxy)phenyl)undecyl)amino-D-ribosyl-eighteen from 丨,3,4_triol (A8)

OBn—The compound Α7 (32·〇7 g, 33 61 〇1) Li (34 〇) bath is widely cooled in an ice bath, and two parts of hydrogenated brain (i 9iQ g, 5〇% combined) Mix to room temperature, *70 minutes. Cool the mixture C' first with water (1.9mL), 1.0N NaOH (3.8mL) and water (1.9

S 20 201228666 mL ) Anxiously The mixture was filtered through a pad of limestone and washed with di-methane (丨〇〇 mL). The filtrate was concentrated and separated with di-methane (35 mL) and water (35 mL). Add 11-(4-(4-fluorophenoxy)phenyl))undecanoic acid (B4) (1127 g, 3 〇 26 mmol) to the separated organic phase, followed by _4 (9 2 mL, 84 mm 〇1) and HBTU (19.12 g, 50.41 mmol). After stirring at room temperature for 12 hours, the mixture was filtered and washed with 50 mL CH.sub.2Cl. The combined filtrate was washed with saturated ammonium sulfate (400 mL) and water (400 mL). The organic phase was concentrated and purified by column chromatography (crude weight = 46 g, 350 g silica gel, ethyl acetate hexane = ye to 1/5 to 1/4) to afford A8 (36.06 g, 28.11 mmol, 84 %) ) rice white wax. 1H-NMR (CDC13, 400MHz) grab 86-7.51 (m, 33H), 5·84 (d ' J=8,0Hz ' 1H) ' 5.44 (s ' 1H), 4.94 (d, J=3.5Hz, 1H ) 4.83 (d, J=11.6Hz, 1H), 4.69~4.74 (m, 3H), 4.63 (d, J=11.6Hz' 1H), 4.57 (d, J=11.6Hz, 1H), 4.50 (d , J=3.9Hz, 1H) ' 4.47 (d, J=3.9Hz, 1H), 4.244.31 (m,1H), 4.16 (d, J=3.1Hz ' 1H) 4.03-4.12 (m,3H), 3.92 (dd, *7=10.3, 3.6Hz, 2H) ' 3.73-3.79 (m,2H), 3.56 (s ' 1H), 3.51-3.53 (m,1H) ' 2.55 (t ' J=7.6Hz ' 2H ) '1.87-1.91 (m, 2H), U9-1.69 (m, 42H), 0.87 (t ' J = 6.6 Hz, 3H). nC-NMR (CDC13, 100MHz) 3172.89,159.76,157.36,155.36,153.36,153.33,138.63,138.52,138.50,138.38,137.81,137.79,129.53,128.84,128.64 '128.42 '128.35,128.31,128.29,128.08,127.88, 127.80 ' 127.69,127.59,127.57,127.55,126.29,120.08, 120.00,118.31 ' 116.24,116.01,100.99,99.59,79.81,79.48,76.68,76.14 ' 75.68,74.33,73.81,73.28,71.88,71.69,69.39,68.13, 62.91, 60.36, 50.32, 36.69, 35.17, 31.90, 31.61, 30.24, 29.78, 29.69 ' 29.67 ' 29.65, 29.59, 29.56, 29.51, 29.42, 29.35, 29.29, 25.8, 25.68, 22.66, 14.17, 14.10. HRMS (ESI) calcd for C82H1 (), 5FN (1) (M+H)+: 1282.7723, found: 1282.7731. Synthesis of 1-0-0-D-galactofuranoside)_2-(l 1-(4-(4-fluorophenoxy)benzene 21 201228666 sterol (C34) group) eleven fluorenyl)amino-D -ribosyl-octadecane-1,3,4-three

Add OH (1.8 g) to a solution of A8 (36.06 g, 2R η , dioxane/nonanol (200 mL, dioxane/sterol = 1/1) under warm hydrogen (5 bar) The mixture was stirred for 10 hours. The mixture was passed through a mixture of sulphuric acid and sulphuric acid/methanol (10) mL of dichloromethane (%). The combined mash was concentrated and purified by column chromatography (3). 〇〇g chopped, dioxin / decyl alcohol = 15/1 to 10/1) to provide crude C34 (17.46 g, 20 ^ mmol 'HPLC purity = 95.72 area%) of white solid, yield Add ethanol (87.5 mL) to crude C34 and warm to 50 ° C, then add propylene (87.5 mL). Cool the solution to room temperature over a period of 3 hours, then cool in an ice bath. Filter the precipitate. Wash with acetone (200 mL) to give c/4 (16.02 g ' 19.21 mmol ' 68% ' purity by HPLC = 97.15 area %)

White solid with a recovery of 92%. Mp : 163. (:. h-NMR (CDC13/CD30D = 1 A, 400 MHz) < 57.26 (d, J = 8.5 Hz, 2H), 7.07-7.17 (m, 4H), 7.00 (dd, > 6.6, 2.0 Hz, 2H), 5.03 (d, */=3.7Hz, 1H), 4.33 (q ' ·7=4.7Ηζ, 1H), 4.05 (d, /=2·7Ηζ, 1H) ' 4.01 (dd,*7=4.6 , 10.8 Hz, 1H), 3.79-3.97 (m, 6H), 3.64-3.72 (m > 2H) > 2.71 (fy=7.4Hz > 2H) » 2.34 (f 7=7.5Hz > 2H) ' 1.29-1.43 (m, 42H), 1.01 (t, J = 6.6 Hz, 3H). 13C-NMR (CDC13/CD30D = 1A, 100 MHz) J173.99, 154.82, 152.97, 137.34 '128.95,119.39,119.31,117.71 , 115.52, 115.29, 99.21, 73.92 ' 71.28, 70.41, 69.69, 69.17, 68.37, 66.63, 61.12, 49.92, 35.74, 34.50, 31.66, 31.27, 31.02, 29.10, 29.06, 28.99, 28.95, 28.88, 28.85, 28.77, 28.70 , 28.60, 25.28, 25.23, 21.99, 13.10. [αΗ5 +57.0 (c 1.0, CH2C12/CH30H: 1/1). C47H77FN03 [M+H]+ s 22 201228666 HRMS (ESI) calcd: 834 5532, found :834 5595. Synthesis of 3,4-di-indole-stupyl-di-p-I (2,3_di-〇_曱曱基_4,6~〇~ stupid subunit-α-D-half Sugar piperazine. South sugar bitter) 2 - (11-(4-phenoxyphenyl) decamuthylamino-D_ribosyl octadecyl-i,3,4-triol (A9) soil

Compound A6 (1 mg, 〇mmol) and compound B12 (33 mg, 0.093 mmol) were used as starting materials, and compound A9 (45 mg '0.036 mmol, 38%) white was provided as a starting material similar to the procedure for the synthesis of A8. Butterfly: h-NMR (CDC13, 400MHz) <57.48-7.52 (m, 2H), 7 20-7 41 (m, 25H), 7·12 (d '"/=8.8Hz, 2H), 7.06 (t, j = 7 3 Hz, 1H), 6.96-7.00 (m, 2H), 6.92 (d, J = 10.4 Hz, 2H), 5.83 (d, 1H) '5.45 (s ' 1H), 4.94 (d, J=3.6 ' 1H), 4.84 (d, J=U 6Hz, 1H), 4.694.75 (m, 3H), 4.63 (d, J=11.6Hz, iH), 4 57 (d, •7=11.6Hz) ' 1H) '4.49 (d, J=11.6Hz ' 1H) '4.48((16Hz, 1H), 4.24-4.31 (m,1H), 4.17 (d,·7=3.2Ηζ,iH) 4 034 12 (m ,3H) ' 3.87-3.96 (m,3H) ' 3.74-3.80 (m,2H),356 (s,1H),3.50-3.56(m,1H) ,2.57(t 'J=7.6Hz,2H), i 82-1 95 (m, 2H), 1.15 - 1.65 (m, 42H) ' 0.88 (t ' J=6 6Hz, 3H). , 3C-NMR (CDC13 ΊΟΟΜΗζ) S 172.89 459.69 Ί54.86 Ί38 62 > 138.51, 138.50, 138.38, 137.89, 137.79 ' 129.60, 129 49, 128.83, 128.41, 128.34, 128.31, 12 8.29,128.07,127 87, 127.82,127.80,127.68,127.57,127.55,126.29,122 79,118.92,118.4,100.98,99.60,79.82,79.48,76 l4,75 68,74.33,73.80,73.27,71.88,71.69, 69.38,68.14, set 9 Bu 50 32, 36.70 >35,21 >31.90 01.61 »30.24 >29.78 >29.69 >29.67 >29 65 > 29.59,29·56,29·5 Bu 29.4 Bu 29 · 34, 29.29, 25.8 〇, 25.68, 22 66, 23 201228666 14.10. (: into (10) milk thistle. [M+H] + HRMS (ESI) calculated value: 1264.7817, found: 1264.7834. Synthesis 3,4-di-0- clinchyl-l-〇-(2,3-two Benzoyl-4,6-fluorene-phenylene-α-D-galactofuranoside-2-(11-(4-isopropoxyphenyl)undecyl)amino-D- Ribosyl-octadecyl-1,3,4-triol (A10)

OBn was prepared in a similar manner to the procedure for the synthesis of A8, compound A6 (100 mg, 〇mmol) and B13 (30 mg, 0.094 mmole) to provide A10 (72.0 mg '0.059 mmol '63%) of white wax. . 1H-NMR (CDC13, 400MHz) (57.21-7.55 (m, 25H), 7.06 (d, J=8.4Hz, 2H) ' 7.78-7.84 (m ' 2H) ' 5.86 (d, J=8.4Hz, 1H) , 5.46 (;s, 1H) '4.95 (d, J=3.2 '1H) '4.85 (d, /=11.6Hz, 1H), 4.7i__48〇(m,3H), 4.63 (d, "7=11.61^ ,1H),4.58 (d,J=li.6Hz, 1H) '4.46-4.54 (m,3H) '4.18 (d,J=3.2Hz,1H),4.〇5_4.14 (m,3H), 3.88—3.97 (m, 3H), 3.75—3·82 (m, 2H), 3 58 (s, 1H), 3.51-3.57 (m, 1H), 2.53 (t '7=7.61^ '2H), 1.83 —1.96 (m, 2H) ' 1.15-1.71 (m, 48H), 0.89 (t, J = 6.6 Hz, 3H). 13C-NMR (CDC13 ΊΟΟΜΗζ) (5172.84 Ί 39.68 > 138.60 Ί 38.49 > 138.46 , 138.36, 137.77, 128.8, 128.39, 128.32, 128.28, 128.26, 128.05, 127.86, 127.79, 127.78, 127.66, 127.54, 126.26, 124.00, 116.89, 116.72, 100.96, 99.54, 79.75, 79.46, 76.10, 75.66, 74.29 , 73.79, 73.25, 71·84, 71.65, 69.35, 68.〇8, 62.88, 50.28, 36.66, 35.04, 31.87, 31.20, 30.19, 29.75, 29.64, 29.50, 29.48, 29.38, 29.37, 29.31, 29.04 25.87,25 stone 4, 22.64,14.07. HRMS (ESI) calculated for C79H1G8N01G[M+H]+: 1230.7973, found: 1230.7968. 24 201228666 Synthesis of 3,4-di-indole-benzyl-di- 2,3_di-〇- μ & thiol-D_ribosyl octadecyl 1,3,4-diol (ah)

Compound A7 (1 〇〇 mg, 〇1〇5 mmol) and B14 (28 mg, 0.093 mmole) were used as starting materials to provide All (63 mg > 0.052 mmol » 56%) in a procedure similar to the procedure for the synthesis of A8. 〇mp : 98°〇〇lH-NMR (CDC13 > 400MHz) (57.21-7.54 (m »25H) >6.92-7.06(m >2H) ^.81-6.87 (m ' 1H) ' 5.87 (d ' JUHz ' 1H) ' 5.45 (s ' 1H), 4.95 (d, /=3.2,1H), 4.84 (d ' /=11 ·6Ηζ ' 1H), 4.69-4.79 (m,3H), 4.63 (d, J=11.6Hz,1H) ' 4.58 (d,·/=11.6Ηζ,1H) ' 4.50 (d, /=11.613⁄4 ' 1H) ' 4.49 (d ' J=11.6Hz,1H), 4.25-4.33 (m , 1H), 4.17 (d, J=2.8Hz ' 1H) 4.04H3 (m, 2H), 3.88-3.97 (m, 3H) '3.74-3.81 (m, 2H) '3.57 (s, 1H), 3.51- 3.56 (m, 1H), 2.54 (t, J = 7.6 Hz, 2H), 1.82-1.96 (m, 2H), 1.15-1.69 (m 42H) O.89 (t ^ = 6.8 Hz θ Η) °13C-NMR (CDC13 ΊΟΟΜΗζ) 5172.84,150.02 (dd,·7=245,13 Hz), 148.55 (dd, J=244, 13 Hz), 139.68, 138.60, 138.49, 138.46, 138.36, 137.77, 128.81, 128.39, 128.32, 128.28, 128.26 , 128.05, 127.86, 127.79 , 127.78, 127.66, 127.54, 126.26, 124.00, 116.89, 116.72, 100.96, 99.54, 79.75, 79.46, 76. (H, 75.66, 74.29, 73.79, 73.25, 71.84, 71.65, 69.35, 68.08, 62.88, 50.28, 36.66, 35.04, 31.87, 31.20, 30.19, 29.75, 29.67, 29.64, 29.50, 29.48, 29.38, 29.37, 29.31, 29.04, 25.78, 25.64, 22.64, 14.07. HRMS (ESI) calcd for C.sub.3, s. 25 201228666 Synthesis of 3,4-di-indole-benzoinyl-κ-(2,3-di-indole-stupyl-methyl-4,6-indenyl-α-D-galactose-paraffin)— 2-(h_(2,4-difluoro))+

Compound A6 (1 mg, 〇1 (5 mmol) and Β15 (28 mg, 〇.〇 93 mmole) were used as starting materials to provide A12 (70 mg, 0.058 mmol). , 62%) of white wax. Η—(CDC13 ' 400MHz) (57.20-7.55 (m,25H), 7.04-7.14 (m, 1H) ' 6.69-6.81 (m ' 2H), 5.89 (d, J=8.3Hz, 1H), 5.45 (s , 1H) 4.95(d »/=3.2Hz ΊΗ) >4.85(d >J=11.6Hz ΊΗ) 4.70-4.79 (m ' 3H), 4.64 (d, J=11.6Hz, 1H), 4.58 (d , J=u.6Hz, 1H) ' 4.50 (d,^/=11.6Hz ' 1H) ' 4.49 (d ' J=11.6Hz,1H), 4.25-4.33 (m ' 1H), 4.17 (d,J= 2.8 Hz, 1H) 4.04~4.13 (m, 2H), 3.88-3.97 (m '3H), 3.74-3.80 (m, 2H), 3.57 (s, 1H), 3.51-3.56 (m ' 1H), 2.57 ( t, J = 7.6 Hz, 2H), 1.82-1.96 (m, 2H), 1.15-1.69 (m '42H), 〇·88 (t, J = 6.6 Hz, 3H) °13C-NMR (CDC13, 100MHz) 3172.90,162.30,138.59,138.50,138.45,138.36,137.78,130.89,128.82 '128.40,128.33,128.30,128,27,128.06 '127.87 ' 127.79,127.68,127.55,126.27,110.07,103.41,99.53,79.75,79.47, 76.11,75.67,74.29, 73.81,73.27,71,85,71·65,69.36,68.05,62.89,50.29,36_67, 31.88,30.19,30.15 '29.76,29·67,29.65,29·51,29.37 29.32, 29.17,28·38 '25.78 '25.66 '22.65,14.08 °C76H1()〇F2N09[M+H]+ HRMS (ESI) calculated value·· 1208.7366, found: 1208.7377. Synthesis 1 -(9-(aD - galactose-glycosyl)-2-(11-(4-phenoxyphenyl)undecyl)amino-D-ribosyl-1,3,4-octadecanol (A15 )

S 26 201228666

A white solid of 15 (2111^'0.026111111〇72%) was obtained from A9 (45 mg, 0.036 mmol) in a procedure similar to the procedure for the synthesis of C34. 111{): 131. (::. 'H-NMR (CD30D/CDC13=1/1 > 400MHz) <57 45 ft » J=8 3Hz » (d '"/=8.1Hz, 2H) '7.04(d, J=8.1 Hz, 2H), 5.04 (d, /=3.3Ηζ, 1H), 4.26 (q, /=7·1Ηζ, 1H) ' 3.79-4.13 (m,10H), 2.73 (t, «/=7·7Ηζ ' 2H) ' 2.36 (t ' /= 7.5 Hz, 2H), 1.65-1.82 (m, 4H), 1.41 ( brs, 38H ) ' 0.89 ( t, J = 7.5 Hz, 3H ). 13C-NMR (CD3OD/CDCl3 =l/l ' 100MHz) 3174.09,157.18,154.36, 137.40 '128.98 '128.92 '122.22 '118.25 '117.71 '99.18,73.88 ' 71.30,70.41 '69.68 '69.17,68.37,66.63,61.10,60.01,35.80, 34.56 '31.61 '31.29 '31.04,29.08,29·02,28.91,28.80,28.72, 28.64,25.30 ' 22.01 ' 19.90 ' 13.15. [啦+37.4 ( cl.O, CH2C12/CH30H : 1/1). C47H78N01()[] HRMS (ESI) calculated for V[+H]+: 816.5626, found: 816.5637. Synthesis 1-(9-(〇1-0-galactose), 2-(11-(4_isopropyl) Oxy)phenyl)undecyl)amino-D-ribosyl-I,3,4-octadecane triol (A10

Compound A16 (34 mg, 〇·〇 44 mmo, 74%) was obtained from A10 (72 mg, 0.059 mmol) in a procedure similar to the procedure for the synthesis of C34. Data for A16: mp: 120°C 0 ]H-NMR (CD30D/CDC13=1/1 5 400MHz) ^7.16 (d 'J=8.5Hz, 2H), 6.90 (d, /=8_5Hz, 2H), 5 .〇l(d, J=3.7Hz, 27 201228666 1H), 4.58-4.66 (m,1H), 4.32 (m,1H),4·03 (d,J=2.6Hz, 1H), 3.99(dd ' /=10.6 '4.8,1H),3.88-3.96(m,2H),3.78-3.88 (m ' 4H) ' 3.62-3.73 (m,2H), 2.64 (t,J=7.6Hz,2H), 2.32 ( t,·7=7·4Ηζ, 2H), 1.61-1.81 (m, 4H), 1.32-1.52 (m, 44H), 0.99 (t, J=6.8Hz ' 3H ). 13C-NMR (CD30D/CDC13=1A, 100MHz) <5174.06,155.10 '134.52,128.54,115.33,99.16,73.81 '71.25 '70.40 '69.65 '69.62 '69.12,68.33,66.60,61.04, 35.75 '35.70,34.35, 31.53, 31·25, 31.08, 29.09, 29.03, 28.97, 28.94, 28.87, 28.85, 28.76 '28.68, 28.59, 25.27, 25.22, 21.96, 21.08, 20.88, 13.08. [啦+36.2 (cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) calcd for C44H79N01 (m.). Synthesis of 1-0-(aD-galactose. Desodium gluconate)-2-(11-(3,4-dioxabenzene)undecyl)amino-indole-ribosyl-1,3,4- Octadecane triol (eight 17)

Compound A17 (37 mg, 0.049 mmo 94%) was obtained from All (63 mg, 0.052 mmol) in a procedure similar to the procedure for the synthesis of C34. Data for A18: mp: 140 ° C 〇1H-NMR (CD3OD/CDC13 = 1/1 400 MHz) (57.06-7.22 (m, 2H) ' 6.98-7.04 (m, 1H), 5.03 (d, J = 3.3 Hz , 1H), 4.29-4.36 (m, 1H), 4.05 (d, J = 2.5 Hz, 1H), 4.00 (dd, "/=10.5, 4.8, 1H) ' 3.89 - 3.96 (m ' 2H), 3.78 - 3.89 (m ' 4H), 3.64 - 3.73 (m, 2H), 2.69 (t, J = 7.5 Hz, 2H), 2.34 (t, J = 7.6 Hz, 2H) ' 1.63-1.83 (m, 4H) ' 1.33 -1.48 (m, 38H), 1.00 (t, J = 6.5 Hz ' 3H). 13C-NMR (CD30D/CDC13 = 1/1, 100 MHz) < 5174. 07, 149.33 (d, J = 247, 13 Hz) , 147.95 (d, J=244, 13Hz), 139.47, 123.56, 116.22, 116.06, 99.18, 73.86, 71.82, 70.40, 69.67, s 28 201228666 69.15,68.34,66.63 '61.08,45·00,35.78,35.73,34.40 , 31.58, 31.28, 30.66, 29.12 '29.06, 29.00 '28.91, 28.85, 28.77, 28.71, 28.44 ' 25.28, 21.99, 13.12. [啦+44.4 (cl.O, CH2C12/CH30H: 1/1). C41H72F2N09[M HRMS (ESI) calculated for +H]+: 760.5175, found: 760.5222. Synthesis of 1-(9-(α-D-galactose π guaranose) 2 - (n_(2,4 - 2) ) ) -D- ribose amino-1,3,4-triol burn eighteen (A18)

OH Compound A18 (39 mg, 0.051 mmo, 88%) was obtained from compound A12 (70 mg, 0 to 58 mmol) in a procedure similar to the procedure for the synthesis of C34. Data for A18: mp: 149 °C. iH-NMR (CD30D/CDC13 = 1/1, 400 MHz) 37.29 (q, >8·1Ηζ, 1H), 6.87-6.97 (m, 2H), 5.05 (d, J = 3.7 Hz, 1H) '4.30- 4.38 (m,1H) '4.07 (d, J=2.9Hz, 1H), 4.03 (dd, «/=10.6,4·4Ηζ ' 1H), 3.91-3.98 (m, 2H), 3.66-3.75 (m, 4H), 3.64-3.73 (m, 2H), 2.73 (t, J = 7.5 Hz, 2H), 2.36 (t, J = 7.6 Hz ' 2H), 1.65-1.86 (m, 4H), 1.24-1.60 (m , 38H), 1.02 (t ^ = 6.6 Hz > 3H) 〇13C-NMR (CD3〇D/CDC13=1/1 ΊΟΟΜΗζ) 5174.09,161.65,159.20,130.48,124.73,110.06,102.62, 99.19,73·90 , 71.31, 70·40, 69·69, 69.17, 68·36, 66.66, 61.11, 50.12, 35.81 '35.76 '31.63, 31·30, 29·59, 29.16, 29.14, 29.09, 29.02, 28.92, 28.87, 28.78 , 28.76, 28.73, 28.56, 27.72, 25.30, 22.01, 13.16. [啦+46.0 (cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) calcd for C^^^^^^^^^^^^^^^^^^^^^^^^ Synthesis of 1-0-(α-D-galactofuranoside)-2_((i〇和,1^-11-(3,4-一气本)-1〇,11-·一十一酿基) Amino-D-ribosyl-1,3,4-octadecyl three 29 201228666 diol and l-0-(aD-galactosepipelanose)—ία·,〗 〖and _ ^—(3 , 4-difluorobenzene)-10,11-dihydroxyundecyl)amino-D-ribose-based H4-octadecane triol (A19) mixture of trans-diol isomers

OH

FF OH was added anti-B21 (32 mg '0.097 mmol), HBTU (62 mg, 0.16 mmol) and NMM (24 pL, 0.23 mmol) to A7 (101 mg, 0.109 mmol) in dioxane (3 mL) in. After stirring at room temperature for 12 hours, the mixture was concentrated and purified by column chromatography (ethyl acetate / hexanes = 1/4 to 1/2 to 1 / 1). Dissolved in dioxane/methanol (m '10 mL)' followed by the addition of pd(〇H)2 (i〇mg). After stirring for 15 hours at room temperature under hydrogen, the mixture was filtered through a pad of calcite and The second gas was washed with decyl alcohol (1A), and the filtrate was concentrated and purified by column chromatography (di- hexane / methanol = 10/1 then 8/1) to afford A19 (34 mg, 0.043) Mp '44%) of white solid.mp: 1〇5.ih_NMr (CDCl3/CD3〇D=l/l,400MHz) (57.17-7.40 (m,3H),5.01 (d,·7=3.6Ηζ ' 1H), 4.62 (d, >4·8Ηζ, 0.75H), 4.50 (d, «/=6.0Hz, 0.25H) ' 4.28-4.36 (m,1H) ' 4.03 (d, J=2.8Hz, 1H ) ' 3.99 (dd ' J=4.8, 10.8 Hz, 1H), 3.87-3.95 (m, 2H), 3.76-3.87 (m ' 4H), 3.61-3.71 (m, 2H), 2.31 (t, </ = 7.4 Hz, 2H) ' 1.31-1.83 (m, 40H), 0.99 (t, J = 6.9 Hz, 3H). 13C-NMR (CDCl3/CD3 〇 D = l/l, 100 MHz) ¢5173.97, 149.42 (dd , J=245, 13Hz), 148. 86 (dd, *7=245, 13Hz), 136.65, 122.46, 116.09, 115.77, 115.27 '115.10,99.16,75.70,75.35,74.74,74.2b 73.94 ' 71.25 ' 70.40,69.65,69.10,68.31,66.52,61.03, 49.91, 35.63 ' 31·94 ' 31.69, 31.23, 31.18, 29.09, 29.04, 29.00, 28.95, 28.83 ' 28.76 ' 28.68, 28.65, 28.53, 25.17, 25.08, 24.96, 21·94, s 30 201228666 13.04. [啦+ 58 3 ( cl 〇, CH 2 Cl 2 /CH 3 〇 H : w ). HRMS (ESI) calculated for C4iH71F2NO "Na[M+Na]+: 814.4893, found: 814.4859. Synthesis of l-0-(aD-galactosepipelanose)-2-((1 〇S, l 1$-11-(3,4-difluorobenzene)-10,11-dihydroxyundecyl) Amino-D-ribosyl-: 1,3,4-octadecane triol, and 1-indole-(aD-galactofuranoside)-2-((1〇足11幻-11-) (3,4-difluorobenzene)_1〇,11-dihydroxyundecyl)amino-D-ribosyl-1,3,4-octadecane triol, (A20) cis-diol Mixture of isomers

OH

FF OH was added cis-A21 (14 mg, 0.042 mmol), HBTU (62 mg, 0.16 mmol) and NMM (24 pL, 0·22 mmol) to A7 (101 mg, 0.109 mmol) of dioxane (3 mL) ) in solution. After stirring at room temperature for 12 hours, the mixture was concentrated and purified by column chromatography (ethyl acetate: hexane = 1/4 to 1/2 to 1/1). The resulting white wax was dissolved in dioxane/methanol U/Bu 10 mL) by adding Pd(0H)2 (1 〇mg). After stirring at room temperature under hydrogen for 15 hours, the mixture was filtered through a pad of sepite and washed with dichlorohydrin/methanol (1/1). The filtrate was concentrated and purified by column chromatography (di-hexanes / EtOAc = 10/1 then 8/1) to afford A2 〇 (2 〇mg, 〇〇25 mmol '60%) as a white solid . Mp : 8〇 Charge. (CDC13/CD30D=1/1 '400MHz) <57.19-7.49 (m,3H) ' 5.02 (d ' J=3.6Hz ' 1H), 4·52 (d ' J=6Hz, 1Η), 4.30-4.37 (m, 1H) ' 4.04 (d, "7=2·8Ηζ,1H), 4.01 (dd, J=4.4, 10.8Hz, 1H), 3.89-3.96 (m,2H) ' 3.78-3.88 (m,4H ), 3.63-3.73 (m, 3H), 2.33 (^ J = 7.6 Hz '2H)' 1.26-1.84 (m, 40H), 1.01 (t, J = 6.8 Hz, 3H) ° 3C-NMR (CDC13/CD30D =1/1 > 100MHz)^174.00 > 149.58 31 201228666 (dd ' /=245 ' 12Hz),149,07 (dd,J=245,12Hz),138.90, 122.46,116.13 ' 115.14 ' 99.21,75.47, 74.79,74.01,71.28, 70.41 '69.69,69.15 '68.34,66.57,61.09,49.90,35.67,31.98,31.77,31.27,29.12,29.03 ' 28.98,28.80,28.68,28.56,25.20, 25.00,21.98,13.08. [啦+5〇.〇 (ci.〇, CH2ci2/CH3OH: 1/1). HRMS (ESI) calcd for C41H71F2NO "Na[M+Na]+: 814.4893, found: 814.4893. Synthesis of l-0-(aD-galactofuranoside)_2-(11-(4-bromo)-i〇, 11-dihydroxyundecyl)amino-D-ribosyl-1,3, 4-octadecane triol (Α21)

Compound A21 (18 mg, 0.024 mmol '28%) was obtained from Α7 (90 mg, 0.094 mmol) and B19 (32 mg, 0.086 mmol). A21 data: rice white wax. NMR (CD30D/CDC13=1/1,400MHz) (57.26-7.51 (m, 5H), 5.02-5.10 (m, 1H), 5.02 (d, J=4.0Hz, 1H) ' 4.23-4.29 (m, 1H) ), 4.06-4.15 ( m ' 1H) ' 3.97-4.03 ( m,2H),3.83-3.96 ( m,6H), 3.68(t,J=10.2Hz,1H),2.84-2.89(m,1H), 2.52 (t, J = 7.4 Hz, 2H), 1.27-1.89 (m, 40H), 1.02 (t, J = 6.8 Hz, 3H). 13C-NMR (CD30D/CDC13 = 1 / 150 MHz) <5174.08, 173.54, 138.50, 128.72, 127.55, 125.39, 99.10, 72.40, 71.92, 70.84, 70.16, 69.92, 69.57, 69.24, 68.23, 63.43, 61.13, 52.30, 43.34, 36.69, 36.39, 35.91, 35.69, 35.26, 33.69, 32.83, 32.03, 31.67, 31.25, 30.90, 30.59, 29.8 Bu 29.30, 29. (H, 28.97, 28.86, 28.77, 28.67, 28.54 > 28.46 > 25.22 > 25.00 > 24.36 > 24.27 > 21.97 Ί 3.09 〇 [°]^+22.7 (dO,CH2C12/CH30H: 1/1). HRMS (ESI) calculated for CnH^NOuDVI+Hf: 778.508 found: 778.5073. 32 201228666 Flowchart 2: Synthesis of compound A23-25 Lactose-p-glucoside) - 2__Amino-Imitated-1,3,4-octadecanetriol (A22) 9h.〇h

Nh2 oh OH 29 Add Pd(OH)2 (220 mg) and three drops of acetic acid to a solution of A7 (52〇 〇 % mmoi) in dichlorohydrazine/decyl alcohol (1/1, 20 mL). The reaction mixture was stirred for 16 hours under a mixture of hexanes and s. Via seconds^, still

The mixture was washed with decyl alcohol. The filtrate was concentrated and dried <RTI ID=0.0> HRMS (ESI) juice of C24H49N〇8H: 480.3536 ‘ found: 480 3515. Synthesis of l-〇-(aD-galactofuranoside)-2-(丨i-p〆-dioxabenzene) eleventhyl)amino-D-ribosyl-1,3,4-octadecane Triol (A23)

〇v^Y^c14h29 OH Add B16 (34mg, 0.1〇mm〇i), HBTU (59mg, 〇16mm〇l) and NMM (23 pL '0.21 mmol) to A22 (50 mg, 0.10 mmol)

= Dioxane / sterol (1/1, 3 mL) solution. The reaction mixture was stirred at room temperature for 12 hours. The mixture was concentrated and purified by column chromatography (dichloromethane / decyl alcohol = 15/1 to 12/1 to 9/1) to afford A23 (16 mg, 0.020 mmo1, 20%) white solid. Mp : 147X. -NMR (CD3〇D/CDCl3=l/l, 400MHz)^7.5l(s,ih),7.35(s,2H), 5.08 (d,7=3.33⁄4,1H),4·33~4.43 (m ,1H),4.08-4.12 (m, 1H) ' 4.06 (dd ' /=10.7 ' 4·0Ηζ,1H),3.824.02 (m,6H), 3.67-3.77 (m,2H),2.86 (t, , 2H), 2.39 (t, J=7_5Hz, 33 201228666 2H), 1.66-1.88 (m ' 4H) ' 1.34-1.60 (m, 38H) ' 1.06 (t, J=6.4Hz, 3H).丨3C-NMR (CD3〇D/CDCl3=l/l, 100 MHz) &lt;5174.05, 138.47 ' 133.89, 131.36, 130.64, 128.41, 126.35, 99.25, 73.99, 71.36 ' 70.42, 69.74, 69.22, 68.42, 66.7 b 61.19 , 49.97, 35.82, 32.41, 31.76, 31.34, 29.20, 29.17, 29.12, 29.06, 28.95, 28.91, 28.81 ' 28.76, 28.69, 25.33, 25.29, 22.06, 13.21. [Q]i) 5+46.8 (cl.O €H2C12/CH30H -1/1) = C41H71Cl2N09Na[M+Na]+ HRMS (ESI) Calculated: 814.4404, found: 814.43 Π. Synthesis of 1-(9-(aD-galactose)-2-(11-(4-carbophenyl)-J-fluorenyl)amino-D-ribosyl-1,3,4-18 Burning triol (A24)

Compound A24 (18 mg, 0.024 mmol' 22%) was obtained from A22 (52 mg, 0.11 mmol) and B17 (32 mg &lt;RTIgt; Data for A24: white solid. Mp : 136 ° C. NMR (CD3OD/CDQ3=m, 400MHz) 37.28 (d, household 8. he, 2H), 7.17 (d, J=8.4Hz ' 2H) ' 4.96 (d, ·7=3.6Ηζ,1H),4.21-4.29 (m,1H), 3.98 (d, J=2.5Hz ' 1H), 3.95 (dd, "7=10.6,4,4, 1H) ' 3.83-3.90 (m ' 2H), 3.72-3.82 ( m ' 4H ) ' 3.58-3.68 ( m, 2H), 2.64 (t, J = 7.6 Hz, 2H) '2_28 (t, J = 7.8 Hz, 2H), 1.57-1.77 (m, 4H), 1.20 - 1.51 (m, 38H) ' 0.95 (t, &lt;/=6.7Hz, 3H). l3C-NMR (CD30D/CDC13=1/b 100MHz) (5173.99, 140.73, 130.53, 129.08, 127.5, 99.15, 73.79, 71.23, 70.34, 69.62, 69.17, 68.32, 66.58, 61.06, 49.87, 35.67, 34.52, 31.53, 31.23, 30.73, 29. (M, 28.95, 28.87, 28.81, 28.75, 28.65, 28.46, 25.24, 21.94, 13.03. [°#+41.7 (cl.O, CH2C12/CH30H: 1/1). C41H72ClN09Na[ HRMS (ESI) calculated for M+Na]+: 780.4793, found: 780.4779. s 34 201228666 Synthesis l-0-(aD-galactofuranoside)_2-(丨丨_(4_bromobenzene)11 Amidino-D-ribosyl-1,3,4-octadecanol (A25)

Compound A25 (22 mg, 0.027) was obtained from A22 (52 mg, 0.11 mmol) and B28 (56 mg, 0·16 mmol).

Mm ' 25% ). A25 data: rice white wax. iH_NMR (CDjOD/CDClfl/l '400MHz) &lt;57.28 (d,·7=8.4Ηζ, 2H) ' 7.20-7.47 (m ' 2H), 5.00 (d, J=3.6Hz, 1H), 4.284.33 ( m, 1H), 4.02 (d, /=2.8Hz, 1H), 3.98 (dd, "/=10·6, 4.6Hz, 1H), 3.863-3.94 (m ' 2H), 3.77-3.87 (m, 4H ), 3.62-3.70 (m, 2H), 2.69 (t, J = 7.6 Hz, 2H), 2.31 (t, "/= 7.6 Hz, 2H) '1.29-1.81 (m, 42H ) ' 0.98 ( t, J =6.6Hz, 3H). 13C-NMR (CD30D/CDC13=1/1, 100MHz) &lt;5171.21, 141.18, 130.44, 129.44, 118.39, 99.4, 74.54, 70.4, 70.13, 69.58, 69_50, 69.07, 68.41, 67.22 '60.95, 49.68, 35· 58,34.5 Bu 31.36, 31.18, 30.62, 28.95, 28.90, 28.81, 28.76, 28.68, 28.6 Bu 28.40, 27.00, 25.21, 24.88, 21.89, 19.90, 19.74, 19.57, 12.96. [a]f+40.7 (cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) calculated forC4lH73BrN09[M+H]+: 802.4469, found: 802.4216. (3) Synthesis Scheme 3: Synthesis of aryl-alkanoic acid Synthesis of (9-carboxymethyl)triphenyl brominated scale (B2)

BrPh3P^^^^Y〇H 10 10-bromodecanoic acid (19.65 g, 78.24 mmol) and triphenylphosphine (21.45 g, 81.78 mmol) were mixed and stirred at 150 ° C for 24 hours. A yellow syrup of Wittigreagent B2 was obtained in 100% yield, which was used without further purification of 201228666.

Synthesis of u_(4-(4-fluorophenoxy)phenyl))undecanoic acid (B4) Potassium tert-butoxide (ι〇·4〇g, 92.68 mmol) to B2 (19.89 g ' 38.81 mmol) at 〇 °C And a mixture of THF (150 mL). The reaction mixture became a red solution. The reaction mixture was warmed to room temperature and stirred for 1 hour. 4-(4-Fluorophenoxy)benzoic acid (B1) (7 5 g, 34·7 mmol) was added to the mixture and stirred at room temperature for 30 min. The reaction mixture was neutralized with 1. 〇 NHC1 and concentrated. The residue was separated with ethyl acetate (2 mL), water (200 mL) (pH adjusted to 5 by adding 1.0 N HCl) and brine (200 mL). The organic phase was separated and concentrated under reduced pressure. The residue was recrystallized from EtOAc / EtOAc (EtOAc:EtOAc) B3 was dissolved in ethanol/ethyl acetate (&quot;;; [, 80 mL), and then Pd/C (10% &apos; 1.08 g) was added. The mixture was stirred at room temperature under hydrogen pressure for 12 hours. The reaction mixture was filtered through a pad of celite and washed with ethyl acetate. The filtrate was concentrated and recrystallized from methanol/water (5/1 '12 mL), filtered and washed with water to afford &lt;RTI ID=0.0&gt; (9.080 g, 24.38 mmol, 90%) of a white solid. Mp : 730C. h-NMR (CDC13, 400MHz) &lt;56.85-7.13 ( m ' 8H ), 2.56 (t, J = 7.6 Hz, 2H ), 2.33 (t, J = 7.4 Hz, 2H) ' 1.22-1.65 (m, 16H) ). 13C-NMR (CDC13, 100MHz) J179.69,159.78,157.38,155.36,153.39,137.88,129.56, 120.09 '120.01,118.33,116.25,116.02,35.18,33.97,31.59, 29.69,29.48,29.44,29.38,29.24, 29.20, 29.03, 24.65. HRMS (ESI) calcd for C.sub.3, s. Synthesis of 11-(4-indolyl)phenylundecanoic acid (B12)

S

36 201228666 Compound B12 ( 1.34 g ' 3.78 mmo, 97%) was synthesized from B2 (3·47 g, 6.76 mmol) and 4-phenyloxybenzaldehyde (1.03 g, 5.20 mmol) in a similar manner to compound B4. . Data for compound B12: white solid, mp: 550C. tH-NMR (CDC13 '400MHz) (56.93-7.35 (m,9H), 2.60 (t ' J=7.4Hz ' 2H), 2.37 (t, J=7.3Hz, 2H), 1.65 (m ' 4H) ' 1.33 (m, 12H) °13C-NMR (CDC13, 100MHz) (5180.35, 157.71, 154.83, 137.87, 130.13, 129.5, 122.73, 118.97, 118.32, 35.18, 34.10, 31.55, 29.45, 29.42, 29.36, 29.22, 29.18, 29.00 , 24.63. Calculated for C23H3Q03Na[M+Na]+HRMS (ESI): 377.2093, found: 377.2053. Synthesis of 11-(4-isopropoxy)phenylidenic acid (B13)

Compound B2 (2.25 g, 4.38 mmol) and 4-isopropoxyfurfural (479 mg, 2.92 mmole) were used as starting materials to provide compound B13 (562 mg, 1.75 mmol). , 60%) of a white solid. Mp: 46 ° C. h-NMEX CDC13,400MHz )37.04( d, "7=8.5Ηζ, 2H ), 6.78 ( d,·7=8.6Ηζ,2H ) ' 4.48 ( m,1H ), 2.50 (t, /=7.5Hz, 2H ) ' 2.32 (t, J = 7.5 Hz, 2H), 1.50-1.61 (m, 4H), 1.25-1.35 (m, 18H). 13C-NMR (CDC13, 100MHz), 79.73, 155.82, 134.93, 129.20, 115.77, 69.91, 35.04, 34.H, 31.69, 29.50, 29.47, 29.40, 29.26, 29.22, 29.12, 29.06, 24.71, 22.11, 21.88. HRMS (ESI) calcd for C2O3O3O[M+Na]+: 343.2249. Found: 343.2227. Synthesis (10 5 or 10Z)) 11-(3,4-difluorobenzene) eleven-10-enoic acid ((£)-B7, and (Z)-B7)

37 201228666

B2 (12.93 g, 25.18 mmol) and THF (80 mL) and 3,4-difluorobenzoquinone (2.35 g, 16.5 mmol) were used as starting materials to provide compound B7 in a procedure similar to the procedure for the synthesis of compound B3. (3.77 g, 12.7 mmol, 77%). The Z-form and the £-type product were separated by n-hexane by recrystallization. Obtain a white solid of (5)-B7. Mp : 66 ° C. h-NMR (CDC13, 400MHz) paper 98-7.14 (m, 3H) ' 6.25 (d '7 = 15.8 Hz, 1H), 6.12 (m ' 1H), 2.33 (t, J = 7.5 Hz, 2H), 2·16 (q ' J=7.0 Hz, 2H), 1.61 (m, 2H), 1.43 (m ' 2H) ' 1.30 (s, 8H). 13C-NMR (CDC13, 100MHz) &lt;5180.57, 150.49 (dd, J=246, 12Hz), 149.31 (dd, J=241, 13Hz), 135.29, 132.35, 127.88, 121.99, 117.13, 114.18, 34.15, 32.91, 29.31 ' 29.22, 29.18, 29.08, 24.70. HRMS(ESI) calculated for C|7H22F202Na[M+Na]+: 3丨9.1486, found: (10)^ obtained (7) one-button colorless oil and 25% inseparable dB7. Synthesis (3,4-diponene)~|-acid (B14)

Compound B7 (1.61 g ' 5.43 mmol) was dissolved in ethanol / ethyl acetate (1/1 '30 mL) and Pd/C (10%, 160 mg) was added to the solution. The mixture was stirred at room temperature for 12 hours under hydrogen pressure. The mixture was filtered through a pad of Shi Xi Ma and washed with ethyl acetate. The mash was shrunk and dried in a vacuum. The white solid (1.61 g, 5.40 mmol, 99%) of compound B14 was obtained mp: 51 〇C. b-NMR (CDC13 '40〇MHZ) Shen.90-7.03 (m,2H), 6.84 (m, 1H ) ' 2.53 (t '"/=7_7Hz ' 2H ), 2.33 (t, J=7.5Hz, 2H ), 1.52-1.64 (m, 4H) ' 1.26 (m, 12H). 13C-NMR (CDC13, 100MHz) &lt;5180.24'150.13 (dd, J=13, 247 Hz), 148.49 (dd, &gt; 13,246 Hz), 147.40 '139.77 '124.05, Π 6.85, 35.09, 34.01, 31.23, 29.43, 29.36, 29.35, 29.18, 29.05, 29.01, 24.64. HRMS (ESI) calculated for C17H24F2 〇2Na[M+Na]+ s 38 201228666: 321.1642, found: 321.1594. Synthesis of 11-(2,4-difluorophenyl)undecanoic acid (B15)

Compound B2 (2.76 g, 5,38 mmol) and 2,4-difluorobenzoic acid (588 mg, 4.14 mmole) were used as starting materials to provide compound B15 (431 mg, 1.45 mmol, 35%) of white solid. Mp : 560C. 々-NMR (CDC13, 400MHz) is 5-7.13 (m,1H), 6.70-6.79 (m ' 2H), 2.66 (t, J=7.6Hz, 2H), 2·31 (t, J=7.4Hz, 2H), l_50-1.62 (m, 4H), 1.26 (m, 12H). 13C-NMR (CDC13, 100MHz) other 80.00, 162.19, 159.80, 130.90, 125.31, 110.69, 103.44, 34.U, 30.15, 29.44, 29.36, 29.33, 29.19, 29.16, 29.03, 28.41, 24.69. HRMS (ESI) calcd for EtOAc (m.). Synthesis of ll-(2,4-dichlorobenzene)undecanoic acid (B16)

Using a procedure similar to that of compound B7, using B2 (2.25 g, 4.38 mmol;) and 2,4-dibenzoic acid (5 (8) mg, 2.86 mmol) as starting materials to provide (10 5 or Chuanxiong))- 11-(2,4-diqibenzene) eleven-10-dilute acid (B9) (576 mg, 1.75 mmo b 61%). This compound was then dissolved (210 mg, 0.638 mm in ethyl acetate (10 mL) and then pd/Bas.sub.4 (21 mg) was added. The mixture was stirred at room temperature for 12 hours under hydrogen pressure. The mixture was filtered and washed with ethyl acetate. The combined filtrate was concentrated and dried in vacuo to afford compound B16 (210 mg &lt;RTI ID=0.0&gt; 400MHz) ^7.32 (d»J=1.9Hz51H)5 7.09-7.15 (m,2H), 2.65 (t ' J=7.8Hz, 2H) ' 2.33 (t, J=7.5Hz, 2H), 1.53-1.63 ( m»4H)&gt; 1.26( m» 12H)〇,3C-NMR(CDC13»100MHz) 39 201228666 ¢5180.00,162.19,159_80,130.90,125.3,110.69,103.44, 34.11,30.15,29.44,29.36,29.33,29.19 , 29.16, 29.03, 28.41, 24.69. Calculated by HRMS (ESI) for C17H24Cl202Na[M+Na]+: 353.1051, found: 353.1046. Synthesis of 11-(4-chlorophenyl)undecanoic acid (B17)

Compound B2 (2.20 g, 4.28 mmol) and 4-chlorobromo (401 mg, 2.85 mmole) were used as starting materials to afford B17 (526 mg, 1.77 mmol, 62%). Mp : 93 ° C. h-NlVlR (CDC13, 400MHz) (57.21 (d ' J=8.4Hz' 1H), 7.08 ( d, J=8.4Hz, 2H ), 2.54 (t ' J=7.5Hz, 2H ), 2.33 (t, / = 7.5 Hz, 2H ), 1.53_4 63 (m, 4H), 1.26 (m, 12H). 13C-NMR (CDC13, 1〇〇mhz) 79.90, 141.28, 131.21, 129.71, 128.27, 35.26, 34.00, 31.35 , 29.69, 29.44, 29.39, 29.36, 29.19, 29.13, 29.01, 24.64. C17H25C102Na [M+Na; H. HRMS (ESI) calc.: 319.1441, found: 319.1435. Synthesis 11-(4-bromobenzene) Acid (B18)

Compound B2 (330 mg, 〇.6 mmol) and 4-bromobenzoic acid (91.5 mg, 0.495 mmole) were used as starting materials to provide B18 (98.0 mg '0.287 mmo) in a similar procedure to the synthesis of B10. 58%) white solids. Mp : 910C. h-NMR (CDC13, 400MHz) 37.37 (d,7=8·3Ηζ,1H), 7.02 (d,J=8.3Hz ' 2H) ' 2.53 (t,J=7.6Hz,2H),2·34 (t , &gt;/=7.5Hz,2H),1.52-1.63 (m,4H),1.20-1.37 (m,12H) 〇丨3C-N!Vni(CDCl3,100MHz)3179.94, 141.79, 141.79,13U2, 130.14, 119.22, 35.3 Bu 34.H, 31.27, 29.44, 29.38, 29.36, 201228666 29.19 ' 29.12, 29.03, 24.68. HRMS (ESI) calcd for C17H26Br02 [M+H]+: 341.1116, Found: 34U111. 11-(4-bromobenzene)-10,11-dihydroxyundecanoic acid (B20)

Add NMO (462 mg ' 3.94 mmol) and osmium tetroxide (2.5 wt % in ί-BuOH, 170 μί, 0.167 mmol) to Bll (389 mg, 1.15 mmol) in tert-butanol/water (4/3, 35 mL) ) in solution. After stirring at room temperature for 15 hours, the reaction was quenched with saturated Na.sub.2SO.sub.3 and concentrated. The residue was separated by two gas (50 mL) and sat. Na^O] (50 mL). The organic phase was washed with brine (50 mL), concentrated and purified by column chromatography (ethyl acetate - hexane = 1/2 then 1 / 1) to afford B20 (256 mg, 0.686 mmol, 60%) ). NMR (CD3〇D/CDCl3=l/l, 400MHz) 67.49-7.56 (m, 2H), 7.28-7.37 (m, 2H) ' 4.59 (d, J = 5.1 Hz, 0.7H), 4.44 (d, J = 6.6 Hz, 0.3H), 3.71 - 3.77 (m, 0.7H), 3.62 - 3.66 (m, 0.3H), 2.45 (t, • / = 7.2 Hz, 2H), 1.27-1.78 (m, 14H). 13C-NMR (CD30D/CDC13=1/b 100MHz) (5169.05, 140.40, 140.16, 130.60, 130.30, 128.18, 120.64, 120.27, 76.44, 75.80, 74.8, 74.27, 31.88, 30.94, 28.92, 28.78, 28.67, 28.63, 28.56, 28.48, 28.45, 28.38, 25.10, 24.88, 24.28. HRMS (ESI) calculated for C17H25Br04Na[M+Na]+: 395.0834, found: 395.0813. Synthesis of L-(-)-menthyl (1 〇 一 11 Mono(3,4-difluorophenyl)-undec-10-enoate (menthyl (£)-B7)

Add L-(-)-menthol (314 mg, 2.01 mmol), EDNHC1 (347 mg, 1.81 mmol) and DMAP (1.2 mg, 0.010 mmol) to (Fanta-B7 (298 mg '1.01 mmol) of dioxane In a solution of the alkane (3 mL), the reaction mixture was stirred for 12 hrs at room temperature at 2020. The mixture was diluted with dioxane (2 mL) and washed with water (20 mL) and concentrated. (Ethyl acetate / η-hexane = 1 / 50) The residue was purified to give a succinyl group (s. _B7 (112 mg, 0.258 mmo, 26%) as a colorless oil. 1H-NMR (CDC13, 400 MHz). 7.13 (m, 3H), 6.24 (d, J = 15.6 Hz, 1H), 6.15-6.24 (m, 1H), 4.11-4.20 (m ' 1H), 2.27 (t ' J = 7.6 Hz, 2H), 2.15 (q, y=6.8Hz &gt; 2H ) Ί .92-1.99( m ΊΗ )»1.80-1.89( m ΊΗ) Ί .55-1.68 (m,4H)' 1.38-1.50(m'3H),1.22- l, 35 (m, 10 Η), 0·77-1·09 (m ' 9H ) ' 0.73 (d, "Ζ^.ΟΗζ ' 3H ). 13C-NMR ( CDC13, 100MHz ) (5173.34 ' 150.39 (dd ' J=245 '13Hz), 149.23 (dd, "/=246, 13Hz), 135.15, 132.24, 127.77, 121.87, 117.00, 114.08, 73.82, 47.00, 40.93, 34.67, 34.25 32.82, 31.33, 29.67, 29.26, 29.14, 29.08, 29.06, 26.22, 25.06, 23.39, 21.97, 20.70, 16.25. HRMS (ESI) for C27H4 〇F2 〇2Na[M+Na]: 457.2894, found: 457.2863. Synthesis (105,111^-11-(3,4-difluorobenzene)-l〇,ll-di-undecanoic acid and (ΙΟΛ,ΙΙΛ)-11-(3,4-diphenyl)-10,11-di By citric acid, cis-(Β21) is used as a mixture of cis-diol isomers ΟΗ 〇

Add hydrazine (103 mg, 0.879 mmol) and iron tetraoxide (2.5 wt ° / 〇in i-BuOH, 38 μί, 0.0037 mmol) to menthyl (E)-B7 (110 mg, 0.253 mmol) tert-butanol / Water (2 Π, 6 mL) solution. After stirring for 20 hours at room temperature, the reaction mixture was quenched with saturated Na.sub.2SO.sub.3 (10 mL). The mixture was concentrated, and the residue was dissolved in ethyl acetate (20 mL) to sat.

S 42 201228666 (2〇 mL) and brine (2〇 mL) were cleaned and dried with MgS〇4, followed by filtration and concentration. The residue was purified by column chromatography (ethyl acetate with hexanes 1/4 followed by 1/3). The resulting colorless oil was dissolved in methanol (5 rainbow), followed by the addition of 1.0 N NaOH (5 mL). After stirring at room temperature for 12 hours, the reaction was neutralized with 1 〇N HCl (5 mL); The residue was purified by column chromatography (ethyl acetate hexanes = 1/2 then 1/1) to afford </ br> </ br> Mp: iopc^H-NMRCCDsOD, 400MHz) 56.99-7.25(m'3H)'4.36(d,J=5.6Hz,1H),3 45-3 52 (m,1H),2.18 (t,J=7.4HZ , 2H), 1.11-U4 (m, 14H). 13C-NMR (CD3OD, 100MHz) (5177.70, 151.29 (dd, J=244, 12Hz), 150.76 (dd, "/=244, 13Hz), 141.48, 124.36, 117.64, 116.87, 77.23, 76.39, 34.39, 33.72, 30.51, 30.41, 30.27, 30.15 ' 26.80, 26.03. HRMS (ESI) of C17H24F204Na[M+Na]+ Calculated value: 353.1540, found: 353.1550. Synthesis (10 feet 115 &gt; and (l〇S,ll and)-Π_ (3,4-difluorobenzene)_(1〇,丨1)_dihydroxyundecanoic acid, trans-(B21) as a mixture of trans-diol isomers

Add NMO ( 494 mg ' 4.22 mmol.) and tetraoxide (2.5 wt % in ί-BuOH ' 186 μι ' 0.0183 mmol) to (Z)-B7 (361 mg, 1.22 mmol) tert-butanol/water (2 /1 '6 mL) in solution. After stirring at room temperature for 20 hours, the reaction mixture was quenched with saturated NaJzO3 (15 mL·). The mixture was concentrated and the residue was taken from ethyl acetate (5 mL). The residue was purified by column chromatography (ethyl acetate / hexanes = 1/2 then hexanes) to afford a mixture of s-B21 (246 mg, 0.745 mmol, 61%, s. Colorless oil. 1H-NMR (CD3OD, 400MHZ)

&lt;57.03-7.25 (m, 3H), 4.36 (d, J = 5.5 Hz, 1H), 3.47-3.57 (m, 1H), 2.16-2.22 (m, 2H), 1.18-1.56 (m, 14H). 13C-NMR 43 201228666 (CD3OD, 100MHz) (5177.73, 151.19 (dd, J=245, 13Hz), 150.72 (dd, "7=245, 13Hz", 141.46, 124.57, 117.49, 117.08, 77.34, 77.25, 76.42, 76.06,34.95,33.75,33.50,30.63,30.51,30.44,30.34,30.20,26.83,26.07 HC17H24F204Na[M+Na]+HRMS (ESI) calculated value: 353.1540, found: 353.1566. (4) Synthesis flow chart 4 Synthesis of Compound C5-C7 Synthesis of 3,4-Di-O-Benzenyl-1-0-(6-azido-2,3,4-tris-quinone-phenylindole-6-deoxy-α- D-galactose glucoside)-2-hexacosanoylamino-D-ribosyl-octadeca-1,3,4-triol (C1)

According to Zhou, XT et al. (&gt; Gong 1 2002, 4, 1267-1270 to synthesize compound Cl. Cl data: 'H-NMR (CDC13, 400 Hz). 35-7.21 (m, 25H), 5.94 ( d, J = 6.0 Hz, 1H ), 4.95 ( d, J = 11 · 4 Ηζ, 1H), 4.82 (d, · 7 = 3.2 Ηζ, 1H), 4.79 - 4.91 (m ' 4H), 4.63-4.55 (m ' 3H), 4.37-4.48 (m, 2H), 4.18-4.30 (m, 2H), 4.00 (dd, J = 3.6, 10.1 Hz, 1H), 3.87 - 3.81 (m, 7H), 3.52 - 3.50 (m, 1H), 1.78-1.79 (m, 74H), 0.86 (t, J = 7.0 Hz, 6H). Synthesis of 1-(9-(6-phenylethylamino)-6-deoxy-α-D - galactose σ 喃 喃 ) ) - hexadecanthamide - 0 - ribosyl - 18 burn -1,3,4- binary leaven (〇 5) and / Ph

Add a solution of triphenylphosphine (10 mg, 0.038 mmol) to Cl (24 mg, 0.018 mmol) in THF / water (10/1 &lt; After mixing for 2 days at room temperature, 201228666 干燥ίίίίίίίίίίίίίίίί The residual yarn was dissolved in the gas imitation &gt;10. ί ί § ’ 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 02 After the uterus, and the thorns 12 j, the mixture was scaled and purified by column chromatography ('B_1 to 1/6 to 1/4) to provide the compound C2. The result of c2 was intermediate i=, di-methane/methanol (i/i, 5 mL) and then Pd(〇H)2 was added. After stirring at room temperature under hydrogen for 15 hours, the mixture was passed through a stone shovel and washed with three gas (1/1). The concentrated filtrate was purified by column chromatography (dioxet/methanol = W) to afford a white wax of CS ( 4 〇 ^, 〇〇 〇〇 4 mmoL 22%). ιΗ—Liji (pyridine 屯, 4〇〇Hz) 37.24-7.43 (m'5H), 5.51 (d, “7=3.8112:,1H), 4.50-4.67 (m, 2H), 4.09~4.51 (m , 8H), 3.89 (s, 2H), 3.82-4. (n (m, 1H), 2.21-2.57 (m, 4H) ' 1.08-1.96 (m, 74H), 0.88 (t, J = 6.1 Hz, 6H). 13C-NMR (pyridine-d5, 150 Hz), not 73.75, 173.46, 142.53, 129.24, 129.20, 126.75, 101.71, 77.08, 72.95, 71.64, 7L34, 70.91 '70.50,68.82 ' 51.89 ' 41.50,38.77, 37.20,34.81,32 67,32.51,30.78,30.55,30.42 ' 30.39,30.32,30.20,29.99,26 90, 26.79 ' 23.32,14.66. [啦+39.3 (cl.O,CH2Cl2/CH3〇H : 1/1 The calculated value of LRMS (ESI) of C58H1()7N209[M+H]+: 975.80, found: 975.67. Synthesis of 1-0-(6-(3-stupylamino)-6-deoxygenated half Lactose α-fantaose is 2-hexadecylamine-D-ribosyl-octadecyl-1,3,4-triol (eg)

OHN/H

people,

C25H51 OH and C14H29

OH is similar to the procedure for the synthesis of C5, using compound Cl (24 mg, 〇〇i8 mmol) and 3-phenylpropionic acid (2.2 mg, 0.018 mmole) as starting material to provide C6 (10 mg '0.010 mmob 55%) ). iH-NMR (ton. 〜 屯, 45 201228666 400 Hz) &lt;57.29-7.30 (m, 5H), 5.50 (d, J = 3.7 Hz, 1H), 5.20-5.30 (m, 1H) ' 4.56-4.65 ( m ' 2H), 4.48 (t, J = 6.6 Hz, 1H), 4.25-4.38 (m ' 5H) '4.15-4.23 (m, 1H), 3.86-3.95 (m, 1H), 3.17-3.26 ( m ' 2H) ' 2·74-2·89 (m, 2H), 2.41-2.55 (m, 2H), 1.08-2.04 (m ' 74H) ' 0.89 (t ' J = 6.7 Hz, 3H).丨3C-NMR (pyridine-d5,400 Hz) 5173.8, 173.52, 149.78, 142.60, 129.32, 129.27, 126.83 '101.78 ' 77.15, 73.00, 71.70, 71.41, 70.98, 70.56, 68.88, 51·94., 38.84, 37· 26,34.88,32.74,32.58,30.86,30.63,20.50,30.47,30.39 '26.97,26.87,23.4〇,14.74•[啦+36.0 (cl.O, CH2C12/CH30H: 1/1). LRMS (ESI) calculated for c59Hi09N2 〇9[M+H]+: 989.8 found: 989.60. Synthesis of 1-(9-(6-(4-phenylbutanyl)_6-deoxygalactose-glycolose)-2-hexadecylamine-D-ribosyl-octadecyl-1 3,4-triol (C7)

Ci4H29 oh provides C7 (9.0 mg, 0.090 mmo 50%) using a compound similar to the procedure for the synthesis of C5 using compound Cl (24 mg, 〇018 mmol) and 4-butyric acid (2.0 mg '0.018 mmole) as starting material. ). 'at 400Hz' J7.27-7.40(m,5H), 5.50(d,J=3.7Hz,1H,' (m,1H) ' 4.554.66 (m,2H),4.48 (t,J=66ilz knife 4.25-4.37 (m,6H) '4.15-4.23 (m,1H),3·87~3.95 (m,Ή) ' 3.16-3.25(m,2H)'2.74—2.89 (m'2H), 2.41~2.55 (m:1H)' 1.02-1.98 (m,74H) ' 0.88 (t ' J=7.2Hz,6H). ' pyridine-d5,400Hz) other 73.30,173.02,142.07,128.82,128 (bar 126.33,101.28, 76.66,72.50,71.19,70.90,7〇如,'7〇' 68.39,51.44,41.06,38.34,36.77,34.38,32.25,32 in Erchuan, 30 30.13,30.01,29.98,29.9,29.79,29.76,29.59,29 , Μ, 26.47, 46 201228666 26.37, 22.9 卜 14.25. [啦+36.9 (cl.O, CH2Cl2/CH3OH: 1/1). 1003.47. C6〇H secret 2〇9[M+H]+ LRMS ( ESI) Calculated value: 1003.83, found: (5) Synthesis scheme 5: Synthesis of compound C20-C31 ^ Synthesis of toluenesulfonyl-α-D-galactose-halfose ^1) 2~(11-(3,4 -monofluorobenzene) eleven-branched) amine-based ribose group], 3,4_18-yard triol (C17)

〇n^VS4h: ★In the ice bath, add /&gt; benzoquinone hydrazine (712 mg, 3.74 mmol) to a solution (20 mL) to A15 ( 2.58 g, 3-40 mmol) of the bite (3 〇 mL) ) in solution. The reaction mixture was returned to room temperature. After stirring for 16 hours, the solvent was evaporated and the residue was purified by column chromatography (dichloromethane / methanol = 1 / 1 to 5 / 1 to 20/1 to 15 / 1) to afford C17 Yellow waxy (which mg, 〇 855 mmo b 25% '100% BRSM, with 2.01 g of starting material). W-NMR (CD30D/CDC13=1/1 '400MHz) (57.96 (d, J=8.3Hz, 2H), 7.56 (d ' J=8.1Hz ' 2H) ' 7.10-7.27 (m ' 2H), 7.02- 7.09 (m, 1H), 5.01 (d ' J=3.2Hz, 1H), 4.29-4.42 (m, 3H), 4.21 (t, /=5.9Hz, 1H) ' 3.96-4.04 (m, 2H), 3.85 -3.95 (m, 2H), 3.81 (dd, J = 4.0 ' 10.6 Hz, 1H), 3.70-3.76 (m, 2H), 2.74 (t, J = 7.6 Hz, 2H) ' 2.62 (s, 3H), 2.35-2.43 (m, 2H), 1.67-1.88 (m ' 4H), 1.36-1.60 (m, 38H), 1.05 (t, JiJHz, 3H). 13C-NMR (CD30D/CDC13=1/1, 100MHz) (5173.84, 149.47 (dd, J=246, 13 Hz) ' 148.00 (dd, J=244, 13 Hz), 144.74, 139.43, 132.04 ' 129.32, 127.44 ' 123.60, 116.22 ' 114.55,99.09,73 87, 71.39,69.27, 68.98,68.51,68.15,68.07,66.95,35.85,34.46,31.71,31.34,30.72,29.21 ' 29.17,29.12,29.06,28.96,28.9b 47 201228666 28.82,28.77,28.50,25.30,22.06,20.67,13.22. C48H78F2NO&quot; HRMS (ESI) calculated for S[M+H]+: 914.5264, found: 914.5228. Synthetic 1-0-(6-azepine i -6-degreased-ct-D-galactose Furans bottom sugar) - 2- (11- (3,4-stretch present) -] acid-yl) -D- ribose amino-1,3,4-triol burn eighteen (C18)

ΟΗ Add sodium azide (322 mg, 4.95 mmo丨) to C17 (1 _63 g, 1.78 mmol) in DMF (15 mL). At 1〇〇. (: The reaction mixture was stirred for 2 days. The mixture was concentrated and purified to give crude C18 (1 15 g, 147 mm 〇丨) by column chromatography (dioxane / methanol = 20/1 to 15/1). , 82%) of a yellow solid. mp: 1 〇 1. (: NMR (CD30D/CDC13 = 1/1, 400 MHz W.25-7.51 (m, 3H), 5.36 (d, J = 3.2 Hz, 1H) , 4_57~4.67 (m ' 1H) ' 4.12-4.42 (m,6H),3.94-4.06 (m,3H),3.74 (dd ' J=12.8,4.8Hz,1H),3.00 (t,J=7.7Hz , 2H), 2.60-2.67 (m ' 2H) ' 1.62—2.15 (m ' 42H), 1.32 (t, ·7=6.8Ηζ, 3H). HRMS (ESI) of CnHwF^OspVi+Hf: 785.5240, Found: 785.5267. ^ Synthetic amino-6-deoxy-α-D-galactose piperanose)-2-(11-(3,4-difluoro)11-decyl)amine _D_ Ribose oxime, octadecyl triol (C19)

OH was added triphenylphosphine (0.74 g, 2.8 mmol) to a solution of C18 (1.11 g, 1.41 mmol) in THF / water (10/1 '33 mL). The reaction mixture was stirred at room temperature 201228666 ' 2 days. The mixture was purified by column chromatography, 1% triethylamine, dichloromethane (methanol = 6/1 to 4/1 to 2/1) to afford 566 g, 0.746 mm. White solid. Mp : wpc. NMR (CD3〇D, 400MHz) paper 95—7.09 (m, 2H), 6.86-6.88 (m, 1Η), 4.82 (d, household 3.2Hz' 1H), 4.13-4.19 (m, 1H), 3.83 (dd , /=10.4,4.43⁄4, 1H),3.75 (d,J=2.0,1H) ' 3.63-3.73 (m,3H),3.59 (dd, •7=10.8,5·6Ηζ,1H),3.44-3.54 (m, 2H), 2.87 (dd, J = 13.2, 7.6 Hz, 1H), 2.72 (dd, J = 13.2, 4, 4 Hz, 1H), 2.51 (t, J = 7.6 Hz, 2H) ' 2'14 (t, J = 7.5 Hz ' 2H), 1.50 - 1.63 (m, 4H), 1.16 - 1.32 (m, 38H) ' 0.82 (t, / = 6.83⁄4, 3H). 13C-NMR (CD3OD, 100MHz) (5176.07, 151.5 (d, J=246, 13Hz), 150.8 ((1, /=243, 12Hz), 141.74, 125.79' 118.16, 118.02, 101.43, 75.90, 73.12, 72.46' 72.02 ' 71.63 ' 70.33,68.35,52.18,43.44,37.46,36.20,33.37,33.26 ' 32.68,31.06,31.02,30.96,30.8.9,30.81,30.73, 30.67 ' 30.62 ' 30.39,27.30,27.2 Bra 23.29.C41H73F2N208[ HRMS (ESI) calculated for M+H]+: 759.5335, found: 759 5319. Synthesis 1-0-(6-(4-nitrophenylethylamino)-6_deoxy-a-D-galactose. South sugar bitter)~2-(11-(3,4-difluorophenyl)undecyl)aminoribosyl, 3,4-octadecane triol (C20)

Adding 4-nitrophenylacetic acid (8.1 mg, 0.045 mmol), HBTU (34 mg, 0.090 mmol) and NMM (20 μιη, 0·18 mmol) to C19 (34 mg, a045 mmo1) of di-methane/ In a solution of sterol (1 Λ, 3 mL). After stirring at room temperature for 16 hours, the mixture was concentrated and purified by column chromatography (dichloromethane/methanol - 30/1 to 20/1). The crude product was dissolved in methylene chloride / methanol 49 201228666 (1/1, 3 mL) and yttrium carbonate (HOBT scavenger, l 〇〇mg) was added to the δ hai bath. The mixture was stirred at room temperature; after mixing for 1 hour, the mixture was filtered and washed with dioxindole / decyl alcohol (1/1). The filtrate was concentrated and dried in vacuo to afford C20 (13 mg &lt;RTI ID=00&0&gt;&gt; ii-NMR (CDC13/CD30D=1/1 '200MHz) &lt;58.25 (d, J=8.7 Hz, 2H), 7·68 (d, /=8.71^, 2H), 6.90-7.21 (m, 3H) , 4.94 ( d, J=3.2Hz, 1H), 4.20~4.26 (m ' 1H), 3.77-3.92 (m, 5H), 3.58-3.74 (m, 6H), 2.63 (t ' J=7.4Hz ' 2H ) ' 2.28 (t, J = 7.6 Hz, 2H), 1.30-1.81 (m ' 42H ), 0.98 ( t, J = 6.8 Hz, 3H ). 13C-NMR (CDC13/CD30D=1/1, 50MHz) 3173.93,170.81,149.17 (dd, 7=246 '13Hz),148.05 (dd,J=244,13Hz),146.43,142.53, 139.35,129.58,123.59 ' 122.95, 116.28, 116.11, 98.99, 73.65, 71.21, 69.35 ' 69.18 ' 68.41 ' 68.14, 66.16, 49.81 ' 41.69, 39.69, 36.34, 35.69, 34.36, 31.61, 31.25, 30.66, 29.04, 28.74, 28.41, 25.27, 21.97, 13.07. [啦+39.3 (cl.O, CH2C12/CH30H: 1/1). (2491'178?2;^3〇11[]\/1+11]+服1\/18^81) Calculated value: 922.5604, found: 922.5629. Long-term synthesis of 1-(9-(6-(2,4-dihydrophenylethylamino)-6-deoxy-a-D-galactose glucopyranoside)-2-(11-(3,4-di) Fluoride)-| — St-based)-amino-D-ribosyl-1,3,4-octadecane triol (C21)

Compound C19 (34 mg, 〇.〇45 ca ιοί) and 2,4-distone succinylacetic acid (10 mg, 0.045 mmole) were used as starting materials to provide C21 (4.0 mg ' in a procedure similar to that for the synthesis of C20. Impurity, 0.0041 mmol, 9%) 0 H-NMR (CDCl3/CD3 〇D=l/l, 600 MHz) (57.39-7.48 (m, 50 201228666 3H), 6.97-7.17 (m, 3H) , 4.98 (d, household 3.2Hz ' 1H) '4.24-4.31 (m, 1H), 3.59-3.93 (m, 10H), 2.65 (t, J = 7.4Hz, 2H), 2.26-2.31 (m, 2H) , 1.14-1.87 (m, 42H), 0.90-1.02 (m, 3H) 〇l3C-NMR (CDCl3/CD3OD=l/l Ί50ΜΗζ) (5173.95 Ί69.65 &gt; 148.64,147.80,139.33,134.76,132.72,129.90 , 129.13, 123.53, 123.15, 116.92, 116.57, 116.13, 110.69, 99. (M, 73.64, 73, 42, 71.16, 69.32, 69.08, 68.12, 66.07, 49.80, 39.45, 39.60, 38.18, 38.13, 36.30, 35.66, 34.33,34.30,33.63,32.01,31.60,31·43 '30.67,30.58 '29.73,29.23,28.39,28.35,28.23,26.30, 25.23 ' 25.17,23.06,22.25,22.20,21.78,12.98.[α]Ρ+47.1 (do 'CH2C12/CH30H :1/1 ) C49H76F2N3Ol 3H[M+H]+hrms (ESI) calculated: 967.5455, found: 967.5485. 1 - (6-(4-tert-butylethylidene)-6-deoxy-ct-D-galactose πD-glycoside: ^2-(11-(3,4-difluorobenzene)undecyl)amino-D-ribosyl-1,3,4-octadecanetriol (C22)

Compound C19 (34 mg, 〇.〇45 mmol) and 4-tert-butylphenylacetic acid (8.6 mg, 0.044 mmole) were used as starting materials to provide C22 (12 mg, 0.013 mmo) in a procedure similar to the procedure for the synthesis of C20. 29%). Mp : 17〇0C. ^-NMR (CDC13/CD30D=1/1 &gt; 400MHz) (57.47 (d &gt; J=8.〇Hz &gt; 2H) ' 7.32 (d '7=8.0Hz ' 2H) ' 6.98-7.22 (m ' 3H) ' 4.97 (d, J=3.2Hz, 1H), 4.29-4.34 (m,1H), 3.80-3.95 (m,5H), 3.76 (dd, J=10.8,4·4Ηζ,1H), 3.61 -3.71 (m, 5H), 3.36 (dd, J=7.8, 13.8 Hz, 1H), 2.68 (t, J = 7.6 Hz, 2H), 2.33 (t, "/= 7.6 Hz, 2H), 1.63-1.82 (m, 4H), 1.31-1.53 (m, 47H), 1.00 (t, 51 201228666 /=6·5Ηζ, 3H). 13C-NMR (CDCl3/CD3OD=l/l, 100MHz), not 73.91, 172.88, 149.40 (dd, J=246, 12Hz) ' 148.02 (dd ' &gt;243 Ί3Ηζ) Ί39.36 Ί31.28 Ί24.96 Ί23.57 Ί16.21 Ί16.05 99.06,73.79,71.30,69.35,68.97,68.40,68.20 , 66.42, 49.84 41.82, 39.39, 35.72, 34.37, 33.66, 31.66, 31.25, 30.65, 30.38 29.14, 29.09 '29.05, 29.03, 28.97, 28.89, 28.83, 28.75, 28.71 28.68, 28.42, 25.28, 25.24, 21.96, 13.06. [a] shovel +36.4 (cl.O CH2C12/CH30H: 1/1). HRMS (ESI) of C53H88F2N209[M+H]+ calculated value: 933.6380, found: 933.6435. Synthesis 1 -6^(6-(4) - &gt; Phenylethylamine-6-deoxy-ci-D-galactose sigma glucoside)-2-(1Η3,4-difluorobenzene)undecyl)amino-D-ribosyl-1,3 , 4-octadecane triol (C23)

化合物 Compound C19 (34 mg 0.045 mmol) and 4-bromophenylacetic acid (9.7 mg, 0.044 mmole) were used as starting materials to provide C23 (15 mg, 0.016 mmol, 35%) of rice in a similar procedure to the synthesis of C20. White solid 〇 mp = 1770C. ^-NMR (CDC13/CD30D=1/Bu 400MHz) 37.54 (d, J=8.4Hz, 2H) ' 7.29 (d, household 8·0Ηζ, 2H) ' 6.97-7.20 ( m,3H ) ' 4.97 ( d, • /=3.6Hz, 1H) 4.28-4.33(m,1H), 3.78-3.92(m,5H) '3.59—3.74 (m '6H), 3.37 (dd, J=7.6, 13.6Hz, 1H), 2.66 (t, J = 7.6 Hz, 2H) ' 2.31 (t '7=7·6Ηζ ' 2H), 1.30-1.81 (m, 42H), 0.98 (t, &gt;6·8Ηζ, 3H). 13C-NMR (CDC13/CD30D=1/1, 1〇〇2) (5173.90, 171.91, 149.53 (dd, J=247, 13Hz), 147.86 (dd, ^=245 Ί2Ηζ) Ί39.35 Ί33.70 &gt ;130.98 Ί30.29 Ί23.58 Ί20.22 » 120.22,116.18,116.02,99.03,73.77,71.26,69·34,69.08, 52 201228666

68.38 '68.15, 66·32 '49.8 Bu 41.48, 39.5 Bu 35.68, 34.35, 3l.63, 31.23, 30.62, 29·Η, 29.08, 29. (U, 28.95, 28·87, 28.81, 28.73, 28.68, 28.66 , 28.40, 25.25, 25.22, 21.94, 13.03. [α]έ5+42 3 (cl.O CH2C12/CH30H:1/1) C49H78BrF2N209 [M+H]+HRMS (ESI) calc.: 955.4859 ' Found: 955 492〇. Synthesis of 1-0-(6-(4-methoxyphenylacetamido)-6-deoxy-a_D-galactose-glycoside (1丨-(3,4-difluorobenzene) eleven Mercapto)-amino-D-ribosyl-1,3,4__+ octane triol (C24) '

Compound C19 (34 mg, 〇〇45 mmol) and 4-methoxyphenemidine (7.5 mg, 0.045 mmole) were used as a material to provide C24 (15 mg '0.017 mmol) in a procedure similar to the procedure for the synthesis of C20. , 38%) white solids. · 172〇C. h-NMR (CDC13/CD30D=1/1,400MHz) 37·36 (d, J=8.8Hz, 2H), 7.12-7.26 (m, 2H), 7.01-7.09 (m, 3H), 5 〇2 ( d \/=3.6Hz,1H),4.32-4.38(m,1H) '3.97(s,3H),3.72—3 96 (m,5H),3.69-3.78 (m,4H) ' 3.65 (s,2H ), 3.40 (dd, «7=7.8, 14.0 Hz '1H), 2.74 (t, J = 7.6 Hz, 2H), 2.38 (t, j = 7.6 Hz, 2H), 1.38-1.89 (m, 42H), 1.05 (t, J = 6.8 Hz, 3H). 13〇-Nmr (CDC13/CD30D=1/1 ΊΟΟΜΗζ) ^173.91 Ί73.06 il49.59 (dd &gt;&gt;247, 13Hz), 148.08 (dd, J=244, 13Hz), 158.27, 129.40, 129.66 Ί26 .43 Ί23.61 Ί16.29 Ί16.12 Ί14.55 Ί13.62 «99.08 » 73.92 *71.39 »61.41 »69.03 &gt;68.41 &gt;68.24 &gt;66.43 &gt;54.47 ^49.78 &gt; 41.57,39.46,35.82,34.46 , 31.80, 31.33, 30.7, 29.22, 29.17, 29.12, 29.11, 29.05, 28.96, 28.90, 28.82, 28.78, 28.75, 28.49, 25.34, 25.3, 22.04, 13.19. [a. +44.3 (cl.O s CH2C12/CH30H: 53 201228666 1/1 ) °C50H81F2N2O 丨〇[M+H]+ HRMS (ESI) Calculated: 907.5859, found: 907.5890. Synthesis of 1-0-(6-(3,4-bis(trifluoromethyl)benzene-acetamide)-6-deoxy-α-D-galactose-glycolate)-2-(11-( 3,4-di-phenylphenyl)undecyl)amino-D-ribosyl-1,3,4-octadecanol (€25)

Compound C19 (34 mg 0.045 mmol) and 3,4-bis(trifluoroindolyl)phenylacetic acid (12 mg, 0.045 mmole) were used as starting materials to provide C25 (11 mg) in a procedure similar to the procedure for the synthesis of C20. , 0.011 mmol, 24%) white solid. Mp : ISOWH-NMR (CDC13/CD30D=1/Bu 400MHz) (57.98 (s, 2H), 7.91 (s, 1H), 769-7.22 (m, 3H), 5·01 (d, J = 3.6 Hz, 1H) '4.28-4.33 (m ' 1H), 3.84-3.99 (m, 5H), 3.83 (s, 2H), 3.78 (dd, J=4.2 ' 10.8Hz, 1H), 3.22-3.32 (m, 3H) '3.42-3.51 (m,1H) ' 2.69 (t, J=7.6Hz, 2H), 2.33 (t, J=7.4Hz, 2H), 1.39-1.82 ( m ' 42H ), 1.00 ( t, J=6.8 Hz, 3H ) (13C-NMRCDCl3/CD3〇D=l/b 100MHz) &lt;5174.04,170.56, 143.17 '139.37,137.65,131.13,130.80,129.10,124.18,123:56,121.47 '120.09,116.22,116.06 , 114.50, 99.07, 73.77, 71.32, 69.40 '69.27,68.42,68.20,66.30,49.99,41.14,39.78,35.75,34·39,31.73,31.27,30.66,29.14,29.09,29.04,28.99, 28.88,28·75 , 28.7, 28.69, 28.42 '25.29, 25.24, 21.98, 13.08. [啦+40.1 (cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) calculated for C51H77F8N209[M+H]+: 1013.5501, Found: i〇i3 5567. Synthesis of 1-0-(6-(3,4-difluorophenylacetamide)-6-deoxy-aD-galactofuranoside)-2_(11-(3,4) - Difluorobenzene)H-mercapto)amino-D-ribosyl-1,3,4-ten

S 54 201228666 Octane triol (C26)

Methyl) and 3,4-difluoro-phenylacetic acid (7.7 mg, 0.045 mmole) were used as starting materials to provide C26 (17 mg, 0.019 mmo, 42%) white solid. Mp : 182°C1H-NMR (CDC13/CD30D=1/1 &gt; 400MHz) 36.91-1.43 (m ' 6H) ' 4.97 (d '7=3·6Ηζ,1H), 4.28 (q, J=4.4, 9.6 Hz, 1H), 3.83-4.01 (m, 4H), 3.80 (dd, &lt;/=3.2, 10_0Hz, 1H), 3.71 (dd'J=4.4' 10.6Hz, 1H) '3.60-3.68 (m, 3H), 3.59 (s, 2H)' 3.38 (dd'J=8.0, 13.6Hz, 1H), 2.66 (t, J=7.6Hz, 2H), 2.30 (t, J=7.6Hz, 2H ) ' 1.32- 1.81 (m, 42H), 0.97 (t, J = 6.8 Hz, 3H). 13C-NMRCDC13/CD30D=1/1, l〇〇MHz)3173.92, 171.63, 150.67 '150.03 ' 149.13,148.25,147.65,146.72,139.34, 131.81,124.72,123.54,117.52,117.34,116.97,116.59,116.42, 116.25 ' 116.08,115.93,99.02,73.75,71.23,69.34,69.15, 68.38 ' 68.14 ' 66.24 ' 49.82,41.06,39.57,35.66,34.33,31.63, 31.23 ' 30.61,29.10,29.07,29.00,28.94,28.85,28.79,28.71 , 28.65 ' 28.38 ' 25.24, 25.20, 21.93, 13.01. [啦+53.8 (cl.0, CH2C12/CH30H: 1/1) ° C49H77F4N209[M+H]+ HRMS (ESI) Calculated: 913.5565 s Found: 913.5606. , into 1-0-(6-(3-trifluoromethyl strep-acetamide)_6_deoxy_a_D4 lactose palladium glycoside)- 2-(1 dioxin) eleven fluorenyl) ribosyl -1,3,4-octadecane triol (C27) 55 201228666

OH was used as a starting material to provide C27 (12 mg, 0.013) using a procedure similar to the procedure for the synthesis of C20 using compound C19 (34 mg, 〇. 〇45 mmol) and 3-trifluoroindoleacetic acid (9.2 mg, 0.045 mmole). Methylene '29%) white solid. Mp : 157 ° C °1H-NMR (CDC13 / CD30D = 1 / 1 400 MHz) ^ 6.96-7.82 (m, 7H), 4.96 (d, J = 3.6 Hz, 1H) ' 4.25-4.30 (m, 1H), 4.03-4.10 (m,1H),3.77-3.91 (m,5H) '3.53-3.74 (m,5H), 3.36-3.44 (m,1H), 2.65(t ,2H), 2.29(t,J=7.6 Hz, 2H), 1.27-1.76 (m, 42H), 0.97 (t 7 = 6.83⁄4, 3H) °13C-NMR (CDC13/CD30D=1/1, 100MHz) (5174.52, 172.19, 150.04 (dd, 々247 '13Hz), 148.52 (dd, household 244, 13Hz), 139.90, 136.43, 132.64, 129.02, 127.67 '125.80, 124.17, 116.76 '116.60, 11U7, 99.64, 74.33, 71.87, 69.93, 69.73, 68.98, 68.76, 66.90,60.57, 50.44 »42.27 &gt;40.16 &gt;36.25 &gt;34.92 &gt;32.20 -31.82 &gt;31.21 &gt;29.68 &gt; 29.65 '29.59,29.53,29.44,29.38,29.30,29.24,28.97,25.83, 25.80,22.52 , 13.60. [啦+47.4 (cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) of C5〇H78F5N209[M+H]+ calculated value: 945.5627, found: 945.561 divination synthesis 1-(9 -(6-(4-nonyl phenylacetamide)-6-deoxy-α-D-galactose sucrose)~2~( 11 -(3,4-difluoro) stetyl) Amine Glycosyl -1,3,4_ octadecane triol (the C28)

S 56 201228666

OH was similar to the procedure for the synthesis of C20 using compound C19 (34 mg, α〇β mmol) and 4-indolylacetic acid (6.8 mg, 0.045 mmole) as starting material to provide C28 (11 mg '0.012 mmcd, 27 %) white solid. Mp : 171 ° C °1H-NMR (CDC13/CD30D = 1/1 '400 MHz ) (57.28-44 (m , 4H) '7.12-7.26 (m '2H), 7.03-7.08 (m, 1H), 5.01 ( d 'J=3.6Hz, 1H) '4.324.41 (m ' 1H), 3.83 - 3.95 (m, 5H), 3.67-3.79 (m, 3H), 3.66 (s, 2H), 3.40 (dd, J= 7.6, 13.6 Hz, 1H), 2.73 (t ' J = 7.6 Hz, 2H) ' 2.37 (t ' J = 7.6 Hz, 2H), 1.32-1.87 (m, 42H), 1.05 (t, J = 6.8 Hz, 3H) °13C-NMR (CDCl3/CD3〇D=l/l, 100MHz) (5173.94,172.96,149.83 (dd,J=247,13Hz),148.02 (dd,J=244,13Hz) '139.42,136.24 ' 131.26,128.86,128.47, 123.42,116.31,116.15,99.10,73.89,71.43,69.40,68.98,68.41,68.25,66.49,49.82,42.07,39.42,35.83,34.47,31,78,31.34,30.73,29.23,29.19, 29.12, 29.06, 28.97, 28.92, 28.84, 28.80, 28.77, 28.5, 25.35, 25.32, 22_06, 20.10, 13.22. [Brown 5+3i 8

(cl.O, CH2C12/CH30H: 1/1). HRMS (ESI) calcd for C50H81F2N2O9 [M+H]+: 891.5910, found: 891.5988. Synthesis of l_〇-(6-(3-indolyl phenylacetamide)-6-degreased-aD-galactose π-downane 2~(ll-(3,4-difluorophenyl)undecyl) Amino-D-ribosyl-I,3,4-octadecanotriol (C29) 57 201228666

Compound C19 (34 mg, α (Η5 mmol) and 3-toluic acid (6.8 mg, 0.045 mmole) was used as starting material to provide C29 (14 mg '0.016 mmol ' 35%) in a procedure similar to the procedure for the synthesis of C20. White solids. mp: 167 〇 C. 々-NMR (CDC13/CD30D = 1/1, 400 MHz) 37.18-7.51 (m, 7H), 5.08 (d, ΧΟΗζ, 1H), 4.36-4.43 (m, iH ), 3.91-4.02 (m, 5H), 3.23 - 3.35 (m, 4H), 3.73 (s, 2H), 3.47 (dd, J = 7.8, 13.8 Hz, 1H), 2.79 (t, / = 7.8 Hz, 2H), 2.57 (s, 3H) ' 2.43 (t, J=7.6Hz ' 2H)' 1.46-1.94 (m, 42H), l.li (t, «/=6.8Hz, 3H ). l3C-NMR ( CDCl3/CD3OD=m, l〇〇MHz) &lt;5173.96, 172.85, 149.52 (dd, *7=245, 13 Hz), 148.13 (dd, /=243, 13 Hz), 139.43, 137.90, 134.27, 129.41, 128.13, 127.37, U5.61, 123.67, 116.35, 116.19, 99.15, 73.99, 71.49, 69.44, 69.00, 68.4, 68.30, 66.53, 49.88, 42.50, 39.46, 35.89, 34.52, 31.91, 31.39, 30.76, 29.28, 29.23, 29. U, 29.01, 28.96, 28.88, 28.84, 28.8, 28.55, 25.38, 25.36, 22.11, 13.29. [. +36 8 (cl.O CH2Cl2/CH3OH: 1/1). C50H8lF2N2O9 [M+H]+ hrms (ESI) Calculated: 891.5910, found: 891.5950. Synthesis 1-0-(6-(2- phenylphenylamine)-6- Deoxy-ct-D-galactose alpha-decanoose 1_(3,4-difluorobenzene)undecyl)amino-D-ribosyl-I,3,4-octadecanol triol (C30) Sense

S 58 201228666

OH was used as a starting material to provide C30 (16 mg, 0.018 mmo, 40%) using a compound similar to the procedure for the synthesis of C20, using compound C19 (34 mg, q.sup.45 mmol) and 2-indolylacetic acid (6.8 mg, 0.045 mmole). White solid. 182°C ° ^-NMR ( CDC13/CD30D=1/1 &gt; 400MHz) δη3Ul ^ (m,4H), 7.01-7.26 (m,3H),4.99 (d, "7=3·6Ηζ,1H), 4.30-4.35 (m,1H) '3.83-3.94 (m,5H), 3.68-3.75 (m,6H), 3.40 (dd,J=8.0,13·8Ηζ ' 1H), 2.72 (t,,2H), 2 45 (s, 3H), 2.36 (t ' J = 7.6 Hz, 2H), 1.32-1.87 (m, 42H), 1.04 (t &gt; J = 6.8 Hz β Η) °13C-NMR (CDC13/CD30D=1 /1 ΊΟΟΜΗζ) J173.86,172.42,149.48 (dd,J=246,13Hz),. 147.94 (dd, /=243 Ί3Ηζ),139.41 Ί36.38 Ί32.67 Ί29.91 Ί29.65 Ί26.99 ^ 125.79 ' 123.63,116.28,116.U,99.15,73.9,71.38,69.38,69.n '68.35,68.20,66.56,49.74,40.27,39.49,35.80,34.45,31.78,31.32,30.70,29.2,29.16,29.10,29.04 , 28.95, 28.90, 28.81 '28.77, 28.74, 28.48, 25.33, 25.29, 22.03, 18.65, 13.17. Wf+38.3 (cl.〇, CH2C12/CH30H: 1/1). HRMS (ESI) calcd for C5qH81F2N2[M+H]+: 89. Synthesis of 1 - Ο-(6-(2-naphthylamine)-6- έ&quot;milk-a-D- ·^Lactose D-dose"-2 -(11-(3,4-two gas) Benzene)--acid-amino)-D-ribosyl-1,3,4-octadecane triol (C31) 59 201228666

Compound C19 (34 mg, α〇β mmol) and 2-naphthylacetic acid (8.4 mg, 0.045 mmole) were used as starting materials to provide C31 (12 mg, 0.013 mmo, 29%) in a similar procedure to the synthesis of C20. White solid. Mp : 178 ° C. b-NMR (CDC13/CD30D = 1/1, 400 MHz) &lt;57.85-8.04 (m, 3H), 7.40-7.69 (m ' 4H) ' 7.05-7.29 (m, 3H), 5.03 (d, J = 3.6) Hz,1H),4.31-4.40(m,1H) '3.87-4.01 (m,6H), 3.72-3.81 (m,4H) ' 3.46 (dd ' J=7.8,14.0Hz,1H), 2.76 (t, &lt;/=7.6 Hz, 2H), 2.38 (t, "/= 8.0 Ηζ, 2H), 1.32-1.90 (m, 42H), 1.08 (t ^ = 6.6 Hz θ Η) °13C-NMR (CDC13/CD30D = 1/1 &gt;15〇MHz) (5173.92,172.58,149.54 (dd,J=244,12Hz),147.93 (dd, •/=240 '13Hz) '142.73,139.39,133.06,131.96,127.78,127.34, 127 (H, 126.97, 126.48, 125.6, 125.20, 123.60, 123.30, 123.14, 117.04, 116.24, 116.09, 110.83, 99.07, 73.85, 71.38, 69.38 &gt; 69.05^68.42 &gt;68.21 &gt;66.45 &gt;49.81 &gt;42.35 &gt;39.52 &gt;35.75 &gt; 34·41,31·74,31·29,30·67,29.72,29.18,29.13,29.07,29.(U, 28.92 &gt;28.68 &gt;28.78 &gt;28.72 &gt;28.45 &gt;25.30 525.28 &gt;22.00 Ί3.12 〇[a]f+8.3 (cl.O,CH2C12/CH30H : 1/1). Synthetic chemical formula (1) NKT cell activation and testing. The structure of the compound of formula 1.201228666

OH wherein R is selected from Table 1 to provide the corresponding compound. Table 1 Compound structure. Compound number, R=

Y A15 X= OPh, Y= Η, Z= H 9H OH 〇ZViT/X A16 X= Oi-Pr, Y= Η, Z= H A17 X= F, Y= F, Z= HH〇\—Hl^ ^1〇A18 X= F,Y= H,Z= F OH I Ξ OH A23 X= Cl,Y= H,Z= Cl 〇^^Y^c14h29 A24 X= Cl,Y= Η,Z= H OH A25 X= Br, Y= Η, Z= H A26 X=F - Y=F - Z=H A27 X=N02 - Y=H &gt; Z=H A28 X=N ( CH3 ) 2,Y=H, Z=H A29 X=F, Y=CF3, Z=H A30 X=i-Pr, Y=H, Z=H A31 X=2-( 5-F)-pyridine, Y=H, Z=H

C34 : X=OPh (4-F) - Y=H - Z=H C4 n=l C5 n=2 C6 n=3

C20 : X=N02, Y=H, Z=H C21 : X=N02 - Y=H - Z=N02 C22 : X= t-Bu, Y= Η, Z= H C23 : X= Br, Y= Η , Z= H C24 : X= OMe, Y= Η, Z= H C25 : X= CF3, Y= CF3, Z= H C26 : X= F, Y= F, Z= H C27 : X=H &gt; Y=CF3 - Z= H C28 : X Η, Y= H, Z= Me

C29 : X= H,Y= Me,Z= H 61 201228666 C30 : X= Me,Υ= Η,Ζ= Η

OH C31

ΗΝ 〇人 / A32

OH

'v^^|^VC14H29 OH A3 3

A3 5 N F A34

A36

OH A37 A3 8

Cr

A19, A20

OH A21 s 62 201228666

9H

A39 Example 2 Activation of antigen presenting cells (APC) A20CDld cells and mNK1.2 cells were used as APCs and effector cells, respectively. Guava ViaCount reagent was used to determine viability and viable cells with Guava EasyCyte Plus. The Mouse IL-2 DuoSet ELISA Development system was used to detect the production of iL_2. The cells and glycolipids were co-cultured at 37 °C and the supernatant was collected after 24 hours of culture. And, after 2 days of culture, cells were collected to measure viability, and the results showed that these sugars were not toxic. As shown in Figure 6, all of the test compounds exhibited activity of Apc activation at this junction. IFN-γ and 11-4 cell hormone secretion Female C57BL/6 mice (16w4d) were sacrificed and their spleens were collected for testing. The cells and glycolipids were co-cultured at 37 C for 3 days, and the supernatant was collected after 3 days of culture (about 6 hours). Next, alarma Bhie (5%/200 ul) was added, and the cells were cultured for 7 hours to measure the proliferation of the cells. Cytokine production was determined using the mouse IL-4 and IFN-γ Duo Set ELISA Devel0pment system. In this test, DMSO was a negative control group and KRN_7 was a positive control group. As shown in Figures 7-9, the compound has been shown to favor Thl cell hormone secretion profile (expression pattern), indicating its applicability against tumor, antiviral/antibacterial, and adjuvant activity. r ϊϋ ϊϋ 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾 巾, '[' Ί彳 Ί彳 业 人士 人士 人士 依 依 依 依 依 63 63 63 63 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 2012 BRIEF DESCRIPTION OF THE DRAWINGS The following drawings are a part of this specification and are intended to further illustrate certain aspects of the disclosure, and may be The invention will be better understood by the detailed description of the embodiments. Figure 1 is a simplified schematic diagram depicting the synthesis of C34, A15-21. Flowchart 1. Reagents and conditions: (a) TfN3, K2C03, CuS04, DCM, MeOH, H2 〇; (b) gasified triphenyl fluorenyl, triethylamine, hydrazine; (c) BnC], NaH, DMF ' 曱 stupid; (d) HC, toluene, MeOH; (e) A5, Me2S2-Tf2, THF '4 A MS; (f) LiAlH4, THF; (g) RC02H, HBTU, NMM, DCM; (h) Pd(OH) 2, H2, MeOH, DCM. Figure 2 is a simplified schematic diagram depicting the synthesis of A23-A25. Flowchart 2. Reagents and conditions: (a) Pd(OH)2, H2 (80 psi), MeOH, DCM, AcOH; (b) RC02H, HBTU, NMM, DCM MeOH. Figure 3 is a simplified schematic diagram depicting the synthesis of formula (4). Flow circle 3. Figure 4 is a simplified schematic diagram depicting the synthesis of compounds C5-C7. Flow chart 4. Reagents and conditions: (a) PPh3, THF, H20; (b) Ph(CH2)nC02H, HBTU, NMM, DCM; (c) Pd(OH)2'H2, DCM, MeOH. Figure 5 is a simplified schematic diagram depicting the synthesis of compounds C20-C31. Flow Figure 5. Reagents and conditions: (a) TsC pyridine; (b) NaN3, DMF; (c) PPh3' THF, H20; (d) RCH2C02H, HBTU, NMM, MeOH, DCM. Figure 6 shows glycosphingolipid-induced IL-2 secretion in the A20CDld and mNK1.2 cell systems. The data is the mean soil standard deviation;, '", meaning no compound. Figure 7 shows IFN-r cytokine secretion by spleen cells from female C57BL/6 mice. Figure 8 shows IL-4 cell hormone secretion by spleen cells from female C57BL/6 mice. 64 201228666 Figure 9 shows the ratio of cytokine secretion obtained from Figure 7 versus Figure 8. [Main component symbol description] Benefit 65

Claims (1)

201228666 VII. Scope of application: 1. A method for preparing a palm compound containing a sugar or a s_ type of a chemical formula (1) ΟΗ^ι (1) i中-,丽' '~=η ^ sister base, thin base, or line stop = base: base or substituted heteroaryl = U 丞' κ3- ΟΗ or Η, R4 = ΟΗ or Η, R 4 , aryl ' or substituted heteroaryl, or pharmaceutically acceptable 5;; nt' of the formula 1 is prepared by the following &amp; ' /, Chinese chemical in the hydrogenation strip _ Continue to the compound of Wei Wei (2): PGO (2) 〇 2. According to the first paragraph of the patent application, it is mainly selected from Pd/C, Pd (OH2), or Reynolds welding:, medium: the = catalyst is a hydroxyl protecting group. &amp; Nickel among them RrOH, and PG system 3. According to the scope of the patent application! In the method of the method, the compound is prepared by the step of the indole bond formation reaction, and the compound of the formula (3) is coupled with the reagent of the T-form: 'to generate the action system for coupling PGO NH2 OPG, r Li OPG (3) '29 201228666 to compound of formula (4): H〇H5 r4 (4) wherein X = alkyl, dilute, R3 = H, OH, r4 = Η, OH, R =矣I. , an aryl group, a heteroaryl group or a substituted heteroaryl group, or a pharmaceutically acceptable compound thereof. 4. The method according to claim 3, wherein the chemical system is reduced by a compound of the following chemical formula : σ PGO PGO 1 n3 opg OPG (5) 5. The method according to claim 4, wherein the reduction is carried out by using a deuterated chain, a halogenated sodium, a deuterium complex, a phosphine complex, It is achieved by enzyme reduction, hydrogenation, or transfer hydrogenation. 6. The method according to item 5 of the patent application, wherein the compound of the chemical formula 5 is prepared by the following: (a) a compound of the formula (6): PGO (6) wherein PG is a hydroxy protecting group and LG is a leaving group, and reacts with a compound represented by the structure of the formula (7). N3 OPGΗ〇ΧΛ^14η29 OPG (7) Next 67 201228666 =) The α-saccharification is carried out to obtain the chemical formula (1) ”:, and optionally, the method of the first item of R:R=!S, which is ..., aryl, heteroaryl or substituted 4ΐί, fluorenyl, or terminated in aryl , substituted aryl, compound preparation = silk, the 彳 (4) secret chemical (8) R3 Vx &gt;~~r4 PGO| HN OPG0χΑΛ一 OPG '29 (8) where PG is a hydroxy-protecting group 2if ° month patent range item 8 'where the compound of formula 8 is wrong by the chemical formula (9) Compound: R3 &gt;-r4 —A Vx PGO| HN opg OPG (9) is prepared by reacting with a compound represented by an alkanoic acid, an aromatic acid, an aryl-alkanoic acid, a substituted aryl-alkanoic acid, and a heterocyclic acid. According to the method of claim 9, wherein the compound of the formula 9 is prepared by reducing the compound of the compound of the formula (1〇): N3 r3 OPG C14H29 Into % 68 s (10) 201228666 11. According to the method of the patent application, the compound straw is prepared from the chemical formula (11) of the chemical formula (11): σ sodium nitrite Replaced by leaving OPG PGO 丨29 wherein R is a leaving group. 12. According to the patent application (11), the compound is prepared from the compound of formula (12): r3Vx々5 OPG PGO H^l opg R4 OPG Item 11 of the method, wherein the chemical formula 11 ϊ -3⁄4^ JL·· uL·.. · (12) by the method of testing and the presence of miscellaneous chlorine , == u The chemical system is prepared by hydrolysis of a compound of formula (9): OPG, V/VR5 pgoA〆^^ broad X, PGO] HN OPG 0 :: OPG 丨29 (13) where R is - The acid or the unstable «protective group. According to the method of claim 13, wherein the chemical formula 13 t is not prepared by the formation of a guanamine bond of a compound represented by the structure of the formula (U): 69 29 201228666 ^IH2 OPG vAt^c14h (H). The method of claim 14, wherein the azide reduction of the compound of the chemical formula 14 is made of OPG 15. The compound according to the scope of the patent application is prepared by the chemical formula (15: OR OPG PGO PGO N3 gPG OPG (15) The method of claim 15, wherein the compound of formula 15 is prepared by a bond of a compound in which Lewis acid is used as a catalyst, and a compound of 6) YORK OR OPG PGO PGO LG (16) wherein K} is a basal protecting group, LG is a leaving group, and R is a vinegar. 17. According to the method of the i-th patent of the patent application, the chemical formula of the bean middle-grade compound: , xAt^c14h29 OH type or S-type ο a pair of palm compound, which contains the enzyme Leu of the chemical formula i R- 201228666 OHp Or an active isoform, variant, substitute, derivative, salt, or ester thereof. 19. A compound of the formula (丨), wherein the compound is prepared by the method according to any one of the claims 1 to 17. ,Ν23〇.—a compound of the formula: ΒηΟ 〇UQ ΗΝ 八R ΡΒη ΒηΟ C14H 29 or 'thin base, terminated in aryl, substituted aryl, heteroaryl aryl silk'' or its medicinal Accepted salts - compounds of the chemical formula: ^ 0Β-1-0Η ΒηΟ, 0 JJ 〇, H, N|Ar ΡΒηBn0*, c14H 29 Ph λ is a zh-based group, terminated at the base of the aryl group, Substituted aryl, hetero-yl, peak heteroaryl, or a pharmaceutically acceptable salt thereof. a group of hybrids: a compound selected from the group consisting of compounds of the following chemical formula: ΒηΟ ΝΗο OBn C14H29 OBn 71 201228666 Or its salts; Or its salts; OH 72 201228666 OH OH OH 73 201228666 21. The plant is prepared according to the method of the 2G item of the scope of the patent application, and the compound is prepared by the method of the first item: the compound of the item and the pharmaceutically acceptable carrier 20 23. According to the scope of claim 22, the tumor growth, efficacy 2, 'sputum' of the patient of the composition is required to provide inhibition. 24. According to the scope of claim 22, the person needs the composition. The patient's immune system, Gongzhile', and 5 things' provide stimulation