Misra, Anup Kumar

Roy, Nirmolendu

NOPR

Indian Journal of ChemistryVo1.36B, May 1997, pp. 434 - 435Synthesis of a tetrasaccharide analoguerelated to the repeating unit of the antigenfrom Klebsiella type 2Anup Kumar Misra & Nirmolendu Roy"Department of Biological Chemistry, Indian Association forthe Cultivation of Science, Jadavpur, Calcutta 700 032, IndiaReceived 3 September 1996; accepted 29 November 1996The disaccharide methyl 2,6-di-0-benzyl-3-0-(methyl-2,3,4-tri-0-benzyl-a-D-glucopyranosyluronate)-~-D-man-nopyranoside 2 has been allowed to react with ethyl2,3,6,2',3',4',6' -hepta-O-acetyl-l-thio-~-D-maltoside 1with methyl triflate as promoter. Removal of blockinggroups from the product affords methyl 3-0-(methyl a-D-glucopyranosyluronate )-4-0-[ 4-0-( u-n-glucopyrano-syl) -(3 -D- glucopyranosyl]-~-D-mannopyranoside 4which is the tetrasaccharide analogue related to therepeating unit of the antigen from Klebsiella type 2. Thestructure of 4 has been confirmed by its IH and 13CNMR spectra.f3-Mannopyranosidic linkages are frequentlyencountered in polysaccharides'< and glyco-conjugates':" and they participate in a variety of~AcAcOOAc~~~SEtAcO1Notebiological functions. Synthesis of oligosaccharidesinvolving !3-D-mannopyranosides is thereforeimportant for understanding the structure-functionrelationship of the biopolymers containing suchresidues. Recently, we have synthesised thetetrasaccharide repeating unit of the antigen fromKlebsiella type 2 (K2). In that connection, it wasalso deemed interesting to synthesise atetrasaccharide analogue related to the repeatingunit of K2, where the two D-glucose moieties area(l-)o4) linked instead of a(l-) 3) as found in thenative antigen. Immunochemical studies (to betaken up in a separate project) including both K2repeating unit and its tetrasaccharide analogue,whose synthesis is reported here, will provideuseful information on the relation betweenstructure and immunological specificity of the K2antigen.a-D-Glcp-( 1~4)-P-D-Glcp-( I~4)-p-D-Manp-OMe3i1o-n-Glcp AAnalogue ofK2COOMeBnO~~Bn~oa-:'r:«:OMeH~OBn(}--J OBn2OR2R20 /R2 ~OCOOMe3. R1 = Ac; R2 z Bn4. R1 = R2 = HOMeThe strategy of block synthesis was utilised in thepresent report. Maltose octaacetate was treated withethanethiol and borontrifluoride etherate indichloromethane to give the thioglycoside 16 in 94%yield. The thioglycoside 1 was allowed to react withthe aceeptor methyl 2,6-di-0-benzyl-3-0-(methyl2,3 ,4-tri-0-benzy l-a- D-glucopyranosyluronate )-~-D-mannopyranoside 25 in the presence of methyltriflate as promoter to give the tetrasaccharidederivative methyl 2,6-di-0-benzyl-3-0-(methyl2,3,4- tri -0-benzy l-a- D-glucopyranosy Iuronate )-4-0-[2,3,6-tri-0-acetyl-4-0-(2,3,4,6-tetra-0-acetyl-a-D-glycopyranosyl)-~D-glucopyranosyll-~D-manno-pyranoside 3 in 73% yield. Zemplen deacetylation"of 3 followed by hydrogenolysis in the presence of10% Pd/C gave the tetrasaccharide analogue methyl3-0-(methyl n-n-glucopyranosyluronate )-4-0- [4-0-( a-D-glucopyranosyl)-~D-glucopyranosyll-~D-mannopyranoside 4 in 60% yield. The III NMRspectrum of 4 showed peaks for methoxyl (8 3.54),methyl ester (8 3.79), ~glucosidic (84.39, J=7 Hz),~mannosidic H-I (8 4.50), a-glucosidic H-I (85.14, J= 3.5 Hz) and a-glucouronosidic H-I (85.20,J=2.4 Hz). The 13C NMR spectrum showed signalsfor 26 carbons which included 4 anomeric carbonsat 8 100.07 (C-l'''), 100.26 (C-l'), 101.17 (C-l)and 102.58 (C-1"), one methoxyl and one methylester at 057.37 and one ester carbonyl at 0 173.0.Experimental SectionGeneral. All reactions were monitored by TLCon silica gel G (Merck). Column chromatographywas performed using silica gel (SRL, 100-200mesh). All solvents were distilled before use and allevaporations were conducted at 40° unless statedotherwise. Optical rotations were measured on aPerkin-Elmer model 241 MC polarimeter at 25°. IHand 13C NMR spectra were recorded on a Jeol FX-100 and Bruker 200 spectrometer respecti vely inCDCl3 (internal standard TMS or dioxane).Methyl 2,6-di-O-benzyl-3-0-(methyl 2,3,4-tri-O-benzyl-a-D-glucopyranosyluronate)-4-0-[2,3,6-tri-O-acetyl-4-0- (2,3,4,6-tetra-O-acetyl-a-D-glu-copyranosyl) -~D-glucopyranosyl] -~[)-manno-pyranoside 3. A solution of 1 (79.6 mg, 0.12mmole),2 (48.8 mg, 0.06 mmole) and MS 4A (500mg) in dry toluene (4 mL) was stirred at- roomtemperature for 1 hr. Methyl trif1ate (66 J,lL, 0.58mmole) was then injected into the mixture andstirring continued for 20 hr at 25°C. The reactionNOTES 435was quenched with triethylamine (0.5 mL) and thereaction mixture filtered through a Celite bed. Thefiltrate was concentrated to a syrup. Columnchromatography of the syrup using toluene-ether(2:1) gave pure 3 (62 mg, 73%), [alo+38.5° (c l.15,CHCl); 'n NMR (CDCI): 8 2.0-2.12 (7s, 21H, 7COCH3), 3.48 (s, J1",2,,7.5 Hz, 1H, H-I ", 5.06 (d,Jr.2, =2 Hz, 1H;H-1'), 7.34 (m, 25H, 5Ph). Anal:Calcd for C47H8S029:C, 50.52; H, 7.94. Found: C,50.46: H, 8.16%.Methyl 3-0-(methyl a-D-glucopyranosyluro-nate) -4-0-[4-0-(a-o-glucopyranosyl) -~D-gluco-pyranosyl] -~D-mannopyranoside 4. A solution of3 (60 mg, 0.05 mmole) in acetic acid (10 mL) wasstirred with Pd-C (150 mg) under hydrogen for 24 hrat room temperature. The reaction mixture wasfiltered through a Celite bed and evaporated todryness. Traces of acetic acid and water wereremoved by repeated coevaporation with toluene.The dried mass was dissolved in 0.05 M sodiummethoxide (5 mL) and stirred at room temperaturefor 4 hr. The reaction mixture was neutralised withDowex SOW-X8 (H+) resin, filtered and evaporatedto a glassy material (23 mg, 60%), [a]o+70° (c, 2.4,H20); IH NMR (D20): 0 3.54 (s, 3H, OCH), 3.79(s, 3H, COOCH3), 4.39 (d, Jr',2 ..=7 Hz, lH, H-I "),4.50 (bs, lH, H-l), 5.14 (d, J\',.2" =3.4 Hz, IH, H-1'''),5.20 (d, J1'.2,=3.5 Hz, lH, H-l'-); 13C NMR(D20, l,4-dioxane as internal standard): 0 57.37(OCH3 and COOCH3), 60.96, 6l.38, 6l.58 (C-6, C-6" and C-6"'), 69.73, 69.80, 7l.72, 72.09, 72.20,73.16 (2 carbons), 73.26, 73.32, 73.74, 73.69, 76.29,77.76,78.37,79.30,81.42, 100.07 (C-1'''), 100.26(C-l'), 101.17 (C-l), 102.58 (C-1") and 173.0(COOCH3). Anal: Calcd for C26H44022:C, 44.07; H,6.26. Found: C, 43.85; H, 6.40%.ReferencesI Kenne L & Lindberg B, Bacterial polysaccharides, in: Thepolysaccharides, Yo\. 2 (Academic Press, New York), 1983,287.2 Stephen A M, Other plant polysaccharides, in: Thepolysaccharides, Vo\. 2 (Academic Press, New York), 1983,97.3 Griffiths A ; & Davies D B, Carbohydr Polymers, 1991,241.4 Sharon N & Lis H, Chern Engineering News, 59,1981,2.5 Misra A K & Roy N, Carbohydr Res, 278, 1995, 103.6 Misra A K & Roy N, Indian J Chern, 34B, 1995,865,7 Lonn H, J Carbohydr Chern, 6, 1987, 301.8 Zemplen G, Ber Dtsch Chern Ges, 59,1926,1254.

Synthesis of a tetrasaccharide analogue related to the repeating unit of the antigen from Klebsiella type 2

http://nopr.niscair.res.in/bitstream/123456789/57134/1/IJCB%2036B%285%29%20434-435.pdf

Synthesis of a tetrasaccharide analogue related to the repeating unit of the antigen from Klebsiella type 2

Abstract

Similar works

Full text

Available Versions

NOPR