Bhaduri, Amiya P

Mathad, Vijayavitthal T

Raj, Kanwal

Shefali

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Indian Joumal of ChemistryVo1.36B, September 1997, pp.808 - 809A convenient method for the synthesesof 4,5-g1ycals tVijayavitthal T Mathad, Shefali, Kanwal Raj &Amiya P Bhaduri"Medicinal Chemistry Division, Central Drug ResearchInstitute, Lucknow 226001, IndiaReceived 28 June 1996; accepted (revised)18 December 1996Pyridinium chlorochromate mediated oxidation of methyl2,3,4-tri- O-acetyl-a-o-hexoses 1,2, and 3 constitutes a new andconvenient method for synthesizing 4,5-glycals.Unsaturated hexoses have been used as chiral syn-thons for the syntheses of natural products likeolivin', actinobolirr', carbomycin and related antibi-otics ' and other complex organic compounds". Theposition of double bond in these sugars (1,2-,2,3- ,3,4- and 4,5- glycals) is of concern for designingthe synthetic strategy for obtaining these molecules.The reported procedures for the preparation of 4,5-glycals involve the use of oxidants like dimethylsul-foxide (OM SO) activated by sulfur trioxide- pyri-dine-triethylamine complex' and oxalyl chloride inOM SO in the presence of triethylamine". This com-munication describes a convenient method for ob-taining 4,5- glycals of some hexoses in. excellentyields using pyridinium chlorochromate (PCC) asoxidant.Partially protected derivatives of hexoses, viz.methyl a-D-glucopyranoside 1, methyl a-D-galac-topyranoside 2 and methyl a-D-mannopyranoside 3were prepared by following the reported proce-dures 7. Oxidation of the protected alcohols 1 and 2with PCC in dry toluene at reflux temperature for8-10 hrs yielded the unsaturated aldehyde 4 whereasalcohol 3 under similar condition gave the aldehyde5 (cf Scheme I) in 70-75% yields as syrupy liquids.Reduction of these aldehydes (4 and 5) with sodiumborohydride in methanol in the presence of AmberliteIR-120 (H+) ion exchange resin gave the protectedglycals 6 and 7 in excellent yields (80-85%).t CDRI Communication No. 5564NoteHO~ oOAeAcO =-L1 OAcH~c~ J! OAc 42 OMsOAe£0\ ~O~OAO\L:(IOMs OMsOAe A6.n.AC~C8. A = HH°l-O,~AD OMsCHOeAO OMsCHOa3. R=Ac 5. A = Ae 7.A=fCi9. A = H --lScheme IOeprotection of these glycals with sodium methoxidein methanol furnished the 4,5-glycals 8 and 9(Scheme I) in 70-75% yields. The structures of all thecompounds were characterised by FAB MS, IHNMR and I3C NMR spectroscopic techniques.Experimental SectionIR Spectra were recorded on a Perkin-Elmer PE557 spectrometer (vmax in ern"). FAB mass spectrawere recorded on a JOEL SX 102/OA 6000 massspectrometer using Argon/Xenon (6kV, lOmA) asthe FAB gas. IHand I3CNMR spectra were recordedon the Bruker WM-400 FT instrument using TMS asinternal reference (chemical shifts in 8, ppm).Syntheses of 4,5-unsaturated aldehydes 4 and 5:General procedure. PCC (0.32g, 1.5 mmole) wasadded portionwise to a stirred solution of desiredcandidate from the compounds 1-3 (0.32g, 1 mmole)in dry toluene (20 mL) and the mixture was refluxed(l100C) for 8-10 hrs. It was then cooled to roomtemperature (25°C) and filtered through Celite. Theresidue obtained was then washed with toluene (3x10mL) and the combined organic extract was con-centrated under vaccum to yield a crude residuewhich was purified by column chromatography oversilica gel. Elution with methanol-chloroform (1 :99,v/v) gave the aldehydes 4 or 5 as a semisolid.4: 'field 72.3%; IR(KBr): 1718(CH=O),1660(C=C); MS:~/z 259(~+1), 281(~+Na); IHNMR (CDCb): 9.25(s, IH, CHO), 5.91(d, J=3Hz,IH, H-4) 5.72 (dd, J=12, 4 Hz,_IH, H-3), 5.20(m,2H, H-l and H-2), 3.45(s, 3H, OMe), 2.12 and2.14(2s, 3Heach, 2xOCOCH3); 13CNMR (CDCb):185.31(CHO), 169.80e* (e, denotes overlapping withother signals); (2xOCOCH3), l48:82(C-5), 116.83(C-4), 98.l9 (C-l), 68.58(C-3), 66.26(C-2), 56.73(OCH3), 20.56 (2xOCOCH3). [Spectra of the 4,5-un-saturated derivatives 4 of methyl 2,3,4-tri-O-acetyl-cc-n-glucopyranoside 1 and methyl 2,3,4-tri-O-acetyl-u-n-galactopyranoside 2 were superimpos-able with each other]5: Yield 73.0%; IR(KBr): 1720(CH=O), 1660(C=C); MS:m/z 259 (~ + 1),281 (M+ + Na); IHNMR (CDCb): 9.25 (s, IH, CHO), 5.86 (d, J=2Hz,IH, H- 4), 5.80 (dd, J=4Hz, IH, H-3), 5.32 (dd,J=4Hz, IH, H-2), 5.l4(d, J=4Hz, IH, H-l), 3.52 (s,3H, OCH3), 2.12e (s, 6H, 2xOCOCH3); l3CNMR(CDCb): 185.63 (CHO), 169.78 and 169.67(2xOCOCH3), 149.10 (C-5),117.69(C-4),98.96(C-I), 64.26(C-3), 63.34 (C-2), 56.59 (OCH3),20.48e (2xOCOCH3)Syntheses of 2,3-di-O-acetyl-a-n-methyl 4,5-glycals 6 and 7: General procedure. To a stirredsolution of the desired compound 4 or 5 (0.25g, 1mmole) in dry methanol (15 mL) in the presence ofAmberlite IR-120 (H+) ion exchange resin (0.20g)was added NaBH4 (0.012g, 0.33 mmole) in portions.The reaction mixture was then allowed to stir at roomtemperature (25°C) for 1 hr, filtered through glasswool into a round bottomed flask containing a dropof acetic acid and was evaporated in vaccuo. Water3 (a) Tatsuta K, Tanaka A, Fusimoto K, Kinoshita M &(20 mL) was then added to it and extracted with Limezawa S,} Am Chern Soc, 99,1977,5826;chloroform (3x30 mL). Usual work-up of the organiclayer furnished a crude residue which was purifiedby column chromatography over silica gel. Elution 4with methanol-chloroform (1 :49, v/v) gave pure al-cohol 6 or 7 as a semisolid.6: Yield. 84%; MS; m/z 261 (M+ + 1),283 (M+ +Na); IH NMR (CDCb): 5.42 (dd, J=3Hz, IH, H-3),5.14 (dd, J- 3Hz, IH, H-2), 5.02 (me, 2H, H-4 andH-l), 4.08 (bs, 2H, H-6), 3.54 (s, 3H, OCH3), 2.12 6and 2.06 (2s, 3H, 2xOCOCH3); 13CNMR (CDCb): 7170.28 and 170.19 (2xOCOCH3), 152.64 (C-5),*Where e denotes overlapping with other signalsNOTES 80997.26 (C-4), 95.69 (C-I), 69.19 (C-3), 66.89(C-2),61.67(C-6), 56.61(OCH3, 20.95 and 20.74 (2 xOCOCH3).7: Yield 85%; MS: m/z 261 (M+ + 1),283 (M+ +Na); IH NMR (CDCb): 5.55 (t, J=3Hz, IH, H-3),5.16 (t,J=4.5Hz, IH, H- 2),5.00 (d,J=6Hz, 1H,.H-l),4.95 (d, J=0.6Hz, IH, H-4), 4.08 (dd, J=3Hz, 2H,H-6), 3.52 (s, 3H, OCH3), 2.10 and 2.09 (2s, 3H each,2 x OCOCH3) : 13C NMR (CDCb): 170.33 and170.18 (2 x OCOCH3) 152.71 (C-5), 97.28 (C-4),96.19 (C- 1),69.21 (C-3), 66.90 (C-2), 61.67 (C-6),57.05(OCH3), 20.98 & 20.81 (2xOCOCH3).Syntheses of 4,5-glycals 8 and 9: General proce-dure NaOMe (0.05 g, 1 mmole) was added to astirred solution of 6.or 7 (0.26 g, 1 mmole) in drymethanol (10 mL) and the mixture was stirred atroom temperature (25° C) for 1 hr. It was then passedthrough band of Amberlite IR-120 (W) ion exchangeresin and the eluent evaporated in vaccuo to yield acrude residue. Purification by column chromatogra-phy over silica gel using methanol-chloroform (1:9v/v) as eluent gave pure 8 or 9 as a semisolid.AcknowledgementAuthors (V T M & Shefali) are thankful to Minis-try of Health & Family Welfare and Indian Councilof Agricultural Research respectively for financialassistance.ReferencesI Frank R W & John T V,} Org Chern., 48,1983,3269.2 RahmanM A& FraserReidBJ,}Arn Chem Soc, 107,1985.5576.(b) TatsutaK, Amemiya Y, Maniwa. S& Kinoshita M, Tet leu.21,1980,2837.Guliano R M, Buzby J H & Macropulos N, J Org Chern,55, l.990, 3555.5(a) Parikh J Rand Doering WVon E,} Am Chern Soc, 89,1967.5505(b) Cree G M, Mackie D W & Parlin A S, Can} Chern, 47,1969,511.Mancuso A J & Swem D, Synthesis, 1981, 165.Whistler R L & BeMiller J N, Methods in carbohydratechemistry, vol. 6 (Academic Press New York) 1972, 411.

A convenient method for the syntheses of 4,5-glycals

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A convenient method for the syntheses of 4,5-glycals

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