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Synlett 2005(7): 1095-1100  
DOI: 10.1055/s-2005-865228
LETTER
© Georg Thieme Verlag Stuttgart · New York

Study of the Regioselectivity of Intra- and Intermolecular Glycosylations of Mannoside Diol Acceptors

M. Belén Cid*, Serafín Valverde*, J. Cristobal López, Ana M. Gómez, Mercedes García
Instituto de Química Orgánica General, Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34(91)4973966; e-Mail: Belen.cid@uam.es;
Further Information

Publication History

Received 25 October 2005
Publication Date:
14 April 2005 (online)

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Abstract

The intramolecular glycosylation of thiomannoside donors linked through C6′ by a phthaloyl group to C3 of a diol mannoside acceptor is described. The unexpected results led us to undertake a systematic analysis of the factors affecting the regioselectivity of the intermolecular process. The substituents on the diol mannoside acceptor have been found to play an important role.

Key words

glycosylation - regioselectivity - stereoselectivity

    References

  • 3a Dwek RA. Chem. Rev.  1996,  96:  683 
    CrossrefPubMedGoogle Scholar
  • 3b Varki A. Glycobiology  1993,  3:  97 
    CrossrefPubMedGoogle Scholar
  • 3c Carbohydrates in Chemistry and Biology   Vol. 1-4:  Ernst B. Hart GW. Sinaӱ P. Wiley-VCH; Weinheim: 2000. 
    CrossrefPubMedGoogle Scholar
  • 3d Glycoscience   Vol. 1-3:  Fraser-Reid B. Tatsuta K. Thiem J. Springer-Verlag; Berlin, Heidelberg: 2001. 
    CrossrefPubMedGoogle Scholar
  • 4a Valverde S. Gómez AM. Hernandez A. Herradón B. López JC. J. Chem. Soc., Chem. Commun.  1995,  2005 
    CrossrefGoogle Scholar
  • 4b Valverde S. Gómez AM. López JC. Herradón B. Tetrahedron Lett.  1996,  37:  1105 
    CrossrefGoogle Scholar
  • 4c Valverde S. García M. Gómez AM. López JC. Synlett  2000,  22 
    CrossrefGoogle Scholar
  • 4d Valverde S. García M. Gómez AM. López JC. Chem. Commun.  2000,  813 
    CrossrefGoogle Scholar
  • 5a Ogawa T. Sasajima K. Carbohydr. Res.  1981,  93:  67 
    CrossrefGoogle Scholar
  • 5b Anikumar G. Nair LG. Fraser-Reid B. Org. Lett.  2000,  2:  2587 
    CrossrefGoogle Scholar
  • 6a Fraser-Reid B. López JC. Radhakrishanan KV. Mach M. Schlueter U. Gómez AM. Uriel C. Can. J. Chem.  2002,  80:  1075 
    CrossrefGoogle Scholar
  • 6b Fraser-Reid B. López JC. Radhakrishanan KV. Mach M. Schlueter U. Gómez AM. Uriel C. J. Am. Chem. Soc.  2002,  124:  3198 
    CrossrefGoogle Scholar
  • 6c Fraser-Reid B. Anilkumar GN. Nair LG. Radhakrishanan KV. López JC. Gómez AM. Uriel C. Aust. J. Chem.  2002,  55:  123 
    CrossrefGoogle Scholar
  • 6d Fraser-Reid B. López JC. Radhakrishanan KV. Nandakumar MV. Gómez AM. Uriel C. Chem. Commun.  2002,  2104 
    CrossrefGoogle Scholar
  • 6e López JC. Gómez AM. Uriel C. Fraser-Reid B. Tetrahedron Lett.  2003,  44:  1417 
    CrossrefGoogle Scholar
  • 6f Uriel C. Gómez AM. López JC. Fraser-Reid B. Synlett  2003,  2203 
    CrossrefGoogle Scholar
  • 6g Fraser-Reid B. López JC. Gómez AM. Uriel C. Eur. J. Org. Chem.  2004,  1387 
    CrossrefGoogle Scholar
  • 7a Arnap J. Haraldsson M. Lönngren J. J. Chem. Soc., Perkin Trans. 1  1985,  535 
    Google Scholar
  • 7b Ogawa T. Nakabayashi S. Agric. Biol. Chem.  1981,  45:  2329 
    Google Scholar
  • 8 Lemanski G. Ziegler T. Tetrahedron  2000,  56:  563 
    CrossrefGoogle Scholar
  • 9 Arias-Perez MS. Santos MJ. Tetrahedron  1996,  52:  10785 
    CrossrefGoogle Scholar
  • 12a Ziegler T. Lemanski G. Angew. Chem. Int. Ed.  1998,  3129 
    CrossrefGoogle Scholar
  • 12b Ziegler T. Lemanski G. Eur. J. Org. Chem.  1998,  163 
    CrossrefGoogle Scholar
  • 12c Ziegler T. Lemanski G. Rakoczy A. Tetrahedron Lett.  1995,  36:  8973 
    CrossrefGoogle Scholar
  • 13a Abel-Rahman AA.-H. Jonke S. El Ashry El SH. Schmidt RR. Angew. Chem. Int. Ed.  2002,  41:  2972 
    CrossrefGoogle Scholar
  • 13b Crich D. Smith M. J. Am. Chem. Soc.  2001,  123:  9015 
    CrossrefGoogle Scholar
  • 13c Kim KS. Kim JH. Lee YJ. Lee YJ. Park J. J. Am. Chem. Soc.  2001,  123:  8477 
    CrossrefGoogle Scholar
  • 14a Stork G. Kim G. J. Am. Chem. Soc.  1992,  114:  1087 
    CrossrefGoogle Scholar
  • 14b Barresi F. Hindsgaul O. Can. J. Chem.  1994,  72:  1447 
    CrossrefGoogle Scholar
  • 14c Ito Y. Ohnishi Y. Ogawa T. Nakahara Y. Synlett  1998,  1102 
    CrossrefGoogle Scholar
  • 14d Fairbanks AJ. Synlett  2003,  1945 
    CrossrefGoogle Scholar
  • 14e Abdel-Rahman AAH. El Ashry El SH. Schmidt RR. Carbohydr. Res.  2002,  337:  195 
    CrossrefGoogle Scholar
  • 14f For a review of intramolecular glycosylation see: Jung K.-H. Müller M. Schmidt RR. Chem. Rev.  2000,  100:  4423 
    CrossrefGoogle Scholar
  • 15 Kametani T. Kawamura K. Honda T. J. Am. Chem. Soc.  1987,  109:  3010 
    CrossrefGoogle Scholar
  • 16 Methyl 3-O-benzoyl-6-O-tert-butyldimethylsilyl-α-d-mannopyranoside (15) was prepared starting from methyl-α-d-mannopyranoside by silylation of the C6 hydroxyl group followed by benzoylation of the dialkylstannylene derivative formed by microwave irradiation. This compound had been prepared previously by: Chung S.-K. Yu S.-H. Bioorg. Med. Chem. Lett.  1996,  6:  1461 
    CrossrefGoogle Scholar
  • 17 Intermolecular glycosylations were carried out following procedure B, previously described for an intramolecular glycosylation reaction using 1 equiv each of the corresponding glycosyl donor and acceptor, at the temperature and for the reaction times specified in the text. The structures of all oligosaccharides were assigned by means of 2D NMR spectroscopy (COSY, HMQC) and mass spectrometry. Regioisomers were identified based on variations in the 1H chemical shift of the free hydroxyl groups after acetylation. The assignment of the configuration (α or β) was based on the CH coupling constant at the anomeric center (J CH ª 160Hz for β-mannosides and J CH ª 170 Hz for α-mannosides)
  • 18 Compound 19 was synthesized from methyl-α-d-mannopyranoside under standard benzoylation conditions in the presence of two equivalents of benzoyl chloride. This methylmannoside 19 had been previously prepared by: Meyers HV. Ojika M. Wiesler WT. Nakanishi K. Carbohydr. Res.  1990,  197:  15 
    CrossrefGoogle Scholar
  • 19 Alais JO. Veyrières A. J. Chem. Soc., Perkin Trans. 1  1981,  377 
    CrossrefGoogle Scholar
1

Present address: Departamento de Química Orgánica, Universidad Autónoma de Madrid, Cantoblanco 28049, Spain.

2

Present address: DDW-Medicinal Chemistry II, GlaxoSmithKline, 28770 Tres Cantos, Madrid, Spain.

10

General Method for the Formation of Diesters 8 and 9. A solution of 6a or 6b, phthalic anhydride (2 equiv) and Et3N (5 equiv) in 20 mL of CH2Cl2 was stirred at r.t. for 4 h. Then, a sat. solution of NH4Cl was added, the mixture was stirred for 15 min, the aqueous layer was extracted with CH2Cl2 (3 × 100 mL), and the combined organic layers were washed with brine, dried over MgSO4 and evaporated to give the corresponding triethylamine salt. This salt was dissolved in toluene and treated with SOCl2 (5 equiv) and 3 drops of DMF, and the mixture was stirred under reflux for 4 h. The reaction mixture was then co-evaporated with toluene several times under vacuum to give the corresponding acid chloride as a yellow oil, which was treated with a solution of the tin derivative (1.1 equiv) prepared as follows: methyl 6-O-tert-butyldimethylsilyl-α-d-mannopyranoside (7) was dissolved in anhyd toluene in an Erlenmeyer flask, then dibutyltin oxide (1.1 equiv) was added. The suspension was heated in a microwave oven (domestic microwave oven LG intellowave 700 W) for periods of 2 min until the solid was completely dissolved. The solution was allowed to reach r.t., then was added to the freshly prepared acid chloride, and the mixture was stirred for 20 h. Silica gel was then added, the slurry was stirred for 1 h, the solvent was evaporated under vacuum, and the solid was directly loaded into a column for flash chromatography. Phenyl 2,3,4-tri- O- methyl-6- O -[methyl- O -(6- O - tert -butyldimethylsilyl-α- d -mannopyranos-3-yloxy)-2-carbonylbenzoyl]-1-thio-α- d -mannopyranoside ( 8a): [α]D +36 (c 0.63, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.83-7.11 (m, 19 H, Ar), 5.65 (d, 1 H, J = 1.2 Hz, H1 ′), 5.27 (dd, 1 H, J = 9.8, 3.1 Hz, H3), 4.72 (d, 1 H, J = 1.3 Hz, H1), 4.53 (m, 2 H, H5 ′ and H6 ′), 4.31 (m, 2 H, H4 ′ and H2), 4.11 (td, 1 H, J = 9.7, 2.6 Hz, H4), 3.97 (dd, 1 H, J = 9.3, 4.9 Hz, H6), 3.91 (dd, 1 H, J = 9.3, 4.9 Hz, H6), 3.89 (br t, 1 H, J = 1.2 Hz, H2 ′), 3.79 (dt, 1 H, J = 9.7, 4.9 Hz, H5), 3.53-3.41 (m, 2 H, H3 ′ and H6 ′), 3.54 (s, 3 H, OMe), 3.52 (s, 3 H, OMe), 3.44 (s, 3 H, OMe), 3.37 (s, 3 H, OMe), 3.14 (d, 1 H, J = 2.6 Hz, C4OH), 2.91 (d, 1 H, J = 4.7 Hz, C2OH), 1.05 (s, 9 H, 3 Me). 13C NMR (75 MHz, CDCl3): δ = 167.8 (CO), 167.2 (CO), 135.5 (2 CH), 134.0, 133.1, 133.0, 132.2, 131.1, 130.6, 129.7, 139.6, 129.1, 129.0, 127.6, 127.3, 100.6, 84.1, 81.5, 78.1, 77.0, 76.4, 71.7, 70.5, 68.3, 66.7, 64.8, 64.8, 61.0, 58.0, 57.5, 54.8, 26.8 (3 C), 19.1 (C). MS (ES): m/z (%) = 894 (100) [M + 18], 899 (75) [M + 23].
Phenyl 2,3,4-tri- O- acetyl-6- O -[methyl- O -(6- O - tert -butyldimethylsilyl-α- d -mannopyranos-3-yloxy)-2-carbonylbenzoyl]-1-thio-α- d -mannopyranoside ( 8b): [α]D +32.2 (c 0.5, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.75 (d, 1 H, J = 7.8 Hz, Ar), 7.68-7.51 (m, 7 H, Ar), 7.45-7.19 (m, 9 H, Ar), 7.14-7.11 (m, 2 H, Ar), 5.43-5.41 (m, 2 H, H1 ′, H2 ′), 5.35 (t, 1 H, J = 9.9 Hz, H4 ′), 5.26 (m, 1 H, H3), 5.22 (dd, 1 H, J = 9.9, 3.1 Hz, H3 ′), 4.65 (d, 1 H, J = 1.5 Hz, H1), 4.54 (ddd, 1 H, J = 9.9, 7.8, 3.5 Hz, H5 ′), 4.35 (dd, 1 H, J = 7.8, 3.5 Hz, H6 ′a and H6 ′b), 4.20 (m, 1 H, H2), 4.0 (dt, 1 H, J = 9.7, 2.8 Hz, H4), 3.91 (dd, 1 H, J = 10.7, 4.7 Hz, H6a), 3.85 (dd, 1 H, J = 10.7, 5.3 Hz, H6b), (m, 1 H, H5) 3.41 (s, 3 H, OMe), 3.14 (d, 1 H, J = 2.9 Hz, C4-OH), 2.88 (d, 1 H, J = 4.7 Hz, C2-OH), 2.02 (s, 3 H, Me), 1.94 (s, 3 H, Me), 1.93 (s, 3 H, Me), 0.98 (s, 9 H, t-Bu). 13C NMR (50 MHz, CDCl3): δ = 170.0 (CO), 169.7 (2 × CO), 167.6 (CO), 167.1 (CO), 135.6, 131.8, 130.7, 129.7, 129.5, 129.4, 129.2, 128.0, 127.7, 100.7, 86.6, 77.0, 71.9, 70.9, 69.4, 69.2, 68.6, 66.9, 66.5, 64.9 (C-6), 63.9 (C-6), 54.8 (OMe), 26.8 (t-Bu), 20.7 (2 × Me), 20.6 (Me), 19.2. ESI+ [M + Na]+: 983.6; ESI- [M + Cl]-: 995.4.

11

Procedure for Intramolecular Glycosylation Reactions.
Method A: diester 8a was co-evaporated 3 times with toluene, 4 Å molecular sieves were added, and the residue was dried under vacuum for 3 h. The mixture was dissolved in CH2Cl2 under argon, and NIS (3 equiv) was added as solid under a stream of argon at r.t. The reaction mixture was stirred for 48 h, then NaHCO3 and Na2S2O3 were added as solids. The mixture was stirred at r.t. for 30 min, then filtered through a short pad of celite, the solvent was evaporated, and the crude product was purified by flash chromatography.
Method B: as for method A, but with the addition of 0.1 equiv of TfOAg after the addition of NIS. In this case the reaction mixture was stirred at -40 °C for 2 h, was left to reach r.t. over a period of 12 h, and was then stirred at r.t. for a further 4 h.
Method C: as for method A, but with the addition of 1 equiv of TfOAg after the addition of NIS and stirring the reaction mixture at 0 °C for 10 min.
Methyl O -(2′,3′,4′-tri- O -methyl-α- d -mannopyranosyl)-(1-2)-6- O - tert- butyldiphenylsilyl-α- d -mannopyranoside-3,6′-phthalate ( 10a): [α]D +43 (c 0.21, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.88 (dd, 1 H, J = 6.6, 2.2 Hz, Ar), 7.58-7.33 (m, 13 H, Ar), 5.57 (d, 1 H, J = 4.4, H1 ′), 5.32 (dd, 1 H, J = 10.2, 3.4 Hz, H3), 4.78-4.74 (m, 2 H, H1 and H6 ′), 4.58 (m, 1 H, H2), 4.43-4.33 (m, 2 H, H6 ′ and H4), 4.12 (m, 2 H, 2 H6), 3.83 (m, 1 H, H5 ′), 3.78 (dt, J = 9.3, 4.1 Hz, 1 H, H5), 3.53-3.51 (m, 1 H, H2 ′), 3.50 (s, 3 H, OMe), 3.45-3.35 (m, 2 H, H4 ′ and H3 ′), 3.41 (s, 3 H, OMe), 3.37 (s, 3 H, OMe), 3.36 (s, 3 H, OMe), 2.82 (d, 1 H, J = 3.5 Hz, C4OH), 1.08 (s, 9 H, t-Bu). 13C NMR (75 MHz, CDCl3): δ = 168.1 (CO), 168.0 (CO), 136.1 (4 CH), 133.5, 133.4, 132.9, 132.8, 132.0, 131.4, 130.5, 130.1, 129.7, 128.8, 128.1 (2 CH), 128.0 (2 CH), 101.4 (C1, J C-H = 166 Hz), 98.0 (C1 ′, J C-H = 175 Hz), 80.6 (C2 ′), 78.9 (C4 ′), 77.6 (C3), 76.0 (C3 ′), 74.6 (C5 ′), 73.0 (C5), 71.8 (C2), 66.8 (C4), 66.3 (C6), 64.8 (C6 ′), 60.5 (OMe), 59.1 (OMe), 58.0 (OMe), 55.1 (OMe), 28.9 (C), 27.2 (3Me). After treatment with pyridine-Ac2O: 1H NMR (300 MHz, CDCl3): δ = 5.55 (t, 1 H, J = 10.0 Hz, H4). MS (ES): m/z (%) = 809 (14) [M + 1], 826 (100) [M + 18], 831 (28) [M + 23].
Methyl O -(2′,3′,4′-tri- O -methyl-β- d -mannopyranosyl)-(1-2)-4- O -acetyl-6- O - tert- butyldiphenylsilyl-α- d -mannopyranoside-3,6′-phthalate ( 11a): [α]D -19 (c 1.07, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.78-7.62 (m, 5 H, Ar), 7.56-7.28 (m, 9 H, Ar), 5.45 (dd, 1 H, J = 16.0, 4.8 Hz, H3), 5.36 (t, 1 H, J = 15.0, H4), 5.07 (dd, 1 H, J = 16.0, 6.0 Hz, H6 ′), 4.77 (d, 1 H, J = 2.7 Hz, H1), 4.67 (d, 1 H, J = 1.6 Hz, H1 ′), 4.49 (dd, 1 H, J = 15.0, 2.7 Hz, H2), 4.22 (dd, 1 H, J = 16.0, 2.7 Hz, H6 ′), 3.88 (ddd, 1 H, J = 13.3, 5.9, 3.8 Hz, H5), 3.73 (m, 2 H, 2 H6), 3.71 (dd, 1 H, J = 4.2, 1.6 Hz, H2 ′), 3.59 (s, 3 H, OMe), 3.53 (dd, 1 H, J = 13.5, 13 Hz, H4 ′), 3.46 (s, 3 H, OMe), 3.44 (s, 3 H, OMe), 3.43 (s, 3 H, OMe), 3.44-3.37 (m, 1 H, H5 ′), 3.19 (dd, 1 H, J = 13.0, 4.2, H3 ′), 1.96 (s, 3 H, Me), 1.02 (s, 9 H, t-Bu). 13C NMR (75 MHz, CDCl3): δ = 169.9 (CO), 168.8 (CO), 167.4 (CO), 136.0 (2 CH), 136.0 (2 CH), 134.2, 133.6, 131.9, 131.6, 130.6, 130.1, 128.5, 128.1 (2 CH), 128.0 (2 CH), 99.3 (C1, J C-H = 168 Hz), 98.6 (C1 ′, J C-H = 156 Hz), 83.1 (C3 ′), 76.0 (C4 ′, C2 ′), 73.3 (C5 ′), 71.9, 71.8, 71.6 (C3, C2 and C5), 67.6 (C4), 63.4 (C6), 62.0 (C6 ′), 61.4 (OMe), 61.1 (OMe), 57.3 (OMe), 55.2 (OMe), 27.0 (3 Me), 21.1 (Me), 19.6 (C). MS (ES): m/z (%) = 809(7) [M + 1], 826 (100) [M + 18], 831 (63) [M + 23].
Methyl O -(2′,3′,4′-tri- O -methyl-α-d-mannopyranosyl)-(1-4)-2- O -acetyl-6- O - tert- butyldiphenylsilyl-α- d -mannopyranoside-3,6′-phthalate ( 12a): 1H NMR (300 MHz, CDCl3): δ = 7.96 (dd, 1 H, J = 7.4, 1.1 Hz, Ar), 7.75-7.35 (m, 13 H, Ar), 5.89 (dd, 1 H, J = 10.7, 3.6 Hz, H3), 5.68 (t, 1 H, J = 2.2 Hz, H2), 5.19 (d, 1 H, J = 3.7 Hz, H1 ′), 5.04 (d, 1 H, J = 9.3 Hz, H6 or H6 ′), 4.72 (d, 1 H, J = 2.2 Hz, H1), 5.58 (t, 1 H, J = 10.3 Hz, H4), 4.04 (dd, 1 H, J = 10.7, 3.0, H6 or H6 ′), 3.96-3.85 (m, 5 H, 2 H6 or 2 H6 ′, H5 ′ H5 and H4 ′), 3.51 (s, 3 H, OMe), 3.42 (s, 3 H, OMe), 3.41 (s, 3 H, OMe), 3.30 (m, 1 H, H2 ′), 3.27 (s, 3 H, OMe), 3.19 (dd, 1 H J = 9.3, 5.5 Hz, H3 ′), 2.17 (s, 3 H, Me), 1.05 (s, 9 H, t-Bu). 13C NMR (75 MHz, CDCl3): δ = 170.3 (CO), 168.2 (CO), 165.5 (CO), 135.7 (2 CH), 135.6 (2 CH), 135.2, 133.5, 133.3, 132.4, 131.2, 130.0, 129.7, 129.6, 127.6 (2 CH), 127.6 (2 CH), 98.2 (C1, J C-H = 172 Hz), 92.6 (C1 ′, J C-H = 160 Hz), 79.2 (C2 ′), 77.1 (C3 ′), 71.1, 69.8, 69.7, 69.2, 68.8 (H4), 64.9 (CH2), 62.3 (CH2), 59.2 (OMe), 58.2 (OMe), 57.9 (OMe), 55.3 (OMe), 26.7 (3 Me), 20.7 (Me), 19.4 (C). After desilylation of 12 with TBAF and treatment with pyridine-Ac2O: 13C NMR (75 MHz, CDCl3): δ = 98.6 (C1, J C-H = 177 Hz), 93.3 (C1 ′, J C-H = 166 Hz). MS (ES): m/z (%) = 809 (2) [M + 1], 826 (100) [M + 18], 831 (40) [M + 23].
Methyl O -(2′,3′,4′-tri- O -methyl-β- d -mannopyranosyl)-(1-4)-2- O -acetyl-6- O - tert -butyldiphenylsilyl-α- d -mannopyranoside-3,6′-phthalate ( 13a): [α]D -15 (c 0.17, CHCl3), 1H NMR (300 MHz, CDCl3): δ = 7.70-7.30 (m, 14 H, Ar), 5.69 (dd, 1 H, J = 6.3, 3.7 Hz, H3), 5.46 (t, 1 H, J = 3.7 Hz, H2), 4.95 (dd, 1 H, J = 11.5, 2.7 Hz, H6 ′), 4.78 (d, 1 H, J = 4.7 Hz, H1), 4.41 (s, 1 H, H1 ′), 4.28 (dd, 1 H, J = 9.8, 6.3 Hz, H4), 4.12 (dd, 1 H, J = 11.5, 6.6 Hz, H6 ′), 4.00-3.88 (m, 2 H, 2 H6), 3.85-3.78 (m, 1 H, H5), 3.52 (s, 3 H, OMe), 3.46 (s, 3 H, OMe), 3.44 (s, 3 H, OMe), 3.43 (s, 3 H, OMe), 3.50-3.26 (m, 2 H, H5 ′ and H2 ′), 3.34 (t, 1 H, J = 8.8 Hz, H4 ′), 3.01 (dd, 1 H, J = 8.8, 2.9 Hz, H3 ′), 2.07 (s, 3 H, Me), 1.09 (s, 9 H, 3 Me). 13C NMR (75 MHz, CDCl3): δ = 170.7 (CO), 167.8 (CO), 167.1 (CO), 136.4 (2 CH), 136.1 (2 CH), 134.3, 133.6, 133.1, 131.8, 131.7, 131.3, 130.4, 129.6, 128.3 (2 CH), 128.2 (2 CH), 102.4 (C1 ′, J C-H = 157 Hz), 99.1 (C1, J C-H = 172 Hz), 83.8 (C3 ′), 77.1 (C4 ′), 76.8 (C5 ′), 74.9 (C4), 74.0 (C3), 73.8 (C2 ′), 72.1 (C5), 70.2 (C2), 64.1 (C6 ′), 63.7 (C6), 61.8 (OMe), 61.2 (OMe), 57.9 (OMe), 55.7 (OMe), 27.1 (3 Me), 21.4 (Me), 19.7 (C). MS (ES): m/z (%) = 809 (5) [M + 1], 826 (100) [M + 18], 831 (16) [M + 23].
Methyl O -(2′,3′4′-tri- O -acetyl-α-d-mannopyranosyl)-(1-2)-α- d -mannopyranoside-3,6′-phthalate: formed by treatment of 10b with TBAF. 1H NMR (400 MHz, CDCl3): δ = 7.94-7.93 (m, 1 H, Ar), 7.55-7.50 (m, 3 H, Ar), 5.69 (d, 1 H, J = 4.7 Hz, H1 ′), 5.33 (dd, 1 H, J = 10.6, 3.7 Hz, H3), 5.24 (dd, 1 H, J = 7.0, 3.8 Hz, H3 ′), 5.06-5.00 (m, 2 H, H2 ′, H4 ′), 4.78 (dd, 1 H, J = 12.3 , 5.0 Hz, H6 ′a), 4.73 (d, 1 H, J = 1.3 Hz, H1), 4.46 (dd, 1 H, J = 3.5, 1.2 Hz, H2), 4.28-4.22 (m, 2 H, H4, H6 ′b), 4.17-4.14 (m, 1 H, H5 ′), 3.82-3.78 (m, 2 H, H6a and H6b), 3.64 (ddd, 1 H, J = 9.7, 6.7, 3.4 Hz, H5), 3.34 (s, 3 H, OMe), 2.81 (d, 1 H, J = 5.3 Hz, C4OH), 2.01 (s, 3 H, Me), 2.00 (s, 3 H, Me), 1.78 (s, 3 H, Me). 13C NMR (75 MHz, CDCl3): δ = 165.7 (CO), 165.5 (CO), 165.1 (CO), 163.7 (CO), 162.6 (CO), 128.7 (C), 127.7, 126.6, 126.4, 124.7 (C), 123.4, 96.6, 89.1, 72.9, 72.7, 72.5, 72.1, 68.8, 68.4, 68.3, 65.5, 64.4, 63.8, 60.6, 60.4, 57.4, 50.6 (OMe), 16.3 (2 × Me), 15.9 (Me).
Methyl O -(2′,3′4′-tri- O -acetyl-α-d-mannopyranosyl)-(1-4)-α- d -mannopyranoside-3,6′-phthalate: formed by treatment of 12b with TBAF. 1H NMR (400 MHz, CDCl3): δ = 7.98 (m, 1 H, Ar), 7.62 (dt, 1 H, J = 7.5, 1.5 Hz, Ar), 7.55 (dt, 1 H, J = 7.5, 1.5 Hz, Ar), 7.43 (m, 1 H, Ar), 5.70 (dd, 1 H, J = 10.7, 3.5 Hz, H3), 5.33 (dd, 1 H, J = 10.0, 3.3 Hz, H3 ′), 5.33 (s, 1 H, H1 ′), 5.24 (t, 1 H, J = 10.0 Hz, H4 ′), 5.01 (dd, 1 H, J = 3.3, 1.5 Hz, H2 ′), 4.83 (dd, 1 H, J = 11.5, 1.2 Hz, H6 ′a), 4.75 (d, 1 H, J = 2.0 Hz, H1), 4.41-4.34 (m, 2 H, H2, H4), 4.20 (br t, 1 H, J = 10.0 Hz, H5 ′), 3.95-3.87 (m, 3 H, H6 ′b, H6a, H6b), 3.83- 3.77 (m, 1 H, H5), 3.38 (s, 3 H, OMe), 2.16 (s, 3 H, Me), 2.10 (s, 3 H, Me), 2.08 (s, 3 H, Me), 2.07 (s, 3 H, Me), 2.11 (s, 3 H, Me), 2.06 (s, 3 H, Me), 1.96 (s, 3 H, Me). 13C NMR (75 MHz, CDCl3): δ = 166.0 (CO), 165.8 (CO), 165.3 (CO), 164.2 (CO), 160.7 (CO), 130.5 (C), 128.3, 125.8, 125.6, 123.1, 122.9 (C), 95.8, 87.5, 66.5, 66.4, 66.2, 66.0, 64.4, 64.2, 63.5, 61.7, 59.2 (C6), 57.3 (C6), 51.1 (OMe), 16.4 (Me), 16.2 (Me), 16.1 (Me). After treatment with pyridine-Ac2O: 1H NMR (300 MHz, CDCl3): δ = 5.56 (m, 1 H, H2). 13C NMR (75 MHz, CDCl3): δ = 98.2 (J C-H = 170 Hz), 91.7 (J C-H = 167 Hz).