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P. I. Abronina et al. / Tetrahedron Letters 52 (2011) 1794–1796
OCHb, ClH2CC), 4.00 (2H, s, ClH2CC), 4.03 (1H, dd, J = 11.5 Hz, J = 4.4 Hz, H-5IIb),
4.37–4.40 (1H, m, H-3II), 4.40–4.44 (1H, m, H-4II), 4.53–4.62 (4H, m, H-4III, H-
4IV, H-5IIIa, H-5IVa), 4.68 (1H, dd, J = 11.9 Hz, J = 3.5 Hz, H-5IIIb), 4.75 (1H, dd,
J = 11.9 Hz, J = 3.5 Hz, H-5IVb), 5.24 (2H, s, H-1II, H-1IV), 5.36–5.39 (3H, m, H-2II,
H-2III, H-3IV), 5.43 (1H, d, J = 4.0 Hz, H-3III), 5.47 (1H, br s, H-1III), 5.49 (1H, br s,
H-2III), 7.12–7.65 (16H, m), 7.90–8.10 (8H, m, Ph). 13C NMR (125.37 MHz) dC
40.27, 40.31 (2ꢃ COCH2Cl), 42.6 (OCH2CH2Cl), 63.2 (2C, C-5III, C-5IV), 65.8 (C-
5II), 67.4 (OCH2CH2Cl), 77.4 (2C, C-3III, C-3IV), 81.1 (C-4II), 81.3, 81.4 (C-4III, C-
4IV), 81.6 (C-3II), 82.5 (2C, C-2III, C-2IV), 82.60 (C-3II), 105.1 (C-1IV), 105.5 (C-1II),
105.8 (C-1III), 128.3, 128.40, 128.45, 128.50, 129.67, 129.73, 129.85, 133.2,
133.46, 133.5, 133.6 (Ph), 165.50, 165.55, 165.90, 165.95, 166.0 (CO).
tetraarabinofuranosides 6 and 7, which are useful building blocks
for the synthesis of larger oligosaccharides related to mycobacte-
rial cell wall components.
Acknowledgments
The authors are grateful to A.S. Shashkov for the acquisition of
NMR spectra on Bruker AVANCE 500 and 600 spectrometers, to
Dr. A.O. Chizhov for recording mass spectra. This work was sup-
ported financially by the Russian Foundation for Basic Research
(project No. 07-03-00830).
Tetrasaccharide 7: Rf 0.52 (toluene–EtOAc 10:1), ESIMS found m/z 1511.2773
[M+Na+]. Calcd. for C75H67Cl3NaO26 1511.2878. ½a 2D4
ꢂ
+53.4 (c 1.0, CHCl3). 1H
NMR (600.13 MHz) dH 3.67–3.74 (2H, m, OCH2CH2Cl), 3.82 (1H, dt, J = 11.1 Hz,
J = 5.6 Hz, OCHa), 3.86–3.95 (6H, m, H-5Ia, H-5II , 2 ꢃ ClH2CC), 3.99 (1H, dt,
a
J = 11.1 Hz, J = 5.6 Hz,OCHb), 4.05 (1H, dd, J = 11.7, 4.2 Hz, H-5IIb), 4.11–4.16
(1H, m, H-5Ib), 4.43 (1H, d, J = 5.8 Hz, H-3II), 4.45–4.49 (1H, m, H-4I), 4.49–4.60
(5H, m, H-5IIIa, H-5IVa, H-4II, H-4III, H-4IV), 4.65–4.70 (1H, m, H-5IIIb), 4.73 (1H,
dd, J = 12.0 Hz, J = 3.5 Hz, H-5IVb), 5.27 (2H, s, H-1I, H-1II), 5.32–5.36 (2H, m, H-
2IV, H-3III), 5.36–5.39 (3H, m, H-1IV, H-3IV, H-2III), 5.44 (1H, s, H-1III), 5.47 (2H, s,
H-2I, H-2II), 5.64 (1H, d, J = 5.0 Hz, H-3I), 7.30–7.58 (21H, m, Ph), 7.88–7.90 (4H,
m, Ph), 7.94–7.98 (4H, m, Ph), 8.01–8.07 (6H, m, Ph). 13C NMR (125.37 MHz) dC
40.3 (OCOCH2Cl), 42.8 (OCH2CH2Cl), 63.3 (2C, C-5III, C-5IV), 65.6 (2C, C-5I, C-5II),
67.4 (CH2O), 76.8 (C-3I), 77.3 (C-3IV), 77.5 (C-3III), 80.9 (C-4III), 81.3 (C-4IV), 81.5
(C-3II), 81.7 (C-4II), 81.9C-2I), 82.1 (C-4I), 82.4 (C-2IV), 82.7 (C-2II, C-2III), 105.3
(C-1III), 105.47, 105.51 (C-1II, C-1IV), 105.57 (C-1I), 128.08, 128.11, 128.17,
128.21, 128.35, 128.50, 128.82, 128.86, 129.00, 129.42, 129.4, 129.51, 129.60,
129.64, 132.89, 132.93, 133.16, 133.23, 133.30 (Ph), 165.16, 165.18, 165.24,
165.34, 165.39, 165.55, 165.61, 165.74 (CO).
References
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8. Reactions sensitive to air and/or moisture were performed under an argon
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13C NMR chemical shifts to the CDCl3 signal (dC 77.0)].
9. Preparation of bis-orthoester
5 (Typical procedure). A mixture of the
thioglycoside 1a (80 mg, 0.167 mmol), diol 3 (46 mg, 0.07 mmol), and freshly
activated 4 Å MS (200 mg) in dry CH2Cl2 (2.5 mL) was stirred for 2 h at ꢁ20 °C.
N-Iodosuccinimide (47 mg, 0.21 mmol) and AgOTf (5.4 mg, 0.021 mmol) were
added at ꢀ40 °C, the reaction mixture was stirred for 15 min at ꢀ20 °C,
then allowed to reach +10 °C over 1 h, the course of the reaction being
monitored by TLC. The reaction was quenched by the addition of saturated
aqueous NaHCO3 (0.1 mL). The mixture was diluted with CH2Cl2 (50 mL),
filtered through Celite, and washed with saturated aqueous Na2S2O3 (50 mL)
and saturated aqueous NaHCO3 (50 mL). The organic layer was dried (Na2SO4)
and concentrated in vacuo. The residue was purified by column
chromatography (gradient toluene to toluene–EtOAc, 10:1) to afford the bis-
orthoester 5 (94 mg, 90%).
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Therapeutic Relevance; Demchenko, A. V., Ed.; WILEY-VCH GmbH and Co
KGaA: Weinheim, 2008; pp 381–415.
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2508–2515; (b) Fürstner, A.; Jeanjean, F.; Razon, P.; Wirtz, C.; Mynott, R. Chem.
Eur. J. 2003, 9, 320–326; (c) Shen, X.-Q.; Xie, L.; Gao, L.; He, L.-L.; Yang, Q.; Yang,
J.-S. Carbohydr. Res. 2009, 344, 2063–2068; (d) Orgueira, H. A.; Bartolozzi, A.;
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12. (a) Hanessian, S.; Adhikari, S.; Szychowski, J.; Pachamuthu, K.; Wang, X.;
Migawa, M. T.; Griffey, R. H.; Swayze, E. E. Tetrahedron 2007, 63, 827–846; (b)
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Can. J. Chem. 1962, 40, 275–282.
Trisaccharide bis-orthoester 4 (mixture of isomers): Rf 0.25 (toluene–EtOAc
10:1). 1H NMR (500.13 MHz, selected signals) dH 6.05 (1H, d, J = 3.7 Hz), 6.16
(1H, d, J = 4.3 Hz). 13C NMR (125.37 MHz, selected signals) dC 42.5, 42.6
(CH2CH2Cl), 45.65, 45.68 (ClH2CC), 104.5, 104.78, 104.99, 105.8, 105.95 (C-1),
122.7, 123.0 (ClH2CC).
13. Rearrangement of orthoester
solution of bis-orthoester 5 (67 mg, 0.05 mmol)) in CH2Cl2 (2 mL) was stirred
L,
5 into tetrasaccharide 7 (Typical procedure). A
Tetrasaccharide bis-orthoester 5: Rf 0.52 (toluene–EtOAc 10:1). ESIMS found m/z
1506.3313 [M+NH4þ]. Calcd for C75H71Cl3O26
N
1506.3324. 1H NMR
with freshly activated 4 Å MS (0.1 g) for 2 h at ꢁ20 °C. TMSOTf (45
l
(500.13 MHz) dH 3.68–3.75 (4H, m, OCH2CH2Cl, ClH2CCIII), 3.77 (1H, d,
J = 3.9 Hz, ClH2CCIV), 3.84 (1H, dt, J = 10.7 Hz, J = 5.4 Hz, OCHa), 3.89 (2H, br s,
0.003 mmol) was added to the reaction mixture at ꢀ40 °C. After 2 h at 20 °C the
reaction was quenched by the addition of saturated aqueous NaHCO3 (0.1 mL).
The mixture was diluted with CH2Cl2 (50 mL), filtered through Celite, washed
with H2O (50 mL) and saturated aqueous NaHCO3 (50 mL). The organic layer
was dried (Na2SO4) and concentrated in vacuo. The residue was purified by
column chromatography (gradient toluene to toluene–EtOAc, 10:1) to afford
tetrasaccharide 7 (24 mg, 80%).
H-5II
,
H-5IIb), 3.92 (1H, dd, J = 4.2 Hz, J = 11.2 Hz, H-5Ib), 4.03 (1H, dt,
a
J = 10.7 Hz, J = 5.4 Hz, OCHb), 4.16 (1H, dd, J = 4.2 Hz, J = 11.2 Hz, H-5Ib), 4.40–
4.44 (1H, m, H-4III), 4.45–4.51 (3H, m, H-4IV, H-4II, H-3II), 4.52–4.58 (1H, m, H-
4I), 4.58–4.62 (4H, m, H-5IIIa, H-5IIIb, H-5IVa, H-5IVb), 5.04 (1H, d, J = 3.9 Hz,
H-2IV), 5.22 (1H, d, J = 3.9 Hz, H-2III), 5.28 (1H, s, H-1II), 5.31 (1H, d, J = 3.9 Hz, H-
3IV), 5.32 (1H, s, H-1I), 5.43 (1H, d, J = 4.4 Hz, H-3III), 5.47 (1H, s, H-2II), 5.54 (2H,
br s, H-2I), 5.65 (1H, d, J = 4.9 Hz, H-3I), 6.05 (1H, d, J = 3.9 Hz, H-1III), 6.14 (1H,
d, J = 3.8 Hz, H-1IV), 7.29–7.65 (20H, m, Ph), 7.90–8.16 (16H, m, Ph). 13C NMR
(125.37 MHz) dC 42.7 (OCH2CH2Cl), 45.3 (ClH2CIII), 45.5 (ClH2CIV), 60.6 (C-5II),
63.65 (C-5III), 63.75 (C-5IV), 65.7 (C-5I), 67.4 (OCH2), 75.6 (C-3II), 76.9 (C-3I, C-
3III, C-3IV), 81.0 (C-4II), 81.6 (C-4III), 81.9 (C-2I,C-4I), 82.2 (C-4IV), 82.8 (C-2II),
86.0 (C-2IV), 86.2 (C-2III), 104.8 (C-1III), 105.1 (C-1IV), 105.5 (C-1II), 105.6 (C-1I),
122.7, 123.1 (ClH2CCIII, ClH2CCIV), 128.5, 129.8, 130.0, 133.3,133.5, 133.6, 133.7
(Ph), 165.2, 165.6, 165.8, 166.1 (CO).
14. Preparation of tetrasaccharide
7 without isolation of orthoester 5 (Typical
procedure). A mixture of the thioglycoside 1b (381 mg, 0.72 mmol), diol 3
(198 mg, 0.30 mmol), and freshly activated 4 Å MS (0.5 g) in dry CH2Cl2 (5 mL)
was stirred for 2 h at ꢁ20 °C. N-Iodosuccinimide (203 mg, 0.90 mmol) and
AgOTf (23 mg, 0.09 mmol) were added at ꢀ45 °C, and the reaction mixture was
stirred for 1 h at ꢀ17 °C, then allowed to reach +4 °C over 3 h, the course of the
reaction being monitored by TLC. The reaction was quenched by addition of
saturated aqueous NaHCO3 (0.1 mL). The mixture was diluted with CH2Cl2
(100 mL), filtered through Celite, and washed with a 1:1 mixture of saturated
aqueous Na2S2O3ꢀNaHCO3 (100 mL). The organic layer was dried (Na2SO4) and
concentrated in vacuo. The residue was purified by column chromatography
(gradient toluene to toluene–EtOAc, 10:1) to afford tetrasaccharide 7 (377 mg,
84%).
Trisaccharide 6: Rf 0.25 (toluene–EtOAc 10:1). ½a D23
ꢂ
+49.0 (c 1.0, CHCl3). ESIMS
found m/z 1171.1963 [M+Na+]. Calcd. for C56H51Cl3NaO20 1171.1937. 1H NMR
(500.13 MHz) dH 3.63 (2H, t, J = 5.6 Hz, OCH2CH2Cl), 3.79 (1H, dt, J = 11.2 Hz,
J = 5.7 Hz, OCHa), 3.87 (1H, dd, J = 11.6 Hz, J = 2.6 Hz, H-5IIa), 3.90–3.98 (3H, m,