The Journal of Organic Chemistry
Note
3H), 7.34−7.26 (m, 6H), 7.17 (brs, 1H), 5.63 (dd, J = 6.5, 3, 1H, H3),
4.65 (d, J = 9.5, 1H, H1), 4.12 (m, 1H, H4), 3.98 (brs, 1H, H2), 3.79
(q, J = 6, 1H, H5), 2.97 (brs, 1H), 1.33 (d, J = 5, 3H, H6); 13C NMR
(CDCl3, 125 MHz) δ 187.3, 137.4, 132.5, 129.1, 128.9, 128.2, 126.2,
123.7, 121.9, 89.3, 84.6, 81.3, 74.6, 70.4, 70.0, 67.7, 16.6; LRMS (ESI,
pos. ion) m/z calcd for C19H21NO4S2 (M + Na) 414.08, found 414.18;
HRMS (ESI, pos ion) m/z calcd for C19H21NO4S2 (M + Na)
414.0810, found 414.0811.
(4 mg, 0.02 mmol), and benzene (5 mL) were used. The product was
obtained as a white powder 7 (24 mg, 82%).
1-Phenyl 2,4-Di-O-benzyl-3,6-dideoxy-1-thio-β-L-xylo-hexo-
pyranoside (1). Sodium hydride (95%, 460 mg, 18 mmol) and
tetrabutylammonium iodide (10 mg, 0.04 mmol) were suspended in
DMF (15 mL). The suspension was cooled to 0 °C and treated with a
solution of 7 (1 g, 4.1 mmol) in DMF (2 mL), while additional DMF
(20 mL) was simultaneously added. After the mixture was stirred for
10 min at 0 °C, benzyl bromide (2.1 mL, 18 mmol) was added
dropwise to the mixture and the reaction was then allowed to warm to
room temperature. After being stirred for 5 h, the reaction mixture was
quenched with saturated aqueous NH4Cl and extracted three times
with CH2Cl2. The organic layer was washed with saturated NaHCO3,
water, and brine, dried over Na2SO4, filtered, and concentrated in
vacuo. The residue was purified by column chromatography on silica
gel (5% ethyl acetate in hexanes) to give 1-phenyl 2,4-di-O-benzyl-3,6-
Phenyl 3-O-Phenoxythiocarbonyl-1-thiol-β-L-fucopyrano-
side (3b). In a foil-covered flask, phenyl 1-thio β-L-fucopyranoside
(4) (100 mg, 0.39 mmol) and dioctyltin dichloride (16 mg, 0.039
mmol) were suspended in dry acetone (8 mL) at 25 °C for 10 min.
Then, reaction was treated with tetrabutylammonium iodide (14 mg,
0.039 mmol), O-phenyl chlorothionoformate (0.07 mL, 0.5 mmol),
and 1,2,2,6,6-pentamethylpiperidine (0.06 mL, 0.5 mmol). After 3 h,
the reaction mixture was quenched with saturated aqueous NH4Cl and
extracted three times with ethyl acetate. The organic layer was washed
with water and brine, dried over Na2SO4, filtrated, and concentrated in
vacuo. The crude sample was purified by column chromatography on
silica gel (20% ethyl acetate in hexanes) to give 3 (138 mg, 90%).
Phenyl 3-O-Phenoxythiocarbonyl-1-thiol-β-L-fucopyrano-
side 3b (1 g scale). The title compound was prepared according
to the above procedure using phenyl 1-thio β-L-fucopyranoside (4)
(1.0 g, 3.9 mmol), dioctyltin dichloride (162 mg, 0.39 mmol),
tetrabutylammonium iodide (144 mg, 0.39 mmol), O-phenyl
chlorothionoformate (0.7 mL, 5 mmol), 1,2,2,6,6-pentamethylpiper-
idine (0.6 mL, 5 mmol), and acetone (80 mL). After 6 h, the crude
product was purified with column chromatography (20% ethyl acetate
dideoxy-1-thio-β-L-xylo-hexopyranoside 1 (1.5 g, 90%): [α]24
=
D
+0.283° (c 1.00, CH2Cl2); 1H NMR (CDCl3, 500 MHz) δ 7.58 (d, J =
6.5 Hz, 2H), 7.31−7.23 (m, 14H), 4.68 (t, J = 14 Hz, 2H, H1, OCH2),
4.49 (t, J = 14 Hz, 2H, OCH2), 4.37 (d, J = 12 Hz, 1H, OCH2), 3.69
(t, J = 10 Hz, 1H, H2), 3.61 (brs, 1H, H5), 3.40 (s, 1H, H4), 2.42 (d, J
= 12 Hz, 1H, H3), 1.49 (t, J = 12.5 Hz, 1H, H3), 1.27 (d, J = 5 Hz, 3H,
H6); 13C NMR (CDCl3, 125 MHz) δ 138.6, 138.3, 134.7, 131.7,
128.8, 128.5, 128.4, 128.3, 127.9, 127.8, 127.7, 127.0, 89.4, 76.7, 75.2,
72.7, 71.6, 71.2, 34.5, 17.2; LRMS (ESI, pos ion) m/z calcd for
C26H28O3S (M + Na) 443.21, found 443.27; HRMS (ESI, pos ion) m/
z calcd for C26H28O3S (M + NH4) 438.2103, found 438.2075.
in hexanes) to give 3b (1.25 g, 83%): [α]24 = +0.033° (c 1.06,
ASSOCIATED CONTENT
* Supporting Information
NMR spectra for 1, 3a, 3b, and 7. This material is available free
D
■
1
CH2Cl2); H NMR (CDCl3, 500 MHz) δ 7.59 (m, 2H), 7.43−7.28
S
(m, 6H), 7.13 (d, J = 7.5 Hz, 2H), 5.39 (d, J = 9.5 Hz, 1H, H1), 4.62
(d, J = 10 Hz, 1H, H3), 4.20 (s, 1H, H2), 4.00 (t, J = 9.7 Hz, 1H, H4),
3.82 (q, J = 6.5 Hz, 1H, H5), 2.56 (brs, 1H), 1.96 (brs, 1H), 1.39 (d, J
= 6.5 Hz, 3H, H6); 13C NMR (CDCl3, 125 MHz) δ 194.4, 153.3,
133.1, 133.1, 131.4, 129.6, 129.2, 128.5, 126.8, 121.9, 88.7, 86.0, 74.7,
69.2, 67.0, 16.6; LRMS (ESI, pos ion) m/z calcd for C19H20O5S2 (M +
Na) 414.06, found 415.18; HRMS (ESI, pos ion) m/z calcd for
C19H20O5S2 (M + NH4) 410.1096, found 410.1072.
AUTHOR INFORMATION
Corresponding Author
■
Notes
General Procedure for the Synthesis of Phenyl 3,6-Dideoxy-
1-thio-β-L-xylo-hexopyranoside (7). Thiocarbonylate 3 (0.25
mmol), tris(trimethylsilyl)silane (TTMSS) (method A) or tributyltin
hydride (Bu3SnH) (method B) (2 equiv), and 2,2′-azobis-
(isobutyronitrile) (20 mol %) were refluxed at 82 °C for 2 h in
benzene (5 mL). When the reaction was complete according to TLC,
it was concentrated in vacuo. The crude sample was purified by
column chromatography on silica gel (40% ethyl acetate in hexanes
followed by 70% ethyl acetate in hexanes) to afford pure 1-phenyl 3,6-
dideoxy-1-thio-β-L-xylo-hexopyranoside 7.
Method A. The title compound was prepared according to the
general procedure using tris(trimethylsilyl)silane (0.07 mL, 0.25
mmol), phenyl 3-O-phenoxythiocarbonyl-1-thio-β-L-fucopyranoside
3b (47 mg, 0.12 mmol) and 2,2′-azobis(isobutyronitrile) (4 mg,
0.02 mmol), and benzene (5 mL) were used. The product was
obtained as a white powder 7 (27 mg, 98%): [α]24D = +0.438° (c 1.04,
CH2Cl2); 1H NMR (CDCl3, 500 MHz) δ 7.56 (dd, J = 2.5, 2 Hz, 2H),
7.35−7.30 (m, 3H), 4.52 (d, J = 10 Hz, 1H, H1), 3.79−3.69 (m, 3H,
H2, H4, H5), 2.45−2.39 (m, 2H, H3), 1.78 (d, J = 8 Hz, 1H), 1.65 (td,
J = 8.5, 3 Hz, 2H, H3), 1.30 (d, J = 6.5 Hz, 3H, H6); 13C NMR
(CDCl3, 125 MHz) δ 132.6, 132.5, 129.1, 128,1, 92.1, 77.2, 69.3, 64.2,
39.0, 17.0; LRMS (ESI, pos ion) m/z calcd for C12H16O3S (M + Na)
263.07, found 263.09; HRMS (ESI, pos ion) m/z calcd for C12H16O3S
(M + NH4) 258.1164, found 258.1139.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Tufts University and the National Science
Foundation division of Chemistry (NSF 1300334) for generous
financial support.
REFERENCES
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(1) Huang, Y.-L.; Wu, C.-Y. Expert Rev. Vaccines 2010, 9, 1257−1274.
(2) DeMarco, M. L.; Woods, R. J. Glycobiology 2008, 18, 426−440.
(3) Stenutz, R.; Weintraub, A.; Widmalm, G. R. FEMS Microbiol. Rev.
2006, 30, 382−403.
(4) Liu, B.; Knirel, Y. A.; Feng, L.; Perepelov, A. V.; Senchenkova, S.
N.; Reeves, P. R.; Wang, L. FEMS Microbiol. Rev. 2013, 38, 56−89.
(5) Samuelsson, K.; Lindberg, B.; Brubaker, R. R. J. Bacteriol. 1974,
117, 1010−1016.
(6) Turek, D.; Sundgren, A.; Lahmann, M.; Oscarson, S. Org. Biomol.
Chem. 2006, 4, 1236−1241.
(7) Chatterjee, S. N.; Chaudhuri, K. Biochim. Biophys. Acta 2003,
1639, 65−79.
(8) Chu, A.-H. A.; Nguyen, S. H.; Sisel, J. A.; Minciunescu, A.;
Bennett, C. S. Org. Lett. 2013, 15, 2566−2569.
(9) Bundle, D. R.; Josephson, S. Can. J. Chem. 1978, 56, 2686−2690.
(10) Lindhorst, T. K.; Thiem, J. Liebigs Ann. Chem. 1990, 1237−
1241.
Method A (Gram Scale). According to the general procedure,
tris(trimethylsilyl)silane (1.5 mL, 5 mmol), phenyl 3-O-phenoxythio-
carbonyl-1-thio-β-L-fucopyranoside 3b (1 g, 2.5 mmol), 2,2′- azobis-
(isobutyronitrile) (82 mg, 0.5 mmol), and benzene (100 mL) were
used. The product was obtained as a white powder 7 (550 mg, 90%).
Method B. According to the general procedure, tributyltin hydride
(0.06 mL, 0.24 mmol), phenyl 3-O-phenoxythiocarbonyl-1-thio-β-L-
fucopyranoside 3b (47 mg, 0.12 mmol), 2,2′- azobis(isobutyronitrile)
(11) Hasegawa, A.; Ando, T.; Kato, M.; Ishida, H.; Kiso, M.
Carbohydr. Res. 1994, 257, 55−65.
(12) Oscarson, S.; Tedebark, U.; Turek, D. Carbohydr. Res. 1997,
299, 159−164.
́ ̌
(13) Ruttens, B.; Kovac, P. Synthesis 2004, 15, 2505−2508.
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dx.doi.org/10.1021/jo501472v | J. Org. Chem. XXXX, XXX, XXX−XXX