Novel Thiosugar Scaffolds
1.35 (s, 3 H, Me, iPr), 1.29 (t, 3 H, CH2CH3), 0.89 (s, 9 H, tBu,
TBDMS), 0.07 (br. s, 6 H, Me, TBDMS) ppm. 13C NMR
(100 MHz, CDCl3): δ = 113.3 (Cq, iPr), 106.7 (C-1), 89.9 (C-4),
86.5 (C-2), 64.0 (C-5), 61.4, 61.3 (C-6, CH2CH3), 27.7 (Me, iPr),
27.2 (Me, iPr), 26.0 (3ϫMe, tBu), 18.4 (Cq, tBu), 14.3 (CH2CH3),
–5.4 (2ϫMe, TBDMS) ppm. HRMS: calcd. for C19H34O6SSi [M
+ Na]+ 441.1738; found 441.1756.
–5.3 (Me, TBDMS) ppm. HRMS: calcd. for C21H36O7SSi [M +
Na]+ 483.1843; found 483.1856.
Data for 17: Rf = 0.28 (EtOAc/petroleum ether, 1:5). [α]2D0 = +88 (c
= 1.1, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 8.04 (s, 1 H,
3
4
4
OCHO), 5.95–5.91 (m, J1,2 = 4.3, J2,3Ј = J3Ј,4 = 1.5 Hz, 2 H, 1-
H, 3Ј-H), 5.69 (dt, 4J2,3Ј = 4J2,4 = 1.5 Hz, 1 H, 2-H), 5.21 (td, 3J5,6a
=
3J5,6b = 6.8 Hz, 1 H, 5-H), 5.14–5.12 (m, 1 H, 4-H), 4.28–4.18
3
2
Data for 14: Rf = 0.37 (EtOAc/cyclohexane, 1:6). 1H NMR
(m, J = 7.1 Hz, 2 H, CH2CH3), 3.87–3.77 (m, J6a,6b = 10.1 Hz, 1
H, 6a-H, 6b-H), 1.48 (s, 3 H, Me, iPr), 1.44 (s, 3 H, Me, iPr), 1.30
(t, 3 H, CH2CH3), 0.88 (s, 9 H, tBu, TBDMS), 0.08 (s, 3 H, Me,
TBDMS), 0.08 (s, 3 H, Me, TBDMS) ppm. 13C NMR (100 MHz,
CDCl3): δ = 164.8 (CO, OCHO), 160.1 (CO), 154.7 (C-3), 117.4
(C-3Ј), 113.4 (Cq, iPr), 105.6 (C-1), 78.6, 78.5 (C-4, C-2), 73.6 (C-
5), 61.1, 61.0 (CH2CH3, C-6), 30.8 (Me, SAc), 27.7 (Me, iPr), 27.4
(Me, iPr), 25.9 (3ϫMe, tBu), 18.3 (Cq, tBu), 14.2 (CH2CH3), –5.3
(Me, TBDMS), –5.3 (Me, TBDMS) ppm. HRMS: calcd. for
C17H30O6SSi [M + Na]+ 413.1915; found 453.1915; calcd. for [M
+ K]+ 469.1655; found 469.1656.
3
(400 MHz, CDCl3): δ = 5.96 (d, J1,2 = 5.3 Hz, 1 H, 1-H), 5.40 (d,
3
3
1 H, 2-H), 4.48 (dd, J5,6a = 7.8, J5,6b = 6.8 Hz, 1 H, 5-H), 4.17–
3
2
4.10 (m, J = 7.1 Hz, 2 H, CH2CH3), 3.83 (t, J6a,6b = 10.1 Hz, 1
H, 6a-H), 3.68 (dd, 1 H, 6b-H), 3.41 (d, part A of AB system,
2J3Јa,3Јb = 16.9 Hz, 1 H, 3Јa-H), 3.14 (d, part B of AB system, 1 H,
3Јb-H), 2.32 (s, 3 H, Me, SAc), 1.44 (s, 3 H, Me, iPr), 1.35 (s, 3 H,
Me, iPr), 1.27 (t, 3 H, CH2CH3), 0.85 (s, 9 H, tBu, TBDMS), 0.04
(s, 3 H, Me, TBDMS), 0.03 (s, 3 H, Me, TBDMS) ppm. 13C NMR
(100 MHz, CDCl3): δ = 194.3 (CO, SAc), 170.8 (CO), 152.2 (C-4),
112.3 (Cq, iPr), 106.6 (C-3), 104.5 (C-1), 85.3 (C-2), 62.7 (C-6),
60.9 (CH2CH3), 41.0 (C-5), 30.6 (Me, SAc), 29.9 (C-3Ј), 28.1
(2ϫMe, iPr), 25.9 (3ϫMe, tBu), 18.4 (Cq, tBu), 14.3 (CH2CH3),
–5.3 (Me, TBDMS), –5.4 (Me, TBDMS) ppm. HRMS: calcd. for
C21H36O7SSi [M + Na]+ 483.1843; found 483.1875.
(3E)-[6-O-(tert-Butyldimethylsilyl)-3-deoxy-1,2-O-isopropylidene-5-
sulfanyl-β-L-lyxo-hexofuranos-3-ylidene]acetic Acid (18): Ethyl
(3E)-[5-S-acetyl-6-O-(tert-butyldimethylsilyl)-3-deoxy-1,2-O-isopro-
pylidene-5-thio-β--lyxo-hexofuranos-3-ylidene]acetate (41 mg,
0.09 mmol) was dissolved in MeOH/H2O (2:1, 1.3 mL), and NaOH
solution (10 , 0.04 mL) was added. The solution was stirred at
room temp. for 1 h, and then neutralized with Amberlite IR-120
H+. After filtration of the resin and evaporation of the solvent, the
residue was purified by column chromatography (EtOAc/petroleum
ether, 1:1) to afford 18 (23 mg, 66%) as a colourless oil; Rf = 0.4
(EtOAc/petroleum ether, 1:1). 1H NMR [400 MHz, (CD3)2CO]: δ
Ethyl (3E)-[5-S-acetyl-6-O-(tert-butyldimethylsilyl)-3-deoxy-1,2-O-
isopropylidene-5-thio-β-
and Ethyl (3E)-[6-O-(tert-Butyldimethylsilyl)-3-deoxy-5-O-formyl-
1,2-O-isopropylidene-β- -lyxo-hexofuranos-3-ylidene]acetate (17): A
solution of ethyl (3Z)-[6-O-(tert-butyldimethylsilyl)-3-deoxy-1,2-O-
isopropylidene-α--ribo-hexofuranos-3-ylidene]acetate (0.241 g,
L-lyxo-hexofuranos-3-ylidene]acetate
(15)
L
0.6 mmol) and dry pyridine (0.1 mL, 1.2 mmol) in dry dichloro-
methane (3 mL) was cooled to –11 °C (MeOH/ice bath) under ar-
gon. Trifluoromethanesulfonic anhydride (0.11 mL, 0.66 mmol)
was added dropwise and the reaction mixture was stirred for
15 min, whilst the temperature was kept below –5 °C. The solution
was diluted with EtOAc (10 mL) and sequentially washed with a
satd. NaHCO3 solution (5 mL) and aq. HCl solution (2 , 5 mL).
The aqueous layer was extracted twice with EtOAc and the com-
bined organic phases were dried with anhydrous MgSO4. After fil-
tration and concentration to dryness, the crude triflate 16 was used
immediately for the next step without further purification; Rf =
0.53 (EtOAc/cyclohexane, 1:5).
= 6.00 (d, 3J1,2 = 4.0 Hz, 1 H, 1-H), 5.97 (t, 4J2,3Ј = 4J3Ј,4 = 1.5 Hz,
4
1 H, 3Ј-H), 5.72 (dt, J2,3Ј
=
4J2,4 = 1.5 Hz, 1 H, 2-H), 5.39–5.35
3
2
(m, 1 H, 4-H), 3.81 (dd, J5,6a = 5.6, J6a,6b = 9.9 Hz, 1 H, 6a-H),
3.71 (t, J5,6b = J6a,6b = 9.9 Hz, 1 H, 6b-H), 3.21 (tdd, 1 H, 5-H),
1.71 (d, JSH,H-5 = 10.1 Hz, 1 H, SH), 1.40 (s, 3 H, Me, iPr), 1.34
3
2
3
(s, 3 H, Me, iPr), 0.92 (s, 9 H, tBu, TBDMS), 0.12 (s, 3 H, Me,
TBDMS), 0.12 (s, 3 H, Me, TBDMS) ppm. 13C NMR (100 MHz,
(CD3)2CO): δ = 166.1 (COOH), 158.4 (C-3), 117.4 (C-3Ј), 112.9
(Cq, iPr), 106.7 (C-1), 79.6, 79.5 (C-2, C-4), 66.5 (C-6), 46.0 (C-5),
27.7 (Me, iPr), 27.6 (Me, iPr), 26.2 (3ϫMe, tBu), 18.8 (Cq, tBu),
14.3 (CH2CH3), –5.2 (Me, TBDMS), –5.3 (Me, TBDMS) ppm.
HRMS: calcd. for C17H30O6SSi [M + Na]+ 413.1425; found
413.1435; calcd. for [M + K]+ 429.1164; found 429.1171.
Potassium thioacetate (75 mg, 0.66 mmol) was added to the crude
triflate 16 in DMF (6 mL). The solution was stirred at room temp.
for 40 min. Water (12 mL) was then added to the solution and it
was extracted with EtOAc (3ϫ5 mL). The combined organic layers
were washed with water and brine and dried with anhydrous
MgSO4. After filtration and evaporation under vacuum, the residue
was purified by column chromatography (EtOAc/petroleum ether,
1:14) to afford 15 (70 mg, 25%) and 17 (15 mg, 6%) as colourless
oils.
3-Deoxy-[2-O,3-C-(1-oxoethan-1-yl-2-ylidene)]-5-thio-L-lyxo-hexo-
pyranose (19): A solution of (3E)-[6-O-(tert-butyldimethylsilyl)-3-
deoxy-1,2-O-isopropylidene-5-sulfanyl-β--lyxo-hexofuranos-3-
ylidene]acetic acid (18 mg, 46 µmol) in aq. TFA (60%, 1 mL) was
stirred at 40 °C for 20 min. The solvent was coevaporated with tol-
uene and the crude product was purified by column chromatog-
raphy (EtOAc) to afford 19 (10 mg, quantitative) as a colourless
1
oil; Rf = 0.41 (EtOAc). H NMR (400 MHz, (CD3)2CO): δ = 6.02
4
4
Data for 15: Rf = 0.41 (EtOAc/petroleum ether, 1:5). [α]2D0 = +67 (c
(br. d, J = 1.5 Hz, 3Јβ-H), 6.00 (t, J2,3Ј = J3Ј,4 = 1.8 Hz, 3Јα-H),
5.22–5.16 (m, 2α-H, 1α-H, 1β-H), 5.10–5.05 (m, 4α-H, 4β-H), 4.98
(dd, 3J1,2(β) = 8.6 Hz, 2β-H), 4.31 (dd, 3J5,6a = 3.5, 2J6a,6b = 11.6 Hz,
1
3
= 1.2, CH2Cl2). H NMR (400 MHz, CDCl3): δ = 5.86 (d, J1,2
=
4
4
4.3 Hz, 1 H, 1-H), 5.83 (t, J2,3Ј = J3Ј,4 = 1.8 Hz, 1 H, 3Ј-H), 5.70
(dt, 1 H, 2-H), 5.42–5.39 (m, 1 H, 4-H), 4.28–4.15 (m, J = 7.1 Hz,
2 H, CH2CH3), 3.87 (ddd, 1 H, 5-H), 3.78 (t, J5,6a
9.6 Hz, 1 H, 6a-H), 3.67 (dd, J5,6b = 5.6 Hz, 1 H, 6b-H), 2.31 (s,
3 H, Me, SAc), 1.47 (s, 3 H, Me, iPr), 1.42 (s, 3 H, Me, iPr), 1.30
(t, 3 H, CH2CH3), 0.89 (s, 9 H, tBu, TBDMS), 0.09 (s, 3 H, Me,
TBDMS), 0.08 (s, 3 H, Me, TBDMS) ppm. 13C NMR (100 MHz,
CDCl3): δ = 194.9 (CO, SAc), 165.1 (CO), 156.3 (C-3), 116.3 (C-
3Ј), 113.0 (Cq, iPr), 105.4 (C-1), 78.5, 78.2 (C-4, C-2), 63.0 (C-6),
6a-H), 3.90 (d, 3J5,CH -6 = 5.8 Hz, 6-CH2), 3.72 (dd, 3J5,6b = 4.3 Hz,
3
2
3
3
= =
2J6a,6b
3
6b-H), 3.40 (ddd, 1 H, 5-H), 3.20 (q, J5,6-CH = J4,5 = 5.8 Hz, 5-
2
H) ppm. 13C NMR (100 MHz, (CD3)2CO): δ = 172.3 (CO, lac),
170.7 (C-3), 116.1 (C-3Ј), 115.8 (C-3Ј), 86.3 (C-2β), 83.0, 76.6, 73.0
(C-2α, C-1α, C-1β), 71.6, 70.2 (C-4α, C-4β), 62.7, 62.1 (C-6α, C-
6β), 50.3, 49.2 (C-5α, C-5β) ppm. HRMS: calcd. for C8H10O5S [M
+ Na]+ 241.0141; found 241.0147; calcd. for [M + K]+ 256.9881;
found 256.9888.
3
60.9 (CH2CH3), 48.9 (C-5), 30.8 (Me, SAc), 27.5 (2ϫMe, iPr), 25.9 1,4,6-Tri-O-acetyl-3-deoxy-[2-O,3-C-(1-oxoethan-1-yl-2-ylidene)]-5-
(3ϫMe, tBu), 18.4 (Cq, tBu), 14.3 (CH2CH3), –5.2 (Me, TBDMS), thio- -lyxo-hexopyranose (20) and 4,6-Di-O-acetyl-l,5-anhydro-3-de-
L
Eur. J. Org. Chem. 2009, 4983–4991
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4989