Synthesis of 1,6-Disulfide-Bridged d-Hexopyranoses
195
2,3,4,6-Tetra-O-acetyl-1-S-phenylsulfonyl-1-thio-
β-D-mannose 17
1,2,3,4-Tetra-O-acetyl-6-S-acetyl-6-thio-β-D-allose 28
The thioacetate 27 (32 mg, 0.1 mmol) was dissolved in CF3COOH/
H2O (4 : 1, 1 mL) and the solution kept (30 min). The solvent was
removed before co-evaporation with PhMe. Sodium (5 mg, 0.2 mmol)
was added to the residue in MeOH (5 mL), and the solution kept (2 h).
The solution was quenched with resin (Amberlite IR-120, H+), and
the mixture was filtered and concentrated. Acetic anhydride (0.14 mL,
1.5 mmol) was added to the residue in pyridine (1 mL), and the solu-
tion kept (4 h). MeOH (1 mL) was added and the mixture concentrated.
Standard workup (EtOAc) and flash chromatography (EtOAc/toluene,
2 : 25) gave the thioacetate 28 as a colourless oil (29 mg, 72%), [α]D
−43.6◦. δH (300 MHz) 2.00, 2.05, 2.11, 2.15 (12H, 4s, OCOCH3), 2.33
(s, SCOCH3), 3.17–3.20 (2H, m, H6), 4.19 (ddd, J4,5 10.1, J5,6 3.8, J5,6
5.1, H5), 4.86 (dd, J3,4 2.9, H4), 4.94 (dd, J1,2 8.7, J2,3 3.0, H2), 5.66 (dd,
H3), 5.95 (d, H1). δC (75.5 MHz) 20.5, 20.6, 20.7, 20.9 (4C, OCOCH3),
29.8 (C6), 30.4 (SCOCH3), 67.5, 68.1, 68.2, 71.7 (C2,3,4,5), 89.9 (C1),
Treatment of the pentaacetate 16 (781 mg, 2.00 mmol) accord-
ing to procedure A (refluxed for 30 min, flash chromatography with
EtOAc/petrol, 3 : 7) gave the benzenethiosulfonate 17 as a colour-
less oil (868 mg, 86%), [α]D +62.8◦. νmax (film)/cm−1 1754 (C=O),
1343, 1150 (S–SO2). δH (600 MHz) 1.95, 1.98, 2.04, 2.15 (12H, 4s,
OCOCH3), 3.55 (dd, J5,6 2.4, J6,6 12.5, H6), 3.81 (ddd, J4,5 10.0,
J5,6 3.7, H5), 4.04 (dd, H6), 4.92 (dd, J2,3 3.4, J3,4 10.0, H3), 5.29
(t, H4), 5.35 (dd, J1,2 1.7, H2), 5.95 (d, H1), 7.54–7.96 (m, Ph). δC
(150.9 MHz) 20.5, 20.6, 20.7, 20.8 (4C, OCOCH3), 61.2 (C6), 65.4,
69.7, 70.0, 71.3 (C2,3,4,5), 87.2 (C1), 127.4, 129.5, 134.3, 145.6 (Ph),
169.4, 169.5, 169.7, 170.5 (4C, C=O). m/z (FAB) 505.0863; [M + H]+
requires 505.0838.
2,3,4-Tri-O-acetyl-6-S-acetyl-1-S-phenylsulfonyl-
1,6-dithio-β-D-mannose 21
•
169.0, 169.3, 169.8 (C=O), 194.8 (SC=O). m/z (EI) 406.0971; [M]+
requires 406.0934.
Treatment of the tetraacetate 20[28] (813 mg, 2.00 mmol) accord-
ing to procedure A (refluxed for 30 min, flash chromatography with
EtOAc/petrol, 3 : 7) gave the benzenethiosulfonate 21 as a colourless
oil (875 mg, 84%), [α]D +65.8◦. νmax (film)/cm−1 1755 (C=O), 1697
(SC=O), 1342, 1149 (S–SO2). δH (300 MHz) 1.90, 1.98, 2.12 (9H, 3s,
OCOCH3), 2.24 (s, SCOCH3), 2.61 (dd, J5,6 3.1, J6,6 14.5, H6), 2.93
(dd, J5,6 5.2, H6), 3.78 (ddd, J4,5 9.8, H5), 4.82 (dd, J2,3 3.3, J3,4 9.8,
H3), 5.14 (t, H4), 5.30 (dd, J1,2 1.7, H2), 5.88 (d, H1), 7.51–7.94 (m,
Ph). δC (75.5 MHz) 20.3, 20.5, 20.6 (3C, OCOCH3), 29.0 (C6), 30.2
(SCOCH3), 66.7, 69.3, 69.8, 72.0 (C2,3,4,5), 86.9 (C1), 127.0, 129.3,
134.0, 145.4 (Ph), 169.4, 169.5 (C=O), 194.2 (SC=O). m/z (FAB)
521.0623; [M + H]+ requires 521.0610.
2,3,4-Tri-O-acetyl-6-S-acetyl-1-S-phenylsulfonyl-
1,6-dithio-β-d-allose 29
Treatment of the tetraacetate 28 (284 mg, 0.700 mmol) according to
procedureA (refluxed for 3 h, flash chromatography with EtOAc/petrol,
1 : 2) gave the benzenethiosulfonate 29 as a colourless oil (288 mg,
79%), [α]D −20.0◦. νmax (film)/cm−1 1755 (C=O), 1697 (SC=O),
1330, 1147 (S–SO2). δH (300 MHz) 1.94, 1.99, 2.16 (9H, 3s, OCOCH3),
2.26 (s, SCOCH3), 2.84 (dd, J5,6 3.5, J6,6 14.4, H6), 3.05 (dd, J5,6
5.1, H6), 3.99 (ddd, J4,5 10.1, H5), 4.70 (dd, J3,4 2.8, H4), 4.91 (dd,
J1,2 10.5, J2,3 2.9, H2), 5.52 (d, H1), 5.59 (dd, H3), 7.50–7.96 (m,
Ph). δC (75.5 MHz) 20.3, 20.4, 20.6 (3C, OCOCH3), 29.4 (C6), 30.2
(SCOCH3), 66.4, 67.2, 67.8, 73.8 (C2,3,4,5), 84.2 (C1), 126.8, 129.1,
133.7, 146.0 (Ph), 168.8, 169.1, 169.6 (3C, C=O), 194.2 (SC=O). m/z
(FAB) 521.0609; [M + H]+ requires 521.0610.
(1S,5S,6S,7S,8S)-6,7,8-Triacetoxy-9-oxa-2,3-
dithiabicyclo[3.3.1]nonane 22
Treatment of the benzenethiosulfonate 21 (260 mg, 0.500 mmol)
according to procedure B (flash chromatography with EtOAc/petrol,
3 : 7) gave the disulfide 22 as a colourless oil (87 mg, 43%), [α]D −145◦.
δH (600 MHz) 2.01, 2.04, 2.15 (9H, 3s, OCOCH3), 2.79 (dd, J4,4 13.7,
J4,5 9.8, H4), 3.32 (d, H4), 4.93 (dd, J5,6 10.0, H5), 5.21 (dd, J6,7 10.0,
J7,8 3.0, H7), 5.35 (t, H6), 5.43–5.44 (m, H1,H8). δC (150.9 MHz) 20.7,
20.9, 21.3 (3C, OCOCH3), 36.9 (C4), 67.7 (C5), 69.2 (C7), 70.2 (C8),
70.5 (C6), 94.1 (C1), 169.77, 169.83, 171.0 (3C, C=O). m/z (FAB)
337.0396; [M + H]+ requires 337.0416.
(1S,5S,6S,7R,8R)-6,7,8-Triacetoxy-9-oxa-2,3-
dithiabicyclo[3.3.1]nonane 30
Treatment of the benzenethiosulfonate 29 (156 mg, 0.300 mmol)
according to procedure B (flash chromatography with EtOAc/petrol,
3 : 7) gave the disulfide 30 as a colourless oil (63 mg, 62%), [α]D −92.9◦.
δH (300 MHz) 2.04, 2.11, 2.12 (9H, 3s, OCOCH3), 2.58 (ddd, J1,4 0.8,
J4,4 14.2, J4,5 2.7, H4), 3.54 (dd, J4,5 3.9, H4), 4.29 (ddd, J5,6 1.8,
H5), 5.00 (dd, J1,8 2.4, H1), 5.31 (dd, J6,7 4.5, H6), 5.63 (dd, J7,8 4.0,
H8), 6.62 (t, H7). δC (75.5 MHz) 20.6, 20.8 (OCOCH3), 29.4 (C4), 65.3
(C7), 69.3 (C6), 71.8 (C5), 72.0 (C8),•75.7 (C1), 169.7, 169.8, 170.1
(3C, C=O). m/z (FAB) 336.0360; [M]+ requires 336.0337.
(1S,5S,6S,7S,8S)-9-Oxa-2,3-dithiabicyclo[3.3.1]-
nonane-6,7,8-triol 14
Treatment of the triacetate 22 (67 mg, 0.20 mmol) according to pro-
cedure C gave the triol 14 as a colourless solid (41 mg, 98%), [α]D
−205◦ (pyridine). δH [300 MHz, (CD3)2SO] 2.23 (dd, J4,4 13.8, J4,5
9.7, H4), 2.72 (d, H4), 3.17 (dd, J6,7 9.2, J7,8 3.0, H7), 4.14 (dd, J5,6 9.6,
H5), 4.57 (dd, H6), 4.66 (dd, J1,8 1.4, H8), 4.84 (d, H1). δC [75.5 MHz,
(CD3)2SO] 36.2 (C4•), 69.1, 71.0, 71.5, 73.2 (C5,6,7,8), 95.1 (C1). m/z
(EI) 210.0016; [M]+ requires 210.0021.
(1S,5S,6S,7R,8R)-9-Oxa-2,3-dithiabicyclo[3.3.1]-
nonane-6,7,8-triol 23
Treatment of the triacetate 30 (67 mg, 0.20 mmol) according to
procedure C gave the triol 23 as a colourless solid (41 mg, 98%), [α]D
−212◦ (pyridine). δH [600 MHz, (CD3)2SO] 2.67 (dd, J1,4 0.6, J4,4 14.0,
J4,5 3.1, H4), 3.30 (dd, J4,5 4.7, H4), 3.82 (dd, J1,8 2.1, J7,8 2.3, H8), 3.98
(dd, J6,7 3.5, H7), 4.17 (ddd, J5,6 3.7, H5), 4.94 (dd, H6), 5.02 (d, H1).
δC [150.9 MHz, (CD3)2SO] 28.1 (C4), 65.3, 71.3, 73.1, 74.9 (C5,6,7,8),
78.1 (C1). m/z (ES) 232.9909; [M + Na]+ requires 232.9918.
5-O-Acetyl-6-S-acetyl-1,2-O-isopropylidene-6-
thio-β-D-allofuranose 27
Potassium thioacetate (685 mg, 6.00 mmol) was added to the tosy-
late 26[18] (1.12 g, 3.00 mmol) in DMF (10 mL), and the mixture stirred
overnight. Concentration of the mixture and standard workup (EtOAc)
followed by flash chromatography (EtOAc/petrol, 2 : 3) gave the thioac-
etate 27 as a colourless oil (605 mg, 63%), [α]D +39.8◦. δH (300 MHz)
1.36, 1.56 (6H, 2s, CH3), 2.07 (s, OCOCH3) 2.33 (s, SCOCH3), 2.37
(br s, OH), 3.03 (dd, J5,6 8.5, J6,6 14.3, H6), 3.39 (dd, J5,6 4.1, H6),
3.83 (dd, J3,4 8.6, J4,5 4.8, H4), 4.04 (dd, J2,3 5.2, H3), 4.56 (dd, J1,2
3.8, H2), 5.19 (ddd, H5), 5.77 (d, H1). δC (75.5 MHz) 20.9 (OCOCH3),
2.49, 26.53[C(CH3)2], 29.5(C6), 30.4(SCOCH3), 71.3, 72.7, 78.6, 79.8
(C2,3,4,5), 103.8 (C1), 112.8 [C(CH3)2], 170.2 (C=O), 194.8 (SC=O).
m/z (FAB) 321.1014; [M + H]+ requires 321.1008.
2,3,4-Tri-O-acetyl-6-S-acetyl-1-S-methylsulfonyl-
1,6-dithio-β-D-galactose 32
Treatment of 1,2,3,4-tetra-O-acetyl-6-S-acetyl-6-thio-α-d-gala-
ctose[29] (2.24 g, 5.50 mmol) according to procedureA (refluxed for 4 h,
flash chromatography with EtOAc/petrol, 3 : 7) gave the methanethio-
sulfonate 32 as colourless plates (2.04 g, 81%), mp 146–147.5◦C, [α]D
+41.5◦ (Found: C 39.0, H 4.9. C15H22O10S3 requires C 39.3, H 4.8%).
νmax (KBr)/cm−1 1754 (C=O), 1696 (SC=O), 1329, 1141 (S–SO2). δH
(300 MHz) 1.89, 1.99, 2.10 (9H, 3s, OCOCH3), 2.27 (s, SCOCH3), 2.87
(dd, J5,6 8.2, J6,6 14.1, H6), 3.10 (dd, J5,6 5.3, H6), 3.42 (s, SSO2CH3),
3.83 (ddd, J4,5 1.0, H5), 5.04–5.21 (m, H1,H2,H3), 5.40 (dd, J3,4 3.1,