PAPER
Convergent Synthesis of Fucoidan Fragments
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4.32 and 4.50 (dd, 2 H, CH2Ph), 4.43 (dd, J3,4 = 3.4 Hz, 1 H, H3),
4.48 (q, 1 H, H5¢), 4.80 (q, 2 H, CH2Ph), 5.04 (d, 1 H, H1), 5.25–
5.41 (m, 4 H, H1¢, H4¢, CH2=CHCH2O), 5.48 (dd, J3¢,4¢ = 3.4 Hz, 1
H, H3¢), 5.68 (d, 1 H, H4), 6.00 (m, 1 H, CH2=CHCH2O), 7.10–8.10
(m, 20 H, 4 Ph).
1H NMR (250 MHz, CDCl3): d = 0.56 (d, J5¢,6¢ = 6.5 Hz, 3 H, 3 H6¢),
1.40 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 1.95 (s, 3 H, CH3), 4.05 (dd,
J1¢,2¢ = 3.6 Hz, J2¢,3¢ = 10.7 Hz, 1 H, H2¢), 4.10–4.30 (m, 5 H, H2, H4,
H5, CH2=CHCH2O), 4.41 (q, 1 H, H5¢), 4.65–475 (m, 4 H, 2
CH2Ph), 5.04 (d, 1 H, H1¢), 5.12 (d, 1 H, H1), 5.22 and 5.29 (dd, 2
H, CH2=CHCH2O), 5.54–5.60 (m, 3 H, H3, H3¢, H4¢), 6.00 (m, 1 H,
CH2=CHCH2O), 7.10–8.10 (m, 20 H, 4 Ph).
Anal. Calcd for C45H48O12: C, 69.20; H, 6.02. Found: C, 69.31; H,
5.97.
Anal. Calcd for C45H48O12: C, 69.20; H, 6.02. Found: C, 69.34; H,
5.99.
Allyl 4-O-Benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→3)-4-O-
benzoyl-2-O-benzyl-a-L-fucopyranoside (23)
To a soln of compound 22 (180 mg, 0.25 mmol) in anhyd CH2Cl2 (8
mL) was add a mixture of AcCl (0.6 mL) and MeOH (15 mL) and
the mixture was kept at r.t. for 12 h. H2O (40 mL) was then added
and the mixture was extracted with CH2Cl2 (3 × 30 mL). The com-
bined organic layers were dried (MgSO4) and concentrated; column
chromatography of the residue gave disaccharide 23; yield: 157 mg
(85%); [a]D –200 (c 2, EtOAc); Rf = 0.44 (D).
Allyl 4-O-Benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→4)-3-O-
benzoyl-2-O-benzyl-a-L-fucopyranoside (26)
O-Deacetylation of 25 (120 mg, 0.15 mmol) as described for prep-
aration of 23 gave disaccharide 26; yield: 92 mg (83%); [a]D –169
(c 2, EtOAc); Rf = 0.35 (B).
1H NMR (250 MHz, CDCl3): d = 0.57 (d, J5¢,6¢ = 6.5 Hz, 3 H, 3 H6¢),
1.36 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 3.84 (dd, J1¢,2¢ = 3.1 Hz,
J2¢,3¢ = 10.3 Hz, 1 H, H2¢), 4.10–4.25 (m, 5 H, H2, H4, H5,
CH2=CHCH2O), 4.30 (q, 1 H, H5¢), 4.38 (dd, J3¢,4¢ = 2.9 Hz, 1 H,
H3¢), 4.65–475 (m, 4 H, 2 CH2Ph), 5.03 (d, 1 H, H1¢), 5.05 (d,
J1,2 = 3.5 Hz, 1 H, H1), 5.22 and 5.39 (dd, 2 H, CH2=CHCH2O),
5.37 (d, 1 H, H4¢), 5.53 (dd, 1 H, H3), 6.00 (m, 1 H,
CH2=CHCH2O), 7.10–8.10 (m, 20 H, 4 Ph).
1H NMR (250 MHz, CDCl3): d = 1.10 (d, J5¢,6¢ = 6.5 Hz, 3 H, 3 H6¢),
1.18 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 3.83 (dd, J1¢,2¢ = 3.3 Hz,
J
2¢,3¢ = 10.1 Hz, 1 H, H2¢), 4.08 (dd, J1,2 = 3.6 Hz, J2,3 = 10.2 Hz, 1
H, H2), 4.12–4.25 (m, 3 H, H5, CH2=CHCH2O), 4.26 (dd,
3¢,4¢ = 5.0 Hz, 1 H, H3¢), 4.40 and 4.60 (dd, 2 H, CH2Ph), 4.44 (q, 1
J
H, H5¢), 4.47 (dd, J3,4 = 3.4 Hz, 1 H, H3), 4.78 (q, 2 H, CH2Ph), 5.02
(d, 1 H, H1), 5.19–5.41 (m, 3 H, H4¢, CH2=CHCH2O), 5.48 (d, 1 H,
H1¢), 5.72 (d, 1 H, H4), 6.00 (m, 1 H, CH2=CHCH2O), 7.10–8.10
(m, 20 H, 4 Ph).
Anal. Calcd for C43H46O11: C, 69.90; H, 6.28. Found: C, 69.91; H,
6.20.
Anal. Calcd for C43H46O11: C, 69.90; H, 6.28. Found: C, 69.98; H,
6.23.
3-O-Acetyl-4-O-benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→4)-
3-O-benzoyl-2-O-benzyl-L-fucopyranosyl Trichloroacetimid-
ate (27)
3-O-Acetyl-4-O-benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→3)-
4-O-benzoyl-2-O-benzyl-L-fucopyranosyl Trichloroacetimid-
ate (24)
Disaccharide 25 (105 mg, 0.13 mmol) was transformed into trichlo-
roacetimidate 27 as described for the preparation of 21; yield: 92 mg
(80%); ratio a/b-isomer ~1:1 (NMR); Rf = 0.79 (a) and 0.67 (b) (B).
Disaccharide 22 (3.00 g, 3.85 mmol) was transformed into trichlo-
roacetimidate 24 as described for the preparation of 21; yield: 2.66
g (78%); ratio a/b isomers ~1:1 (NMR); Rf = 0.77 (a) and 0.62 (b)
(C).
a-Isomer
1H NMR (250 MHz, CDCl3): d = 0.51 (d, J5¢,6¢ = 6.5 Hz, 3 H, 3 H6¢),
1.38 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 1.95 (s, 3 H, CH3), 3.99 (dd,
J1¢,2¢ = 3.4 Hz, J2¢,3¢ = 10.1 Hz, 1 H, H2¢), 4.28 (d, J3,4 = 2.8 Hz, 1 H,
a-Isomer
H4), 4.33 (q, 1 H, H5¢), 4.35–4.38 (m, 2 H, H2, H5), 4.60–4.80 (m,
4 H, 2 CH2Ph), 5.00 (d, 1 H, H1¢), 5.46 (d, J3¢,4¢ = 2.2 Hz, 1 H, H4¢),
5.50 (dd, 1 H, H3¢), 5.55 (dd, 1 H, H3), 6.68 (d, 1 H, H1), 7.10–8.10
(m, 20 H, 4 Ph), 8.70 (s, 1 H, NH).
1H NMR (250 MHz, CDCl3): d = 0.85 (d, J5¢,6¢ = 6.5 Hz, 3 H, 3 H6¢),
1.25 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 1.85 (s, 3 H, CH3), 3.93 (dd,
J1¢,2¢ = 3.4 Hz, J2¢,3¢ = 10.1 Hz, 1 H, H2¢), 4.25 (dd, J1,2 = 3.4 Hz,
J2,3 = 10.2 Hz, 1 H, H2), 4.42 (q, 1 H, H5), 4.45 (q, 1 H, H5¢), 4.39
and 4.59 (dd, 2 H, CH2Ph), 4.53 (dd, J3,4 = 3.2 Hz, 1 H, H3), 4.75
and 4.85 (dd, 2 H, CH2Ph), 5.22 (d, J3¢,4¢ = 3.0 Hz, 1 H, H4¢), 5.40
(d, 1 H, H1¢), 5.42 (dd, 1 H, H3¢), 5.77 (d, 1 H, H4), 6.73 (d, 1 H,
H1), 7.10–8.10 (m, 20 H, 4 Ph), 8.70 (s, 1 H, NH).
b-Isomer
1H NMR (250 MHz, CDCl3): d = 0.63 (d, J5¢,6¢ = 6.5 Hz, 3 H, H6¢),
1.47 (d, J5,6 = 6.5 Hz, 3 H, H6), 1.95 (s, 3 H, CH3), 4.00–4.04 (m, 2
H, H5, H2¢), 4.18 (d, J3,4 = 3.4 Hz, 1 H, H4), 4.21 (dd, J1,2 = 7.5 Hz,
J2,3 = 9.9 Hz, 1 H, H2), 4.42 (q, 1 H, H5¢), 4.60–4.80 (m, 4 H, 2
CH2Ph), 5.07 (d, 1 H, H1¢), 5.28 (dd, J3,4 = 3.1 Hz, 1 H, H3), 5.48
(d, J3¢,4¢ = 3.6 Hz, 1 H, H4¢), 5.58 (dd, 1 H, H3¢), 5.93 (d, 1 H, H1),
7.10–8.10 (m, 20 H, 4 Ph), 8.80 (s, 1 H, NH).
b-Isomer
1H NMR (250 MHz, CDCl3): d = 0.78 (d, J5¢,6¢ = 6.4 Hz, 3 H, 3 H6¢),
1.32 (d, J5,6 = 6.5 Hz, 3 H, 3 H6), 1.86 (s, 3 H, CH3), 3.90 (dd,
J
1¢,2¢ = 3.4 Hz, J2¢,3¢ = 10.1 Hz, 1 H, H2¢), 4.02 (q, 1 H, H5), 4.10–
Anal. Calcd C44H44Cl3NO12: C, 59.70; H, 5.01; N, 1.58. Found: C,
59.89; H, 4.88; N, 1.69.
4.14 (m, 2 H, H2, H3), 4.28 (q, 1 H, H5¢), 4.29 and 4.55 (dd, 2 H,
CH2Ph), 4.73 and 4.87 (dd, 2 H, CH2Ph), 5.17 (d, J3¢,4¢ = 3.0 Hz, 1
H, H4¢), 5.35 (d, 1 H, H1¢), 5.42 (dd, 1 H, H3¢), 5.68 (d, 1 H, H4),
5.93 (d, J1,2 = 7.5 Hz, 1 H, H1), 7.10–8.10 (m, 20 H, 4 Ph), 8.78 (s,
1 H, NH).
Allyl 3-O-Acetyl-4-O-benzoyl-2-O-benzyl-a-L-fucopyranosyl-
(1→3)-4-O-benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→3)-4-O-
benzoyl-2-O-benzyl-a-L-fucopyranosyl-(1→3)-4-O-benzoyl-2-
O-benzyl-a-L-fucopyranoside (28)
Glycosylation of disaccharide 23 (695 mg, 0.94 mmol) with disac-
charide 24 (918 mg, 1.04 mmol) as described in the general proce-
dure gave tetrasaccharide 28; yield: 1.22 g (89%); [a]D –264 (c 1,
EtOAc), Rf = 0.77 (C).
1H NMR (250 MHz, CDCl3): d = 0.62, 0.78, 1.05, 1.18 (4 d, 12 H,
12 H6), 1.78 (s, 3 H, CH3), 3.80, 3.95, 4.03, 4.07 (4 dd, 4 H, 4 H2),
4.14–4.60 (m, 15 H, 4 H5, 3 H3, 3 CH2Ph, CH2=CHCH2O), 4.80 (q,
2 H, CH2Ph), 4.97 (d, J1,2 = 3.6 Hz, 1 H, H1), 5.05 (d, J3¢¢¢,4¢¢¢ = 3.1
Anal. Calcd C44H44Cl3NO12: C, 59.70; H, 5.01; N, 1.58. Found: C,
59.85; H, 4.98; N, 1.65.
Allyl 3-O-Acetyl-4-O-benzoyl-2-O-benzyl-a-L-fucopyranosyl-
(1→4)-3-O-benzoyl-2-O-benzyl-a-L-fucopyranoside (25)
Glycosylation of monofucoside 17 (500 mg, 1.26 mmol) with
trichloroacetimidates 21 (753 mg, 1.38 mmol) as described in the
general procedure gave disaccharide 25; yield: 855 mg (87%); [a]D
–155 (c 1, EtOAc); Rf = 0.48 (B).
Synthesis 2006, No. 23, 4017–4031 © Thieme Stuttgart · New York