Supporting Information
© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2006
1
Highly Efficient Syntheses of Hyaluronic Acid Oligosaccharides
Lijun Huang, Xuefei Huang*
Department of Chemistry
The University of Toledo
2801 W. Bancroft St. MS 602
Toledo, OH 43606 (USA)
2
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
OBnO
OBz
SO
O
8
MeO
(400 MHz, CDCl3)
3
250 200 150 100 50 0
OBnO
OBz
SO
O
8
MeO
(100 MHz, CDCl3)
4
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
OBnO
OBz
STol
OPMB
HO
17(400 MHz, CDCl3)
5
250 200 150 100 50 0
(100 MHz, CDCl3)
OBnO
OBz
STol
OPMB
HO
17
6
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
OBnO
OBz
STol
OPMB
TBSO
11(400 MHz, CDCl3)
7
250 200 150 100 50 0
OBnO
OBz
STol
OPMB
TBSO
11(100 MHz, CDCl3)
8
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
(400 MHz, CDCl3)
OBnO
BzO
PMBOTBSO O
ONPhth
STolO
OPh
14β
9
250 200 150 100 50 0
(100 MHz, CDCl3)
OBnO
BzO
PMBOTBSO O
ONPhth
STolO
OPh
14β
10
(400 MHz, CDCl3)
OBnO
BzO
PMBOTBSO O
ONPhth
OCH3
OO
Ph
15
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
11
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CDCl3)
OBnO
BzO
PMBOTBSO O
ONPhth
OCH3
OO
Ph
15
12
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
(400 MHz, CDCl3)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
PMBOTBSO
OO
PhthN
OO
Ph
19
13
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CDCl3)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
PMBOTBSO
OO
PhthN
OO
Ph
19
14
11 10 9 8 7 6 5 4 3 2 1 0
(100 MHz, CDCl3)
OBnO
BzO
PMBOHO O
ONPhth
OCH3
OO
Ph
22
15
180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
(400 MHz, CDCl3)
OBnO
BzO
PMBOHO O
ONPhth
OCH3
OO
Ph
22
(100 MHz, CDCl3)
OBnO
BzO
PMBOHO O
ONPhth
OCH3
OO
Ph
22
16
12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2
(400 MHz, CD2Cl2)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhOO
PhthN
OO
PhO
BnOBzO
PMBOO
OTBSO
PhthN
OO
Ph
28
17
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CD2Cl2)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhOO
PhthN
OO
PhO
BnOBzO
PMBOO
OTBSO
PhthN
OO
Ph
28
18
12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2
(600 MHz, CD2Cl2)
OBnO
BzO
PMBOTBSO
OO
PhthN
OO
PhO
BnOBzO
PMBOO O
O
PhthN
OO
PhO
BnOBnO
PMBOO
OCH3
29
19
250 200 150 100 50 0
(150 MHz, CD2Cl2)
OBnO
BzO
PMBOTBSO
OO
PhthN
OO
PhO
BnOBzO
PMBOO O
O
PhthN
OO
PhO
BnOBnO
PMBOO
OCH3
29
20
12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2
(600 MHz, CDCl3)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
PMBOO
OO
PhthN
OO
PhO
BnOBzO
PMBOTBSO
OO
PhthN
OO
Ph
30
21
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CDCl3)
OBnO
BzO
PMBOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
PMBOO
OO
PhthN
OO
PhO
BnOBzO
PMBOTBSO
OO
PhthN
OO
Ph
30
22
13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1
(600 MHz, CDCl3)
OBnO
BzO
HOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
HOO O
OPhthN
OO
PhO
BnOBzO
HOTBSO O
OPhthN
OO
Ph
36
23
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CDCl3)
OBnO
BzO
HOO O
OPhthN
OCH3
OO
PhOBnO
BzO
HOO O
OPhthN
OO
PhO
BnOBzO
HOTBSO O
OPhthN
OO
Ph
36
24
10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
(400 MHz, CD2Cl2)
OBnO
BzO
BnOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
BnOO
OO
PhthN
OO
PhO
BnOBzO
BnOTBSO
OO
PhthN
OO
Ph
37
O O O
25
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
(100 MHz, CD2Cl2)
OBnO
BzO
BnOO
OO
PhthN
OCH3
OO
PhO
BnOBzO
BnOO
OO
PhthN
OO
PhO
BnOBzO
BnOTBSO
OO
PhthN
OO
Ph
37
O O O
26
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
(400 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
HOHO
HO2CO O
OAcHN
HOHO
38
OHO
HO
HO2CHO O
OAcHN
HOHO
27
200 150 100 50 0
(100 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
HOHO
HO2CO O
OAcHN
HOHO
38
OHO
HO
HO2CHO O
OAcHN
HOHO
28
(600 MHz, D2O)
OHO
HO
HO2CHO O
OAcHN
OCH3
HOHO
39
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
29
9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0
(600 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
HOHO
HO2CHO O
OAcHN
HOHO
40
30
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
(100 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
HOHO
HO2C
HO OO
AcHN
HOHO
40
31
9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
(600 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
OAcHN
HOHO
41
OHO
HO
HO2COO
HOAcHN
HOHO
32
190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10 -20
(150 MHz, D2O)
OHO
HO
HO2CO O
OAcHN
OCH3
HOHOO
OAcHN
HOHO
41
OHO
HO
HO2COO
HOAcHN
HOHO
33
7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
( 600 MHz, D2O)
OHO
HO
HO2CO
OCH3O
HOHO
HO2CO O
OAcHN
HOHO
42
OHO
HO
HO2CHO O
OAcHN
HOHO
34
200 150 100 50 0
( 150 MHz, D2O)
OHO
HO
HO2CO
OCH3O
HOHO
HO2CO O
OAcHN
HOHO
42
OHO
HO
HO2CHO O
OAcHN
HOHO