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