Cette publication est accessible gratuitement

Regio- and Stereoselective Syntheses of Chiral Heterocyclic
Carbohydrate Conjugates; Cesium Fluoride-Celite: A Solid Base for
Syntheses of Esters, Ethers, Thioesters, Thioethers and Symmetrical

Regio- und stereoselektive Synthesen von chiralen heterozyklischen
Kohlenhydratkonjugaten; Cäsiumfluorid-Celit: Eine feste Base für die
Synthese von Estern, Ethern, Thioestern, Thioethern und
symmetrischen Disulfiden


der Fakultät für Chemie und Pharmazie
der Eberhard-Karls-Universität Tübingen

zur Erlangung des Grades eines Doktors
der Naturwissenschaften


vorgelegt von
Syed Tasadaque Ali Shah II
Im Namen Gottes, voller Gnaden und Erbarmen

In the Name of Allah, the Most Beneficent, the Most Merciful

Tag der mündlichen Prüfung: 04-08-2003
Dekan: Prof. Dr. H. Probst
1. Berichterstatter: Prof. Dr. Dr. h. c. W. Voelter
2. Berichterstatter: Prof. Dr. U. Weser IV
Die vorliegende Arbeit wurde unter Leitung von Herrn Prof. Dr. Dr. h.c.
Wolfgang Voelter in der Zeit von Oktober 2000 bis August 2003 an der
Abteilung für Physikalische Biochemie des Physiologich-chemischen
Instituts der Universität Tübingen durchgeführt.


to my mother

Ruqaya BiBi (Late)
Whose praise and encouragement has supported and guided me
throughout my life


I would like to express my sincere gratitude and appreciation to my
supervisor Prof. Dr. Dr. h.c. Wolfgang Voelter for his guidance, continued
interest and inspiration throughout the course of Ph.D. research.
I am most grateful to the DAAD (Deutscher Akademischer Austausch-
dienst) for providing me a Ph.D. scholarship.
I am also heartily thankful to Dr. Khalid M. Khan (H.E.J. Research
Institute of Chemistry, University of Karachi, Karachi-Pakistan) and prof.
Michael Duszenko and his coworkers for their support and help.
Sincere appreciation and love is due to my father Syed Wazir Ali Shah,
mother, brothers and sisters for their encouragement and valuable
support during all my life.
For their support and stimulating discussions I would like to express my
special thanks to my colleagues and friends, especially to Miriam Fecker,
Angelica M. Heinrich, Dr. Hartmut Echner, Dr. Muhammad Abbas, Dr.
Muhammad Saeed, Dr. Raid Abdel-Jalil, Dr. Syed Abid Ali, and Dr.
Wieland Stock.
I want to express my deepest and special thanks to Shasta Lea Schnittker
for her support and encouragement and also to my friends Alexander
Faust, Jörg Schäfer, Mohammad Aslam, Martell Rieckmann and Tim
Conze for providing me a charming company at Tuebingen University.


B.I. 2,3-Anhydropentoses: Synthesis of Starting Materials 3
B.I.1. Synthesis of benzyl 2,3-anhydro-β-L-ribopyranoside (6) 3
B.I.2. 4 α-D-ribopyranoside (15)
B.I.3. Synthesis of benzyl 2,3-anhydro-4-O-triflyl-ribopyranosides 5
B.I.4. 6 α-D-lyxopyranoside (18)
B.II. Regioselective Conversion of Anhydro Sugars into 7
Halohydrins and X-Ray Study
B.III. Sodium Hydride/Hexamethylphosphoric Triamide: A New 14
Efficient Reagent towards the Synthesis of Protected 1,2-
and 5,6-Enopyranosides
B.IV. A Stereospecific Synthesis of Chiral 2,3-Dihydrobenzo-[1,4]- 22
dithiane and 2,3-Dihydromethylbenzo-[1,4]-dithiane Deriv-
B.IV.1. Bioactivity of methylbenzodithiane (69) against trypanoso- 25
B.IV.2. In vitro toxicity of compound 69 in trypanosomes 26
B.V. An Efficient Synthetic Approach towards Thioesters and 30
Thioethers Using CsF-Celite as a Solid Base VIII
B.VI. Cesium Fluoride-Celite: A Solid Base for Efficient 37
Syntheses of Aromatic Esters and Ethers
B.VII. A Novel Method for the Syntheses of Symmetrical Disulfides 44
Using CsF-Celite as a Solid Base
C.I. Synthesis of Starting Materials
C.I.1. 48 Benzyl 2,3-anhydro-β-L-ribopyranosides (6)
C.I.1.1. 49 Benzyl β-L-arabinosopyranoside (2)
C.I.1.2. 49 Benzyl 3,4-O-isopropylidene-β-L-arabinopyranoside (3)
C.I.1.3. O-isopropylidene-2-O-p-tolylsulphonyl-β-L-arab- 49
ino pyranoside (4)
C.I.1.4. 50 Benzyl 2-O-p-tolylsulphonyl-β-L-arabinopyranoside (5)
C.I.1. 50 Benzyl 2,3-anhydro-β-L-ribopyranosides (6)
C.I.2. 50 α-D-ribopyranoside (15)
C.I.2.1. 50 Tetrabenzoate of β-D-arabinopyranoside (8)
C.I.2.2. 51 2,3,4-Tri-O-benzoyl-β-D-arabinopyranosyl bromide (9)
C.I.2.3. 51 Benzyl 2,3,4-Tri-O-benzoyl-α-D-arabinopyranoside (10)
C.I.2.4. 52 Benzyl α-D-arabinopyranoside (11)
C.I.2.5. 52 Benzyl 3,4-O-isopropylidene-α12)
C.I.2.6. O-isopropylidene-2-O-tolylsulphonyl-α-D-arabi- 52
nopyranoside (13)
C.I.2.7. 53 Benzyl 2-O-tolylsulphonyl-α-D-arabinopyranoside (14)
C.I.2. 53 Benzyl 2,3-anhydro-α-D-ribopyranoside (15) IX
C.I.3. 53 Benzyl 2,3-anhydro-4-O-triflyl-β-L-ribopyranoside (16) and
benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside (17)
C.I.3.1. 54 O-triflyl-β-L-ribopyranoside (16)
C.I.3.2. 54 Benzyl 2,3-anhydro-4-O-triflyl-α-D-ribopyranoside (17)
C.I.4. 54 Benzyl 2,3-anhydro-α-D-lyxopyranoside (18)
C.II. General Procedure for the Preparation of Halodeoxy Sugars 55
C.II.1. Benzyl 3-chloro-3-deoxy-β-L-xylopyranoside (19) 55
C.II.2. 55 Benzyl 3-bromo-3-deoxy-β20)
C.II.3. 56 Benzyl 3-iodo-3-deoxy-β-L-xylopyranoside (21)
C.II.4. 56 Benzyl 3-chloro-3-deoxy-α-D-xylopyranoside (22)
C.II.5. 56 Benzyl 3-bromo-3-deoxy-α23)
C.II.6. 57 Benzyl 3-iodo-3-deoxy-α-D-xylopyranoside (24)
C.II.7. 57 Benzyl 3-chloro-3-deoxy-α-D-arabinopyranoside (25)
C.II.8. 58 α26)
C.III. General Procedure for Dehydrohalogenation and Dehydro- 58
C.III.1. 2,3,4,6-Tetra-O-acetyl-2-hydroxy-D-glucal (33) 58
C.III.2. 2,3,4,6-Tetra-O-benzoyl-2-hydroxy-D-glucal (3459
C.III.3. 2,3,4,6-Tetra-O-acetyl-2-hydroxy-D-galactal (37) 60
C.III.4. 2,3,4-Tri-O-acetyl-2-hydroxy-L-xylal (40)
C.III.5. 2,3,4-Tri-O4261
C.III.6. 2,3,4-Tri-O-acetyl-2-hydroxy-L-arabinal (4462 X
C.III.7. 6-Deoxy-1,2,3,4-di-O-isopropylidene-L-arabino-hex-5-enop- 62
yranoside (48)
C.III.8. 63 Methyl 4-O-benzyl-6-deoxy-3-C-methyl-2-O-methyl-α-D-rib-
ohex-5-enopyranoside (52)
C.III.9. 63 1,2,3,4-Tetra-O-benzoyl-6-deoxy-β-D-xylohex-5-enopyrano-
side (56)
C.III.10. 3,4-Di-O-acetyl-hex-1,2:5,6-dienopyranoside (28) 64
C.III.11. 65 2,3,6-Tri-O-benzoyl-4-O-(2,3,4,5-tetra-O-benzoyl-β-D-galac-
topyranosyl)-1,5-anhydro-D-arabinohex-1-enitol (58)
C.IV. General Procedure for the Preparation of Chiral Benzodi- 65
thiane and Methylbenzodithiane
C.IV.1. 66 1,2-Dihydro-(benzyl 3,4-dideoxy-α-D-arabinopyranoso)-[3,-
4-b]-benzo-[1,4]-dithiane (68)
C.IV.2. β-L-arabinopyranoso)-[3,4- 66
b]-benzo-[1,4]-dithiane (70)
C.IV.3. 67 1,2-Dihydro-(benzyl 3,4-dideoxy-α-D-arabinopyranoso)-[3,-
4-b]-methylbenzo-[1,4]-dithiane (69)
C.IV.4. 67 β-L-arabinopyranoso)-[3,4-
b]-methylbenzo-[1,4]-dithiane (71)
C.IV.5.1. Cultivation of trypanosomes 68
C.IV.5.2 Determination of metabolites 68
C.V. General Procedure for the Preparation of Thioethers and 69