Organizing Committee

Institute of Organic Chemistry of the Polish Academy of Sciences, 01-224 Warsaw, Poland

1,3-Dipolar cycloaddition of lactones 1 and 2 with nitrones 3 and 4 provides adducts 5-11.¹ In the case of the nitrone 3 and lactones 1 and 2 only one adduct was formed, 5 and 8, respectively, as a result of the exo addition, anti to t-butoxyl at C-3 of the dipole. On the other hand, the nitrone 4 with both lactones 1 and 2 affords corresponding exo adducts 7, 10 and 11 which are accompanied by endo ones 6 and 9. This result should be compared with the same reactions performed on δ-lactones. In all, so far, investigated cases, the formation of endo adducts was not observed.

1. Pasniczek, K.; Socha, D.; Jurczak, M.; Frelek, J.; Suszczyńska, A.; Urbańczyk-

Lipkowska, Z. Chmielewski, M. J. Carbohydr. Chem., 22, 613 (2003).

2. Jurczak, M.; Mostowicz, D.; Panfil, I.; Rabiczko, J.; Socha, D.; Chmielewski, M. in

Targets in Heterocyclic Systems, Attanasi, O., Ed.; Springer: Berlin, 2001; Vol. 5, p. 59.

HIGHLY DIASTEREOSELECTIVE ALLYLATION

OF CHIRAL OXIME ETHERS

Joanna CHAŁKO,^a Janusz JURCZAK^a,b
a Department of Chemistry, University of Warsaw, 02-093 Warsaw

^b Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw

[e-mail]

Various derivatives of allylamines are widely used in the preparation of natural products, including carbohydrates.¹ The methods for the preparation of chiral allyl amines and their derivatives are mainly based on the diastereoselective nucleophilic addition of allylometallic reagents to the C=N bond.

We found that among many compounds bearing the azomethine group, aldoxime ethers are interesting substrates for the asymmetric allylation reaction. As a convenient substrate we have chosen O-alkyloximes derived from glyoxylic acid modified by Oppolzer’s chiral auxiliary.

The best results were obtained when allylation was carried out under Barbier conditions. In this case, we were able to get desired O-alkilhydroxylamines as a single

(2S)-enantiomer and with 55% overall yield.

1. Trost, B. M.; Van Vranken, D. L. J. Am. Chem. Soc. 1993, 115, 444

RECENT PROGRESS IN THE PREPARATION OF SOME GLYCOCONJUGATES AND ANALOGUES FROM EASILY AVAILABLE CARBOHYDRATE BASED-SYNTHONS

Yves QUENEAU
Laboratoire de Chimie Organique, UMR 5181 CNRS-UCBL-INSA

INSA, Bât. J. Verne, 20 avenue A. Einstein, 69621 Villcurbanne Cedex, France

tel [phone]; fax. [phone]; e-mail: [e-mail]

Carbohydrate-containing natural products such as glycopeptides, glycolipids, as well as oligosaccharides are present about everywhere in living systems and are responsible for numerous and important biological processes. There is therefore a need for compounds with exact or similar structure to those glyconjugates in order to study their function and eventually to interfere in some biological pathways.

Being involved in the use of very available carbohydrates for chemistry, we have been interested in the preparation of some sucrose derivatives close to natural compounds such as derivatives similar to gallotannins found in some Chinese rhubarbs having antioxidant properties or some glycolipids analogues of Cord factors with lamellar thermotropic behaviour. The synthesis of such compounds as well as some of their properties will be described, with a focus on how to overcome the inherent difficulties of regioselectivity when starting from unprotected substrates without multiplying the protection-deprotection steps.
Also, we will present some recent progress in the preparation of some neoglycoconjugates based on the use of CMGLs (carboxymethyl glycoside lactones) which are bicyclic lactones easily obtained either by degradation of available disaccharides or by construction from monosaccharides. Compounds in the families of pseudo-disaccharides, pseudo-glycopeptides and pseudo-glycolipids will be described.

For recent relevant work of our group, see: Gallic esters of sucrose as efficient radical scavengers in lipid peroxidation, C. Dufour, E. Da Silva., P. Potier, Y. Queneau and O. Dangles, J. Agric. Food. Chem., 50, 3425-3430 (2002); A bilayer to monolayer phase transition in liquid crystal glycolipids, V. Molinicr, P.H.J. Kouwer, Y. Queneau, J. Fitremann, G. Mackcnzic et J. W, Goodby J. Chem. Soc., Chem. Commun,, 2860-2861 (2003); Straightforward route for anchoring a glucosyl moiety on nucleophilic species: ręaction of amines and alcohols with carboxymethyl 3,4,6-tri-O-acetyl--D-glucopyranoside 2-O-lactone, J. Org. Chem., 68, 6672-6678 (2003); The chemistry of unprotected sucrose: the selectivity issue, Y. Quencau, J. Fitremann and S. Trombotto, C. R. Chimie., 7, 177-188 (2004).


SYNTHESIS AND ANTIBODY RECOGNITION OF CHLAMYDIAL LIPOPOLYSACCHARIDE
Alla ZAMYATINA*^a, Harald SEKLJIC^b, Helmut BRADE^b,

Stephen V. EVANS^c, Paul KOSMA^a
a Dept. of Chemistry, Univ. of Natural Resources and Applied Life Sciences, Vienna

^bMedical and Biochemical Microbiology, Research Center Borstel, Germany

^c Dept. Biochemistry and Microbiology, Univ.Victoria, Canada

[e-mail]; [e-mail]

Chlamydiae are obligatory intracellular Gram-negative pathogens which are responsible for a variety of acute and chronic diseases in animals and humans, such as urogenital infections and trachoma [1]. In addition, Chl. pneumonia infections may be associated with atherosclerosis. Although chlamydial LPS is at least ~10 times less active than enterobacterial endotoxins, its role in local chronic infections and inflammatory processes needs to be clarified [2]. Based on the structural data on C. trachomatis serotype L2 LPS [3], chlamydial tetraacyl Lipid A and pentaacyl Lipid A has been synthesized and was fully characterized.

In addition, synthesis of neoglycoconjugates containing chlamydia-specific and cross-reactive Kdo-ligands allowed for a detailed characterization of the binding of monoclonal antibodies to these bacterial epitopes using serology, NMR-methodology and crystallography [4].



Binding of a Kdo trisaccharide to mAb S-25 Pentaacyl chlamydial Lipid A

Acknowledgments: Financial support by FWF (P13843-CHE and P 17407)
References:

[1] Moulder, J. W. Microbiol. Rev. 1991, 55, 143-190.

[2] Heine, H.; Müller-Loennies, S.; Brade, L.; Lindner, B.; Brade. H. Eur. J. Biochem. 2003,

270, 440-450.

[3] Zamyatina, A., Sekljic, H., Brade, H., Kosma, P. Carbohydr. Res. 2004, 60, 12113-12137.

[4] Nguyen, H.P., Seto, N.O.L., MacKenzie, C.R., Brade, L., Kosma, P., Brade, H., Evans, S.V., Nature Struct. Biol. 2003, 10, 1019-1025. Nature Struct. Biol. 2003, 10, 1019-1025.




THIOGLYCURONIDES: SYNTHESIS AND APPLICATION IN THE ASSEMBLY OF ACIDIC OLIGOSACCHARIDES

Leendert J. VAN DEN BOS, Herman S. OVERKLEEFT, Gijsbert A. VAN DER MAREL
Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands

e-mail: [e-mail]

Uronic acids are present in a wide array of biologically relevant oligosaccharides, polysaccharides and glycoconjugates.¹ Hence, flexible and straightforward synthesis routes towards these important molecules should have major impact on research in glycobiology. Although it is well established that thioglycosides are versatile synthons en route towards such carbohydrate motives, approaches in which thioglycuronic acids are employed are scarce. This can be explained by the lack of efficient synthetic protocols for the preparation of suitably protected thioglycuronides. In addition, thioglycuronic acids have been shown to be rather poor glycosyl donors, generally requiring the presence of activating protecting groups.

The potency of the recently developed novel sulfonium based activator systems 4a and 4b encouraged us to implement the highly unreactive thioglycuronides (2) in our recently developed glycosylation sequence² to effectively provide acidic oligosaccharides. This evidently called for an efficient mode of synthesis to access a wide variety of thioglycuronic acid synthons. We here present the 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO)/[bis(acetoxy)-iodo]benzene (BAIB) mediated³ chemo- and regioselective oxidation of readily available partially protected thioglycosides as a powerful means to obtain the corresponding thioglycuronic acids.⁴ After esterification of the carboxylate functions, these partially protected thioglycuronides 2 can be incorporated in the synthesis towards acidic oligosaccharides (e.g. trisaccharide 5).

FUNCTIONALIZATION OF THE HOMOALLYLIC BRIDGE IN HIGHER SUGAR PRECURSORS

Sławomir JAROSZ, Katarzyna SZEWCZYK, Anna GAWEŁ
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, POLAND; [e-mail]

Recently we proposed a convenient method of the synthesis of higher sugar homoallylic alcohols (2) from allyltin derivatives 1.¹ Suitable functionalization of the C-2 and C-3 carbon atoms might provide the 2-hydroxy-3-deoxy derivative 4. This structural unit occurs in e.g.

11-carbon atom antibiotic sugar – tunicamine.²

We faced a big problem in conversion of compound 2 into a deoxy higher sugar precursor 3. The Barton-McCombie reduction³ of the hydroxyl group in 5 did not afford the expected compound 3 but, provided two other products 6 and 7.⁴ Mechanism of these transformations will be discussed.

1. 
   Jarosz, S.; Szewczyk, K.; Luboradzki, R.; Gaweł, A. Tetrahedron: Assymetry, 2004, 15, 1719.
   
2. 
   Takatsuki, A.; Arima, G.; Tamura, J. J. Antibiot., 1971, 24, 215.
   
3. 
   review: Crich, D.; Quintero, L. Chem. Rev., 1989, 89, 1413.
   
4. 
   Jarosz, S.; Szewczyk, K.; Gaweł, A.; Gomez, A.M.; Lopez, J.C. Polish J. Chem., 2005, 79, 231.
   

SYNTHESIS OF STRUCTURAL ANALOGS OF NATURAL PRODUCTS

Pál HERCZEGH

Department of Pharmaceutical Chemistry, University of Debrecen and

Research Group for Chemistry of Antibiotics of the Hungarian Academy of Sciences

H-4010 Debrecen, Hungary

The following topics will be discussed:

1. 
   Swainsonin and castanospermin analogs
   

Polyhydroxyindolizidines and quinolizidines have been prepared with the use of hetero-Diels-Alder and 1,3-dipolar cycloaddition reactions of sugar derivatives.

2. 
   Cycloadditions of nitrilimines
   

Stereochemistry of inter- and intramolecular cycloaddition reactions of sugar derived nitrilimines have been studied.

3. 
   Synthesis of sialyl Lewis X oligosaccharide analogs
   

Sulfonyl Lewis X derivatives were synthesized.

4. 
   Preparation of conagenin antibiotic analogs
   

Diastereoisomers of the immunostimulant antibiotic conagenin was performed starting from simple sugars.

5. 
   A new synthesis of 2-deoxyamino sugar glycosides.
   

Some simple 2-deoxyamino sugar glycosides have been prepared using sulfonylnitrene additions of glycals.

6. 
   A glycan synthesis by sugar polymerisation
   

The poly-Ferrier reaction of a glucal derivative led to a mixture of unsaturated glycans.

TRIMETHYLENE DITHIOACETALS OF CARBOHYDRATES:

NEW DEVELOPMENTS

Hartmut REDLICH
Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität,

Corrensstraße 40, 48149 Münster, Germany

The dithian function is a powerful instrument in organic synthesis, due to its value for the concept of 'Umpolung'¹. Sugar dithians are easily available from all basic sugars². They have found various applications in natural product syntheses³. This lecture will deal with developments in applying trimethylene dithioacetals of carbohydrates in new synthetic fields, covering:

1. Sugar dithians in glycoside syntheses

Closing a missing link

2. Orthoesters of sugar dithians

A surprisingly easy entrance for a new protecting group strategy on open chain polyols

3.The trimethylene dithioacetal of D-glucosamine

Intramolecular C-C and C-N bond formation to yield highly substituted N-containing carbacycles or iminosugars

A CONVENIENT ROUTE TO HIGHLY OXIDIZED CARBOBICYCLES

FROM SUGAR ALLYLTINS

Sławomir JAROSZ, Marcin NOWOGRÓDZKI
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland; [e-mail]

Higly oxidized analogues of decalin such as 1 are attractive drug candidates. Their ability to inhibite function of glicosydases are thought to originate from carbocyclic skeleton (carboanalogues of sugars).

Stereoselective synthesis of such molecules is of interest in our group. We examine the “chiral pool” approach to derivatives of 1 from simple sugars (an example from glucose).

The derivative 3 is further oxidized into epoxides 4a and 4b. Opening of the oxirane ring with different nucleophiles led to interesting products 5.¹ Opening with selenide anion and further oxidation/elimination of selenoxide led to the product of formal basic rearrangement of the epoxide 4a, which is further modified towards highly substituted decalin derivatives.

1. 
   Jarosz, S.; Skóra, S. Tetrahedron: Asymmetry, 2000, 11, 1433 – 1448
   

.

ITERATIVE, ORTHOGONAL STRATEGY FOR OLIGOSACCHARIDE SYNTHESIS BASED ON THE REGIOSELECTIVE GLYCOSYLATION OF TRIOL ACCEPTORS WITH PARTIALLY UNPROTECTED

N-PENTENYL-ORTHOESTERS

A. M. GÓMEZ, A. AGOCS, C. URIEL, B. FRASER-REID, J. Cristóbal LÓPEZ
Instituto de Química Orgánica General (CSIC, Madrid, SPAIN) and ^a Natural Products and Glycotechnology Research Institute Inc.,(NPG),Durham, North Carolina, USA

We have studied an iterative protocol based on the regioselective glycosyl coupling of D-mannose triols (e.g. 2) with partially unprotected n-pentenyl orthoester glycosyl donors (e.g. 1) (a, Scheme) which, permits the synthesis of linear and branched oligosaccharides with minimum protecting groups tampering. In this strategy, the glycosyl donor possesses two orthogonal protecting groups which can be selectively manipulated thus paving the way for regioselective glycosidation strategies (b, c or d, Scheme) leading to linear (b or c, Scheme) or branched (d, Scheme) oligosaccharides.

LEWIS ACID CATALYZED DIASTEREOSELECTIVE ALLYLATION OF CHIRAL ACTIVATED KETONES

Tomasz BAŁAKIER,^a Janusz JURCZAK^a,b
a Department of Chemistry, University of Warsaw, 02-093 Warsaw

^b Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw

[e-mail]

Allylation of carbonyl compounds has become a well established methodology for the stereoselective construction of carbon-carbon bonds, providing an elegant synthesis of allylic alcohols. However, due to the lower reactivity of ketones, it has been examined mostly for aldehydes.¹ This fact prompted us to study the diastereoselectivity in the allylation reaction of chiral activated ketones, such as pyruvic and phenylglyoxylic acid derivatives, leading to formation of quaternary stereogenic centers.

We tested variety of allylic reagents in the reaction with chiral pyruvates and phenylglyoxylates. The influence of Lewis acids on the reactivity and diastereoselectivity of the reaction was also studied. The desired allylic alcohols were obtained in good to excellent yield and diastereoselectivity.

1. Denmark, S.E.; Fu, J. Chem. Rev. 2003, 103, 2763

,¹ M. S. Sigman, P. Vachal, E. N. Jacobsen, Angew. Chem. 2000, 112, 1336-1338, Angew. Chem. Int. Ed. Engl.

2000, 39, 1279-1281.

² A. Berkessel, D. Menche, C. A. Sklorz, M. Schröder, I. Paterson, Angew. Chem. 2003, 115, 1062-1065.

1^() (a) Glycochemistry: Principles, Synthesis, and Applications, Wang, P.G.; Bertozzi, C.P., Eds.; Marcel Dekker: New York, 2001; pp 425 - 492 (b) For a recent review on the synthesis of glycosaminoglycans: Yeung, B.K.S.; Chong, P.Y.C.; Petillo, P.A. J. Carbohydr. Chem. 2002, 21, 799 – 865.

2^() Codée, J.D.C.; Van den Bos, L.J.; Litjens, R.E.J.N.; Overkleeft, H.S.; Van Boom, J.H.; Van der Marel, G.A. Org. Lett. 2003, 5, 1947 – 1950

3^() De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli, G. J. Org. Chem. 1997, 62, 6974 – 6977.

4^() Van den Bos, L.J.; Codée, J.D.C.; Van der Toorn, J.C.; Boltje, T.J.; Van Boom, J.H.; Overkleeft, H.S.; Van der Marel, G.A. Org. Lett. 2004, 6, 2165 – 2168. Van den Bos, L.J.; Litjens, R.E.J.N.; Van den Berg, R.J.B.H.N.; Overkleeft, H.S.; Van der Marel, G.A. Org. Lett. 2005, published on-line.

1 D. Seebach, Synthesis 1969, 17-36

2 O. Kölln, H. Redlich, Synthesis 1995, 11,1376, ibid. 1383, ibid. 1996, 7, 825 , ibid. 8, 963

3 a) R. Bextermöller, H. Redlich, K. Schnieders,S. Thormählen, R. Fröhlich, Angew. Chem.1998, 110, 2612-16

b) Review: M. Yus, C. Najera, F. Foubelo, Tetrahedron, 59 (2003) 6147-6212