MXPA94001390A - Solution and phase-solid formation of glicosidi links - Google Patents

Abstract

The invention relates to the method that allows the rapid construction of oligosaccharides and other glycoconjugates. Methods of forming multiple oligosaccharide ligatures in solution in a single step are disclosed. The invention takes advantage of the discovery that the relative reactivity of residues containing anomeric sulfoxides and nucleophilic functional groups can be controlled. In another aspect of the invention, the reactivity of the activated anomeric sugar sulfoxides is used in a solid phase method for the formation of glycosidic bonds. The disclosed methods can be applied to the preparation of specific oligosaccharides and other conjugates, as well as to the preparation of glycosidic libraries comprising mixtures of several oligosaccharides, including glycoconjugates, which can be classified for biological activity.

Description

SOLUTION AND PHASE-SOLID FORMATION OF GLYCOSIDIC LINKS The gentlemen DANIEL E. KAHNE, of North American nationality, with address at 148 Poe Road, city of ? Princeton, State of New Jersey, in the United States of North America, inventor, cedes, sells and transfers to THE TRUSTEES OF PRINCETON I IVERSITY, North American society, with address in Washington Road, Post Office Box 36, city of Princeton, State of New Jersey, United States of America, all rights to the invention described below: EXTRACT OF DISCLOSURE The invention is related to the method that allows the rapid construction of oligosaccharides and other glycoconjugates. Methods of forming multiple oligosaccharide ligatures in solution in a single step are disclosed. The invention takes advantage of the discovery that the relative reactivity of residues containing anomeric sulfoxides and nucleophilic functional groups can be controlled. In another aspect r of the invention, the reactivity of the activated anomeric sugar sulfoxides is used in a solid phase method for the formation of glycosidic bonds. The disclosed methods can be applied to the preparation of specific oligosaccharides and other conjugates, as well as to the preparation of glycosidic libraries comprising mixtures of various oligosaccharides, including glycoconjugates, which can be classified for biological activity. 1. FIELD OF THE INVENTION The present invention is generally related / d with the methods that allow the rapid construction of oligosaccharides and other glycoconjugates. More particularly, the present invention relates to the methods of forming multiple glycosidic bonds in solution in a single step. The present invention takes advantage of the discovery that the relative reactivity of the glycoside residues containing anomeric sulfoxides and the nucleophilic functional groups can be controlled. In another aspect of the present invention, the reactivity of the activated anomeric sugar sulfoxides is used in a solid phase method for the formation of glycosidic bonds. The disclosed method can be applied to the preparation of specific oligosaccharides and other conjugates, as well as for the preparation of glycosidic libraries comprising mixtures of several oligosaccharides, including glycoconjugates, which can be classified for biological activity. 2 . BACKGROUND OF THE INVENTION 2.1 General Background Oligosaccharide chains of glycoproteins and glycolipids play important roles in a wide variety of biochemical processes. Both found on cell surfaces and circulating in biological fluids, these glycosidic residues act as recognition signals "that intervene or mediate key events in normal cell function and development. They are involved in fertilization, embryogenesis, neuronal development, hormonal activities, inflammation, cell proliferation, and in the organization of different types of cells within specific tissues. They are also involved in the ordering and secretion of glycoproteins as well as the elimination of glycoproteins from the plasma of the circulation. In addition to its positive role in maintaining health, oligosaccharides are also involved in the attack of the disease. For example, oligosaccharides on cell surfaces function as acceptors of viruses and toxins, as well as more benign ligands. Modified cell surface carbohydrates in tumogenesis and metastasis. The structures of the oligosaccharides that measure inflammation and help prevent infection can, when it occurs at high levels, stimulate the development of chronic inflammatory diseases. (Some references in the roles of oligosaccharides produced by eukaryotes in health and disease include: Hakomori TBS, 1984, 45; Feizi et al., TIBS, 1985, 24; Rademacher et al., Annu., Rev. Biochem. 1988, 57, 785; Feizi TIBS, 1991, 84; Dennis and Laferte Cancer Res. 1985, 45, 6034; Fhisman J. Membr. Biol. 1982, 69, 85; Markwell et al., PNSA USA, 1981, J78, 5406; Wiley and Skehel J. Annu. Rev.

Biochem. 1987, 56, 365; Kleinman et al. PNAS USA, 1979, 76, 3367, -Walz et al. Science 1990, 250). Although bacteria do not produce the same types of oligosaccharides or other conjugates as eukaryotes, prokaryotes, however, produce a wide variety of glycosylated molecules. Many molecules have been isolated and found to have antitumor or antibiotic activity. Bacterially produced glycosylated molecules that have potential therapeutic utility include chromomycin, caliceamine, spermicin, and cyclamycins. In all these - cases the carbohydrate residues have been shown to be important for biological activity. However, the precise functions of carbohydrate residues are not well understood and there is no good understanding of structure-activity relationships. Due to its diverse roles in health and disease, oligosaccharides have become "a major x- * research focus." It is widely accepted that the development of technology to 1) detect and 2) block or otherwise regulate some of the abnormal functions of the oligosaccharides could lead to significant improvements in health and well-being.On the other hand, it should be possible to exploit some of the normal functions of oligosaccharides (eg, various recognition processes) for other purposes, including sharing of drugs to specific cell types In addition, it may be possible to develop new antitumor agents from glycosylated molecules ^ Synthetics reminiscent of glycosylated bacterial antitumor agents. There are outstanding efforts to develop products related to oligosaccharides, including diagnostic kits to detect carbohydrates associated with various diseases, vaccines to block infection by viruses recognizing cell surface carbohydrates, drug delivery vehicles that recognize * carbohydrate receptors, and monoclonal antibodies, which recognize abnormal carbohydrates, for use as medicines. The timely development of these and other biomedical products based on carbohydrates depends on the one hand on the availability of technology to produce oligosaccharides and other conjugates in a fast and efficient way and in practical quantities for basic and development research. In particular, there is a need for methods that allow the rapid preparation of glycosidic libraries comprising mixtures of several oligosaccharides or other glycoconjugates which could then be classified for a particular biological activity. It has been shown, for example, that screening of peptide mixtures is an efficient way to identify active compounds and elucidate structure-activity relationships. There are many ways to chemically generate various mixtures of peptides and determine the active compounds. See, for example, Furka et al. Int. J. Peptide Protein Res. > 1982, 32, 487; Lam et al. Nature 1991, 354, 82; Houghten Nature 1991, 354, 84; Zuckermann et al. Proc. Natl. Acad. Sci. USA 1992, 89/4505; Petithory Proc. Natl. Acad. Sci. USA, 1991, 88, 11510; Geys proc. Natl. Acad. Sci. USA, 1984, 81, 3998; Houghten Proc. Natl. Sci. USA, 1985, 82., 5131; Fodor Science 1991, 251, 767. We are not aware of effective methods to generate diverse mixtures of oligosaccharides and other glycoconjugates for screening purposes. ' 2. 2. Anthracyclines Cyclamycin 0 (1, below) an anthracycline antibiotic isolated from Streptomyces capoamus, possesses high inhibitory activity in vi tro against experimental tumors. This medicine is comprised of aglycone, e-pyrromycinone and a trisaccharide. See, Bieber et al. J. Antibiot. 1987, 40 1335. The trisaccharide contains two repeating units of 2-deoxy-L-fucose (A, B) and one unit of sugar keto (C), L-cinerulosa. All sugars are linked together through an axial bond 1-4. Although cycloomycin was discovered almost thirty years ago, little is understood about their function because insufficient quantities of natural sources are available. Consequently, the best way to obtain their analogues is to be obtained by deglycosylation of other readily available antibiotics, such as marcelomine, musetamycin and cinerubin. There are efficient strategies in the literature for the coupling of trisaccharide to aglycone. See, for example, Kolar et al. Carbohydr. Res. 1990, 208, 111. However the methods for the construction of the trisaccharide suffer from limitations of above all in ease and efficiency. Anthracycline antibiotics act as mediators in the metabolism of several species of Streptomyceae. They are therapeutic drugs that have been used extensively in the treatment of several solid tumors and leukemias. See, Arcamine, F. Doxorubicin Anticancer Antibiotics; Academic Press: New York, 1981. The aglycone of all anthracyclines consists of a tricyclic quininoid system with functionalized cyclohexane grouping. Several patterns of substitution frequently found among the aglycones are delineated, below.

Daunomycinone (R1 = H) ß-Rhodomycinone (R1 = H) Adriamycinone (R1 = OH) 1-OH-β-Rhodomycinone * Aclavinone e-pirromicma A common characteristic of all anthracycline antibiotics is an oligosaccharide residue attached to the C-7 hydroxyl group of the aglycone. The sugar residue in this position can be a mono, di or trisaccharide. The most frequently found sugars include daunosamine, rhodosamine, 2-deoxy-L-fucose and L-cinerulosa.

CÜ-L-Daunosamine a-L-Rhodosamine or; -L-Deoxifucosa Q! -L-Cinerulosa a-L-Rhodinosa Q! -L-Aculosa On the basis of several studies conducted on the antibiotics of anthracycline, daunomycin, adriamycin, and aclacinomycin, it has become increasingly clear that the oligosaccharide components of these natural DNA bonds play an important role in the binding and recognition of DNA. See, Bieber et al, Supra. However, little is known about the actual function of sugars, in part because it is difficult to selectively modify these medications. The first chemical synthesis of cyclamycin 0 was carried out by S. J. Danishefsky and collaborators. See, Suzuki et al J. Am. Chem. Soc. 1990, 112, 8B95. 2. 2.1 Synthesis of Oligosaccharides 2-Deoxi Complex conjugates such as anthracyclines and auric acid are of considerable scientific and pharmaceutical interest and have been applied extensively in cancer chemotherapy. A structural characteristic The characteristic in these compounds is the presence of 2-deoxy oligosaccharides. Actually, several types of alpha- and beta-2-deoxy glycosides in bioactive molecules exist naturally. In addition to the auric acid antibiotics, cardiac glycosides, avermectins, erythromycins, and ediin antibiotics can be found. The efficient construction of these 2-deoxy glycosides, particularly 2-deoxy-β-glycosides, has been a problem of prolonged permanence in the "carbohydrate chemistry". Controlling β-stereo selectivity in 2-deoxy sugars is difficult because it may not be stereostarily assisted from the C-2 position. In general, the specific therapeutic effect of these drugs is believed to be caused by aglycone, whereas sugars are thought to be responsible for the regulation of pharmacokinetics. It is expected that by modifying the carbohydrate pool, it is possible to increase the efficacy and also decrease the cytotoxicity of these drugs. The development of sugar analogues requires good synthetic methods for the construction of 2-deoxy oligosaccharides. Unfortunately, the glycosylation methods available for the synthesis of 2-deoxy oligosaccharides are generally unsatisfactory. Because glycosyl 2-deoxy donors lack a substituent at the C-2 position, they are unstable. They decompose rapidly in most glycosylation reactions, resulting in poor glycoside yields. In fact, one of the best existing methods for the construction of 2-desoxy oligosaccharides, the glical method frustrates this problem by not actually using 2-deoxy glycosyl donors directly. This procedure, which is one of the most widely used glycosylation methods, involves a two-stage process. In the first stage, a 1,2-anhydro sugar (glical) is treated with an appropriate electrophile, E +, to form a 1,2-onium intermediate. The nucleophile attacks the glycoside from the opposite side, with 1,2-trans-configured ligands. In the second step, the substituent on C-2 is removed to form the desired 2-deoxy glucoside. 2. 3. Methods of solution to obtain Oligosaccharides Currently there are two ways to obtain oligosaccharides. The first is by isolation from natural sources. This concept is limited to the existence in natural form of the oligosaccharides that are produced in large quantities. The second way is through enzymatic or chemical synthesis. The variety of oligosaccharides available through enzymatic synthesis is limited because the enzymes used can only accept certain substrates. Chemical synthesis is more flexible than enzymatic synthesis and has the potential to produce a huge variety of oligosaccharides. The problem with chemical synthesis has been that it is extremely expensive in terms of time and labor. This problem is a consequence of the way in which the synthesis of the oligosaccharides has been carried out to date. The oligosaccharides are formed from monosaccharides linked by glycosidic ligatures. In a typical chemical synthesis of an oligosaccharide, a fully protected glycosyl donor is activated and allowed to react with a glycosyl acceptor (typically another monosaccharide having an unprotected hydroxyl group) in the solution. The glycosylation reaction itself can take anywhere from a few minutes to days, depending on the method used. The coupled product is then purified and chemically modified to transform it into a glycosyl donor. The chemical modification may involve several stages, each stage requiring a subsequent purification. (A "single stage" is defined as a chemical transformation or a set of transformations carried out within a single reaction vessel without the need for intermediate isolation or purification steps.) Each purification is time consuming and may result in loss significant material The new glycosyl donor, a disaccharide, is then coupled to another glycosyl acceptor or receptor. The product is then isolated and chemically modified as above. It is not usual for the synthesis of a trisaccharide to require ten or more steps from the component monosccharides. In a recent example, the fully protected trisaccharide side chain of an antitumor antibiotic called cyclamycin 0 was synthesized in 14 stages with 9% yield based on the component monosaccharides. See, Suzuki et al, supra. In this way, the time and expense involved in the synthesis of oligosaccharides has been a real obstacle to the development of carbohydrate drugs and other biomedical products. One way to increase the speed and efficiency of oligosaccharide synthesis is to develop methods that allow the construction of multiple glycosidic ligatures in a single step. Prior to the present discovery, the applicants were not aware of a method involving the regioselective formation of multiple glycosidic ligatures and that would provide a rapid, efficient and high-throughput process for the production of oligosaccharides. 2. 4. Solid phase synthesis of Oliaosaccharides In addition to reducing the number of stages involved in the synthesis of oligosaccharides, one can increase the speed and efficiency of a synthetic process by eliminating the need for isolation and purification. Theoretically, the elimination of the need for isolation and purification can be carried out by developing a solid process for the synthesis of oligosaccharides. Due to the magnitude of the potential advantages of solid phase synthesis, there have been previous attempts to synthesize the oligosaccharides in a solid phase. Solid phase methods for synthesis make isolation and purification unnecessary because the reagents and decomposition products can be removed by washing simply from the resin bonded product. This advantage translates into enormous savings in terms of time, labor and performance. (The advantage of solid methods over solution methods for the synthesis of peptides and nucleic acids has been amply demonstrated.These advantages could, of course, extend to the solid phase synthesis of oligosaccharides. peptides, see, for example, Barany, G. and Merrifield, RB 1980, In the Peptides = On Peptides, Gross, E. Meienhofer, J. Eds., Academic Press, New York, Vol. 2, pp. 1- 284). Until 1971, Frechet and Scherch outlined the requirements for solid pass synthesis of oligosaccharides. See, Frechet and Scherch J. Am. Chem. Soc. 1971, 93, 492. First, the resin must be compatible with the reaction conditions. Second, the solid support must contain the appropriate functionality to provide a link in the glycosidic center (or elsewhere), said bond is inert to the reaction conditions but can be easily cleaved to remove the oligosaccharide at the end of the synthesis. Third, the appropriate protective group schemes must be unmasked for the next coupling reaction. The other hydroxyls must be protected by "permanent" blocking groups that will be removed at the end of the synthesis. Fourth, the glycosylation reactions must be efficient, temperate and go to term to avoid failsequences. Fifth, the stoichiometry of the anomeric centers must be maintained during the coupling cycles and must be predictable based on the results obtained in solution for any given donor / acceptor pair. Sixth, the separation of the permanent blocking groups and the binding to the polymer must leave the oligosaccharide intact. Unfortunately, although it has been generally accepted that solid phase synthesis of oligosaccharides is a desirable goal, and although Frechet and Schuerch (as well as others) t had the ability to delineate a strategy for the solid phase synthesis of oligosaccharides, none, before the present discovery had been able to implement such a strategy. In previous attempts to synthesize oligosaccharides in insoluble resins, coupling performance was low and stoichiometric control was inadequate, particularly for the construction of ß-glycosidic ligations (ie 1,2-trans glycosidic ligations in which the glycosidic linkage in the anomeric sugar position is trans towards the sugar substituent bond at C-2). These problems have been attributed to the fact that the reaction kinetics in the solid phase are slower than those in solution. See, Eby and Schuerch, Carbohydr. Res. (Carbohydrate Research) 1975, 39, 151. The consequence of such unfavorable kinetics is that most glycosylation reactions, which can work reasonably well in solution, simply do not work well in a solid phase in terms of control stoichiometric and performance. Thus, for example, Frechet and Schuerch found two glycosylation reactions, which involve the displacement of an anomeric halide in the presence of a catalyst, predominantly given by the β-anomer (ie, the 1,2-trans product) but mixtures given in the solid phase. Frechet and Shuerch concluded that it would be necessary to use the group participation of vencidad to form ligatures in the solid phase. Again, however, it has been found that neighboring participation groups (GPVs) frequently deactivate glycosyl donors to the point where existing glycosylation methods can not be adapted to the solid phase. Frequently, glycosyl donors could be broken down in the resin mixture before the glycosylation takes place. See for example Eby and Scherch, supra. On some occasions the resin is also allowed to decompose due to the hardness of the conditions required for glycosylation. In addition, for many GPV there is a significant problem with the transfer of acyl from the glycosyl donors to the free glycosyl acceptors in the resin. This side of the reaction clogs the resin and prevents further reaction. Frechet has reviewed the problems encountered when trying to implement a strategy for the synthesis of solid phase oligosaccharides. See, Frechet, Polimer-supported Reactions in ^? Organic Synthesis (Reactions supported in polymers in the Organic synthesis), pag. 407, P. Hodge and C. Sherrinton, Eds., John Whiley & amp; amp;; Sons, 1980. He has concluded that solid phase synthesis of oligosaccharides is still not competitive with solution synthesis "mainly due to the lack of appropriate glycosylation reactions". There have been several efforts to overcome the unfavorable reaction kinetics associated with solid phase reactions by the use of double resins. In the best example to date Douglas et al. used a soluble polyethylene glycol resin with a succinic acid linker and achieved 85-95% coupling performance using a glycosylation method known more than 80 years ago (the Koenings-Knorr reaction) with excellent anomeric stoichiometric control. See, Douglas et al. J. Am. Chem Soc. 1991, 113, 5095. Soluble resins may have advantages for some glycosylation reactions because they offer a more "solution-like" environment. However, stepwise synthesis in soluble polymers requires that the intermediate solution be precipitated after each step and crystallized before other sugar residues can be coupled. On the other hand, several additions of the same reagents are required to carry the reaction to completion. In the previous cases, for example, Douglas et al. had to repeat the same coupling reaction five times to achieve high performance. Each repetition requires a precipitation step to wash off the reagents. Product can be lost with each stage of precipitation. In addition, the repeated precipitations make the process consume a lot of time. Thus, the use of the soluble resin for the synthesis of the oligosaccharides fails to provide all the potential advantages associated with solid phase synthesis using insoluble resins. A new method for glycolization involving anomeric sugar sulfoxides was reported by Kahne et al. See, Kahne et al. J. Am. Che. Soc 1989, 111, 6881. The anomeric sugar sulfoxides were activated with equimolar amounts of glycosyl donors activated with triflic anhydride in the presence of a blocked base. The glycosyl donors activated with triflic anhydride proved to be completely reactive in solution and can be used to glycosylate extremely non-reactive substrates under mild conditions. However, this report was limited to solution reactions, and there was no suggestion that solid-phase reactions could be carried out with any degree of utility. Thus, the state of technique emphasizes the prevailing and unmet need for a glycosylation method that is provided for rapid, efficient and high-yield oligosaccharide synthesis. Furthermore, an efficient synthesis of the oligosaccharides in the solid phase has not been demonstrated which provides all the previously mentioned advantages of the solid phase methods. 3. SUMMARY OF THE INVENTION The present invention provides methods for the construction of multiple glycosidic ligatures in solution using anomeric sugar sulfoxides as the glycosyl donors for the sequential construction of glycosidic bonds in the solid phase, with control over the stoichiometric configuration of the anomeric ligation. . In this way, depending on the selected conditions and the initial materials, the a- or β-anomers can be produced in the solid phase using anomeric sugar sulfoxides as glycosyl donors. The methods of the present invention can be applied to the preparation of specific oligosaccharides or glycoconjugates or to the preparation of mixtures of various oligosaccharides or glycoconjugates for the creation of libraries that can be screened subsequently to detect compounds having a desired biological activity. The present invention also relates to the discovery that the activation of sulfoxides with catalytic amounts of an activating agent provide very good yields of condensation products under very mild conditions. Preferably, the activating agent is a strong organic acid, such as trifluoromethanesulfonic or "triflic" acid (TfOH), p-toluenesulfonic acid (TsOH) or metasulfonic acid (MsOH), more preferably TfOH acid. In particular, it has been found that for the construction of 2-deoxy glycosides, the catalytic glycosylation process described herein is considered the option method. A preferred embodiment of this aspect of the invention, which involves the synthesis of 2-deoxy glycosides via catalyzed glycosylation of triflic acid, is described in greater detail below. Other objects of the present invention will be apparent to anyone of ordinary skill in the art under consideration of the present disclosure. 4. BRIEF DESCRIPTION OF THE FIGURES Figure 1 illustrates a method of synthesizing trisaccharide protected from cliclamicin 0 in one step from the component monosaccharides. Figure 2 illustrates a process of forming 2-deoxy fucose homopolymers in one step. Figure 3 illustrates a process of synthesizing mixtures of conjugates having biological activity, including potential DNA ligation activity. The glycoconjugates thus produced can subsequently be screened (ie, for DNA binding activity) to evaluate the preferred length and preferred sugar residues of the oligosaccharide portion of the glycoconjugate base of the activity being tested. Figure 4 illustrates the methods of forming and removing two exemplary types of linkages from a solid support (e.g., polystyrene resin). Figure 5 illustrates an apparatus used to carry out solid phase synthesis of oligosaccharides. Figure 6 illustrates the general scheme for the synthesis of a β-linked disaccharide in the solid phase. Figure 7 illustrates the general scheme for the synthesis of an alpha-linked disaccharide in the solid phase. Figure 8 illustrates the general scheme for the synthesis of a trisaccharide in the solid phase.

Figure 9 is a 1H NMR spectrum of the monosaccharide 1 of Figure 1. Figure 10 is an XH NMR spectrum of the monosaccharide 2 of Figure 1. Figure 11 is a 1H NMR spectrum of the monosaccharide 3 of Figure 1. Figure 12 is a 1H NMR spectrum of the monosaccharide 5 of Figure 1. Figure 13 shows an expanded region of the 1H NMR spectrum of 5, in which the anomeric protons of the trisaccharide are labeled. Figure 14 is an X NMR spectrum of the disaccharide 4 of Figure 1. Figure 15 represents a scheme for the synthesis of cyclin 0. Figure 16 depicts a scheme for the synthesis of a trisaccharide. Figure 17 depicts a scheme for the synthesis of selected disaccharides.

. DETAILED DESCRIPTION OF THE INVENTION The following is a detailed description of the preferred embodiments of the present invention. 5.1 Definitions Activating agent: a chemical agent that in glycosyl sulfoxide reacts with the anomeric sulphoxide group, making the anorectic carbon susceptible to attack* Nucleophilic In the case of bifunctional sugars or glycosidic residues, the activating agent is also capable of deprotecting a blocked nucleophilic group under the same condition used to activate the anomeric sulphoxide group. Acid scrubber: A chemical agent such as any base that sequesters protons, thereby minimizing side reactions that are promoted by the acidic conditions. Phthalic acid purifier - A chemical agent such as methyl propionate that specifically sequesters sulfenic acid, typically resulting in the formation of unreacted monophenyl sulfoxide. In the absence of a sulfenic acid scavenger, sulfenic acid reacts with itself to form diphenyl disulfide monosulfoxide and water. Water interferes with the glycosylation reaction. Bifunctional: The characteristic of a sugar or glycosidic residue to be able to function under the activation of both a glycosyl donor and a glycosyl acceptor under the conditions of the single-step processes of the present invention. Biological activity: Any activity exhibited by a compound that has potential for physiological, pharmacological, diagnostic or therapeutic applications.

Carbohydrate acceptor: Any molecule that binds to any carbohydrate. Typically the molecule is a macromolecule such as a protein or DNA. Gl i coccon played: any compound or molecule that is covalently bound to a glycosidic residue. Glycoside: Any sugar containing at least one pentose or hexose residue in which the anomeric carbon supports a non-hydrogen substituent. Typically the non-hydrogen substituent is a heteroatom, such as nitrogen, oxygen, phosphorus, silicon or asufre. Glycosyl acceptor: Any compound that contains at least one nucleophilic group which, under the conditions of the single-step process of the present invention, is capable of forming a covalent bond with the anomeric carbon of a glycosyl donor. As referred to herein, a glycosyl acceptor is any sugar or glycoconjugate containing unprotected hydroxyl, amino, or mercapto groups or such groups that are blocked by protecting groups that can be removed in situ, i.e., under the conditions of the process of a single stage of the present invention. Glycosyl donor: A sugar or glycosidic residue that holds a sulphoxide group on the anomeric carbon, which group activates the anomeric carbon susceptible to attack by the necleophilic group of a glycosyl acceptor to form the glycosidic bond.

Glycosid libraries: A mixture of oligosaccharides of veriating sequences which can be subjected to a screening procedure to identify compounds or molecules that exhibit biological activity. Such libraries may also include several glycoconjugates. Monofunctional glycosyl acceptor: A glycosyl acceptor as in the above definition, with the additional proviso that the ability to act as a glycosyl donor at the same time (i.e., under the conditions of the single-step process of the present invention) ) is specifically excluded. Monofunctional glycosyl donor: A glycosyl donor as in the above definition, with the additional proviso that the ability to act as a glycosyl acceptor at the same time (i.e., under the conditions of the single-step process of the present invention) ) is specifically excluded. Monofunctional glycosyl unit: a sugar that is either a glycosyl acceptor or a glycosyl donor but does not have the ability to function as both when activated under the conditions of the single-step process of the present invention. Oligosaccharides: A glycosidic residue that has three or more units of monosaccharide linked by glycosidic bonds. Potential glycosyl acceptor: Any compound containing at least one nucleophilic group that is optionally available to form a covalent bond with the anomeric carbon of a glycosyl donor. Single-stage reaction: A single-stage reaction is defined as a chemical transformation or a set of transformations carried out in a "single" reaction vessel without needing intermediate isolation or purification steps (ie, a stage or a reaction vessel). Temporary Protective Groups: A blocking or protective group that can be removed in situ, preferably, but not necessarily, under the same conditions used to activate an anomeric sulfoxide group. . 2. GENERAL METHODS The following general methods have been divided into two main categories: the first concerns reactions in solution involving the formation of multiple glycosidic linkages and the second is related to the synthesis of oligosaccharides in which the growing oligomer is linked to a solid support. . 3 FORMATION OF MULTIPLE GLYCOSIDIC LINKS One or more donors having alkyl or aryl sulfoxides in the anomeric position and one or more glycosyl acceptors having one or more free hydroxyls and / or other nucleophilic groups (eg, amines) and / or the protected hydroxyl of silyl ether are combined in a reaction vessel. The resulting mixture can include both monofunctional glycosyl donors and glycosyl acceptors as well as bifunctional glycosyl units, ie, saccharides which can function simultaneously as glycosyl donors and acceptors. However, in order to form more than one glycosidic link (i.e., to produce a trisaccharide or a larger L product), at least one of the reactants must be a bifunctional glycosyl unit. The glycosyl acceptors and donors can be blocked by an appropriate protecting group, including, but not limited to, ether, ester, acetamido, or thioester protecting groups, in one or more positions. However, it is understood that a protecting group of ester (or acetamide or thioester) in C-2 of a glycol donor will influence the stereochemical result of glycosylation, resulting in a 1,2-trans-glycosidic bond. The mixture of glycosyl donors and acceptors is dissolved under anhydrous conditions in a non-nucleophilic solvent, including, but not limited to, toluene, ether, tetrahydrofuran (THF), methylene chloride, chloroform, propionitrile, their mixtures. It has been found that the change of solvent influences the stereochemical results of glycosylation for reactions in which the participation of the neighboring group is not involved. In general for a given β donor / acceptor pair, the use of a non-polar solvent, such as toluene, results in the formation of a high percentage of alpha isomer, while the use of more polar solvent, such as propionitrile, results in the production of a high percentage of beta anomer. The reaction is initiated by the addition of an effective amount of an activating agent. In a particular embodiment of the present invention, 0.5 equivalents of triflic anhydride, plus 1.5 equivalents of base (as an acid scavenger), are added to the reaction mixture. (The equivalents are related to glycosyl sulfoxide). A catalytic amount of triflic acid (eg, <0.05 equiv.) May also be used, preferably together with excess sulfenic acid scavenger (eg, 20 equiv. Of methyl propionate). It has been found that catalytic triflic acid is preferred when the reaction mixture contains deoxy glycosyl donors or when one of the glycosyl acceptors in the reaction is a silyl ether. On the other hand, the triflic anhydride when the maximum reactivity of the donors is important. However, it should be noted that the moderately basic conditions that are obtained with the use of triflic anhydride are not effective to deprotect certain silyl ethers (e.g., t-butylsilyl ethers). On the other hand, although the use of triflic anhydride plus 2,6-diterbutyl-4-methyl pyridine will result in the in situ deprotection of the trimethyl silyl ethers, the use of triflic anhydride plus a stronger base ( such as Hunig's base) will not. Thus, both deactivating agents can be used in reactions involving a bifunctional glycosyl unit containing a hydroxyl protected from silyl ether, although triflic anhydride only works under a specific set of conditions (change of base, change of protective group of silyl). In another case, the two activation methods are usually unalterable). The methyl propiolate or other sulfenic acid scavenger and / or activated molecular sieves can be added to the reaction either before or after the addition of the activating agent. Sulfenic acid scavengers significantly improve the glycosylation performance when the catalytic triflic acid is used as the activating agent. The reaction is usually carried out at low temperature (preferably in the range of about -78 ° C to as low as about -100 ° C) but can be allowed to proceed at higher temperatures, in some cases as hot as room temperature. The reaction is quenched by the addition of aqueous bicarbonate and extracted. The reaction mixture can then be subjected to a purification process and / or the product (s) deprotected if necessary. The procedure can be used to construct specific oligosaccharides or mixtures of several oligosaccharides or other glycoconjugates for classification Go or scrutiny for biological activity. In particular embodiments of the present invention, it has been found that the reactivity of different glycosyl donors can be modulated by manipulation of the chemical structure and electronic nature of the anomeric sulfoxide. Such manipulation is due, in part, to the discovery that the limiting step in the glycosylation reaction is carried out in the superoxide by the action of the activating agent. It has subsequently been shown that the reactivity of glycosyl sulfoxides can be influenced by manipulation of the oxygen nucleophilicity of the sulfoxide. Generally, the higher the nucleophilic sulfoxide oxygen, the faster the glycosylation reaction. Thus the electron donor substituents in the R 'group attached to the sulfoxide increase the nucleophilicity of the sulfoxide oxygen and accelerate the reaction rate. In contrast, electron-sequestering groups increase the nucleophilicity of the sulfoxide oxygen and slow down the reaction. For example, p-methoxyphenyl glucosyl perbenzylated sulfoxide reacts faster than the corresponding unsubstituted phenyl sulfoxide. The ability to influence the nucleofilid of the different sulfoxides and from there to manipulate the reactivity of the different glycosyl donors has been exploited in particular embodiments of the present invention. For example, * this ability allows sequential glycosylations to take place in solution, as illustrated in Figure 1. In still other embodiments of the present invention, multiple glisidic linkages are formed in the solution using glycosyl silylated acceptors. The sillyl ethers are excellent glycosyl acceptors when the triflic catalytic acid is the activating agent and the trimethylsilyl ethers work well as glycosyl acceptors when the triflic anhydride is the activating agent and 2,6-diter-butyl-4-methyl- Pyridone is the base. However, they can be unmasked to fit. (Hence the requirements for slightly acidic conditions in the glycosylation reaction when the silyl ethers are used as glycosyl acceptors). Because the silyl ethers must be unmasked to couple, they react more slowly than the deprotected alcohols. In this way, it has been demonstrated that one can modulate the reactivity of two glycosyl acceptors of other similar cases by the selective use of silyl protecting groups. In the selected embodiments of the present invention, the length distribution of the oligosaccharides or glycosidic residues of the conjugates produced can be influenced by the variation of the ratio of monofunctional glycosyl acceptors and of the monofunctional glycosyl donors to glycosyl units bifunctional in the reaction mixture. For example, it has been shown that higher ratios of monofunctional glycosyl acceptors to bifunctional glycosyl units in the reaction mixture lead to polymers of shorter length. The total concentration of the reactanes also influences the distribution length. (See, Sections 6.6 and 6.8 and Figures 2 and 3, below) In the particular embodiments of the present invention, it may be desirable to include only two or three different types of sugars in the reaction mixture and to manipulate the reactivity of donors and acceptors for that a specific oligosaccharide is produced. An example of this procedure is given in sections 6.6, below. In still other embodiments of the present invention, it would be desirable to include several different types of sugars in the reaction mixture for the purpose of generating a chemically diverse mixture of oligosaccharides or glycoconjugates for the creation of libraries that can be classified for biological activity. An example of such a method is illustrated in section 6.6 and in figure 3, below. Chemical diversity can be influenced by the manipulation of the number of different sugars included in the mixture. Chemical diversity will also be a function of the order in which the different pairs of glycosyl donors / acceptors react. The order in which the different donor / acceptor pairs of glycosyl react will depend, on the one hand of the relative reactivity of the donor / acceptor pairs. The relative reactivity of the donor / acceptor pairs can be manipulated in various ways, as already described above (for example, by manipulating the structure of the sulphoxide groups and by protecting some glycosyl acceptors with silyl ethers to decrease the reason to which they react). Other factors that influence the relative reactivity of glycosyl donors and acceptors, such as the presence of electronegative protective groups in the sugar rings or the presence of steric hydration can also be exploited. See, for example Binkley Modern Carbohydrate Chemistry, Marcel Dekker, Inc: New York, 1988; also, Paulsen Angew. Chem Int. Ed. Engl. 1982, 22., 156. Hence, potentially many factors can be taken into account in the implementation of the disclosed method of forming multiple glycosidic linkages to produce various mixtures. . 4. Catalytic Activation of Anommeric Sulfoxides In another part of this disclosure, the activation of the trimeric anhydride of anomeric sulfoxides was discussed and the mechanism of this glycosylation reaction discussed. The triflic anhydride reacts with the sulfoxide to form a trifloxy sulfonium salt that is extremely reactive. In the presence of the base, half an equivalent ^^ T * full of triflic anhydride was sufficient to activate an equivalent of sulfoxide. Phenyl trifluoromethanesulfenate (PhSOTf) generated during the course of the reaction evidently activated the remaining 0.5 mg of the sulfoxide sugar (see below). In fact, others have used sulfonate esters to activate thioglycosides. For example, Ogawa et al. uses selenium phenyl triflate to activate the phenyl and alkyl thioglycosides. See, Ito and Ogawa Tetrahedron Lett. 1987, 28 2723. h In the absence of the base, however, less than 0.05 equivalents of triflic anhydride activated a full sulfoxide equivalent. Because trifloxy phenyl sulfonate (PhSOTf) and combindo triflic anhydride did not amount to more than 0.1 equivalents, some other species generated in the reaction were activating the sulfoxide in a catalytic cycle. It was reasoned that the catalyst in question was triflic acid (TfOH). TfOH has been used by others to activate other glycosyl donors. See, for example, more recently, Lonn Glycoconjugate J. 1987, 4, 117; Mootoo et al. J. Am Chem. Soc 1989, 111, 8540; Evans et al. J. Am. Chem. Soc. 1990, 112, 7001; and Veenem et al. Tetrahedron Lett. 1990, 31, 1331. It was further discovered that typically only catalytic amounts are required because the acid is generated within the reaction. To determine whether TfOH can activate anomeric sulfoxides, the following experiment was conducted using perbenzylated glucose sulfoxide 1 as the glycosyl donor and primary alcohol C-6 as the glycosyl acceptor (see scheme below). Sulfoxide 1 (1.5 equivalents) was treated with triflic acid (0.05 equivalents) at -78 ° C in methylene chloride. This step was followed by the addition of nucleophile (1-0"equivalents) to the reaction.All the sulfoxides were consumed to form the product, indicating that the triflic acid in catalytic amounts activates the anomeric sulfoxides. . 4.1. Mechanisms Although not intended to be limited in theory, the following interpretation of mechanics is offered for the benefit of interested readers. The stereochemical result for glycosylation using the catalytic triflic acid method was identical to that obtained from the stoichiometric method of triflic anhydride. It was surprising that both reactions come from the same reactive intermediate, for example, an ozone ion or a pair of bound ions. With the TFOH method, however, the yield for the desired disaccharide 3 was low. A significant amount of lactol, 4, and 1,1-dimer, 5, were produced as byproducts (see below). The nature of these by-products indicated to the present applicant that the water was present in the reaction. In particular, if the ozone ion is trapped by water, a lactol will form. If the anomeric lactol then traps another ozone ion, a 1,1-dimer of the glycosyl donor would be formed. 1 2 3 4 5 A. 1.5 eq 1.0 eq Tf2 ° 'bas > - 55% 25% 9% B. 1.5 eq 1.0 eq Tf0H »• 35% 41% 15% C. 1.5 eq 1.0 eq Tf ° H '» - 60% 23% 5% HC-CCOOMe R = H with Tf20; R = Si (CH3) 3 with TfOH To avoid the formation of water, the glycosylations were conducted scrupulously under anhydrous conditions, using activated molecular sieves. However, despite these precautions was observed in the formation of products accounted for 40% of the mass balance. This last observation suggested that this water was formed during the course of the reaction, possibly during the disproportionation of the phenyl sulfenic acid.

Ozonium As illustrated in the scheme, above, the first stage of the catalytic cycle is the tendency of the sulfoxide to form a sulfonium salt. The sulfonium salt then drives the phenyl sulphonic acid (PhSOH) to form an ozone ion or a pair of bound ions. The nucleophile traps the ozone ion, subsequently regenerating the TFOH. In each catalytic cycle, a sulfoxide molecule forms a product and generates a sulfenic acid molecule as a by-product. Sulfenic acids are a class of organosulfur compounds that have eluded insulation due to their instability. They are highly reactive with both the electrophiles and the nucleophiles. Sulfenic acids easily suffer from disproportion until they reach thiosulfinate esters and water. The postulated mechanism for disproportion, which incorporates its dual electrophilic / nucleophilic character, is illustrated below.

SPh + H20 . 4.2. ADDITION OF DEPURERS FOR SULPHENIC ACIDS Sulfenic acids are easily added to electron-deficient alkenes and alkynes to form vinyl sulfoxides. In this way, it may be possible to trap these compounds with a sulfenic acid scavenger before they self-condense. Examples of alkenes and alkynes frequently used to trap sulfenic acids include methyl propionate, methyl propiolate, styrene and methyl dicarboxylate. The above compounds were classified as potential scavengers, and methyl propiolate was found to be the most effective. In a typical reaction, 1 and 2 were allowed to react with TFOH in the presence of methyl propiolate (20 equivalents). The yield of the reaction was improved from 35% (in the absence of methyl propiolate) to 45% (in the presence of methyl priolate). Although the performance of the reaction improved, quantities of 4 and 5 were still produced. From here, additional ways to prevent disproportionation of sulfenic acid are still suggested. . 4.3 The use of silyl ethers as nucleophiles It was observed that the use of silyl ether protected the alcohols as nucleophiles could also minimize the development of water. The silyl ethers could react under light reaction to produce the desired condensation product of disaccharide, TMSOTf and phenyl sulfenic acid. Sulfenic acid could be expected to then react with TMSOTf to form silyl phenyl sulfonate (PhSOSi (CH3) 3), thereby regenerating triflic acid (See below). It was reasoned that because silylated sulfonates are much more stable than sulfenic acids and can be expected to not be disproportioned so rapidly, silylated sulfonates could help minimize water production. See Nakamura J: Am. Chem. Soc. 1983, 105, 7172.

PhSOH + TMSOTf > PhS0Si (CH3) 3 + TfOH As a result, perbenzylated glucose sulfoxide 1 (1.5 equivalents) was treated with triflic acid (0.05 equivalents) in methylene chloride at 78 ° C. Silyl ester of the nucleophile (2b) was added to the reaction. After obtaining the desired trisaccharide 3 was isolated as the best product in the yield of 60%. (See the first reaction template in section 5.4.1.) Thus, by using the silyl ester of the nucleophile, the yield in the reaction dramatically improved, ie, from 35% to 60%. . 4.4. Application of the catalytic method for the synthesis of 2-Deoxy Oligosaccharides In subsequent investigations the scope of the catalytic triflic acid method to activate sulfoxides was explored. Table 1 shows a comparison of catalytic triflic acid and the stoichiometric methods of triflic anhydride for glycosylation using a range of 2-deoxy glycosyl sulfoxides as the glycosyl donors. The 2-Deoxy glycosyl sulfoxides are notoriously unstable and tend to give low yield of coupled product (See Table I). The stoichiometric triflic anhydride method for the activation of sulfoxides does not always give good results with 2-deoxy glycosyl donors. However, the triflic acid catalytic method works very well, because presumably the temperate conditions of the reaction minimize the decomposition of the 2-deoxy sulfoxides. In fact, the use of triflic acid improves the glycosylation performance by at least 50% for all the cases examined.

TABLE I. Synthesis of 2-Deoxy Glycosides Glycosyl Acceptor Input * Glycosidc Glycosidc Donor Performance Ratio to Tf., 0 TfOH (g: ß) 1"ACA ° óX? 0Ac 8p0? S? 7 5 ° 88% 5'1 AcO" SPh 2 6 * R = H, with triflic anhydride; R = 0 Si (CH3) 3, with triflic acid.

As can be seen from the results listed in Table I, the yields obtained from the catalytic glycosylation method are compatible with -do &- best- reports reported in the literature for the various glycal methods. In addition, catalytic TfOH can be used to activate sulfoxides even in the presence of acid-sensitive functional groups (Table 1, Entry 2). . 5. ASPECTS OF THE METHODS OF CATALYTIC TfOH AND ESTEOUIOMETRIC Tf-O TO ACTIVATE SULFOXIDES The two methods of glycosylation complement each other. The catalytic method of triflic acid is advantageous when the sulfoxide is unstable. The reaction conditions are temperate; therefore the decomposition of the glycosyl donors is minimized. Therefore, side reactions such as triflation or nucleophilic sulfenization that can result in decreased yields for glycosylation, do not occur with the TfOH catalytic method. However, the triflic acid method for the activation of sulfoxides is also significantly decreased and requires slightly higher temperatures (-78 ° C to -30 ° C) compared to the trilic anhydride method. Additionally, the catalytic method is not efficient when protective groups that snatch electrons are present in the glycosyl donor. The stoichiometric glycosylation method Tf20, on the other hand, works extremely well for glycosyl donors with protective groups that snatch electrons. It may be the best method of glycosylation when the neighboring participation group is used to obtain stereo-selectivity. An important point to note is that neither triflic acid nor triflic anhydride activate anomeric phenyl sulfides under the reaction conditions used (Table I, Entry 5). Because anomeric sulfides can readily convert to sulfoxides under extremely mild conditions (mCPBA, CH2C12, -78 ° C to 0 ° C) both methods lend themselves easily to interactive strategies for the synthesis of oligosaccharides. Thus, it has been shown that the anomeric sulfoxides can be activated by glycosylation with a catalytic amount of a strong organic acid, such as a triflic acid. The glycosylation reaction proceeds under very mild conditions and offers the following advantages: (i) the decomposition of sulfoxides is minimal under the conditions of the reaction; and (ii) the problems of nucleophilic triflation and sulfenylation are eliminated. these advantages are significant especially in the context of the solid phase synthesis of oligosaccharides, where the sulphonylation or triflation of the nucleophile can result in the uptake of an increasing oligosaccharide chain in a resin, and hence, the culmination of the synthesis. This catalytic method complements the triflic anhydride method, and is especially useful for the construction of 2-deoxy oligosaccharides. In fact, the catalytic method of triflic acid has been employed in the efficient construction of the 2-deoxy trisaccharide of cyclamycin 0, as described elsewhere in the present disclosure. Finally, we have shown that neither triflic anhydride nor triflic acid activates the anomeric phenyl sulfides under the reaction conditions used, - therefore, both methods are coded by themselves to interactic strategies for the synthesis of oligosaccharides. . 6. APPLICATION OF THE SINGLE STAGE GLICOSILATION METHOD TO THE SYNTHESIS OF ANTRYCYCLIN ANTIBIOTICS We have found that the order of reactivity of the different sulfoxides can be controlled by varying the substituents in the para position of the phenyl ring. Consequently, we have succeeded in synthesizing the trisaccharide of cyclamycin 0 to be synthesized stereoselectively in the 25% yield from the monosaccharide components in a single step. The synthetic step is sketched in the figure . The salient features of the synthesis include the use of a catalytic method of glycosylation of triflic acid to construct all the 2-deoxy glycosic bonds stereoselectively. Also, the trisaccharide holds a phenyl sulfide at the ring anomeric center A. Anomeric phenyl sulfides are stable ("disarmed") for the conditions that activate the animéricos sulfoxides for glycosylation. These can easily be oxidized under mild conditions. Thus, the sulphoxide glycosylation method lends itself to an interactive strategy for the synthesis of oligosaccharides. The sufficiency in ring A of the cyclamic acid trisaccharide was oxidized to the corresponding sulfoxide with mCPBA and then coupled to the aglycone.

We have discovered that the step that limits the ratio of the glycosylation reaction mediated with sulfoxide is the triflate of the sulfoxide. The reactivity of the phenyl sulfoxides can therefore be modulated by varying the substituent in the para position of the phenyl ring. The tendency of the observed reactivity is co o-follows.- p-OMe > p-H > p-N02 From here, when perbenzyl parathyloxy glucose phenyl sulfoxide 27 (2.0 eq) and perbenzylated glucose phenyl sulfoxide 28 (2.0 eq) were mixed together in CH2C12 and treated with triflic anhydride (1.0 eq), base (2.0 eq) and nucleophile 29 (2.0 eq) at -78 ° C, it was observed by TLC that the phenyl sulfoxide parametoxy was activated selectively.

The product isolated after chromatography included the disaccharide (80%) and an unreacted phenyl sulfoxide (<60% yield). However, when the same reaction was conducted in the presence of excess triflic anhydride, both sulfoxides 27 and 28 were activated, presumably in a sequential manner, to give the glycosylated product. On the other hand, additional emulation experiments revealed that the reactivity of glycosyl- (nucleophilic) receptors can also be manipulated. Thus, the phenyl sulfoxide 2-deoxy fucose perbenzoylated 32 (2.0 eq), the nucleophile 31A (1.0 eq), the silyl ether 31B (1.0 eq), and the base (2,6-di-tert-butyl pyridine) -4-methyl, 2.0 eq) were premixed in CH2C12 and cooled to -78 ° C. This reaction mixture was then treated with triflic anhydride (1.0 eq). The reaction was followed by TLC which indicated that the sulfoxide 32 and the nucleophile 31a were consumed (to form the disaccharide in 60% yield) while the silyl ether 31b remained unreacted.

In another experiment, an excess of sulfoxide 32 (5.0 eq) was used; in this case, nucleophile 31a was first consumed followed by silyl ether 31b. Silyl ethers react more slowly than unprotected alcohols such as glycosyl * acceptors, presumably because they must first be discarded. Having demonstrated that the ability to manipulate the reactivity of glycosyl donors and glycosyl acceptors, the synthesis of the cyclamine trisaccharide was followed according to Figure 15. It was expected that the p-methoxy B phenyl sulfoxide would be activated. first, letting it react with the alcohol C-4 of A to form the disaccharide AB. Then, the phenyl sulfoxide C would be activated and coupled with the disaccharide AB to form the desired trisaccharide ABC. . 6.1. Synthesis of a stage of the trisaccharide Sulfoxide 21, and 22 and nucleophile 23 were premixed and dissolved in a 1: 1 mixture of ether-methylene chloride at 78 ° C. Methyl propiolate (20 eq), followed by a catalytic amount of triflic acid (0.05 eq) were added to this solution. The reaction was stirred at -70 ° C for an hour and a half and then quenched by stripping in a saturated solution of sodium bicarbonate.

The desired trisaccharide 49 was the largest isolated product in 25% yield after flash chromatography. Other trisaccharides were not isolated from the reaction mixture. The only other significant coupled product isolated was the disaccharide 48, the precursor of the trisaccharide. The reaction has taken place in a sequential manner as expected with the methyl sulfoxide p-methoxy B activated first and then reacting with the free C-4 hydroxyl of the nucleophile A to form the disaccharide AB (48). Subsequently, the methyl sulfoxide C is activated and reacts with the disaccharide AB to form the desired trisaccharide ABC (49). Staying with the proposed mechanism, when the same reaction is conducted at -100 ° C (nitrogen nitrogen-hexane bath), the isolates are the disaccharide AB 75 silyl ether (60% yield) together with the non-activated sulfoxide C. The execution of the experiment at low temperature thus confirms the nature of the reaction stage. The performance of the first glycation stage is not limited by some undesirable cross coupling, but by the instability of the glycosyl donors, particularly keto sulfoxide C, which decomposes easily at room temperature even in the absence of an activating agent . In reality, less than 5% of the cross-coupling disaccharide of phenyl sulfoxide 21 and free alcohol 23, although 21 is present in excess. No disaccharide of the cross coupling of phenyl sulfoxide 21 and 22 was detected. The presence of the ketone functional group in the pyranose ring may contribute to the instability of this sulfoxide. In an effort to increase above all the glycosylation performance, the use of an appropriately protected form of the keto sulfoxide was explored. . 6.2. Improving the performance of the BC coupling Because the disaccharide AB, 48 and the nucleophile 23 are structurally very similar, the nucleophile 23 was chosen as a model compound for the glycosyl acceptor in the glycosylation reaction with C. The precursor of keto sulfide , the equatorial acohol C-4, was chosen as the glycosyl donor. The effect of the different protective groups at the C-4 center was examined.

Glycosyl acceptor glycosyl 52 The use of a C-4 alcohol suitably protected from the glycosyl donor dramatically improved the glycosylation performance (40-60%). However, for all cases examined, there was a loss of stereochemical control in the middle of the year, as illustrated in Tabala II, immediately below. - - - Table II. The effect of protective groups on C-4 Protective Group Performance • of Reason R (51) disaccharide (52): ß CH3CO 40% 1: 2 pMeOC6HsCH2 60% 1: 2 TBDMS 60% 1: 1 TBDPS 60% 1: 1 ______ The presence of protected C-4 axial hydroxyl was also anaylized in ring C. In this case, alpha stereoselectivity was obtained, however, two additional steps following glycosylation were required. This includes the deprotection of the C-4 alcohol followed by the oxidation of the axial alcohol to the ketone. These additional stages f result in the decrease of the total yield. In this way, although a yield of 25% for a synthesis stage of the trisaccharide appears modest, lacking additional manipulations of the functional groups, it makes the synthesis efficient. . 6.3. Coupling of the trisaccharide to the aglycon e-pyrromycinone The trisaccharide has an anomeric phenyl sulfide in the A ring. This sulfide was oxidized to sulfoxide using mCPBA. The e-pirromicinone 15 (1.0 eq) and the trisaccharide sulfoxide 50 (3.0 eq) were dissolved in a 1: 1 mixture of ether-methylene chloride and cooled to -78 ° C. Methyl propiolate (20 eq) was added to the reaction mixture, followed by a catalytic amount (0.05 eq) of triflic acid. ljF Thin layer chromatography (TLC) taken immediately after the addition of triflic acid indicated the presence of a new spot just above the aglycone. After being produced and purified by chromatography, this new compound was identified by NMR spectrography to be coupled the aglycone to the trisaccharide (54). The coupling constant JH.H of 3 Hz for the anomeric proton was consistent with the stereochemistry of the glycosidic bond. . 6.4 Deprotection of Cyclamycin To complete the synthesis of Cyclamycin 0 the removal of the benzyl ester protecting groups in ring A and B was required. The benzyl esters were removed by hydrogenolysis using Pd (OH) 2 on carbon as the catalyst . Unfortunately, under these reaction conditions, in addition to the benzyl ethers the aglycone was also cleaved. In retrospect, this was not surprising because the C-7 hydroxyl of the aglycone to which the sugar is bound resembles a benzyl ether. Thus, to obtain intact cyclazimine, the hydrogenolysis conditions may not be used. To avoid this problem, the protecting groups in the sugar rings A and B need to be changed. The benzyl ethers for methoxy can be easily cleaved under oxidation conditions using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). See, for example, Ikemoto and Schereiber J. Am. Chem. Soc. 1990, 112, 9657; Horita et al. Tetrahedron, 1986, 42, 3021; Oikawa et al. Tet. lett. 1984, 25, 5393; and Carbohydrates, Ed. Collins, P.M: Chapman and Hall; New York, 1987. Thus, a 1: 1 mixture of marcelomycin (which has a trisaccharide at the C-7 position of the aglycone) and ring A (with benzyl ether protecting group p-methoxy in C -3) were treated with an excess of DDq. Under these reaction conditions only the benzyl ether p-methoxy in ring A was hydrolyzed while the marcelomycin remained intact. Based on these results, the protecting groups in the cyclamicin trisaccharide can be preferably changed from benzyl ethers to benzyl p-methoxy ethers.

PMB = para-methoxybenzyl the monosaccharides 21, 22a and 23a can be used to synthesize the desired cyclamicin trisaccharide in one step (20% yield) followed by the customary procedure. This trisaccharide sulfide was oxidized to the sulfoxide with mCPBA and then coupled to the aglycone using the catalytic method of glycosylation of triflic acid. Deprotection of the coupled product 54a required the removal of the para-methoxy benzyl ethers. The coupled product 54a (1 mg) was treated with DDQ in CH2C12 and stirred at room temperature for 10 hours. The reaction proceeded neatly to give cyclamycin 0 quantitatively. . 7. SYNTHESIS OF TRACED OLIGOSACARIDOS THROUGH CONTROLLED POLYMERIZATION: FORCED LIBRARIES OF HOMOPOLIMEROS 2-DESOXI FUCOSE The sulfoxide 2-deoxy fucose B used for the synthesis of a stage of the trisaccharide cyclamicin is a bifunctional sugar. It contains a delivery group in the anomeric center (p-methoxy p-sulphide) and can serve as a glycosyl donor, and addition, has a silyl ether in the C-4 center and can also serve as a glycosyl acceptor. The most common 2-deoxy sugars found in bioactive natural products are 2, 6-dideoxy sugars. These are frequently found as dimers or trimers attached to an aglycone. Given our success with the synthesis of a complicated trisaccharide in one stage, we would be amazed if it were possible to extend this idea for the rapid assembly of oligosaccharides through controlled polymerization. The B 2, 6-dideoxy ring presented an opportunity to explore the possibility of homopolymer synthesis in a single reaction.

Sulfoxide 22 (2.0 g.) And nucleophile 55 (1.0 g.) Were premixed in a 1: 1 mixture of ether methylene chloride and cooled to -78 ° C. the reaction mixture was treated with the base (2.0 eq) and with triflic anhydride (1.0 eq) (see above). Thin layer chromatography that was taken shortly after indicated the presence of two new related spots -with the product ^ After chromatography two products were isolated and characterized by NMR spectroscopy. These products were disaccharide AB 56 (45% yield) and trisaccharide ABB (57) (20% yield). The JH-H coupling constants for the anomeric protons were consistent with the alpha stereochemistry for all the glycosidic linkages. This result indicated that the 2-deoxy fucose homopolymers can be formed stereoselectively in one step. To determine if higher order polymers of 2-deoxy fucose could be obtained, the number of equivalents of sulfoxide B (22) used in glycosylation was increased. 58 n = 2 59 n = 3 60 n = 4 When 5.0 equivalents of B and l.O equivalents of A were used, a statistical mixture of di, tri, tetra, penta and hexasaccharides was obtained in a single reaction, as noted above. Thus, by using the sulfoxide method it is possible to rapidly synthesize a mixture of 2-deoxy fucose homopolymers through controlled polymerization. - The sulfoxide glycosylation method is powerful and versatile. It can be used to rapidly synthesize a complicated trisaccharide such as cyclamycin from monosaccharide components in a single reaction. This strategy could be extended to synthesize a hexasaccharide from component disaccharides in one step. In addition, through the use of bifunctional sugars it is possible to synthesize a mixture of homopolymers (of variable chain length) in a single step with the sulfoxide method. So far, we have examined only 2-deoxy fucose as a substrate for the controlled polymerization reactions. However, this strategy could in principle be extended to include other bifunctional substrates as well.

By using a combination of the one-step strategy and controlled polymerization it is possible to very rapidly synthesize oligosaccharide libraries with several bound aglycones, as shown above. These oligosaccharide libraries can be chosen for DNA binding, for example, for example, using DNA affinity chromatography. Such a study will help to elucidate the characteristics in the oligosaccharides that DNA binding provides.

The glycosylation method is fast, flexible and efficient for the construction of oligosaccharides using conventional concepts. The reactivity of glycosyl donors by varying the substituent in the para position of the phenyl ring. The electron-donating substituents accelerate the reaction rate relative to the unsubstituted case, while the electron-snaring groups slow down the reaction rate. The reactivity of the glycosyl acceptors can also be modulated. Silyl ethers react more slowly in glycosylations than free alcohols. This allows the controlled formation of two or more glycosidic ligatures in a single reaction. This strategy was used to synthesize the cyclamic acid trisaccharide or stereoselectively from single-stage "onosaccharide" components, in addition to the sugars bifunctions can be used to synthesize oligosaccharide libraries.The sulfoxide method is thus a versatile method of glycosylation which allows the rapid synthesis of oligosaccharides through controlled polymerization. . 8. FORMATION OF GLISIDIC LIGADURES IN THE SOLID PHASE A potential glycosyl acceptor is bound to an insoluble support (hereinafter called the resin) through a ligature that can easily be split at the end of the synthesis using conditions that do not harm to glycosidic ligatures). The resin can be any insoluble polymer that increases in organic solvents and that has sites for the binding of the glycosyl acceptor. Preferred resins include, but are not limited to, polystyrene resins, such as Merryfield resin and PEG-derived polystyrene resins, such as TentaGell resins. The type of the link depends on the type of functional sites available in the polymer phase and the glycosyl acceptors. Because the polystyrene-based resins can be made functional with chloromethyl substituents, the bond typically is a benzyl ether formed by nucleophilic displacement of a benzyl chloride in the resin with a free hydroxyl in the glycosyl acceptor.

Alternatively, a benzyl ester which is formed by nucleophilic displacement of a benzyl chloride in the resin with the salt of an acid in the glycosyl acceptor can be used. (Fig. 4) Both types of bonds can be easily hydrolyzed at the anomeric carbon of glycosyl acceptor by treating the resin with Hg (II) compound. Alternatively, the ether bond can be hydrolyzed by methanolysis as is done in the ester-to-resin bonds in peptide synthesis. The Hg (II) method is preferred for the treatment of aliquots of the resin to minotore the extent of the reaction. The Hg (II) method is also preferred when the lactol of the finished oligosaccharide is desired as the final product. The methanolysis method is preferred when the sulfide of the finished oligosaccharide is deeaso as the final product (Fig. 4) The potential glycosyl acceptor can be any molecule having one or more potentially reactive nucellofils, including potentially reactive hydroxyls, amines, and / or thiols, with the proviso that it also has a suitable site for bonding with the resin. A potentially reactive nucleophile is a free nucleophile or a nucleophile with a temporary protection group that can be easily removed once the glycosyl acceptor is bound to the resin. The potential glycosyl acceptor can also have permanently protected nucleophiles, which are nucleophiles that can not be unprotected under the conditions that are used to remove the temporary protection groups. The potential glycosyl acceptor may be a sugar or some other molecule having nucleophile, including, but not limited to, steroids, amino acids or peptides, polar lipids, polycyclic aromatic compounds, and the like. See for example Binkley, above. Following the binding to the resin, the potentially reactive nucleophile is selectively deprotected, and the derived resin is lyophilized overnight and stored in a desiccator until use. The resin is then placed in a specially designed reactor with a glass frit. Some openings are sealed, for example with rubber septums (See for example Fig. 5). There may be variations in the appliances in general. However, the important feature can be listed as follows: a) An entry to add solvents and dissolved reagents to the reaction chamber and which is appropriate to maintain an anhydrous atmosphere; (in the apparatus shown, a septum over a cup-shaped opening allows the addition of solvent and dissolved reagents by cannula or syringe needle while preventing the explosion of the reaction chamber from outside air.) In a preferred embodiment of the reactor , this input is also equipped with a T-connector or similar adapter that allows double entry as a window to release inert gases, such as nitrogen, argon, to prevent the development of excess pressure inside the device). b) A reaction chamber to maintain the resin and the reactive solution, which is equipped with a flux or filter of such porosity so that the unbonded components, such as dissolved reactants not reacted, but not resin, can be worked from the reaction chamber; c) A porthole, located on the side of the frit, which is opposite the input side, for the introduction of an inert gas; the gas passes through the frit, thereby stirring the reaction mixture, and settling on top of the reaction mixture, thus maintaining an anhydrous atmosphere within the reaction chamber. (As evident in Fig. 5, argon or nitrogen passes through the resin from below, opposing solvent flow through the flux and stirring the resin simultaneously. In a preferred embodiment, this hatch is equipped with a connector in T or similar adapter to allow the hatch to be vacuumed to remove the solvents under vacuum). It should also be noted that the configuration of the apparatus is such that the apparatus up to the level of most reaction chambers can be submerged in a cold bath. Hence, below the alkaline flux, the apparatus can be U-shaped, as shown in Fig. 5m, so that the gas hatch can be placed above the cooling medium. Next, an inert gas, such as argon or nitrogen, preferably argon, is passed through the resin for about 1 hour. The resin is then suspended in 3-5 ml of anhydrous collide including but not limited to toluene, ether, THF, methylene chloride, chloroform, propionitrile, or mixtures thereof). From the discussion in the previous section it is understood that the solvent change the stereochemical result of glycosylation for reactions in which the participation of neighboring group is not involved. The flow of argon is adjusted to shake the resin gently and avoid the solvent draining or draining through the flux. A glycosyl solfóxido is dissolved dissolved low anhydrous conditions in 2-4 ml of anhydrous solvent and transferred by cannula to the reactor containing the resin. The glycosyl sulfoxide may also have protecting groups present elsewhere in the molecule. If the saccharide chain is to be further extended, the glycosyl sulfoxide should have at least one temporary protection group. Typically glycosyl sulfoxide is added in excess of 2-4 times relative to the amount of glycosyl sulfoxide acceptor added. The reactor containing the resin is then submerged in a cold bath at -78 ° C. To activate the glycosl donors for reaction, either 0.05 equiv. of triflic acid (eg, catalytic) or 0.5 equiv. of triflic anhydride diluted in a large volume of anhydrous solvent are added to the reaction mixture under anhydrous conditions. The molar equivalents # are identified in relation to the amount of glycosyl sulfoxide used. In addition, large volume dilution means that the net volume of the activating agent is diluted at least 100 times by the addition of the appropriate volume of solvent (for example, 1 μL net of activating agent is added in at least 99 μL of solvent before being added to the donor). The addition of the activating agent can be carried out, for example, with the aid of a cannula. Other suitable activating agents in the present method include, but are not limited to, an alkyl- or arylsilyl triflate (e.g., trimethylsilyl triflate) an alkyl- or arylsulfenyl tri-lato, and an alkyl- or aryl-selenium triflatonyl. If the protons are generated in the reaction (as when 0.5 equivalents of triflic anhydride are used to activate the sulfoxide), a purifying acid must be present in the reaction mixture. In addition, unless the activating agent is used in catalytic entities (eg, <0.1 equivalents relative to glycosyl sulfoxide), the activating agent should be diluted approximately 100 times or more prior to addition, has been discovered with anhydride When the dilution is critical, the triflation of the glycosyl acceptors in the resin is thus avoided. Next, the resin is suitably stirred by the flow of argon. Typically the reaction is allowed to continue for approximately 30 minutes after which the resin is # Rinse repeatedly to remove byproducts and unreacted glycosyl donors. If desired, the reaction can be monitored by removing the aliquots from the resin, washing the resin to remove the reactants and then hydrolyzing the resin bond. Alternatively, if the glycosyl acceptor is a sugar that is bound to the resin by means of a sulfur derivative bonded to the anomeric carbon, the linkage to the anomeric carbon can be hydrolyzed with an Hg (II) compound. Hydrolysis by Hg (II) is preferred to monitor the extent of the glycosylation reaction. The products and the progress of the reaction can be analyzed by thin layer chromatography using comparison standards. For example, after hydrolysis by Hg (II) of an aliquot of the reaction mixture, the soluble products are analyzed by TLC. The absence of monosaccharide redisium that was bound to the resin is taken as an indication that the reaction has proceeded to its completion. to obtain the products, the resin is typically washed repeatedly with methylene chloride followed by methanol (preferably, about 10 cycles). The coupling can be repeated if necessary to bring the reaction to term. In another case, if the chain of the saccharide to be extended, the temporary protective groups are now removed, the resin washed repeatedly to remove the reactants and another glycosyl sulfoxide is added before. At the end of the synthesis and washing to remove reagents, the disaccharide, oligosaccharide or glycoconjugate is removed from the resin. The product can then be and / or unprotected if desired. Alternatively, the disaccharide, oligosaccharide or glycoconjugate may be used while bound to the resin in the screening procedure to elucidate the biological activity. Strategically, mixtures of oligosaccharides can also be produced by solid phase synthesis and screening for biological activity, to produce the mixtures, more than one different type of sulfoxide is added to the resin in one or more synthesis cycles. It may be desirable to vary the sugars only in one position in the synthesis to test the structural requirements in that position. In this way, the structure-activity relationship can be evaluated quickly both in the cases where a particular carbohydrate and its acceptor are known. Alternatively, it may be desirable to vary the sugars in various positions in the synthesis by producing a complex mixture that can be screened for ligation to several acceptors. In both cases, if activity is detected, the active compound (s) can be identified using methods similar to those used in the peptide component of the mixtures produced by solid phase synthesis. See, 61 for example, Fuka et al, Int. Peptide Protein Res. 1992, 37, 487; Lam et al Nature 1991, 354, 82, Houghten, R. A: Nature # 1991, 354, 84; Zuckerman et al. Proc. Natl. Acad. Sci. USA 1992, 89, 4505; Petithory Proc. Natl. Acad. Sci. USA 1991, 88, 11510; Geyse et al. Proc. Natl. Acad. Sci. USA 1984, 81, 3998; Houghten Proc. Natl. Acad. Sci. USA 1985, 82/5131; Fodor et al. Science 1991, 251, 767. 6. EXAMPLES The following specific examples are provided to aid the reader in various practical aspects of the present invention. As these examples are merely illustrative, none of the following descriptions should be construed as limiting the present invention in any way. Such limitations are, of course, defined only by the accompanying clauses. 6. 1 Synthesis of trisaccharide cyclamycin 0 in a single step. Figure 1 shows an embodiment of the process papra the formation of glycosidic bonds in solution, which is a specific trisaccharide, trisaccharide cyclamycin 0 is synthesized stereospecifically in protected form in a single step from monosaccharide components. monosaccharides 1, 2, and 3 are combined at a ratio of 3: 2: 1, as shown (417 mg, 1.812 mmol, 541 mg, 1.2 mmol, and 165 mg, or 604 mmol, respectively). The water is removed from the mixture by distilling the azeotrope from anhydrous toluene, (this # Drying step is carried out by dissolving the sugar mixture in toluene (ca 30 ml) and stirring the toluene in a rotary evaporator under vacuum. The anhydrous sugar mixture is then used directly or stored under inert gas, until needed). The anhydrous sugar mixture is then dissolved in 20 ml of anhydrous methylene chloride in a 50 ml flask of flame drying. Then, 20 ml of freshly distilled diethyl ether containing 20 equivalents of methyl propiolate is added. (The methyl propiolate ester is used to purify the sulphonic acid that is produced in the reaction). The solution is then cooled to -78 ° C. A catalytic amount of triflic acid (5.3 μl, 0.05 eq.) Is added dropwise and the reaction is allowed to warm from -78 to -70 ° C over a period of 45 minutes and then quenched with NaHCO 3. The biphasic mixture is then extracted with CH2C12 (3 x 15 ml). The organic extracts are combined, dried in anhydrous Na2SO4 and concentrated. The largest product, trisaccharide 5, is isolated in 25% yield, based on monosaccharide 3, after extraction with ethyl acetate and flash chromatography on silica gel (20% ethyl acetate / petroleum ether). The H NMR spectrum of trisaccharide 5 is shown in Figures 12 and 13. The stereoselectivity achieved is a function of the donor / acceptor pairs and the glycosylation conditions (solvent, temperature). We have found that the catalytic triflic acid does not anomerize the glycosidic ligatures in an appreciable proportion below -30 ° C. No other trisaccharide was produced. In effect, the only other detected synfluent product detected from the reaction is disaccharide 4 (Scheme 1 of Fig. 1, yield of 15%; 1H NMR, Fig. 14), prcusser to disaccharide 5. less than 55 of disaccharide of the cross coupling of phenyl sulfoxide 1 and free alcohol 3 is detected even though 1 is present in excess, no cross-coupling disaccharide of 1 is detected. Thus, the yield of trisaccharide 5 in the reaction is not limited by any undesirable covalent bond. However, the instability of glycosyl donors, particularly keto sulfoxide 1, which decomposes easily at room temperature even in the absence of activating agent, can affect performance. The product of the reaction indicates that the glycosylation took place sequentially, with the p-sulfoxide p-methoxy 2 being activated faster than the phenyl sulfoxide 1, and the C-4 (3) alcohol reacting faster than the ether 2 of silil of C-4. Consistent with this sequence, if the reaction is turned off at -100 ° C, only if the silyl ether of disaccharide 4 can be isolated (60%). Finally, it should be noted that the trisaccharide (5) in the one-step reaction has an anomeric phenyl sulfide in the a ring. Anomeric phenyl sulfides are stable ("disarmed") to the conditions that activate the phenyl sulfoxides for glycosylation, but these can not easily be oxidized under mild conditions. See, Mootoo et al. J. M. Chem. Soc. 1988, 110, 5583; Veenman and Van Boom Tet. Lett. 1990, 31, 275; and Metha and Pinto Tet. Lett. 1991, 32, 4435. Thus, the sulfoxide glycosylation reaction also presents itself well for an iteractive strategy for the J 'tk. synthesis of oligosaccharides. See, Friesen and Danishefsky J. Am. Chem. Soc. 1989, 111, 6656; Halcom and Danishefsky J. Am. Chem. Soc. 1989, 111, 6661; Mootoo et al. supra; Veeneman and Van Boom, supra; And Mehta and Pinto, supra; Nicolau et al. J. Am. Chem. Soc. 1984, 106, 4189; Mootoo et al J. Chem. Soc. 1989, 111, 8540; Barrett et al J. Am. Chem. Soc., 1989, 111, 1392. Cyclamic acid trisaccharide 5 is oxidized to the corresponding sulfoxide in 89% yield (1.2 eq mCPBA, CH2C12, -78 ° C to -50 ° C, 2 hr) and is ready for coupling to the chromophor of cyclamycin. Monosaccharide 1 is prepared from L-rhamnose in 60% of the total yield CH NMR; Fig. 10) and 3 E NMR; Fig. 11) is prepared from L-fucose with total yields of 47% and 52%, respectively. See, Giese et al. Angw Chem. Int. Ed. Engl. 1987, 26, 233. According to another method of the present invention, the preparation of the individual starting materials, their orchestrated condensation to form the trisaccharide of interest, and their subsequent coupling to an aglycone is described with • more detail below. 6. 1.1. Phenyl-3-0-benzoyl-2,6-dideoxy-1-thio-alpha-L-qlactopyranoside Ola) Compound 37 (1.41 g, 5.9 mmol) is dissolved in dichloromethane and cooled to -78 ° C under argon. Sodium hydride (566 mg, 23.6 mmol) is added to this solution. There is energetic effervescence. After ten minutes, benzoyl chloride (2.05 ml, 17.7 mmol) is added to the solution. The reaction is stirred at -78 ° C for half an hour, heated gradually to -60 ° and then quenched by emptying in a saturated solution of NaHC03. The resulting solution is extracted with CH2C12 (3 x 50 ml); The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. Flash chromatography (20% ethyl ether-petroleum ether) gives the product as a white solid (1.6 g, 70%) Rf = 0.3 (20% ethyl ether-petroleum ether). XH MNR (CDC3, 270 Mhz) d 8.3 (m, 2H), 7.8-7.2 (m, 8H), . 85 (d, J = 5.94 Hz), 4.1 (bs, ÍH, h-4), 2.78 (dt, J = 5.93, 12.86 Hz, ÍH, H-2ax), 2.3 (dd, J = 4.95, 13.19 Hz, H-2eq), 2.12 (bs, ÍH, OH), 1.41 (d, J = 6.60 Hz, 3H, CH3). 6. 1.2. Phenyl-3,4-0-benzoyl-2,6-dideoxy-1-thio-alpha-L-galactopyranoside (32a) This compound is synthesized from phenyl-3,4-0-diacetyl-2,6-didesoxyl -thio-alpha-L-galactopyranoside 36 in the following two-step sequence: (i) NaOMe / CH3OH, IR (120) of amberlite plus ion-exchange resin; and (ii) benzoyl chloride, pyridine. Rf (TLC) = 0.3 (30% ethyl acetate-petroleum ether). XH NMR (CDC13, 270 MHz) d 8.1-7.7 (m, 6H), 7.5-7.7 (m, 9H), 5.71 (m, 1H, H-3), 5.61 (bs, ÍH, H-4), 5.48 (d, J = 5.28 Hz, ÍH), 4.33 (q, J = 6.27 Hz, ÍH, H-5), 2.45 (dt, J = 3.63, 12.54 Hz, ÍH, H-2 «), 2.17 (dd, J = 4.95, 12.54 Hz, lH, H-2eq), 1.25 (d, J = 6.27 Hz, 3H, CH3). 13C NMR (CDC13, 67.5 Mhz) d 169.49, 164.88, 161.88, 134.11, 130.77, 130.00, 129.28, 129.13, 128.56, 128.44, 128.28, 128.12, 127.83, 83.33, 69.93, 67.81, 65.74, 53.22, 30.67, 16.17. 6. 1.3. Phenyl-3,4-0-benzoyl-2,6-dideoxy-1-sulfinyl-alpha-L-qlactopyranoside (32) Sulfide 32a (900 mg, 1.99 mmol) is dissolved in dichloromethane and cooled to -78 ° C (acetone bath / dry ice) under argon. MCPBA (483 mg, 2.80 mmol) is added and the reaction is stirred at -78 ° C for one hour. The reaction is gradually heated to 0 ° C over a period of two hours and then quenched by emptying in a saturated solution of NaHCO 3. The resulting biphasic mixture is extracted with CH2C12 (3 x 25 ml). The organic layers are combined, washed with brine and dried over Na2SO4. Flash chromatography (40% ethyl ether-petroleum ether) gives sulfoxide 32 as a white crystalline solid (690 mg, 80% yield) Rf (TLC) = 0.4 (40% ethyl acetate). Petroleum). 1H NMR (CDC3, 270 MHz) d 8.1-7.65 (m, 6H), 7.5-7.2 (m, 9H), 5.9 (m, HH, H-3), 5.68 (d, J = 2.64 Hz, HH, H -4), 4.71 (d, J = 5.61 Hz, ÍH, Hl), 4.63 (q, J = 6.27 Hz, ÍH, H-5), 2.80 (dd, J = 5.28, 14.19 Hz, ÍH, H-2eg ), 2.55 (dt, J = 5.94, 12.53 Hz, ÍH, H-2 ^), 1.27 (d, J = 6.27 Hz, 3H, CH3). 6. 1.4. 3,4-0-benzoyl-2,6-dideoxy-galactopyranosyl-alpha- (1-a-4) -phenyl-3-O-benzoyl-2,6-dideoxy-1-thio-alpha-L-qlactopyranoside ( 33) Sulfoxide 32 (177 mg, 0.4 mmol), nucleophile 31a (80 mg, 0.2 mmol), silyl ether 31b (93 mg, 0.2 mmol) and base (82 mg, 0.4 mmol) are premixed and azeotroped three times with toluene A freshly distilled CH2C12 is added to a 25 ml flame-dried flask under argon. The azeotrope reactants are dissolved in 10 ml of CH2C12 and added to the flask, which is then cooled to -78 ° C. After 10 minutes triflic anhydride (33.6 μl, 0.2 mmol) is added. The reaction is followed by TLC (30% ethyl ether ether oil). TLC indicates that the nucleophile 31a has reacted completely while the silyl ether 31b remains unreacted. The reaction is heated gradually to -60 ° C over a period of two hours and then quenched by emptying in a saturated solution of NaHCO 3. The resulting solution is extracted with CH2C12 (3 x 15 ml), dried over anhydrous Na2SO4 and concentrated in vacuo. Flash chromatography (30% ethyl ether-ethyl acetate) gives the disaccharide 33 as a white crystalline solid (85 mg, 60% yield). Rf = 0.4 (30% ethyl acetate-petroleum ether). XH MNR (CDC3, 270 Mhz) d 8.1-7.9 (m, 6H), 7.6-7.1 (m, 14H), 5.8 (d, J = 5.28 Hz, 1H, Hl), 5.74 (m, ÍH, H-3 ), 5.47 (m, ÍH, H-3), 5.43 (d, J = 1.98 Hz, H-4), 5.21 (d, J = 1.98 Hz, H- 4 '), 4.54 (q, J = 6.27 Hz) , H-5), 4.39 (q, J = 6.60 Hz, ÍH, H-5 '), 4.20 (d, J = 2.31 Hz, ÍH, H-an), 2.96 (dt, J = 5.61, 12.87 Hz, ÍH, H-2), 2.20 (3m, 3H), 1.28 (d, J = 6.60 Hz, 3H, CH3), 0.47 (d, F J = 6.27 Hz, 3H, CH3), 0.47 (d, J = 6.27 Hz, 3H, CH3). 13C NMR (CDC13, 67.5 Mhz) d 165.95, 165.90, 165.69, 134.94, 133.42, 133.11, 132.92, 131.06, 129.91, 129.88, 129.85, 129.76, 129.69, 129.57, 128.91, 128.58, 128.42, 128.23, 127.01, 98.93 8379, 75.33, 70.34, 70.10, 67.60, 67.63, 65.71, 30.98, 30.21, 17.41, 16.08. 6.2 SYNTHESIS OF THE RING A The synthesis of ring A begins with L-fucose, and is carried out in six stages with a total yield of 60%, according to the scheme below.

Re 6.2.1. l, 3,4-0-Tri-0-acetyl-2,6-dideoxy-alpha-L-qacto-octopyranoside (35) To a solution of tetra-O-acetyl-fucose (5.0 g, 15.05 mmol) in 10 ml of Glacial acetic acid is added 15 ml of bromic acid (30%) dropwise and the resulting solution is stirred at room temperature. After two hours the reaction is completed. It is made to finish under anhydrous conditions by emptying the reaction mixture in a flask containing 25 g. of anhydrous sodium carbonate (Na2C03) suspended in 200 ml of carbon tetrachloride. The reaction mixture is stirred at room temperature for 45 minutes and filtered. The procedure is repeated with the filtrate. The resulting solution was then concentrated in vacuo to yield crude bromide 34 (5.2 g, 80%). This is used without further purification in the next step. A freshly distilled liter of benzene is added to a two-liter, three-necked flask equipped with a reflux condenser and an addition funnel. The fucose bromide 34 (5.2 g, 12.7 mmol) is dissolved in benzene (15 ml) and added to the flask. The resulting mixture is heated to reflux. AIBN (200 mg, 1.21 mmol) is added to this solution. After 30 minutes tributyl tin anhydride (4.91 ml, 18.25 mmol) in benzene (100 ml) is added dropwise to the reaction mixture over a period of about 16 hours via the addition funnel. At the end of this time, the reaction mixture is then cooled to room temperature and concentrated in vacuo. Flash chromatography (25% ethyl acetate-petroleum ether) gives the product 35 (2.5 g, 81%) # as a white critaline solid. Rf (TLC) = 0.3 (25% ethyl ether ethyl ether). ? E NMR (CDC13, 270 MHz) d 6.24 (d, J = 2.64 Hz, H, Hl), 5.22 (m, H, H-3), 5.17 (t, J = 0.66 Hz, H, H4) , 4.11 (q, J = 5.94 Hz, ÍH, H-5) 2.13 (s, 3H), 2.06 (s, 3H), 1.97 (s, 3H), 1.10 (d, J = 6.6 Hz, 3H, CH3); 13C NMR (CDC13, 67.9 MHz) d 170.13, 169.65, 168.82, 91.51, 68.87, 66.93, 65.86, 28.37, 29.60, 20.42, 16.14, 16.01. 6. 2.2. Phenyl-3,4-0-Tri-0-diacetyl-2,6-dideoxy-1-thio-alpha-L-galactopyranoside (35) Compound 35 (2.5 g, 9.11 mmol) and thiophenol (1.12 mL, 10.94 mmol ) are dissolved in dichloromethane (100 ml) and cooled under argon at -78 ° C. Et20-BF3 is added to the solution (5.6 ml, 45.5 mmol) per drip via a syringe. The reaction is maintained at low temperature for one hour and then gradually heated to 0 ° C and turned off when it is poured into saturated aqueous NaHCO 3. The resulting biphasic mixture is extracted with CH2C12 (3 x 50 ml); the organic layers are combined, dried over anhydrous Na2SO4 and concentrated. Flash chromatography of raw material (15% petroleum ethyl ether acetate) gives the sulfide 36 as a white solid (2.1 g, 71% yield). Rf (TLC) = 0.3 (15% ethyl acetate-petroleum ether). ? MNR (CDC13, 270 MHz) d 7. 5-7.2 (m, 5H), 5.73 (d, J = 5.61 Hz, ÍH, H-l), 5.29 (m, ÍH, H-3), . 23 (bs, 1H, H-3), 4.56 (q, J = 0.6 Hz, ÍH, H-5), 2.49 (dt, 11 J = 5.94 Hz, 12.87 Hz, ÍH, H-2ax), 2.38 (s) , 3H, OAC), 2.06 (m, 1H, Hz, 3H, CH3). 13C NMR Hz) d 170.51, 169.87, 159.54, 134.33, 124.54, 1114.54, 84.58, 69.69, 67.18, 65.51, 55.22, 20.70, 20.60, 16.34. 6. 2.3 Phenyl-2,6-dideoxy-l-thio-alpha-L-galactopyranoside (37) Compound 36 (2.1 g, 6.48 mmol) is dissolved in methanol (50 ml) and sodium methoxide (420) is added to the solution mg, 7.78 mmol). The reaction is stirred at room temperature for one hour. An FTA (40% ethyl acetate-petroleum ether) taken at the end of this time indicates that the reaction is complete. The solution is neutralized with IR amberlite (120) plus resin for ion exchange (1.0 g). The solution is filtered through a porous funnel, washed with ethyl acetate and concentrated to produce the diol 37. This compound is used in the next step without extra purification. 6. 2.4 Phenyl-3-0-benzyl-2,6-dideoxy-1-thio-alpha-L-galactopyranoside (23) A solution of 37 (923 mg, 3.84 mmol) and dibutyl tin oxide (956 mg, 3.84 mmol) in benzene (60 ml) is heated to reflux in a flask attached to a Dean-Stark apparatus. After 15 hours the reaction is cooled to room temperature and tetrabutylammonium bromide (1.24 g, 3.84 mmol) is added followed by bromide (5 ml, 8.4 mmol). The resulting mixture is refluxed further for two hours, then cooled to room temperature and concentrated in vacuo. Chromatography of the crude product (15% ethyl ether-petroleum ether) gives the sulfide 23 as a white solid (1.10 g, 90% yield). Rf (TLC) = 0.5 (30% ethyl acetate-petroleum ether). lH NMR (CDC13, 270 MHz) d anomer d 7.40-7.41 (m, 10H), 5.57 (d, J = 5.61 Hz, ÍH, Hl), 4.49 (s, 2H), 4.18 (q, J = 6.6 Hz, ÍH, H-5), 3.74 (m, ÍH, H-3), 3.70 (d, J = 3.63 Hz, ÍH, H-4), 2.20 (dt, J = 5.61, 12.5 Hz, ÍH, H-2 ), 2.14 (bs, ÍH, OH), 1.95 (m, ÍH, H-2 '), 1.17 (d, J = 6.6 Hz, 3H, CH3). 13C NMR (CDC13, 67.9 MHz) d 137.72, 135.20, 130.76, 128.84, 128.52, 127.92, 127.67, 126.83, 83.93, 73.514, 70.13, 68.46, 66.83, 30.67, 16.61. HRMS m / e 330.1290 (M +) calculated for C19H2203S 330.1290. 6. 3 SYNTHESIS OF THE B RING The synthesis of the B ring is accomplished as follows: 6. 3.1. 4-Methoxyphenyl-3,4-0-diacetyl-2,6-dideoxy-1-thio-L-galactopyranoside To a solution of 35 (1.95 g, 7.14 mmol) in distilled dichloromethane (100 ml) is added 4-methoxy thiophenyl (1 ml, 8.56 mmol) and the resulting mixture is cooled to -78 ° C. To this is added Et20-BF3 dropwise (4.4 ml, 35.70 mmol). The reaction mixture is stirred at low temperature for half an hour then heated gradually to -30 ° C and terminated by emptying to a saturated solution of NaHCO 3. Mix - ^ = resulting is extracted with CHC12 (3 x 30 ml). The organic extracts are combined, dried over Na 2 SO 4, filtered and concentrated under vacuum. The crude product is purified by flash chromatography (20% ethyl acetate-petroleum ether) to give sulfur 38 (2.12 g, 85%) Rf (TLC) = 0.4 (20% ethyl ether-petroleum ether) ). 1 H NMR (CDC 13, 270 MHz) d 7.40 (d, 2 H), 6.8 (d, 2 H), 5.51 (d, J = 5.61 Hz, Í H, H 1), 5.26 (m, H, H 3), 5.19 ( t, J = 2.97 Hz, 1H, H-4), 4.54 (q, J = 6.6 jfc Hz, ÍH, H-5), 3.77 (s, OCH3), 2.32 (dt, J = 5.61, 12.80 Hz, H- 2), 2.12 ((S, 3h), 2.02 (dt, J = 4.62, 12.80 Hz, ÍH, H-2 '), 1.98 (S, 3H), 1.07 (d, J = 6.61, 3H, CH3 ); 13C NMR (CDC13, 67.9 MHz) d 170.51, 169.87, 159.54, 134.33, 124.54, 114.54, 84.58, 69.69, 67.18, 65.51, 55.22, 30.24, 20.79, 20.60, 16.34; HRMS m / e 354.1140 (M +) caled for C17H220SS 354.1137. 6. 3.2. 4-Methoxyphenyl-2,6-dideoxy-1-thio-L-galactopyranoside (39) To the solution of 38 (1.0 g, 2.82 mmol) in methanol was added sodium methoxide (183 mg, 3.38 mmol). The mixture of f reacted > n is stirred at room temperature for two hours and then neutralized by the addition of Amberlite resin (l.g). The reaction mixture is filtered and concentrated in vacuo to give the diol 39 (760 mg, 100%). This is used in the next step without further purification. Rf (TLC) = 0.1 (50% ethyl acetate-petroleum ether). ^ NMR (CDC13, 270 MHz) d anomer d 7.35 (d, 2H), 6.80 (d, 2H), 5.41 (d, J = 5.28 Hz, ÍH, Hl), 4.41 (q, J = 6.6 Hz, ÍH, H-5), 3.95 (m, ÍH, H-3), 3.76 (s, OCH3), 3.65 (d, J = 2.64 Hz, ÍH, H-4), 2.01 (m, 2H, H-2, 2 '), 1.23 (d, J = 4.6 Hz, 3H, CH3). 6. 3.3. 4-Methoxyphenyl-3-0-benzyl-2,6-idesoxy-1-thio-L-galactopyranoside (40) A solution of 39 (2.13 g, 7.90 mmol) and dibutyl tin oxide (1.96 g, 7.90 mmol) in Benzene (200 ml) is heated to reflux in a flask coupled with a Dean-Stark apparatus. After 15 hours the reaction mixture is cooled to room temperature and added with tretabutyl ammonium bromide (2.54 g, 7.90 mmol) followed by benzyl bromide (2.82 ml, 23.7 mmol). The resulting mixture is refluxed for two more hours, then cooled to room temperature and concentrated under vacuum. Chromatography of the crude product (15% ethyl acetate-petroleum ether) gives the sulfide 40 as an (2.5 g., 88%). Rf (TLC) = 0.25 (20% ethyl acetate-petroleum ether). 'H NMR (CDC13, 270 MHz) d 7.5-7.25 (m, 7H), 6.81 (d, J = 8.91, 2H), 5.49 (d, J = 5.61 Hz, ÍH, Hl), 4.6 (s, 2H) , 4.32 (q, J = 6.59 Hz, 1H, H-5), 3.85 (m, ÍH, H-3), 3.82 (d, J = 3.3 Hz, ÍH, H-4), 3.77 (s, 0CH3) , 2.25 (dt, J = 5.94, 12.8 Hz, ÍH, H-2), 2.2 (bs, OH), 1.72 (m, ÍH, H-2 '), 1.27 (d, J = 6.59 Hz, 3H, CH3 ). 13C NMR (CDC13, 67.9 MHz) d 159.25, 137.66, 134.03, 128.33, 127.70, 127.52, 124.98, 114.37, 84.81, 73.40, 69.87, 68.35, 66.55, 55.06, 30.24, 16.47. HRMS m / e 360.1835 (M +) calculated for C23H2404S 360.1396. 6. 3.4. 4-Methoxyphenyl-3-0-benzyl-2,6-dideoxy-l-thio-4-0- (trimethylsilyl) -L-galactopyranoside (41) A solution of 40 (1.4 g, 3.88 mmol) and triethylamine (1.62 ml) , 11.64 mmol) in dichloromethane (100 ml) is cooled to -78 ° C under argon. To this solution is added dropwise TMSOTf (825 μl, 4.27 mmol). The reaction is stirred at low temperature for 30 minutes and then quenched by emptying it in a solution of saturated NaHCO 3. The resulting mixture is extracted with CH2C12 (3 x 30 ml). The organic extracts are combined, dried over Na 2 SO 4 and concentrated. Flash chromatography (10% ethyl ether-petroleum ether) gave the product 41 as an oil. Rf (TLC) = 0.85 (15% ethyl acetate-petroleum ether). 2H NMR (CDC13, 270 MHz) d 7.32 (d, J = 8.58 Hz, 2H), 7.28 (m, 5H), 6.79 (d, J = 8.91, 2H), 5.52 (d, J = 5.28 Hz, ÍH, Hl), 4.55 (d, J = 0.99 Hz, 2H), 4.21 (q, J = 6.60 Hz, ÍH, H-5), 3.79 (bs, ÍH, H-4), 3.76 (S, 0CH3), 3.66 (m, ÍH, H-3), 2.32 (dt, J = 5.61, 12.54 Hz, ÍH, H-2), 1.97 (m, ÍH, H-2 '), 1.14 (d, J = 6.59 Hz, 3H , CH3), 0.11 (s, 9H, TMS). 13C NMR (CDC13, 67.9 MHz) d 138.19, 133.67, 128.15, 127.46, 127.39, 125.55, 114.32, 85.16, 74.26, 71.05, 70.16, 67.76, 55.03, 30.11, 16.99, OR .5. HRMS m / e 432.1808 (M +) calculated for C23H3204SSi 432.1790. 6. 3.5. 4-Methoxyphenyl-3-0-benzyl-2,6-dideoxy-1-thio-4-0- (trimethylsilyl) -L-galactopyranoside (22) To a solution of sulfide 40 (402 mg, 0.93 mmol) in dichloromethane ( 60 ml) an excess of solid sodium bicarbonate (1.0 g) is added and the resulting mixture is cooled to -78 ° C. To this suspension is added mCPBA (193 mg, 1.11 mmol) and the resulting mixture is stirred at low temperature for 30 minutes. The temperature of the reaction mixture is gradually raised to 0 ° C in a period of one hour and then finished by emptying it in a solution of saturated NaHCO 3. The resulting mixture is extracted with CH2C12 (3 x 30 ml). The organic extracts are combined, dried over anhydrous Na2SO4 and concentrated under vacuum. Flash chromatography (30% ethyl ether-ether acetate) gives sulfoxide 22 (400 mg, 96%) as a white solid. Rf (TLC) = 0.4 (30% ethyl acetate-petroleum ether). XH NMR (270 MHz, CDC13) d 7.51 (d, J = 8.58 Hz, 2H), 7.4-7.2 (m, 5H), 6.97 (d, J = 8.58, 2H), 4.62 (d, JM = 11.88 Hz, ÍH), 4.47 (d, J = 5.27 Hz, ÍH, Hl), 4.02 (q, J = 6.60 Hz, ÍH, H-5), 3.9 (m, 1H, H-3), 3.84 (bs, ÍH, H-4) 3.83 (s, 0CH3), 2.63 (dd, J = 4.62, 13.86 Hz, ÍH, H-2), 2.02 (dt, J = 5.61, 13.85 Hz, 1H, H-2 '), 1.12 ( d, J = 6.26 Hz, 3H, CH3), 0.09 (s, 9H, TMS). 6. 4 SYNTHESIS OF THE C RING The C ring is prepared as follows: # 6. 4.1. Methyl-4-0-acetyl-2,3,6-tridesoxy-L-erythro-hexopyranoside (44) To a solution of Methyl-4-0-acetyl-2,3,6-tridesoxy-L-erythro-hexa- 2-enopiradoside 43 (2.0 g, 0.01 mmol) (see, Martin et al Carbohydr, Res. 1983, 115, 21) in bezeno, is added the catalyst Pd (0H) 2 / C (200 mg) and the resulting suspension is shaken in a Parr shaker under H2 (50 psi). After two hours the reaction mixture is filtered through zeolite and concentrated under vacuum to give 44 (2.0 g, 100 yield) This is used in the next step without further purification Rf (TLC) = 0.4 (30% of ethyl ether ethyl ether) XH NMR (CDC13, 270 MHz) d 4.63 (s, ÍH, H-4), 4.52 (bt, ÍH, Hl), 4.32 (q, J = 6.27 Hz, ÍH, H-5), 3.22 (s, 0CH3), 2.02 (s, 3H, OAc), 1.9 (m, ÍH, H-3 '), 1.85-1.65 (, 3H, H-2, 2', 3), 1.02 (d, J = 6.27 Hz, 3H, CH3) 13C NMR (CDC13, 67.9 MHz) d 169.14, 96.78, 72.96, 65.85, 53.70, 28.68, 23.69, 20.29, 17.34 HRMS m / e 187.0971 (M +) calculated for C9H1S04 187.0970. 6. 4.2. Phenyl-4-0-acetyl-l-thio-2,3,5-tridesoxy-β-L-arabino-hexapyranoside (45a) To a solution of 44 (2.3 g, 12.23 mmol) and thiophenol (1.5 ml, 14.67 mmol) ) in dichloromethane (100 ml) cooled to -78 ° C is added dropwise BF30Et2 (4.5 ml, 36.69 mmol). The reaction is stirred at low temperature for 30 minutes, heated gradually to -60 ° C and culminates in a saturated solution of NaHCO3. The resulting mixture is then extracted with CH2C12 (3 x 25 ml), - the organic layers are combined, dried over Na 2 SO 4, and concentrated under vacuum. Flash chromatography (15% ethyl ether-petroleum ether) gives sulfoxide 45a (3.0 g, 92%) as a white solid. Rf (TLC) = 0.4 (15% ethyl acetate-petroleum ether). XH NMR (270 MHz, CDC13, MHz) d 7.55-7.2 (5H), 5.52 (d, J = 4.95 Hz, ÍH, H-4), 4.59 (dt, J = 4.42, 10.23 Hz, ÍH, Hl), 4.30 (m, 1H, H-5), 2.2-2.1 (m, 2H, H-3, 3 '), 2.09 (s, 3H, OAc), 1.9-1.75 (m, sH, H-2, 2' ), 1.17 (d, J = 5.95 Hz, 3H, CH3). HRMS m / e 266.0970 (M +) calculated for C14H1803S 266.0977. 6. 4.3. Phenyl-4-0-hydroxy-l-thio-2 / 3,5-trideoxy-β-L-arabino-hexapyranoside (45b) To a solution of 45a (3.0 g, 11.27 mmol) in methane (100 ml) was added. add sodium methoxide (365 mg, 6.76 mmol). The reaction mixture is stirred at room temperature for two hours and then neutralized by adding Amberlite resin (2.0 g) and stirred for 15 minutes. The reaction mixture is filtered and concentrated in vacuo to give the alcohol 45b (2.57 g, 100%). This is used without further purification in the next step. Rf (TLC) = 0.2 (25% ethyl acetate-petroleum ester). XR NMR (270 MHz, CDC13) d 7.5-7.2 (m, 5H), 5.49 (d, J = 4.62 Hz, ÍH, Hl), 4.1 (m, ÍH, H-4), 3.3 (m, ÍH, H -5) 2.2-1.6 (m, 4H, H-2, 2 ', 3, 3'), 1.2 (d, J = 5.49 Hz, ÍH, CH3). 6. 4.4. Oxidation to Ceto sulphide (46) A solution of oxalyl chloride (5.5 ml, 11.16 mmol) is dichloromethane (150 ml) is treated with DMSO (1.5 ml, 22 mmol) at -78 ° C. After 10 minutes, a solution of the alcohol 45b (2.7 g, 10.15 mmol) in dichloromethane (15 ml) and trimethylamine (7 ml, 50.75 mmol) is added to the reaction mixture. The reaction mixture is stirred at low temperature for 30 minutes, then heated to 0 ° C and quenched upon emptying in a solution of NaHCO 3. The resulting mixture is extracted with CH2C12 (3x 30 ml); The resulting layers were combined, dried over Na2SO4 and concentrated under vacuum. Flash chromatography (15% ethyl acetate-petroleum ether) gives acetone 46 (2.20 g, 97%) as a pale yellow oil. Rf (TLC) = 0.35 (15% ethyl acetate-petroleum ether). XH NMR (CDC13, 500 MHz) d 7.65-7.20 (m, 5H), 5.52 (t, J = 6.59, 6.96 Hz, ÍH, Hl), 4.49 (q, J = 6.6 Hz, ÍH, H-5), 2.65-2.40 (m, 3H, H-3, 3 ', 2), 1.93 (m, ÍH, H-2'), 1.22 (d, J = 6.59 Hz, 3H, CH3). 13C NMR (CDC13, 67.9 MHz) d 209.58, 134.40, 131.49, 128.91, 127.35, 82.78, 71.54, 34.98, 28.85, 14.63. HRMS m / e 222.0718 (M +) calculated for C12H1402S 222.0715. 6. 4.5. Oxidation of keto sulfide to sulfoxide To a solution of sulfide 46 (418 mg, 1.88 mmol) in dichloromethane (40 ml) is added an excess of solid sodium bicarbonate (1.0 g) and the result of the mixture cooled to -78 ° C . To this solution is added mCPBA (455 mg, 2.63 mmol) and the reaction mixture stirred at low temperature for 30 minutes. The temperature of the reaction mixture is slowly raised to 0 ° C and then quenched and then poured into a saturated solution of NaHCO 3. The result of the mixture is extracted with CH2C12 (3 x 30 ml), the organic layers are combined, dried over anhydrous Na2SO4 and concentrated in vacuo. Flash chromatography (40% ethyl ether-petroleum ether acetate) gives sulfoxide 21 (380 mg, 85%) as a pale yellow oil. Rf (TLC) = 0.25 (40% ethyl acetate-petroleum ether). XH NMR (CDC13, 500 MHz) d 7.65-7.42 (m, 5H), 4.64 (t, J = 5.93 Hz, ÍH, H-1), 4.59 (q, ÍH, H-5), 2.80-2.40 (m , 3H, H-3, 3 ', 2), 1.8 (m, ÍH, H-2'), 1.29 (d, J = 6.93 Hz, 3H, CH3). 6. 4.6. 3-0-Benzyl-2, 6-dideoxy-4-0- (trimethylsilyl) -aL-galactopyranosyl- (1-4) -phenyl-3-0-benzyl-2,6-dideoxy-1-thio-oi- L-galactopyranoside (47) Sulfoxide 22 (350 mg, 0.78 mmol) and nucleophile 23 (129 mg, 0.39 mmol) are premixed and azeotroped together three times with distilled toluene, freshly distilled diethyl ether (9 ml) is added to a Flame-dried bottle under argon and cooled to -78 ° C. The premixed reactants are dissolved in 6 ml of distilled dichloromethane and added to the flask. This is followed by the addition of Hunig's base (136 μl, 0.38 mmol). Triflic anhydride (65.5 μl, 0.19 mmol) is added to the reaction after being stirred for 5 minutes. The reaction is followed by TLC (10% ethyl ether-petroleum ether). The reaction is heated to -70 ° C and quenched by emptying into a saturated solution of NaHCO3. The result of the solution is extracted with CH2C12 (3 x 15 ml); The organic layers are combined and dried over anhydrous Na 2 SO 4. The solution is concentrated under vacuum and purified by flash chromatography (5% ethyl ether-petroleum ether) to give the product 47 as an oil (95 mg), 40% yield). Rf (TLC) = 0.8 (10% ethyl acetate-petroleum ether). 'HNMR (CDC13, 270 MHz) d 7.45-7.10 (m, 10H), 5.68 (d, J = 5.28 Hz, ÍH), 5.07 (bs, ÍH), 4.67 (d, J ^ - ^ 12.54 Hz, ÍH) , 4.55 (d, JAB = 12.54 Hz, ÍH), 4.53 (s, 2H), 4.23 (q, J = 6.60 Hz, ÍH), 4.17 (q, J = 6.60 Hz, ÍH), 3.85 (d, J = 2.64 Hz, HH), 3.73 (m, 2H), 3.68 (d, J = 1.32 Hz, HH), 2.33 (dt J = 6.93, 12.54 Hz, HH), 2.02 (m, HH), 1.19 (d, J = 6.60 Hz, 3H), 0.89 (d, J = 6.27 Hz, 3H), 0.06 (S, 9H). 13C NMR (CDC13, 67.9 MHz) d 138.63, 138.29, 135.32, 130.93, 128.90, 128.85, 128.59, 128.49, 128.20, 127.61, 127.55, 127.32, 126.89, 84.39, 74.26, 73.79, 73.76, 71.14, 70.25, 68.10, 67.43 , 31.72, 29.54, 17.37, 17.23, 16.65, 0.63. 6. 4.7. 3-0-Benzyl-2, 6-disesoxy-aL-galactopyranosyl- (1-4) -phenyl-3-O-benzyl-2,6-dideoxy-1-thio-aL-galactopyranoside (48) The disaccharide product of the previous section 47 (70 mg, 0.11 mmol) is dissolved in freshly distilled THF. The tetrabutylammonium fluoride (500 μl, 5 mmol) is added to the solution. The reaction is completed in one hour. The completion is made by emptying the reaction mixture in NaHCO 3 solution and extraction (3 x 15 ml) with THF. The organic layers are combined and concentrated under vacuum. The product 48 is used without further purification in the next step. Rf (TLC) = 0.4 (25% ethyl acetate-petroleum ether). XH NMR (CDC13, 270 MHz) d 7.5-7.2 (m, 10H), 5.69 (d, J = 5.27 Hz, HH), 5.03 (d, J = 2.97 Hz, HH), 4.66 (d, JAB = 12.54 Hz , ÍH), 4.60 (d, JAB = 11.55 Hz, ÍH), 4.56 (d, JM = 11.22 Hz, ÍH), 4.50 (d, JM = 11.22 Hz, ÍH), 4.27 (q, JiiB = 6.93 Hz, ÍH) ), 4.22 (q, J ^ - ^ 6.60 Hz, ÍH), 3.90 (m, ÍH), 3.86 (bd, J = 2.31 Hz, ÍH), 3.74 (m, ÍH), 3.72 (bs, ÍH), 2.12 (bs, OH), 1.91 (m, 2H), 1.19 (d, J = 6.60 Hz, 3H), 1.01 (d, J = 6.60 Hz, 3H). 13C NMR (CDC13, 67.9 MHz) d 138.10, 138.01, 135.22, 130.86, 128.83, 128.46, 128.40, 127.79, 127.67, 127.63, 127.39, 126.88, 99.15, 84.30, 74.84, 73.64, 73.21, 70.34, 70.07, 68.30, 67.97 , 65.86, 31.65, 29.83, 17.34, 16.62. 6. 4.8. Trisacarido ABC (49) Sulfoxide 21 (60 mg, 0.22 mmol) and nucleophile 48 (61 mg, 0.11 mmol) are premixed and azeotroped three times with distilled toluene. Freshly distilled dichloromethane (1 ml) and diethyl ether (5 ml) are added to a flame-dried flask and cooled under argon at -78 ° C. The premixed sulfoxide and nucleophile are dissolved in dichloromethane (3 ml) and added to the cooled flask). This is followed by the addition of Hunig's base (40 μl, 0.22 mmol). After five minutes the triflic anhydride (18.5 μl, 0.11 mmol) is added to the flask. The reaction is stirred for two hours between -78 ° C and -70 ° C. The reaction is then extinguished by pouring it into a saturated solution of NaHCO3. The reaction mixture is extracted with CH2C12 (3 x 15 ml), the organic layers combined and dried over anhydrous Na2SO4. The solution is concentrated under vacuum and purified by flash chromatography (20% ethyl ether-petroleum ether) to give trisaccharide 49 (18 mg, 25% yield). 6. 5. Synthesis of one step of cyclamycin 0 trisaccharide Sulfoxides 21 (417 mg, 1812 mmol, 3.0 eq.), 22 (541 mg, 1.2 mmol, 2.0 eq.) And nucleophile 23 (165 mg, 0.604 mmol , 1.0 eq.) Are premixed and completely dried by azeotropization three times with distilled toluene. The starting materials are dissolved in freshly distilled CH2C12 (20 ml) and added to a 50 ml flask flame dried under argon. To this reaction mixture is added 20 ml of freshly distilled Et20 followed by methyl propylate (9.06 mmol, 15 eq.). The bottle is cooled to -78 ° C using an acetone / dry ice bath). After 5 minutes, triflic acid (5.3 μl, 0.06 mmol, 0.05 eq.) Is added dropwise to the reaction mixture. The reaction is followed by TLC (20% ethyl ether-petroleum ether). The reaction mixture is slowly heated to -70 ° C for a period of one hour and then extinguished when it is emptied into a solution of NaHCO 3 x 15 ml). The combined organic extracts are dried over anhydrous Na2SO3 and concentrated. Flash chromatography (20% ethyl ether-ether acetate) leaves the trisaccharide 49 (99 mg 25%) as a colorless oil. Rf (TLC) = 0.2 (20% ethyl acetate-petroleum ether). 1H NMR (CDC13, 500 MHz) d 7.45-4.20 (m, 15H), 5.67 (d, J = 4.85 Hz, ÍH), 5.07 (d, J = 2.64 Hz, ÍH), 4.98 (t, J = 3.36 Hz , ÍH), 4.66 (d, J = 1.32 Hz, ÍH), 4.19 (q, J = 6.6 Hz, ÍH), 3.88 (m, ÍH), 3.84 (bs, ÍH), 3.73 (m, ÍH), 2.52 (m, ÍH), 2.28 (m, ÍH), 2.23-2.02 (m, 2), 1.19 (d, J = 6.60 Hz, 3H), 0.90 (d, J = 5.27 Hz, 3H), 0.88 (d, J = 6.60 Hz, 3H), 13C NMR (CDC13, 67.9 MHz) d 211.13, 139.13, 138.94, 135.74, 131.74, 131.63, 129.20, 128.69, 128.60, 127.87, 127.81, 127.72, 127.69, 127.31, 99.57, 98.22, 84.80, 75.79, 74.98, 74.69, 74.19, 73.40 , 71.85, 70.45, 68.44, 67.59, 34.25, 31.88, 31.09, 29.89, 17.48, 17.35, 14.93. 6. 5.1. Cyclamycin Trisaccharide (49a) Sulfoxides 21 (190 mg, 0.8 mmol, 3.5 eq.), 22a (230 mg, 0.48 mmol, 2.0 eq.) And nucleophile 23 (85 mg, 0.24 mmol, 1.0 eq.) Are premezy. and completely dried by azeotropization three times with distilled toluene. The initial materials are then dissolved in freshly distilled CH2C12 (5 ml) and added to a flame-dried flask under argon. To this reaction mixture is added 5 ml of freshly distilled Et20 followed by methyl propiolate (4.8 mmol, 20 eq.). The bottle is cooled to -78 ° C using an acetone / dry ice bath. After 5 minutes, triflic acid (5.3 μl, 0.06 mmol, 0.05 eq.) Is added dropwise to the reaction mixture. The reaction is followed by TLC (20% ethyl ether-petroleum ether). The reaction mixture is slowly heated to -70 ° C for a period of half an hour and then quenched by introducing it into a saturated solution of NaHCO 3 (30 ml). The resulting biphasic mixture is extracted with CH2C12 (3 x 15 ml). The combined organic extracts are dried over Na2SO4 anhydrous and concentrated. Flash chromatography (30% ethyl ether-petroleum ether) leaves the trisaccharide 49a (35 mg 20%) as a colorless oil. Rf (TLC) = 0.3 (30% ethyl acetate-petroleum ether). 6. 5.2. Oxidation of sulfur to sulfoxide Trisaccharide sulfide 49a (20 mg, 09.027 mmol) is dissolved in 15 ml of freshly distilled CH2C12 deposited in a 25 ml flask. To this solution is added solid NaHC03 (500 mg) followed by mCPBA (7.8 mg, 0.045 mmol). The reaction is followed by TLC (40% ethyl ether-petroleum ether.) The reaction mixture is slowly heated to -60 ° and quenched by pouring into a saturated solution of NaHCO 3, The resulting biphasic mixture is extracted with CH 2 C 12 (3). x 10 ml) The organic layers are combined and dried over anhydrous NA2SO4 The trisaccharide sulphoxide 50a is obtained as an oil (19 mg) It is used without purification for glycosylation. 6. 5.3. Degradation of Marcelomycin to obtain Aglycone 6-pyrromycinone Marcelomycin, an anthracycline antibiotic isolated from complex bohemian acid, has the same aglycone e-pyrromycinone as cyclazimine (see the following). (Marcelomycin is a generous gift from the Bristol-Myers Squibb company.) Aglycone can be obtained by removing trisaccharide marcelomycin with acid hydrolysis.

The drug (75 mg) is stirred in methanolic HCl (25 ml, 0.1 N) for two hours. At the end of this the Marcelomycin (75 mg, 0.175 mmol) is dissolved in methanolic HCl (25 ml, 0.1 N) and stirred at 50 ° C for two hours. At the end of this time the reaction mixture is concentrated under vacuum and purified by preparative thin layer chromatography (15% methanol-chloroform). Aglycone e-pyrromycinone is separated as a bright red solid (21 mg, 54% yield). 6. 5.4. Coupling of trisaccharide to aglycone Sulfoxide 50a (19 mg, 25 μmol) e-pyrromycinone (6 mg, 14.15 μmol) and stilbene (2.5 mg, 14 μmol) are premixed and azeotroped three times with distilled toluene. Freshly distilled ether (2 ml) is added to a 15 ml flask flame dried and cooled with argon at -78 ° C. The azeotropized reactants are dissolved in distilled dichloromethane (3 ml) and added to the flask. After 10 minutes, triflic anhydride (0.118 μl, 0.7 μmol) is added to the flask and the reaction is followed by TLC (15% ethyl ether ethyl ether acetate). The reaction mixture is gradually heated to -50 ° C and extinguished when it is poured into a saturated solution of NaHCO3. The resulting mixture is extracted with diclomethane (3 5 ml); the organic layers are combined and dried over anhydride Na2SO4 the solution is concentrated under vacuum and purified by flash chromatography (15% ether-methylene chloride followed by 10% methanol-methylene chloride). The product is separated as a bright red solid (0.75 mg, 16% yield). # 6.6. Synthesis in a single container of homopolymers of different length FIG. 2 illustrates another aspect of the present invention which allows the synthesis of "homopolymers" of different length. Here, alpha-linked homopolymers of 2-deoxy fucose with different length distribution are produced by mixing in separate bottles of different proportions of the bifunctional sulfoxide 4-methoxy phenyl-3-0-benzyl-4-0- trimethylsilyl-2-deoxy l-sulfinyl-ce-L-fucopyranoside, B, with the monofunctional glycocyl methyl-3-0-benzyl-2-deoxy-Qi-L-fucopyranoside, A, and the 2,6-di-t-butyl base -4-methylpyridine (2 equivalents relative to sulfoxide). The following table indicates the proportion of reactant that is used for each of the experiments 6.6.1.-6.6.5. The mixtures are first completely dried by means of azeotropic distillation of toluene (preferably, three times, as mentioned above). The mixtures are then each dissolved in 2.5-5 ml of methylene anhydride chloride and added to 25 separate flasks of 25 ml dried to flame under argon. An equal volume of freshly distilled diethyl ether is added to each reaction mixture. The flasks are cooled to about -78 ° C using an acetone / dry ice bath. After 5 minutes, a methylene chloride solution of triflic anhydride (1.0 equivalent relative to B) is added dropwise to the reaction mixtures. The reaction is monitored by thin layer chromatography using 15% ethyl acetate / petroleum ether as the diluent.

After warming to -70 ° C for a period of about half an hour, the reaction mixtures are quenched with a saturated solution of NaHCO 3 (approximately 30 ml each). Each of the results of the biphasic mixtures is extracted with methylene chloride (3 x 15 ml). The organic extracts are combined, dried over Na2SO4 anhydride and concentrated. Flash chromatography (1: 5 ethyl acetate / petroleum ether) is used to separate the glycosolate produced by each reaction. The length distribution of "homopolymers" produced is based on the variation with the concentration of A to B and also with the total concentration of reactants in the reaction mixture, as shown in Table III below.

TABLE III Relative Quantities of Various "Homopolymers" Produced as a Function of Molar Reactor Ratios and Total Concentration AB A-B CE NMR, given below) AB2 A-B-B (? NMR, given below) AB3 A-B-B-B (XE NMR, given below) AB4 A-B-B-B-B (XH NMR, given below) ABS A-B-B-B-B (XE NMR, given below) More specifically, the result of the reaction described above, can be obtained by premixing sulfoxide (320 mgs, 0.714 mmol, 3.0 eq.), Neophyloil (60 mgs, 0.238 mmol, 1.0 eq.) And base (147 mgs, 0.714 mmol). , 3 eq.). The resulting mixture is then dried by azeotropic distillation of toluene. The reagents are then dissolved in 2.5 ml of distilled CH2C12 and added to a 25 ml flask dried under argon. The bottle is then cooled to -78 ° C and 2.5 ml of Et20 are added to the reaction. (The sulfoxide concentration is approximately 0.144 mmol / ml.) After 10 minutes Tf20 (1.5 eq., 0.357 mmol, 60 μl) is added. The reaction is maintained at -78 ° C for 1/2 hour, then it is allowed to warm to -70 ° C and stir it at this same temperature for an additional 1/2 hour. The reaction is quenched by pouring the reaction mixture into a saturated solution of NaHCO 3, followed by extraction of CH 2 C 13 3 times, drying and anhydrous Na 2 SO 4 concentration. The purification is carried out by flash chromatography: 15% EA / PE; 20% EA / PE. The structures of the various oligosaccharides are supported by the NMR data of the proton (270 MHz, CDC13), in which the non-terminal of B are labeled as X, X1 or X2, etc .: # AB disaccharide: d 5.08, bs , ÍH, H1B; 4.81, d, 1H, HIA; 4.7-4.5, 4H benzyl methylenes, -4.2 q, ÍH, H5B; 3.9-3.7, m, 5H, H3A, H4A, H4B, H3B, H5A; 3.3 S, 3H, methoxy; 1.8-2.1, 4H, H2A, H2B; 1.21, d, 3H, H6A (methyl); 0.9, d, 3H, H6B (methyl) ppm.

Trisaccharide AXB: d5.06, S, ÍH, H1B; 5.01, s, ÍH, H1X; 4.82, d, ÍH, HIA; 4.75-4.45, m, 6H benzyl methylene, - 4.21, q, 2H, H5X, H5B; 3.91-3.64, m. 7G, H3A, H3X, H3B, H5A, H4A, H4X, H4B; 3.29, S, -H, Al methoxy; 2.08-1.80, d, 3H, H6A; 1.23, d, 3H, H6A (methyl) d? .90, 3d, 6H, H6X, H6B (?? metils) ppm.

AXjXaB tetrasaccharide: d 5.27, d, ÍH, H1B; 4.99, d, 2H, H1X1; Hl2; 4.81, d, ÍH, HIA; 4.72-4.45, m, BH benzyl methylenes; 4.2 m, 3 H, H5XX H52, H5B; 3.90-3.62, m. 9H, H5A, H4A, H4X1, H4X2, H4B, H3A, H3X1 # H3X2, H3B; 3.29, s, 3H; 2.05-1.80, 8H, 2-deoxy, CH2A, CH2XX, CH2X2, CH2B; 1.22, d, 3H, H6A (methyl); 1.9-1.8, 9H, H6X. *., H6X2, H6B (?? metils) ppm.

XjXaXsB pentasaccharide: d 5.06, S, ÍH, H1B; 4.95, S, 3H, HlXj. H1X2, HX; 4.79, ÍH, S, HIA; 4.7-4.4, m, 10H, benzyl methylenes, -4.15, m, 4H, H5X17 H5X2, H5X3, H5B; 3.3, S, 3H, Al methoxy; 1.2, 3H, d, H6A (methyl); 0.85, 12H, m, E6Xl t H6X2, H6X3, H6B (?? metils) ppm.

X ^ X ^ B hexasaccharide: d 5.05, S, ÍH, H1B, -4.98, S, 4H, HXlf H1X2, H1X3, H1X4; 4.7-4.4, 12H, benzyl methylenes; 4.2-4.1, 5H, H5XX, H5X2, H5X3, H5X4, H5B; 2.1-1.8, m, 12H, H2A, H2X-L, H2X2, H2X3, H2X4, H2B; 1.2 d, 3H, H6A (methyl); 0.9-0.8, m, 15H, H6XX, H6X2, H6X3, H6X4, H6B (?? metils) ppm. 6. 7. Controlled Polymerization Reactions According to the other method of the present invention, a controlled polymerization reaction is carried out as follows: Sulfoxide 22 (250 mg, 0.58 mmol), nucleophile 53 (73 mg, 0.29 mmol), and base 2, 6 ditert-butyl-4-methyl pyridine (118 mg, 0.58 mmol) are premixed and azeotroped three times with distilled toluene. To a 25 ml flamed flask, freshly distilled diethyl ether (5 ml) is added and cooled under argon at -78 ° C. The azeotropized reagents are dissolved in distilled dichloromethane (5 ml) and added to the flask, after 10 minutes triflic anhydride (48.5 μl, 0.28 mmol) is added to the flask. The reaction is stirred at -70 ° C for 45 minutes and then quenched when it is poured into a saturated solution of NaHCO 3. The resulting biphasic mixture is extracted with CH2C12 (3 x 15 ml); the organic layers are combined and dried over Na2SO4 anhydride. The solution is concentrated under vacuum and purified with flash chromatography (15% ethyl acetate-petroleum ether). The disaccharide AB 54 (70 mg, 45%) trisaccharide ABB 55 (40 mg, 20% are separated as oils AB disaccharide: Rf (TLC) = 0.4 (15% ethyl ether acetate). 'H NMR (CDC13, 270 MHz,) d 7.4-7.2 (m, 10H), 5.06 (bs, 1H, H, 4.81 (d, J = 2.97 Hz, ÍH, H-l '), 4.68 (d, JAB = 12.53 Hz , ÍH), 4.54 (s, 2H), 4.50 (d, JM = 10.89 Hz, ÍH), 4.16 (q, J = 6.26 Hz, ÍH, H-5), 3.9 (m, ÍH, H-3), 3.8 (s, ÍH, H-4), 3.75 (q, J = 5.94 Hz, ÍH, H-5 '), 3.70 (m, ÍH, H-3'), 3.67 (d, J = 1.65 Hz, ÍH , H-4), 3.27 (S, 3H, 0CH3), 2.1 (m, 3H, H-2's), 1.8 (dd, J = 4.62, 12.21 Hz, ÍH, H-2ax), 1.21 (d, J = 6.6 Hz, 3H, CH3), 0.9 (d, J = 6.27 Hz, 3H, CH3), 0.06 (s, 9H), 13C NMR (CDC13, 67.9 MHz) d 138.61, 128.24, 128.14, 127.57, 137.32, 127.27, 127.19, 99.27, 98.89, 74.17, 73.78, 72.91, 71.13, 70.22 70.04, 67.28, 66.80, 54.67, 30.77, 29.51, 17.51, 17.21, 0.58. 6. 8. Synthesis in a single container of glycoconjugates with Potential DNA Ligament Activity The strategy to form multiple glycosidic ligands in solution can be used to synthesize in the same reaction many glycoconjugates with potential DNA binding activity. Depending on the situation, the glycoconjugates can be separated and screened individually by DNA ligament activity or can be screened as mixtures. For example, a mixture of glycoconjugates, each composed of a potential DNA intercalator and an oligosaccharide side chain, and differing from each other only in the length of the oligosaccharide side chain, are synthesized as in Example 6.6., But using a ratio of 4: 1 from bifunctional donor to glycosyl acceptor. Specifically, the 2-deoxy fucosyl sulfoxide derivative B (908 mg, 1.90 mmol), the glycosyl A acceptor (294 mg, 0.48 mmol), and 2,6-ditert-butyl-4-methyl pyridine (779 mg, 3.80 mmol) are combined, dried by azeotropic toluene distillation three times and then dissolved in 10 ml of a 1: 1 mixture of ether / methylene chloride (freshly distilled solvents). The solution is transferred to a flame-dried flask under argon. The bottle is cooled to -78 ° C using an acetone / dry ice bath. After 5 minutes, 161.1 μl (0.96 mmol) is added triflic anhydride by dripping to the. reaction mixture. The reaction is slowly heated to -70 ° C for a period of half an hour and then quenched by pouring it into a saturated solution of NaHCO3 (30 ml). The mixture is extracted with methylene chloride (3 x 15 ml). The combined organic extracts were dried over Na2SO4 anhydride, filtered and the solvent removed under vacuum. The reaction is dissolved in 10 ml of wet methylene chloride and treated with excess dichlorodicyanoquinone (DDQ) at room temperature for one hour to remove the benzyl p-methoxy ether protecting groups. The solvent is then removed under vacuum and the components are separated by flash chromatography on silica gel. Their relative affinity with respect to DNA is evaluated to determine the preferred length of the oligosaccharide side chain. Affinity chromatography can be used to identify oligosaccharides that are linked to particular acceptors. For example, a mixture of compound is passed over a column containing a solid support which is attached to the acceptor of interest (or bound, if the mobile phase contains a mixture of potential acceptors). Compounds that are bound to the acceptor are retained on the column longer than compounds that are not. The compounds can be fractionated according to their affinity for the acceptor. In this way, acceptors that bind carbohydrates can be attached to the solid support. Carbohydrate acceptors can be composed of DNA (double or single stranded), RNA, proteins, oligosaccharides, or other molecules. Methods for linking nucleic acids, proteins, and oligosaccharides to solid supports for use in affinity chromatography have been described. See: (a) Temper Chromatography of Nucleic Acids and Proteins, Schott, H. Marcel Dekker, Inc. New York, 1984; (b) Glycoconjugates: Composition, Structure and Function, Alien, H. J.; Kasailus, E. C, Eds. Marcel Dekker; NY 1992 (and references inside). (NOTE: Retention times can be used to quantify affinities for simple compounds passed under the affinity column.) In another example, the glycosyl A acceptor (FIG 3) is premixed with 2,3-p-methoxy benzyl- 4-trimethylsilyl ramosyl sulfoxide C (FIG 3) and left to react under conditions (eg, temperature, solvent, concentration, donor / acceptor ratio) identical to those described above. After excitation and removal of the benzyl p-methoxy protecting groups with DDQ, as above, the glycoconjugate mixture is separated by flash chromatography on silica gel and the relative affinities of the different compounds with respect to the DNA are determined. The glycoconjugates produced by the methods described above are compared with respect to their ability to bind to DNA. In this way, the effects of different sugars on the ligament affinity of DNA can be compared to the preferred sugars identified. The glycosyl A acceptor in FIG. 3 is made from the appropriate protected derivative glycosylation derivative (obtained by the procedures of Inhoffen et al., Croatica Chem. Acta. 1957, 29, 329; Trost et al. J. Ah. Chem. Soc. 1977, 99, 8116; and Stork and Hagerdorn J. Am. Chem. Soc. 1978, 100, 3609) with compound B (FIG.3) using Tf20-Hunig base CH2Cl2 / ether (1: 1) at low temperature. After a standard excitation (including extraction, as described in the other examples included herein) and remission of solvent, the product mixture is dissolved in methylene chloride and treated with an excess of tetrabutylammonium fluoride at 0 ° C. The solvent is then removed in vacuo and the product separated by flash chromatography.

The general process described above can also be applied to the synthesis of mixtures of glycoconjugates containing many different sugars. In this case, two or more bifunctional glycosyl donors are used in the reaction. After deprotection, the resulting mixture of glycoconjugates can be screened for DNA ligand activity by weighing it under the DNA affinity column. The compounds can be fractionated according to their retention times on the affinity column. Compounds with long retention times can be separated and identified using standard methods for structure elucidation. 6. 9. Additional Modes Illustrating the Catalytic Glycosylation Method The following examples describe the glycosylation methods mediated by catalytic amounts including reactions involving glycosyl silylated acceptors. 6. 9.1. 1, 2,3,4-Tetra-0-acetyl-6-0- (trimethylsilyl) -D-glucopyranose (2b) The following procedure is typical for all nucleophil silations. Alcohol 2a (600 mg, 1.85 mmol, 1.0 eq.) And triethyl amine (775 μl, 3.43 mmol, 3.0 eq.) Are dissolved in distilled methylene chloride and cooled to -78 ° C under argon. Trimethyl silyl triflate (394 μl, 2.03 mmol, 1.1 eq.) Is added to the reaction mixture. The reaction is followed by TLC. After 30 minutes the reaction is extinguished by pouring it into a saturated solution of NaHCO3. The resulting biphasic mixture is extracted with CH2C12 (3 x 25 ml). The organic layers are combined and dried over Na2SO4 anhydride. Purification by flash chromatography produces the ether silyl 2b (700 mg, 90%) as a white solid. Rf (TLC) = 0.6 (40% ethyl acetate-petroleum ether). XE NMR (270 MHz, CDC13) d 5.69 (d, J = 8.25 Hz, ÍH, Hl), 5.25 (t, J = 9.24 Hz, ÍH, H-3), 5.15 (t, J = 9.24 Hz, 1H, H-4 =, 5.12 (t, J = 8.28, 9.25 Hz, ÍH, H-2), 3.8-3.7 (m, 3H, H-5, H-6, 6 '), 2.1-2 (m, 12H , OAc), 0.5 (S, 9H, TMS). 6. 9.2. a, a.-1, 1-Dimero of Perbenzilate Glucose (5) The 1,1-dimer perbenzilate glucose is identified as follows: Rf (TLC) = 0.8 (25% ethyl ether-petroleum ether acetate). t NMR (270 MHz, CDC13) d 7.4-7.1 (m, 40H), 5.19 (d, J = 3.30 Hz, ÍH), 5.16 (d, JAB = 11.55 Hz, ÍH), 5.02 (d, JAB = 10.89 Hz , 1H), 4.97 (d, JAB = 12.21 Hz, ÍH), 4.90 (d, JAB = 10.89 Hz, ÍH), 4.89 (d, JAB = 10.89 Hz, ÍH), 4.83 (d, JAB = 10.89 Hz, ÍH) ), 4.82 (d, JAB = 3.30 Hz, ÍH), 4.81 (d, JM = 11.54 Hz, ÍH), 4.75 (d, JAB = 12.21 Hz, ÍH), 4.69 (d, JAB = 12.21 Hz, ÍH), 4.59 (bs, 2H), 4.55 (d, JAB = 11.88 Hz, HH), 4.52 (d, JAB = 10.88 Hz, HH), 4.49 (bs, 2H), 4.34 (d, JM = 12.21 Hz, HH), 4.21 (m, HH), 4.15 (t, J = 9.24, 9.47 Hz, ÍH), 3.82 (t, J = 9.24, 9.9 Hz, HH), 3.7-3.45 (m, 7H). • 6. 9.3. Synthesis of 3,4,6-Tri-0-benzyl-2-deoxy-D-glucopyranosyl- (1-6) -1,2,3,4-tetra-O-acetyl-jS-D-glucopyranose (7) The following procedure is typical of all glycosylation reactions performed under catalyzed acid conditions using TfOH: Sulfoxide 6 (140 mg, 0.258 mmol, 1.5 eq.) And nucleophile 2 (69 mg, 0.172 mmol, 1.0 eq.) They are premixed and completely dried by "azeotropization" 3 times with distilled toluene. The starting materials are then dissolved in 8 ml of freshly distilled CH2C12 and added to a 25 ml flask flame-dried under argon. The bottle is cooled to -78 ° C using an acetone-dry ice bath. Methyl propylate (230 μl, 2.58 mmol, 15 eq.) Is added to this solution as a sulfenic acid scavenger. After the solution is stirred at -78 ° C for 2 minutes, triflic acid (1.1 μl, 0.0129 mmol, 0.05 eq.) Is added. The reaction is followed by TLC (25% petroleum ethyl ether acetate). The reaction mixture is slowly heated to -30 ° C for a period of 1 hour, and then quenched by pouring it into a saturated solution of NaHCO 3 (25 ml). The resulting mixture is extracted with CH2C12 (3 x 15 ml). The organic extracts are combined, dried with Na2S04 anhydride, and f concentrated. Flash chromatography (25% ethyl ether-petroleum ether) gives disaccharide 7 (116 mg, 88%) as a white solid. Rf (TLC) = 0.3 (25% petroleum ethyl ether acetate). XH NMR (270 MHz, CDC13) d 7.4-7.2 (m, 15H), 5.75 (d, J = 8.25 Hz, 1H, Ha), 5.32 (t, J = 9.24 Hz, ÍH, Hc), 5.21 (t, J = 9.57 Hz, HH, Hd), 5.20 (t, J = 8.24, 9.24 Hz, HH, Hb), 4.99 (d, J = 2.64 Hzz, HH, Hl), 4.95 (d, JAB = 11.21 Hz, HH ), 4.71 (bs, 2H), 4.66 (d, JAB = 11.87 Hz, ÍH), 4.59 (d, J ^ ll.22 Hz, ÍH), 4.55 (d, JAB = 11.88 Hz, ÍH), 4.10 (m , ÍH, He), 3.85-3.50 (m, 7H), 2.36 (dd, J = 4.94, 12.86 Hz, ÍH), 2.15 (s, 3H), 2.10 (s, 3H), 2.05 (s, 3H), 1.95 (s, 3H), 1.70 (m, ÍH). 6. 9.4. Methyl-6-deoxy-3,4-isopropyl-ideno-2-0 - (trimethylsilyl) -jS-D-galactopyranoside (8) Component 8 is synthesized from D-fucose by the following sequence of three steps: (i) MeOH, H +; (ii) acetone, H3P04 (cat); (iii) TMSOTf, Et3N, CH2C12, -78 ° C. Rf (TLC) = 0.5 (15% ethyl acetate-petroleum ether). 1H NMR (CDC13, 270 MHz) d 4.03 (d, J = 8.24 Hz, ÍH, Hl), 3.98 (dd, J = 5.28, 7.26 Hz, ÍH), 3.97 (dd, J = 5.40, 1.98 Hz, HH) , 3.84 (dq, J = 1.98, 6.6 Hz, ÍH, H-5), 3.49 (S, 3H, OCH3), 3.47 (dd, J = 7.59, 5.49 Hz, ÍH), 1.48 (S, 3H, CH3) , 1.38 (d, J = 6.6 Hz, 3H, CH3), 1.31 (s, 3H, CH3), 0.5 (S, 9H, TMS). 13C NMR (CDC13, 67.9 MHz) d 109.38, 103.70, 80.52, 76.48, 74.45, 68.58, 56.64, 28.02, 26.34, 16.49, 0.31. 6.9.5. 3,4,6-Tri-0-benzyl-2-deoxy-D-glucopyranosyl-a- (1 = 2) - methyl-6-deoxy-3,4-isopropyl-idene-jd-D-galactopyranoside (9) Rf (TLC) = 0.5 (25% ethyl acetate-petroleum ether). XE NMR (CDC13, 270 MHz) to anomer d 7.4-7.15 (m, 15H), 5.30 (d, J = 2.97 Hz, ÍH), 4.86 (d, JAB = 10.89 Hz, ÍH), 4.64 (d, J = 1.65 Hz, 2H), 4.62 (d, JAB = 12.20 Hz, HH), 4.53 (d, JAB = 10.89 Hz, HH), 4.45 (d, JAB = 12.20 Hz, HH), 4.06 (d, J = 8.25 Hz , ÍH), 3.70 (t, J = 9.56 Hz, ÍH), 3.46 (s, 0CH3), 2.02 (ddd, J = 0.99, 4.95, 12.87 Hz, ÍH), 1.65 (dt, J = 3.62, 12.87 Hz, ÍH), 1.40 (s, CH3), 1.36 (d, J = 6.6 Hz, 3H), 1.24 (s, 3H). 13C NMR (CDC13, 67.9 MHz) d 13.8.91, 138.83, 138.32, 128.28, 128.23, 127.92, 127.79, 127.45, 127.42, 127.38, 109.35, 103.95, 97.45, 78.39, 78.20, 77.70, 76.31, 76.12, 74.95, 73.45 , 71.73, 70.53, 68.73, 68.48, 56.58, 35.47, 28.08, 26.34, 16.49. 6. 9.6. Phenyl-4-0-acetyl-2,3,6-trideoxy-l-sulfinyl-aL-erythro-hexopyranoside (10) Compound 10 is synthesized from L-rhamnal in three steps, a) H2 (1 atm), Pd (OH) 2 / C, CSH6; b) BF3-OEt2, thiophenol, CH2C12, -78 ° C to -60 ° C; and c) mCPBA, CH2C12, -78 ° C at -60 ° C. Rf (TLC) = 0.4 (25% ethyl ether ethyl ether). XH NMR (CDC13, 270 MHz) ß anomer (sulfide) d 7.5-7.2 (m, 5H), 5.54 (d, J = 4.95 Hz, H-4), 4.81 (dd, J = 1.98, 12.1 Hz, ÍH, Hl), 4.6 ( m, 2H, H-3, 3 '), 4.3 (m, HI, H-5), 2.2 (m, 2H, H2, 2'), 2.1 (s, 3H, OAc), 1.19 * (d, J = 5.94 Hz, 3H, CH3). 13C NMR (CDC13.67.9 MHz) ß anomer (sulfide) d 169.80, 130.98, 130.73, 128.58, 128.49, 83.79, 67.15, 29.95, 25.34, 20.82, 18.00, 17.44. 6. 9.7. 4-0-Acetyl-2,3,6-trideoxy-L-erythro-hexopyranosyl-Qi- (1 = 6) -1,2,3,4-tetra-0 -acetyl-jS-D-glucopyranose (11) Rf (TLC) = 0.3 (25% ethyl acetate of JÉL petroleum). aH NMR (CDC13, 270 MHz) oí anomer d 5.63 (d, J = 7.92 Hz, ÍH), 5.20, (t, J = 9.24 Hz, ÍH), 5.19 (t, J = 9.57 Hz, ÍH), 4.61 (dd, J = 1.98, 8.58 Hz, ÍH), 4.33 (ddd, J = 4.61, 10.23, 10.23 Hz, ÍH), 3.94 (dd, J = 3.96, 11.22 Hz, ÍH), 3.71 (m, ÍH), 3.56 (dd, J = 2.96, 11.22 Hz, ÍH), 2.05 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.96 (s, 3H), 1.95 (s, 3H), 1.11 (d, J = 6.59 Hz, 3H). 13C NMR (CDC13, 67.9 MHz) d 170.19, 170.12, 168.18, 169.15, 168.95, 100.85, 91.79, 73.03, 72.96, 70.34, 68.60, 66.01, 29.54, 26.88, 21.07, 20.76, 20.64, 20.54, 20.50, 18.01, 17.72 . 6. 9.8. Phenyl-3, 4-bis-0- (4-methoxy-benzonyl) -1-sulfinyl-D-digitoxose (13) Compound 13 is synthesized from digitoxose by the following sequence of three steps: (1) pOMeC6H4COCI, pyridin; »(Ii) thiophenol, Et20-BF3, CH2C12; (iii) mCPBA. Rf (TLC) = 0.2 (40% ethyl acetate-petroleum ether). 1H NMR (CDC13, 270 MHz) to anomer (sulfoxide) d 8.09 (d, J = 8.91 Hz, 2H), 7.87 (d, J = 9.24 Hz, 2H), 7.70 (m, 2H), 7.55 (m, 3H ), 6.94 (d, J = 8.90 Hz, 2H), «6.85 (d, J = 8.91 Hz, 2H), 5.84 (q, J = 3.31 Hz, ÍH) 5.10 (dd, J = 2.63, 2.97, ÍH), 5.04 (m, ÍH), 4.49 (dd, J = 1.64, 5.13 Hz, ÍH), 3.83 (s, 3H, OCH3), 3.82 (s, 3H, 0CH3), 1.28 (d, J = 5.95 Hz, 3H). 6. 9.9. Phenyl-3,4-0- (4-methoxy-benzoyl) -β-D-digitoxosyl- (0) -N-hydroxyethyl carbamate (14) Rf (TLC) = 0.45 (anomer, 40% ethyl acetate) petroleum ether). 1H NMR (CDC13, 270 MHz) to anomer d 8.03 (d, J = 8.91 Hz, 2H), 7.79 (d, J = 9.24 Hz, 2H), 6.88 (d, J = 9.24 Hz, 2H), 6.77 (d, J = 9.01 Hz, 2H), 5.60 (q, ÍH), 5.12 (d, J = 4.62 Hz, ÍH), 4.95 (d, J = 2.97, 10.23 Hz, ÍH), 4.78 (m, ÍH), 4.18 (q, 2H), 4.17 (m, ÍH), 3.84 (s, OCH3), 3.79 (s, 0CH3), 2.37 (dd, J = 3.3, 15.51 Hz, ÍH), 2.19 (m, ÍH), 1.26 ( t, J = 6.93 Hz, 3H), 1.25 (d, J = 6.27 Hz, 3H). 13C NMR (CDC13, 67.9 MHz) d 165.48, 165.17, 163.53, 163.45, 157.42, 131.97, 131.75, 122.65, 121.92, 113.62, 113.59, 100.69, 100.61, 72.21, 65.90, 63.65, 62.08, 55.40, 32.04, 17.53, 14.44 R £ (TLC) = 0.5 (ß anomer, 40% ethyl acetate, petroleum ether). 1 H NMR (CDC13, 270 MHz) ß anomer d 7.92 (d, J = 8.91 Hz, 2H), 7.78 (d, J = 8.91 Hx, 2H), 6.89 (d, J = 8.91 Hz, 2H), 6.77 (d , J = 9.24 Hz, 2H), 5.74 (q, ÍH), 5.23 (dd, J = 2.31, 9.23 Hz, ÍH), 4.93 (dd, J = 2.97, 9.23 Hz, ÍH), 4.23 (q, ÍH) , 4.16 (q, 2H), 4.17 (m, ÍH), 3.85 (s, OCH, 3.79 (s, OCH3), 2.36 (m, ÍH), 2.04 (m, ÍH), 1.29 (d, J = 6.27 Hz , 3H), 1.23 (t, J = 6.93 Hz, 3H) .13C NMR (CDC13, 67.9 MHz) d 165.10, 164.91, 163.61, 163.55, 131.85, 122.18, 121.83, 113.74, 113.59, 101.77, 72.31, 69.21, 67.41 , 62.19, 60.34, 55.44, 55.38, 33.29, 18.01, 14.38. 6. 9.10. Phenyl-2,3-0-benzonyl-6-deoxy-l-thio-jS-L-galactopyranoside (15) Compound 15 is synthesized from L-fucose by the following sequence of four steps: (i) Ac20, pyridine; (ii) thiophenol, Et20-BF3; (iii) NaOMe, CH30H, amberlite H + resin; (iv) CßH5C0Cl, DMAP. Rf (TLC) = 0.6 (40% ethyl acetate-petroleum ether). XH NMR (CDC13, 270 MHz) d 8.0-7.9 (m, 4H), 5.64 (t, J = 9.89 Hz, ÍH), 5.27 (dd, J = 2.97, 9.9 Hz, ÍH), 4.86 (d, J = 9.9 Hz, ÍH), 4.09 (d, J = 2.97 Hz, ÍH), 3.87 (q, J = 6.27 Hz, ÍH), 1.40 (d, J = 6.27 Hz, 3H). 6. 9.11. Phenyl -3,4-acetyl-2,6-dideso-l-sulfinyl-L-galactopyranoside (16) Compound 16 is prepared from 1,3,4-tri-o-acetyl-2-deoxy-a-L-fucose by the following two-step sequence: (i) thiophenol, Et20-BF3; and (ii) mCPBA. Rf (TLC for a sulfide) = 0.3 (15% ethyl acetate-petroleum ether). XH NMR (CDC13, 270 MHz) at sulfur d 7.5-7.2 (m, 5H), 5.73 (d, J = 5.61 Hz, ΔH, Hl), 5.29 (m, ΔH, H-3), 5.23 (bs, 1H) , H-3), 4.56 (q, J = 6.6 Hz, ÍH, H-5), 2.49 (dt, J = 5.94, 12.87 Hz, ÍH, H-2., 2.38 (s, 3H, OAc), 2.06 (m, ÍH, H-2eq), 1.99 (s, 3H, OAc), 1.13 (d, J = 6.6 Hz, 3H, • CH3). 13C NMR (CDC13, 67.9 MHz) d 170.51, 169.87, 159.54, 134.33, 124.54, 114.54, 84.58, 69.69, 67.18, 65.51, 55.22, 20.79, 20.60, 16.34. Rf (TLC for a sulfoxide) = 0.25 (30% ethyl ether ether ethyl ether acetate). XH MR sulfoxide 01 anomer (CDC13, 270 MHz) d 7.6-7.3 (m, 5H), 5.43 (m, HH), 5.26 (bd, J = 2.64 Hz, HH), 4.52 (d, J = 5.61 Hz, HH) ), 4.32 (q, J = 6.6 Hz, ÍH), 2.47 (dd, J = 5.28, 14.18 Hz, ÍH), 2.14 (dt, J = 5.61, 14.19 Hz, ÍH), 2.10 (s, 3H, OAc) , 1.98 (s, 3H, OAc), 1.12 (d, J = 6.26 Hz, 3H). 6. 9.12 3,4-0-Acetyl-2,6-dideoxy-L-galactopyrans i-at- (1 = 4) - phenyl-3,4-benzoyl-6-deoxy-l-thio-jß-L - galactopyranoside (17) Rf (TLC) = 0.4 (30% ethyl acetate-petroleum ether). 1H NMR (CDC13, 270 MHz) 7.9 (m, 4H), 7.55-7.25 (m, ÍH), 5.55 (t, J = 10.23 Hz, ÍH), 5.20 (dd, J = 2.96, 10.22 Hz, ÍH), 5.12 (m, ÍH), 5.02 (bd, J = 1.98 Hz, ÍH), 4.94 (bs, ÍH), 4.84 (d, J = 9.9 Hz, ÍH), 4.15 (d, J = 2.97 Hz, ÍH), 3.96 (q, J = 6.27 Hz, ÍH), 3.86 (q, J = 6.27 Hz, ÍH), 2.04 (s, 3H), 2.0 (s, 3H), 1.94 (m, 2H), 1.35 (d, J = 6.27 Hz, 3H), 0.33 (d, J = 6.27 Hz, 3H). 13C NMR (CDC13 / 67.9 MHz) d 170.44, 169.62, 166.05, 164.95, 133.51, 133.36, 133.01, 131.49, 129.78, 129.62, 129.12, 128.65, 128.44, 128.27, 128.18, 99.49, 85.42, 76.86, 75.27, 74.68, 69.56 , 67.47, 66.50, 65.27, 29.70, 20.85, 20.56, 17.32, 15.77. 6. 10 Synthesis of a β-linked Disaccharide in the Solid Phase A 10 ml of DMF solution containing 0.338 g (0.350 mmol) of cesium acetate phenytoglycoside 2, 3, 4-tribenzyl-6-tritylgalactose-1-p-hydroxy-phenytoglycoside cesium acetate (X, FIG 6) is added 0.356 g (0.385 mmol of Cl eq, 1.1 equiv.) of Merrifield resin (BACHEM Bioscience). This mixture is stirred with a manually operated stirrer for 24 hours under an argon atmosphere at 75 ° C. At this time, the polymer is poured into a porous Gooch funnel and repeatedly washed with methanol and methylene chloride. The funnel is then dried for 4 hours in a lyophilizer jar at 20 millitor. A mass change of 0.244 is recorded, which is calculated to be at 85% chemical yield with respect to the cesium salt. The polymer in the porous Gooch funnel is then treated with vacuum filtration at a moderate flow rate with 40 ml of 10% trifluoroacetic acid (TFA) in methylene chloride until the yellow color becomes apparent in the filtrate. (TFA is used to remove the triethyl protecting groups.) The polymer is then repeatedly washed with methanol and methylene chloride. The funnel, together with the resin-bonded nucleophile, are dried for 4 hours in a lyophilizer jar at 20 milliliters before the "concentration". A mass change of 0.065 g is subsequently measured, which is calculated to be 83% chemical yield with respect to the cesium salt. The concentration of the resin-bonded nucleophile (X-resin), FIG. 6) is then calculated to be 0.544 mmol / g. 200 mg (for example, 0.11 mmol) of derived resin are lyophilized overnight in the reactor and then purged for 1 hour with argon. The resin is then suspended in 5 ml CH2C12. 4 equivalents (0.44 mmol) of 2-pivaloyl-3, 4-benzyl-6-p-methoxy benzyl galactosyl penyl sulfoxide (Y, FIG. 6) and 6 equivalents (0.66 mmol) 2,6-di-t-butyl- 4-methyl pyridine are dissolved in 5 ml of methylene chloride and added by cannula to the reactor. The mixture is gently stirred by means of argon flow for 30 minutes at room temperature and then the reactor vessel is immersed in a cold bath to cool it to -60 ° C. 2 equivalents (0.22 mmol) of triflic anhydride diluted a hundred fold (v / v) in methylene chloride are added slowly (for 15 minutes) to the reactor. The resulting reaction mixture is gently stirred for 1 hour.

After the reaction is completed, as indicated by the Hg (II) hydrolysis method and the TLC analysis, the solvent and primary reagents are then emptied from the reactor vessel, and the resin mixture is repeatedly rinsed with methanol and followed by methylene chloride. Subsequently, the resin mixture is suspended in 15 ml of methylene chloride and then treated with excess Hg (OCOCF3) 2 for 8 hours to adhere the glycosidic bond to the resin. (Note: only 5 minutes are needed to remove enough product from the resin to monitor the reaction by TLC analysis.) The solvent is allowed to pour from the resin. Additional solvent is then used to rinse the resin. The filtrates are then combined, extracted three times with water and concentrated by evaporation. The desired 8-linked disaccharide is obtained by flash chromatography on silica gel. The non-bound disaccharide is separated from the reaction. The thio-sugar X of FIG. 6 is prepared from the available 1,6-anhydroglucose, by treatment with benzyl bromide followed by acid hydrolysis (H2S04-THF-H20), tritylation (trityl-pyridine chloride) of the more reactive primary alcohol C6, and from the treatment of lactol resulting with the disulfide XX and tri-n-butyl phosphino (for example, the standard procedure for making thiophenyl glycosides from lactoles). The disulfide XX is produced by reaction of the available 4-hydroxythiophenol disulfide, with c-bromo-methyl acetate.

Disulfide XX The sulfoxide Y in Figure 6 is prepared from readily available penta-acylated galactose using the following sequence of reatives: (1) BF3 / etherthiophenol; 82) hydroxide; 83) acetone-H +; (4) sodium hodride-benzyl p-methoxy bromide; (5) pivaloyl chloride; (6) mCPBA. Each stage is well known in the art and is carried out under standard conditions. (V-ease, list of "Reference Standards" below in section 6.15, discussion of which are incorporated herein for reference). The disaccharide produced from the reaction of X and Y is subjected to methanolysis (to remove it from the resin) and is characterized by NMR spectroscopy of ^ ?. Relevant data include: (CDC13) 5.58ppm (d, J = 5.3 Hz, Hl of thio-sugar), 5.47 ppm (dd, J = 7.9, ao.2 Hz, H2 of pivaloyl sugar C2), 4.45 ppm (d, partially covert, Hl of pivaloyl sugar C2). 6. 11 Synthesis of an alpha-linked disaccharide in the solid phase The sodium salt of a glycosyl acceptor (X, Fig 7) is bound to the Merrifield resin by the standard method (DMF, 80 ° C, 24h) following the coupling and washing (as described in Example 6.10) the resin It is lyophilized and heavy. The load is calculated at 0.52 mmol / g of the mass gain. 200 mg (i.e., 0.1 mmol) of the derived resin are lyophilized overnight in the reactor (Fig. 7) and then purged for one hour with argon. The resin is then suspended in 5 ml. of methylene chloride. $ equivalents (0.4 mmol) of perbenzylated fucosyl sulfoxide Y and 6 equivalents of 2,6-di-butyl-4-methyl pyrridine are dissolved in 5 ml of methylene chloride and added by injection to the reactor. The mixture is gently stirred by argon flow for 30 minutes and then the vessel is immersed in a cold bath allowed to cool to -60 ° C. Two equivalents (0.22 mmol) of triflic anhydride diluted 100 fold in methylene chloride are added slowly by decantation (approximately 15 minutes) to the reactor. The reaction is stirred gently for 1 hour. The solvent and unbound reagents are subsequently drained from the reactor and the resin mixture is washed repeatedly with methane followed by methylene chloride. Subsequently, the reaction mixture is suspended in 15 ml of methylene chloride and then treated with excess of Hg (0C0CF3) for 8 hours to split the glycosidic ligation of the resin (only five minutes are required to remove sufficient product from the resin to remove the resin). monitor the reaction by TLC analysis): The solvent is allowed to drain from the resin as above. The resin is then washed with additional solvent and combined by filtration, extracted three times with water and concentrated by evaporation. Silicon gel chromatography gives only the desired alpha-linked disaccharide. The thio-sugar X in Figure 7 is prepared from the corresponding glusamine readily available by treatment with the following reagents: (1) phthalic anhydride; (2) acetic anhydride; (3) tetrachlorotin-4-hydroxy thiophenol; (4) hydroxide; (5) benzaldehyde-H +; (6) NaH, under conditions "that are standard in the art, (see, section 6.15, below).

Sulfoxide Y in Figure 7 is made from paracetylated fucose by sequentially treating the starting material with BF3 / etherate-thiophenol, followed by hydroxide, followed by bezyl bromide, and * then with mCPBA. All these steps are normal and well known in the art. The disaccharide produced from the reaction of X and Y followed by treatment with Hg (0C0CF3) 2 (to remove it from the resin) is characterized by NMR of 1H. Relative data: CDC13) 5.6 ppm (apparent t, J = 7.6 Hz, Hl of phthalimide sugar C2), 3.35 ppm (d, J = 7.6 Hz, OH of lactol, phthalimido sugar after hydrolytic resin removal w / hg (II), 4.9 ppm (d, J = 2.8 Hz, Hl of fucose derivatives). 6. 12 SOLID PHASE S NTESIS OF S TRISACARIDE X DE LE IS The sodium salt of the glycosyl acceptor (X, Fig. 8) is bound to the Marrifield resin using the method (DMF, 80 ° C, 24 h) After using the general linking procedure described in detail in Example 6.10, the rehydroxide is suspended in 5 ml of methylene chloride. Four eq. of 2, 3, 4, 6-galactosyl pivaloylated sulfoxide and e & base equivalents (as above) are dissolved in 5 ml of methylene chloride. The reactive solution is then added to the resin, and the reaction mixture is cooled to -60 ° C. 2 equivalents of triflic anhydride diluted one hundred times (v / v) in methylene chloride are added.

After 30 minutes, the resin is "drained" and washed repeatedly with methylene chloride and methanol. The * resin is then suspended in 5 ml of methylene chloride and cooled to 0 ° C. % ml. Then a 1: 2 solution of trifluoroacetic acid / methylene chloride is added and the resin is stirred gently for 5 hours. The resin is then "drained" and rinsed several times with methylene chloride and methanol. Following a final rinse with anhydrous methylene chloride, the resin is suspended in 5 ml. of methylene chloride. 4 equivalents of triethylsilyl fucosyl Z 2, 3, 4-sulfoxide and 6 equivalents of the hindered base (ie, the one used above) are dissolved in 5 ml of methylene chloride and added to the resin. The reaction mixture is cooled to -60 ° C. 2 equivalents of triflic anhydride are diluted one hundred times in methylene chloride and slowly added by syringe to the reaction. After shaking gently for 30 minutes, the resin is "drained" and rinsed. The trisaccharide is then removed and isolated from the resin using Hg (OCOCF3) 2, as described above in Example 6.10. The thio-sugar X in Figure 8 is prepared from readily available glucosamine by treatment with (1) phthalic anhydride; (2) acetic anhydride; (3) tetrachlorotin-4-hydroxy thiophenol; (4) benzyl bromide; (5) hydroxide; (6) bezaldehyde-h +; (9) pivaloyl chloride; (10) hydrogenation, Pd (OH) 2; (11) NaH. Again all stages are standard, including the conditions for deprotection of the benzyl protecting group in the 4-hydroxy thiophenyl glycoside, which are typical for debenzylation. In the debinding stage, the splitting of the sugar to sulfide bond is not observed. Sulfoxide Y in Figure 8 is prepared by treating perpivoloylated galactose with BF3 / etherate-thiophenol, followed by mCPBA. The sulfoxide Z in Figure 8 is prepared by treating peracetylated fucose with BF3 / etherate-thiophenol, followed sequentially by hydroxide, triethylsilyl chloride and mCPBA. Similarly, other blood group sugars are easily synthesized, including but not limited to Lewis A and Lewis B. 6.13 ADDITIONAL EXPERIMENTS LEADED IN THE SOLID PHASE Referring to Figure 16, in particular, cesium fluoride (157.2 mg, 1.03 mmol, 1.1 eq.) And Merrifield resin (1 mol eq of Cl per gram) (1.0975 g, 1.10 mol, 1.1 eq) to a solution of 1 freshly prepared (803.5 mg, 0.94 mmol, 1.0 eq) in DMF (20 ml) The resulting suspension is shaken mechanically under an argon atmosphere at 60 ° C for 24 hours. The derived resin-sugar is then isolated by vacuum filtration and washed with DMF (3 x 10 ml) methanol (3 x 10 ml) and CH2C12 (5 x 10 ml) and dried under vacuum overnight to give the resin 2 (1.4738 g, mass, calculated in mass gain, 0.34 mmol / g).

IR (KBr disk) 1734 cm "1 (?, C = 0) JÉto Resin 2 is then washed with 10% trifluoroacetic acid in CH 2 Cl 12 (20 ml) to remove the protecting group. Subsequently, resin 3 is washed with CH2C12 (10 x 10 ml) and dried under vacuum overnight IR (KBr disk) 1734 cm "1 (?, C = 0), 1734 cm'1 (br,?, OH). To obtain resin 5, add 3 (95.4 mg) to the solution of sulfoxide 4 (122.1 mg, 0.156 mmol, 1.0 eq) and 2,6-di-tert-butyl-4-methyl-pyridine (98.2 mg, 0.468) mmol, 3.0 eq) in f CH3C12 (7.0 ml) and the suspension is cooled to -78 ° C. After 10 minutes, triflic anhydride (13.1 μl, 0.078 mmol, 0.5 eq) in CH2C12 (5 ml) is added dropwise over a period of 20 minutes. Ten minutes after finishing adding, the reaction is heated to -60 ° C in a period of 20 minutes. The reaction is quenched by the addition of NaHCO3. The resin is collected by suction filtration and washed with methanol (2 x 10 ml), water (1 x 10 ml) methanol (1 x 10 ml) and then CH2C12 (10 x 10 ml). The product resin 5 is then dried under vacuum overnight, after which the glycosylation is repeated. The product resin 6 is obtained as follows: the resin 5 (112.7 mg) is washed with 10% trifluoroacetic acid in CH2C12 (20 ml). It is then washed with CH2C12 (10 x 10 ml) and dried under vacuum overnight. The product resin 7 is obtained from resin 6 as follows: resin 6 (110.7 mg) is added to a solution of sulfoxide 4 (123.5 mg, 0.158 mmol, 1.0 eq.) And 2,6-di-tert-butyl- Jff 4-methyl-pyridine (99.3 mg, 0.474 mmol, 3.0 eq) in CH2C12 (7.0 ml) and the suspension was cooled to -78 ° C. After 10 minutes, triflic anhydride (13.3 μL, 0.79 mmol, 0.5 eq) in CH2C12 (5.0 mL) is added dropwise over a period of 20 minutes. Ten minutes after finishing adding, the reaction is heated to -60 ° C in a period of 20 minutes. The reaction is quenched by the addition of NaHCO3. The resin is isolated by filtration and washed with methanol (2 x 10 ml), water (1 x 10 ml), methanol (1 x 10 ml) and then CH2C12 (10 x 10 ml). The product resin 7 is then dried under vacuum overnight, after which the glycosylation is repeated. Finally, compound 8 is obtained from resin 7 as follows: resin 7 (113.6 mg) is washed with 10% trifluoroacetic acid in CH2C12 (20 ml). It is then washed with CH2C12 (10 x 10 ml) and suspended in pyridine (10 ml). Acetic anhydride (183.7 μl, 1.932 mmol, 1.0 eq) and 4-dimethyl-aminopyridine (4.7 mg, 0.039 mmol, 0.02 eq) are added to the suspension under argon. The mixture is stirred overnight and then quenched by the addition of methanol (200 μl). The resin is isolated with methanol and washed with methanol (2 x 10 ml) and CH 2 C 12 (10 x 10 ml). The free compound 8 is released from the resin by treating it with bis (trifluoroacetate) mercury (II) in wet methylene chloride, as described above, for example, for the synthesis of the disaccharide 13. (compound 8) XH NMR (500 MHz , CDC13) d 4.42 (d, J = 8. 06 Hz, Hj. "), 4.49 (d, J = 8. 06 Hz, H), 6. 27 (d, J = 3.67 Hz, HJ 13C NMR (69 MHz), CDC13) d 91. 6, 101. 0, 101. 3 (anomeric carbon atoms) 6.14 SYNTHESIS OF SOLID PHASE OF DISACCHARIDES 13 AND 16 According to the scheme of Figure 17, the residue 9 of phtha-protected N-acetyl glucosamine is bound to a solid support, as follows: Merrifield resin (1.4075 g, 1% covalent bond, chloromethylated styrene / divinylbenzene copolymer, approximately 1 mmol Cl / g, Aldrich is added. ) to a freshly prepared solution (1.42 g, 2.693 mol) in DFM (20 ml) .The suspension is mechanically shaken at 60 ° C under argon for 24 hours.The resin of the sugar derivative is isolated by fi ltration, washed with DFM (5 x 10 ml), methanol (3 x 10 ml) and CH2C12 (10 x 10 ml) and dried under vacuum overnight to give 1.7466 g of resin-attached 10. The level of the filler was calculated to be 0.414 mmol / g (based on mass gain) IR (KBr) 1670, 1716 cm "1 (? , C = 0); 3470 cm "1 (?, C = 0) Resin 10 is coupled to sulfoxide 11, a fucose unit, to give 12 (glycosidic bond), as follows: Compound 10 (218.4 mg) is added to the solution of sulfoxide 11 (204.1 mg, 0.3776 mmol, 1.0 eq) and 2,6-di. -ter-butylpyridine (236.7 mg, 1.127 mmol, 3.0 eq.) in CH2C12 (7.0 ml). The suspension is cooled to -60 ° C and after 10 minutes, triflic anhydride (31.7 μL, 0.1883 mmol, 0.5 eq) in CH2C12 (5 mL) is added dropwise over a period of 20 minutes. Ten minutes after finishing adding, the reaction is slowly heated to -30 ° C, and 30 minutes later, it is quenched by the addition of saturated aqueous sodium bicarbonate. The resin is isolated by filtration, washed with methanol (2 x 10 ml), water (2 x 10 ml) methanol (1 x 10 ml) and CH2C12 (10 x 10 ml) and dried in vacuo overnight to give 12 The final product 13 is obtained as follows: Hg (OCOCF3) 2 (120.5 mg, 0.2824 mmol) and water (a few drops) are added to a suspension of 12 (222.0 g) in CH2C12 (20 ml). After 5 hours the mixture is filtered through cotton. The filtrate is washed with saturated sodium bicarbonate, dried over Na 2 SO 4, filtered in concentrated in vacuo. The residue is purified by flash chromatography (35% EtOAC-pet ether) to give 33.9 mg of 13 (59% yield) as a colorless solid. This solid could be further purified by RP-HPLC (column C-18, 60 to 98% MeCN in water about 30 minutes), Tt15.7 minutes. E NMR (500 MHz, CDC13) d 4.81 (d, J = 3.66 Hz, Hl unit of fucose), 5.59 (d, J = 8.42 Hz, Hl unit of glucosamine). ^ NMR (69 MHz, CDC13) d 81.9, 93.3, 101.2 (anomeric carbon atoms). Similarly, the resin 10 can be coupled to a galactose unit, 14, to provide the resin 15 (β-glycosidic binding), as follows: compound is added (184.0 mg, 0.414 meq / g) to a solution of sulfoxide 14 (208.0 mg, 0.325 mmol) and 2.6, di-tert-butylpyridone (204.3 mg, 0.975 mmol) in CH2C12 (7 mL). The suspension is cooled to -60 ° C and Et after 10 minutes, a solution of triflic anhydride (31.7 μl, 0.1883 mmol, 0.5 eq) in CH2C12 (5 ml) is added dropwise in a period of 20 minutes. Ten minutes after finishing adding, the reaction is slowly heated to -30 ° C and after 10 minutes is quenched by the addition of saturated aqueous sodium bicarbonate. The resin is isolated by filtration and washed with methanol (2 x 10 ml), water (2 x 10 ml) methanol (10 ml) and CH2C12 (10 x 10 ml) and then vacuum dried overnight to give 15. obtain the best results, the glycosylation procedure is repeated. The product is removed from the resin using the Hg (II) reagent. Hg (OCOCF3) 2 (325.0 mg, 0.2824 mmol) and water (a few drops) are added to a suspension of 15 (222.0 g) in CH2C12 (20 ml). after 5 minutes the mixture is filtered through cotton. The filtrate is washed with saturated sodium bicarbonate, dried over Na 2 SO 4 / filtered and concentrated in vacuo. The residue is purified by flash chromatography (35% EtOAC pet ether) to give 19.4 mg of 16 (28% yield). This solid could be further purified by RP-HPLC (column C-18, 60-95% MeCN in water, about 30 minutes), Rt26.1 minutes. Hx NMR (500 MHz, CDC13) d 4.69 (d, J = 7.69 Hz, Hx of galactose residue), 5.32 (dd, J = 7.32, 8.8 Hz, E ± of glucosamine residue). E NMR (69 MHz, CDC13) d 93.5, 98.8, 101.7 (anomeric carbon atoms). 6. 15 REFERENCE TO WÍk STANDARDS Most of the above-mentioned transformations (protection: becylation, benzilidonation, acetone, esterification, and carbo- or silo-acidification of the sugars; deprotection: debenzylation, acid hydrolysis or benzylidenes, or acetonates, basic hydrolysis of esters, removal of silyl groups with fluoride under acidic conditions) are described in Binkley, R. Modern Carbohydrate Chemistry, Marcel Dekker, Inc.: New York. 1988. The methods to convert I lapels or anomeric esters to thiophenyl groups (to produce thiophenyl glucosides) are well-formed. See, for example, Ferrier et al. Carbohydr. Res. 1973, 27, 55; Mukaiyama et al. Chem. Lett. 1979, 70, 161, - Hanessian et al. Carbohydr. Res. 1980, 80, C17; Garegg et al. Carbohydr. Res. 1983, 116, 162; and Nicolaou et al. J Am. Chem. Soc. 1983, 105, 2430. Of the principles set forth herein, it should be apparent to one ordinarily skilled in the art that the ability to manipulate the reactivity of glycosyl donors and glycosyl acceptors, to control the order in which glycosylation takes place, can be exploited to synthesize many other oligosaccharides or glycoconjugates, quickly, efficiently and in high yield, under homogeneous conditions (in solution) or heterogeneous (in the solid phase).

Claims (5)

1. NOVELTY OF THE INVENTION Having described the present invention, it is considered as a novelty and, therefore, the content of the following is claimed as property: CLAIMS 1. - A method of forming regioselective glycosidic bonds in a single step comprising: (a) treating a first bifunctional glycoside (PG) in an organic solvent with an effective amount of an activating agent (AA), said PG (i) having a substituent of anomeric sulfoxide, and (ii) characteristics of glycosyl reception and glycosyl donation that are manifested in the presence of AA; and (b) allowing multiple glycosylation reactions to proceed such that two or more glycosidic linkages are formed in a single step.
2. 2. The method of claim 1 wherein said PG is treated with the AA in the presence of a second glycoside (SG) different from said PG, said SG being either a glycosyl acceptor or a glycosyl donor.
3. 3. The method of claim 2, wherein said SG is a glycosyl donor.
4. 4. The method of claim 2, wherein said SG is a glycosyl acceptor.
5. 5. The method of claim 4, wherein said three or more glycosides linked by two or more glycosidic ligands include the sequence SG- (PG) n in which n is an integer greater than or equal to 2. 6.- The method of claim 1 or 5, wherein more than one type of PG is present during the reaction, such that a portion of said three or more glycosides linked by three or more glycosidic linkages are comprised of different glycosidic residues. 7. - The method of claim 2, wherein said PG is treated with the AA in the presence of a third glycoside (TG) different from said PG, said SG, and said TG, said TG being either a glycosyl donor when said SG is a glycosyl acceptor or a glycosyl acceptor when said SG is a glycosyl donor. 8. The method of claim 7, wherein said TG is a glycosyl donor. 9. - The method of claim 7, wherein said TG is a glycosyl acceptor. 10. The method of claims 1, 2, 6, or 7, wherein approximately one-half of one equivalent or less of AA is used for each equivalent of PG present. 11. The method of claim 10, wherein a catalytic amount of AA is used. 12. The method of claim 7, wherein said PG, SG, TG are present in molar proportions in the range of about 1 to 20: about 1 to 20: about 1 to 20, respectively. 13. The method of claim 7, wherein said three or more glycosides combined by two or more glycosidic ligands include the sequence TG- (PG) n-SG or SG- (PG) n-TG in which n is an integer greater than or equal to 1. f 14. - The method of claim 13, wherein more than one type of PG is present during the reaction, such that said PG in any of said sequences is comprised of different glycosidic residues. 15. The method of claims 1, 2, 6, or 7, wherein the organic solvent is substantially anhydrous. 16. The method of claim 15, wherein the organic solvent is selected from the group consisting of a non-polar aromatic solvent, a cyclic aliphatic ether, an acyclic aliphatic ether, a halogenated aliphatic hydrocarbon, or an aliphatic nitrile. 17. The method of claim 10, wherein the triflic anhydride is used as the AA together with an effective amount of a scrubbing or scrubbing acid. 18. The method of claim 11, wherein said triflic anhydride is used as the AA together with an effective amount of a sulphonic acid scavenger. 19. The method of claim 1, wherein said PG derives its potential glycosyl acceptor characteristics from a glycosidic group that is free, or if blocked, can be unprotected in situ. 20. The method of claim 19, wherein said nucleophilic group is a hydroxyl group. 21. The method of claim 19, wherein said nucleophilic group is an amino group. 22. The method of claim 19, wherein said nucleophilic group is a sulfuryl group. 23. - The method of claim 4 or 9, wherein said SG or TG is bound at the anomeric carbon to a biologically active molecule. 24. The method of claim 23, wherein said biologically active molecule is selected from the group consisting of steroids, peptides, lipids, and polycyclic aromatic compounds. 25. The method of claim 23, wherein said biologically active molecule interacts with polynucleotides. 26. The method of claim 1, wherein said PG is comprised of 2-10 monosaccharide units. 27. A method of forming a glycosidic ligature in a single solid phase comprising: (a) exposing, in an organic solvent, a glycosyl acceptor (AG) ligature to a solid support to a glycoside (G) having a sulfoxide group activated anomeric, said AG having glycosyl reception characteristics and said G having glycosyl donation characteristics; and (b) allowing a multiple glycosylation reaction to proceed such that a glycosidic bond is formed which binds said AG to the anomeric carbon of said G. 28.- A method of forming a 1,2-transglycosylic ligand in a single solid phase comprising: (a) exposing, in an organic solvent, a glycosyl acceptor (AG) ligature bound to a solid support to a glycoside (G) having an activated anomeric sulfoxide group, and a neighbor participation group (GPV) in C-2, said AG having glycosyl acceptor characteristics and said G having glycosyl donor characteristics; and (b) allowing a multiple glycosylation reaction to proceed such that a glycosidic bond is formed which binds said AG to the anomeric carbon of said G, and which linkage is trans to said GPV. 29. The method of claim 28, wherein said GPV is a pivalyl group. 30. A method of forming a disaccharide in a solid phase comprising: (a) exposing, in an organic solvent, a first glycoside (Gl) linked to a solid support to a second glycoside (G2) having an activated anomeric sulfoxide group, said Gl having glycosyl acceptor characteristics and said G2 having glycosyl acceptor characteristics; (b) allowing a multiple glycosylation reaction to proceed such that a glycosidic linkage is formed, which binds said Gl to the anomeric carbon of said G2, to provide a disaccharide that is bound to the solid support and having a G1-ligation sequence G2 31. The method of claim 30, which is carried out in the presence of an effective amount of a scrubbing acid or sulfenic acid scavenger. 32. The method of claim 30, wherein said G2 possesses a nucleophilic group blocked by a temporary protective group (GPT). 33. The method of claim 32, further comprising: (c) removing said GPT to expose the glycosyl acceptor characteristics of G2, - (d) exposing the unprotected binding support disaccharide to a third glycoside (G3) having an activated anomeric sulfoxide group, said G3 has glycoside donor characteristics; (e) allowing a glycosylation reaction to proceed in such a way that a glycosidic ligation is formed, which binds said G2 to the anomeric carbon of said G3, to »Provide an oligosaccharide which is linked to the solid support and which has a sequence of G1-G2-G3. 34. The method of claim 33, wherein said G3 possesses a nucleophilic group blocked by a temporary protective group (GPT) and steps (c), (d) and (e) are repeated, unless a fourth glycoside, to provide an oligosaccharide that is linked to the solid support and has a sequence of G1-G2-G3-G4. 35. The method of claim 34, in which sequential glycosides are introduced to the growing oligosaccharide chain. 36. The method of claim 33, which further comprises intermediate washing steps. 37. The method of claim 30, 33, 34 or 35, wherein more than one type of Gl, G2, G3, G4 or subsequent glycosides are used to provide a glycosidic library comprising a mixture of several oligosaccharides. 38.- A chemical composition comprising: (i) a glycoside of the formula (I), which has potential characteristics of glycosyl acceptor and glycosyl donor, (I) F in which Xlf X2 or X3 can independently be a hydrogen, nitrogen, oxygen, or sulfur atom, - R 'and R4 can be an aromatic or aliphatic group comprising from 1-25 ^ carbon atoms; Rx, R2 or R3 each may independently be H, an aromatic or aliphatic group comprising from 1-25 carbon atoms, except that when * Xx, X2 or X3 is H, then the corresponding R17 R2 or R3 is not present , - said F aromatic or aliphatic groups of R ', Rx, R2, R3 or R4 optionally further comprise nitrogen, oxygen, phosphorus, silicon, or sulfur atoms; (ii) an activating agent capable of eliciting the manifestation of both glycosyl acceptor and glycosyl donor characteristics of said glycoside. 39.- A glycoside of the formula (II), which has potential characteristics of glycosyl acceptor and glycosyl donor wherein x, X2 or X3 independently can be a hydrogen, nitrogen, oxygen, or sulfur atom; R 'and R4 can be an aromatic or aliphatic group comprising from 1-25 carbon atoms; R1 # R2 or R3 each can be independently H, an aromatic or aliphatic group comprising from 1-25 carbon atoms, except that when Xx, X2 or X3 is H, then the corresponding Rx, R2 or R3 is not present; said aromatic or aliphatic groups of R ', R1 # R2, R3 or R4 optionally further comprise nitrogen, oxygen, phosphorus, silicon, or sulfur atoms; and with the proviso that when R3 is not H, the ligature R3-X3 is susceptible to ligation cleavage under the same conditions used to activate the anomeric sulphoxide group, thus allowing the manifestation of both glycosyl acceptor and donor characteristics. of glycosyl of said glycoside. 40.- A compound of formula (III), which has potential characteristics of glycosyl acceptor and glycosyl donor, in which n can be an integer greater than zero; X1 # X2 or X3 independently can be a hydrogen, nitrogen, oxygen, or sulfur atom; R 'and R4 can be an aromatic or aliphatic group comprising from 1-25 carbon atoms; Rx, R2 or R3 * each may be independently H, an aromatic or aliphatic group comprising from 1-25 carbon atoms, except that when Xlf X2 or X3 is H, then the corresponding Rx, R2 or R3 is not present; said aromatic or aliphatic groups of R ', Rj., R2, R3 or R4 optionally further comprise nitrogen, oxygen, phosphorus, silicon, or sulfur atoms, - and with the proviso that when R3 is not H, the ligation R3-X3 is susceptible to ligation cleavage under the same conditions used to activate the anomeric sulfoxide group, thus allowing the expression of both glycosyl acceptor and glycosyl donor characteristics of said glycoside. 41.- A glycosidic library comprising a mixture of oligosaccharides formed by the method of claims 1, 2, 5, 6, 13, 14, 26, or 35. 42.- The glycosidic library of claim 41, wherein said Oligosaccharide mixture includes homopolymers of varying lengths substantially comprised of the same glycoside units. 43.- The glycosidic library of claim 41, wherein said mixture of oligosaccharides includes a heteropolymer comprised of different glycoside units. 44. The glycosidic library of claim 44, wherein said mixture further includes heteropolymers of varying lengths. 45. The glycosidic library of claim 2 or 7, wherein more than one type of SG or TG is present during the reaction. 46. The method of claims 30, 33, 34 or 35, wherein said Gl, G2, G3, G4 or subsequent glycosides are comprised of mono-, di-, or polysaccharide residues are present during the reaction. 47. A catalytic method of forming a glycosidic linkage comprising: (a) providing a mixture comprising a glycosyl donor (DG), holding an anomeric sulphoxide group and a glycosyl acceptor (RG), having glycosyl acceptor characteristics, an organic solvent under anhydrous conditions, - (b) cooling said mixture below room temperature, - (c) adding to said mixture a catalytic amount of an activating agent (AA) effective to activate the said anomeric sulphoxide group (DG ); (d) allowing a catalytic reaction to proceed under conditions effective to provide for the formation of a glycosidic bond between said DG and said AG. 48. The method of claim 47, wherein said mixture further comprises a sulfenic acid scavenger (ADAS), said ADAS is effective to sequester any sulfenic acid formed in the course of said reaction. 49. The method of claim 47, wherein said cooling step includes cooling said mixture to a temperature below -30 ° C. 50.- The method of claim 47, wherein said cooling step includes cooling said mixture to -78 ° C. 51.- The method of claim 50, wherein the conditions of step (d) include letting the reaction heat up to -78 ° C. 52. The method of claim 47, wherein said mixture includes DG comprising a DG2-deoxy. 53. The method of claim 47, wherein said mixture includes AG that supports a nuceophilic group. 54. The method of claim 53, wherein said nucleophilic group comprises an unprotected hydroxyl group. 55. The method of claim 53, wherein said nucleophilic group comprises a blocked hydroxyl group. 56. The method of claim 55, wherein said blocked hydroxyl group is blocked by a silyl protecting group. 57. The method of claim 47, wherein said AG comprises triflic acid. 58. The method of claim 47, wherein said ADAS comprises excess of methyl propiolate. 59. A catalytic method of forming a glycosidic linkage comprising: (a) providing a mixture comprising a glycosyl donor (DG), supporting an anomeric sulfoxide group and a glycosyl acceptor (AG) having glycosyl acceptor characteristics, an organic solvent under anhydrous conditions, - (b) cooling said mixture below -30 ° C; (c) adding to said mixture a catalytic amount of an activating agent (AA) comprising triflic acid, effective to activate the anomeric sulphoxide group of said DG; (d) allowing a catalytic reaction to proceed under conditions effective to provide for the formation of a glycosidic bond between said DG and said AG. The method of claim 59, wherein said mixture further comprises an excess of sulfenic acid scavenger (ADAS) in said effective ADAS to sequester any sulfenic acid formed in the course of said reaction. 61.- The method of claim 59 wherein said mixture includes an AG that supports a nucleophilic group. 62. A catalytic method of forming a glycosidic linkage comprising: (a) providing a mixture comprising a glycosyl donor (DG), holding an anomeric sulfoxide group, and a glycosyl acceptor (GA) holding a nucleophilic group blocked by a group silyl protector, in an organic solvent under anhydrous conditions; (b) cooling said mixture to about -78 ° C; (c) adding to said mixture a catalytic amount of an activating agent (AA), comprising triflic acid, effective to activate the anomeric sulphoxide group of said (DG), - (d) allow a catalytic reaction to proceed under conditions effective to provide the formation of a glycosidic link between said DG and said AG. 63. - The method of claim 47, wherein said mixture includes an AG and a DG dissolved in the organic solvent. 64.- The method of claim 47, wherein said mixture includes a ligature of AG or DG to a solid resin. The method of claim 47, wherein said mixture includes a DG dissolved in the organic solvent and an AG bond to a solid resin. 67.- The method of claim 47, wherein said mixture includes a DG present in an equimolar amount relative to AG. The method of claim 47, wherein said mixture includes an AG present in an amount that is approximately 0.05 molar equivalents relative to AG. 69. The method of claim 47, wherein said mixture includes an ADAS present in an amount that is approximately 20 molar equivalents relative to AG. 70. The method of claim 47, wherein the organic solvent comprises methylene chloride. 71. The method of claim 59, wherein said mixture includes a DG comprising a DG 2 -deoxy. 72. - The method of claim 62, wherein said mixture includes a DG comprising a DG 2 -deoxy. 73. A library of glycosidic compounds comprising a mixture of oligosaccharides of varying sequence or length, each oligosaccharide of said mixture having at least one glycosidic linkage that is obtained through the activation and condensation of an anomeric sulfoxide donor glycosyl group. The library of claim 73 wherein said mixture comprises oligosaccharides of the formula A- (X) n, wherein n is an integer greater than or equal to zero, A represents a first terminal glycosidic residue, B represents a second terminal glycosidic residue and X represents an intermediate glycosidic residue between A and B. 75. - The library of claim 74 wherein n is. an integer greater than or equal to 1. 76. - The library of claim 75 wherein F X represents different intermediate glycosidic residues. 77.- The library of claim 73, 74, 75 or 76 wherein said mixture comprises glycoconjugates of said oligosaccharides. 78. An oligosaccharide comprising three or more glycosidic residues prepared by the method of clause 1, 27 28 or 30. 79. The oligosaccharide of claim 78, which is a Lewis blood group sugar. 80. The oligosaccharide of claim 79, which is selected from the group consisting of Lewis X, Lewis A or Lewis B. IN WITNESS WHEREOVER, I have signed the above description and novelty of the invention, as attorney of THE TRUSTEES OF PRINCETON UNIVERSITY, in Mexico City, on the 23rd day of February 1994. p.p. THE TRUSTEES OF PRINCETON UNIVERSITY