CHEMICAL COMPOUNDS

Abstract: The present invention relates to benzaldehyde derivatives which are useful as anticancer agents, antiviral agents, antibacterial agents, immunopotentiators and/or as agents which may be used for combating illnesses which arise due to an elevated cell proliferation and/or for combating auto immune diseases. Some of the compounds of this invention are novel per se.

Description: Chemical Compounds The present invention relates to benzaldehyde derivatives which are useful as anticancer agents, antiviral agents, immunopotentiators and/or as agents which may be used for combating illnesses which arise due to an elevated cell proliferation and/or for combating auto immune diseases. Some of the compounds of this invention are novel per se. Most of the presently used anticancer agents are cytotoxic in their action. Although these agents have shown good results in treatment of some cancers like lymphoma, leukaemia and testicular cancer, they often produce severe and unacceptable side-effects limiting the possibility for an effective treatment. Furthermore, in several types of cancer like in solid tumours (carcinoma), chemotherapy has so far proven to be of limited value since established cytostatic drug seldom improves the prognosis for the patient. The ability of cancer cells to develop resistance against cytotoxic products is also a main reason for the failure in their use in the treatment of solid tumours. There is thus a great need for new anticancer agents having fewer side effects and having a more selective action on malignant cells. It is known among other from EP-0215395, JP-63264411, JP-8800940, JP-55069510 and EP-0283139 that benzaldehydes and derivatives thereof exhibit a selective anticancer effect. Aldehydes react with a range of O, S or N nucleofilic entities like hydroxy groups, sulfhydryl groups and amino groups to form carbonyl condensation products like acetals, mercaptals, aminals, etc. However, with primary amines, the reaction normally take the form of Schiff s base (imine) adduct formation. It is well known that in vivo Schiff s base formation is involved in key biochemical processes like transamination, decarboxylation and other amino acid modifying reactions mediated by pyridoxal phosphate, the action of aldolase on fructose di-phosphate in the glycolysis and the condensation of retinal with rhodopsin in the process of vision. It is also known that carbonyl condensation reactions are involved in transmembrane signalling events, for example in generating an immune response. The formation of imines proceeds through a two-stage mechanism: The addition of the amino nucleofile to the carbonyl group to form a carbinolamine (aminohydrin) intermediate followed by a dehydration step to generate the C=N double bond. Both steps are reversible, but are facilitated at different pH values. As a consequence, the reaction occurs according to a characteristic bell-shaped pH/rate profile with the highest over-all reaction rates being found at moderate acidities. R— =N— R' + H 2 0 aldehyde amine carbinolamine imine However, the formation of Schiff s bases are known to take place readily also in physiological conditions, and many carbonyl condensation reactions are well known in vivo (E. Schauenstein et. al., Aldehydes in biological systems. London, Pion Ltd. 1977). The Schiff s base tend to be a reactive species itself and is prone to further reaction resulting in the addition of nucleofilic agents to the double bond. For certain sulfur-containing amines, in particular the amino acids cystein and methionine, and for glutathione, the initially formed Schiff s base can undergo reversible internal cyclization in which the sulfhydryl group adds to the imine to form thiazolidine carboxylate (M. Friedman, The chemistry and biochemistry of the sulfhydryl group in amino acids, peptides and proteins, Oxford, Pergamon Press, 1973). aldehyde cystein thiazolidine carboxylic acid Evidence for reactions between carbonyl compounds and free amino groups of proteins to form reversible Schiff s base linkages was reported by G. E. Means and R. E. Feeney 5 (Chemical Modification of Poteins, pp. 125 - 138, San Francisco, Holden-Day, 1971). Aromatic aldehydes are in general more reactive than saturated aliphatic aldehydes, and Schiff s bases can be formed even without removal of the water formed during the reaction. (R. W. Layer Chem. Rev. 63 (1963), 489 - 510). This fact is important when considering formation of Schiff s bases under physiological conditions. Using 10 haemoglobin as a source of amino groups Zaugg et. al. (J. Biol. Chem. 252 (1977), 8542 - 8548) have shown that aromatic aldehydes have a two- to threefold increased reactivity over aliphatic aldehydes in Schiff s base formation. An explanation for the limited reactivity of alkanals could be the fact that in aqueous solution at neutral pH a very large excess of free aldehyde is required to shift the equilibrium in favour of Schiff s base 15 formation (E. Schauenstein et. al., Aldehydes in biological systems. London, Pion Ltd. 1977). Benzaldehyde and salicylaldehyde readily form Schiff s base imines with membrane amino groups, and high equilibrium constants have been measured for benzaldehyde 20 reacting with amines (J. J. Pesek and J. H. Frost, Org. Magnet. Res. 8 (1976), 173 - 176; J. N. Williams Jr. and R. M. Jacobs Biochim Biophys Acta. 154, (1968) 323 - 331). With salicylaldehyde, the imine could achieve extra stabilisation due to hydrogen bonding between the lone-pair electrons of the imine nitrogen and the orto hydroxyl group (G. E. Means and R. E. Feeney, Chemical Modification of Poteins, pp. 125 - 138, San 25 Francisco, Holden-Day, 1971; J. M. Dornish and E. O. Pettersen Biochem. Pharmac. 39 (1990), 309 - 318). We have previously shown by radio labelling images that benzaldehyde do not enter the cell, but adhere to the cell membrane (Dornish, J.M. and Pettersen, E.O.: Cancer Letters 30 29 (1985) 235-243). This is in agreement with an earlier study, showing that benzaldehyde interacted with the membrane proteins of E. coli (K.Sakaguchi et. al. Agric. Biol. Chem., (1979), 43, 1775-1777). It was also found that pyridoxal and pyridoxal-5 -phosphate both protect the cells against the cytotoxic anti-cancer agent cis-DDP. Cis-DDP exerts its action in the nucleus within the cell. While pyridoxal in principle could penetrate the lipophilic cell membrane, this possibility is blocked for pyridoxal-5-phosphate because of the ionic phosphate group on the latter. Pyridoxal-5 -phosphate thus have to exert its protective effect by acting from outside the cell membrane. A spectral shift in the absorbance of pyridoxal-5-phosphate to lower wavelengths observed simultaneously is consistent with Schiff s base adduct formation between the aldehyde and cell membrane amino groups (J. M. Dornish and E. O. Pettersen, Cancer Lett. 29, (1985), 235 -243). These findings suggest that aldehydes bind to amines and other nucleofilic entities on the cell membrane to form Schiff s bases and other condensation products. It is known that stimulation of cell growth is mediated by a cascade of events acting from outside the cell membrane. In the same way, the derivatives in the present patent application may act by forming adducts with ligands on the cell membrane, triggering impulses inside the cell with significance on cell growth parameters like protein synthesis and mitosis, and on the expression of tumour suppressor genes and immune responses. Since the condensation reactions are reversible, cellular effects can be modulated as a result of a shift in equilibrium involving ligating species. The presence of dynamic equlibria at a chemical level is consistent with the reversible and non- toxic way of action observed with the benzaldehyde derivatives. Inhibition of the protein synthesis exerted by benzaldehyde derivatives is very well studied in vitro in our research group. In solid tumours the reduced protein synthesis may result in a lack of vital proteins which lead to cell death. In normal cells there is a potential capacity for protein synthesis which is higher than in most cancer cells of solid tumours. This is demonstrated by comparison of the cell cycle duration in normal stem cells, which is often below lOh, and thus shorter than that of most cancer cells of solid tumours, which is typically 30-150h (see Gustavo and Pileri in: The Cell Cycle and Cancer. Ed. : Baserga, Marcel Dekker Inc., N.Y. 1971, p 99). Since cells, as an average, double their protein during a cell cycle, this means that protein accumulation is higher in growth-stimulated normal cells than in most types of cancer cells. Keeping in mind this difference between normal and cancer cells, there is another difference of similar importance: while normal cells respond to growth-regulatory stimuli, cancer cells have reduced or no such response. Thus, while normal cells, under ordinary growth conditions, may have a reserve growth potential, cancer cells have little or no such reserve. If a protein synthesis inhibition is imposed continuously over a long period of time on normal cells as well as on cancer cells, the two different types of cells may respond differently: Normal tissue may make use of some of its reserve growth potential and thereby maintain normal cell production. Cancer tissue however, have little or no such reserve. At the same time the rate of protein accumulation in most cancer cells is rather low (i.e. protein synthesis is only slightly greater than protein degradation). Therefore the protein synthesis inhibition may be enough to render the tumour tissue imbalanced with respect to protein accumulation, giving as a result a negative balance for certain proteins. During continuous treatment for several days this will result in cell inactivation and necrosis in the tumour tissue while normal tissue is unharmed. To date, the most tested compound inducing reversible protein synthesis inhibition and displaying anti-cancer activity is 5, 6-benzylidene-dι -ascorbic acid [zilascorb( 2 H)]. The protein synthesis inhibiting activity of this prior art compound is described in detail by Pettersen etal. (Anticancer Res., vol. 11, pp. 1077-1082, 1991) and in EP-0283139. Zilascorb( 2 H) induces tumour necrosis in vivo in human tumour xenografts in nude mice (Pettersen et al., Br. J. Cancer, vol. 67, pp. 650-656, 1993). In addition to zilascorb( 2 H), the closest prior art compound related to cancer treatment is 4,6-O-Benzylidene-D-glucopyranose (Compound 1) . These two compounds are known to possess a general anti-cancer activity and have been tested in clinical trials against a number of cancer diseases. However, no particular cancer afflicted organs or tissues projected as more suitable for treatment with these compounds, and commercial development was not justified. We have now surprisingly found that benzaldehyde derivatives of sugars of the hexose type, (including 4,6-O-(Benzylidene-dι)-D-glucopyranose, Compound 2) give an unexpected strong effect on cancer in certain organs or tissues. We cannot yet explain the mechanism for this selectivity, but we believe that this is connected to the affinity of the sugar moiety of the derivatives to certain cells or tissues. We have found that certain of our new products like for instance Compound 8, (2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose) gives an unexpected good effect in a nude mice model (see Example 3, Table 1). 3 of 8 mice were free of tumours, which is an unusual result in similar experiments on immunosupressed species. The reason for this effect could be that the acetamido moiety has a high affinity to hyaluronic acid receptors. It is known that malignant tumours are rich on hyaluronic acid and hence rich on corresponding receptors. We have also found in our experiments that the deuterated analogue of these compounds are substantially more effective than the corresponding proton analogues. This difference in effect is very striking in our experiment on cell adhesion (see Example 5 and also Example 8). When a hydrogen atom is substituted by the twice as heavy deuterium isotope, the kinetic properties of the molecule are altered as the rate in breaking the C-D bond is lowered compared to breaking the C-H bond. It is known among others from M.I. Blake et.al., J. Pharm. Sci. 64 (1975), 367-391 that deuteration of drugs may alter their pharmacological function. It is also known in the art (EP 0 283 139 and Anticancer Res. 15: 1921-1928 (1995)) that when the acetal proton in 4,6-O-benzylidene-D-glucopyranose is substituted with deuterium (Compound 1 versus Compound 2), this can affect both the protein synthesis and the cell surviving fraction measured in vitro. We believe that one possible explanation for this D-isotope effect at a chemical level is related to slower oxidation of deuterated benzaldehyde to inactive benzoic acid, resulting in a longer half-life of the deuterated active ingredient at a cellular level. However, to demonstrate a significant difference in the surviving fraction of NHIK 3025 cells exposed to Compounds 1 resp. 2, drug concentrations of more than 6 mM must be applied. The difference in protein synthesis inhibition was very small when these cells were exposed at 1-10 mM concentration. The inventors now performed a completely different kind of experiment: The adhesion force between NHIK 3025 cells and the substratum was measured after pre-incubation of the cells in solutions of Compounds 1 and 2 (see Example 5). Even at 1 mM concentration, an astonishing D-isotope effect was shown. Surprisingly, Compound 2 significantly reduced the adhesion force to 1/3 relative to control, whereas Compound 1 did not lead to significant reduction. The inventors believe that Compound 2 may have interfered with the biosynthesis of integrins, reducing the cell's ability to attach to the substratum. Integrins are structural trans-membrane proteins crucial for binding cells to the extracellular matrix and for cell-cell interactions. Inhibiting the function of the integrins could thus directly affect the metastasising ability of cancer cells. The experiment indicate that integrines could be especially sensitive to protein synthesis inhibition. Thus, Compound 2 could well be used for prevention of metastatic processes in cancer development. The chemical induced carcinogenesis has a similar mechanism as the cancerogenesis induced by certain virus types like hepatitis B and C, certain papilloma virus, certain herpes virus etc. Especially this will be the case in the development of liver cancer in hepatitis B and C infected patients. It is therefore presumable that a prophylactic treatment of these patients with products of this invention could prevent or delay the development of liver cancer. Also the fact that these products show a low toxic profile would make them suitable for such a treatment. It is known from UK Patent application 9026080.3 that benzaldehyde compounds, previously known as anti cancer agents may be used for combating diseases resulting from an abnormally elevated cell proliferation. Such compounds also exert an effect on cells having an abnormally elevated cellular proliferation rate, and accordingly the compounds may be used for treatment of diseases such as psoriasis, inflammatory diseases, rheumatic diseases and other auto immune disorders like Ulcerous colitt and Morbus Crohn, and allergic dermatologic reactions. Dermatologic abnormalities such as psoriasis are often characterised by rapid turnover of epidermis. While normal skin produces about 1250 new cells/day/cm 2 of skin consisting of about 27,000 cells, psoriatic skin produces 35,000 new cells/day/cm 2 from 52,000 cells. The cells involved in these diseases are however "normal" cells reproducing rapidly and repeatedly by cell division. While the renewal of normal skin cells takes approximately 311 hours, this process is elevated to take about 10 to 36 hours for psoriatic skin. Today psoriasis, inflammatory diseases, rheumatic diseases and other auto immune disorders are treated with corticosteorids, NSAIDs and in serious cases, with immunosupressive agents like cytostatica and cyclosporins. All these drugs can give serious side-effects. It is thus a great need for products giving less side-effects. It is known that aromatic aldehydes and certain acetal derivatives thereof have a growth-inhibitory effect on human cells which is by its nature reversible. Growth inhibition induced by these compounds is primarily due to a reduction in the protein synthesis by cells. (Pettersen et al., Eur.J. Clin. Oncol., vol. 19, pp. 935-940, 1983 and Cancer Res., vol. 45, pp. 2085-2091, 1985). The inhibition of protein synthesis is only effective as long as these agents are present in the cellular microenvironment. The synthesis of cellular protein is, for instance, rapidly restored to its normal level following removal of the agent from the cells (i.e. within 1 h in most cases). This leads to the effect that the normal cells are left without damage after treatment with the above compounds. The ability of cells to transmit signals via cell-contact ( adhesion ) dependent mechanisms has been studies over many years. These mechanisms are especially important for the reactivity of circulating cells like lymphocytes, macrophages etc., and also for instance for methastatic cells to be anchored in tissues to establish new tumours. The possibility to alter the adhesion characteristic of cells which are monitoring the immune or inflammatory response might be of great therapeutic value for the treatment of many diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus erythematosis, acne, Bechterew's arthritis, progressive systemic sclerosis (PSS), seborrhea and other auto immunic disorders like Ulcerous colitt and Morbus Crohn. The immune system is carefully designed to identify and eliminate any material recognised as non-self, whether it originates from a bacteria-, virus- or protozoal infection, or abnormal cells like cancer. In order to provide a specific response to the huge range of biotic variation represented by the invaders, the immune system has to be highly diversified. However, over- stimulation of this finely tuned system can lead to various allergic- and inflammatoric reactions and cause auto-immune diseases. The rejection of beneficial transplants is also difficult to overcome. It is therefore a big therapeutic challenge to modulate the immune system, either by up-regulating or down-regulating a specific response. In an immunological recognition process, a fragment of a foreign protein is confined in the groove of the class II MHC protein on the surface of an antigen presenting cell (APC). Attached to this MHC-antibody complex is also the receptor of a T helper cell. To activate a T helper cell, at least two signals must be provided: The primary signal is mediated by the antigen itself, via the class II MHC complex and augmented by CD4 co-receptors. The second signal can be provided by a specific plasma-membrane bound signalling molecule on the surface of the APC. A matching co-receptor protein is located on the surface of the T-helper cell. Both signals are needed for the T-cells to be activated. When activated, they will stimulate their own proliferation by secreting interleukin growth factors and synthesising matching cell-surface receptors. The binding of interleukins to these receptors then directly stimulates the T-cells to proliferate. In the 1980'ties, it was recognised that a cyclodextrin benzaldehyde inclusion complex could stimulate the immune system by augmentation of the lymphokine activated killer cells in a murine model (Y. Kuroki et. al., J. Cancer Res. Clin. Oncol. 117, (1991), 109 - 114). Studies made in vitro have later revealed the nature of the chemical reactions at the APC-donor/T-cell receptor interaction site responsible for the second co-stimulatory signal, and that these take form of carbonyl-amino condensations (Schiff s base formation). Moreover, these interactions can be mimiced by synthetic chemical entities. These findings open up for new therapeutic opportunities for artificially potentiating the immune system. In WO 94/07479 use of certain aldehydes and ketons which forms Schiff s bases and hydrazones with T-cell surface amino groups are claimed. In EP 0609606 Al the preferred immuno stimulating substance is 4-(2-formyl-3-hydroxyphenoxymethyl) benzoic acid (Tucaresol), a compound originally designed to cure sickle cell anaemia. This substance is administered orally and is systemically bioavailable. The potential of Tucaresol in curing a number of diseases including bacteria-, virus- and protozoal infections, auto-immune related illness and cancer is presently being investigated (H.Chen and J. Rhodes, J.Mol.Med (1996) 74:497-504) and combinational strategies where Tucaresol is administered together with a vaccine to cure chronic hepatitis B, HIV and malignant melanoma are currently under development. By measuring immuno parameters in vitro, and assessing effects in vivo, a bell shaped dose/response profile was revealed (H.Chen and J. Rhodes, J.Mol.Med (1996) 74:497-504). This otherwise somewhat unusual dose/response relationship can be justified by assuming that at high concentration of the aldehyde drug will saturate the co-stimulatory ligands necessary for the effective binding of APC to the T-cell and therefor will be inhibitory. A dose sufficient for achieving a dynamic equilibrium providing co-stimulation without blocking intercellulary ligating, seems to be optimal. In general, aldehydes are intrinsically unstable due to oxidation. 4-(2-Formyl-3-hydroxyphenoxymethyl) benzoic acid (Tucaresol) which is disclosed in EP-0609606, is considerably more potent in vivo than in vitro. This may be because of the drug's susceptibility to oxidation in aqueous solutions in vitro (H.Chen and J. Rhodes, J.Mol.Med (1996) 74:497-504). Many aldehydes are too reactive to be administered as such, and benzaldehyde, even proven to be an active anti cancer drug in vitro, is highly irritating and unsuitable for direct in vivo application. In a biotic system, the aldehyde carbonyl group will react rapidly with nucleofilic entities predominantly present in all body fluids. These unwanted by-reactions could lead to fast drug metabolisation and difficulty in controlling serum level of the active drug. Controlling the drug at a cellular level within a narrow concentration window is crucial for achieving an effective immune potentiation. Tucaresol is orally administered as an unprotected aldehyde, and one might suspect drug deterioration and difficulties in controlling pharmacokinetics. The benzaldehyde derivatives 4,6-benzylidene-D-glucose and the deuterated analogue (Compound 1 and 2) have proven to possess high bioavailability either administered i.v. or per oz. Bioavailability measured as serum level after oral administration of Compound 2 to BALB mice was 93-99% (CB. Dunsaed, J.M. Dornish and E.O. Pettersen, Cancer Chemother. Pharmacol. (1995) 35: 464-470). Moreover, the glucose moiety can possess affinity to receptors present at the cell surface, thereby improving drug availability at a cellular level. The free aldehyde can easily be released by hydrolysis of the acetal, making the carbonyl group available for Schiff s base formation at the target ligands. In the present patent application, the aldehydes are derivatised with biologically acceptable carbohydrates like glucose, galactose and others to form acetals. The sugar moiety will thus contribute by improving stability and enhancing bioavailability of the aldehyde function to the target cells. This surprisingly leads to more effective carbonyl condensation reactions and easier controllable pharmacokinetics by using our compounds as compared with previously known compounds. In order to compare Compound 2 with Tucaresol, cell inactivation and protein synthesis inhibition were measured in the presence of equal concentrations of the two drugs. As can be seen from Fig. 4 and Fig. 5, it was shown that Compound 2 was more effective than Tucaresol with respect to both measured parameters. The immune stimulating effect of the invented compounds may also be used in the treatment of certain virus diseases in combination with other anti-viral therapy like anti-viral drugs or vaccines. Many virus types, after the first infection, incorporate with the cell nucleus and are inactive for a long period of time. Oncogenic viruses like hepatitis B and C, certain retro virus and certain papilloma virus may cause development of cancer. In these latent period it is very difficult to cure the virus infection. These viruses can often be triggered by immune responses to cause viremia, and in this stage make it possible to get rid of the virus infection. The ability of the benzaldehyde derivatives to trigger the immune response may be used in combination with antivirals or vaccines to develop a treatment for these diseases. It is a main object of the invention to provide new compounds for prophylaxis and/or treatment of cancer and disorders related to the immune system. Another object of the invention is to provide new compounds being able to potentiate immune responses giving a possibility to combat infectious diseases caused by virus, bacteria, fungus and other micro organisms. A third object of the invention is to provide compounds for prophylaxis or treatment of cancer and diseases related to immune disorders not giving toxic side-effects. A fourth object of the invention is to provide compounds for prophylactic treatment to prevent the development of liver cancer in persons with Hepatitis B or C infection. A fifth object of the invention is to provide compounds for effective and favourable prophylaxis and/or treatment of cancer in tissues and cells having receptors with affinity to corresponding sugar moieties. A sixth object of the invention is to provide compounds for treatment of diseases related to the immune system like psoriasis, bowel inflammations, arthritis, SLE, PSS etc. These and other objects by the invention are achieved by the attached claims. The compounds of the present invention have the general formula (I): (I) wherein L is H or D; Ar is phenyl or substituted phenyl with 1-3 substituents, the substituents which are the same or different, are selected from the group comprising alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms, phenyl, halogen, nitro, cyano, NH 2 , NHR 1 , N(R') 2 , NHC(O)R' or N[C(O)R'] 2 wherein R 1 which is the same or different, is alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms, OR 2 or OC(O)R 2 wherein R 2 is H, D, alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms, SR 2 , CA(OR 1 ) 2 or CA[OC(O)R'] 2 wherein A is H or D, C(O)R 2 , COOR 3 wherein R 3 is H or alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms or CON(R 3 ) 2 wherein R 3 is the same or different; Y is selected from the atoms or groups comprising H, D, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms, fluoro, chloro, nitro, OR 2 , OC(O)R 2 , SR 2 , NH 2 , NHR 1 , N(R ] ) 2 wherein R 1 is the same or different, NHC(O)R' or N[C(O)R'] 2 wherein R 1 is the same or different; R is H, D, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms, or a pharmaceutical acceptable salt thereof. It is understood that any stereoisomer according to formula (I) is comprised in the present invention. Compounds 5, 6, 1, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (see table on page 18-21) are new per se. Detailed description of the invention The invention is further explained below by examples and attached figures and tables. Description of the figures Fig. 1: The data represent an experiment where NHIK 3025-cells were treated with Compound 8 (O) or Compound 9 (•) for 20 hours at 37°C while attached to plastic Petri dishes. Surviving fraction means fraction of cells able to form a macroscopic colony following treatment. Each point represents the mean value of colony counts from 5 parallel dishes. The standard errors are smaller than the size of the symbols. Fig. 2: The data represent an experiment where NHIK 3025-cells were treated with Compound 5 (O) or Compound 7 (*) for 20 hours at 37 °C while attached to plastic Petri dishes. Surviving fraction means fraction of cells able to form a macroscopic colony following treatment. Each point represents the mean value of colony counts from 5 parallel dishes. Vertical bars indicate standard errors and are shown when exceeding the symbols. Fig. 3: The data represent an experiment where NHIK 3025-cells were treated with Compound 12 (■) for 20 hours at 37°C while attached to plastic Petri dishes. Surviving fraction means fraction of cells able to form a macroscopic colony following treatment. Each point represents the mean value of colony counts from 5 parallel dishes. Vertical bars indicate standard errors and are shown when exceeding the symbols. Fig. 4: The data represents an experiment where NHIK 3025-cells were treated with Compound 2 (Δ) or Tucaresol (•) for 20 hours at 37°C while attached to plastic Petri dishes. Surviving fraction means fraction of cells able to form a macroscopic colony following treatment. Each point represents the mean value of colony counts from 5 parallell dishes. The standard errors are shown when exceeding the size of the symbols. Fig. 5: The rate of protein synthesis relative to untreated control of NHIK 3025-cells treated with Compound 2 (■) or Tucaresol (A) for 1 hour at 37°C. The rate of protein synthesis was measuered by amount of [ 3 H]-valine incorporated during the first hour after start of drug treatment. Protein synthesis rate was measured relative to the total amount of protein in the cells. Data are representative for one experiment performed in quadruplicate. Standard errors are indicated when exceeding the size of the symbols. Fig. 6: Mean tumour growth curves of tumour line SK-OV-3 ovarian carcinoma xenograft implanted in nude mice are shown. Mice were treated daily i.v. with 1 mg/kg Compound 8 (T) and 7.5 mg/kg Compound 8 (A). ■, Control group received 0.9% NaCl. Each data point represents the mean tumour volume of 4 to 5 mice related to the tumour volume at day 1. Vertical bars represent standard error. Fig. 7-12 show morphologic appearance of SK-OV-3 tomours from each of the following 3 groups: The placebo-treated group of animals (figures 7 and 8), the group treated with 1 mg/kg/day of Compound 8 (figures 9 and 10) and the group treated with 7.5 mg/kg/day (figures 11 and 12). Tumours were fixed in formalin, embedded in paraffin, sliced in 6 mm slices and stained with haematoxylin and eosin. Magnification is 40 times. Fig. 13: Mean spheroide volume growth curves of cell line T-47D breast carcinoma are shown. The spheroids were treated with 0.1 mM Compound 8 (A) and 1.0 mM Compound 8 (T) dissolved in medium. ■ ,Control. Each data point represents the mean spheroid volume of 6 to 11 spheroids. Vertical bars represent standard error. Fig. 14 shows microscopic photographs of sections of 3 differently treated NHIK 3025 cell spheroids, one untreated control (A), one treated with 0.1 mM Compound 8 for 4 days (B) and one treated with 1.0 mM Compound 8 for 4 days (C). Fig. 15-18: The data show the fraction of nuclei within each of the interphase stages, Gl, S and G2, having the RB-protein bound in the nucleus following treatment with Compound 8. Fig. 19-20: Rate of protein synthesis relative to that of control cells for NHIK 3025 cells (figure 19) and T-47D-cells (figure 20). Each point represent the mean of measurements from 4 parallell samples. Standard errors are indicated by vertical bars when exceeding the symbols. Fig. 21: Median adhesion forces for cells exposed to different benzaldehyde derivatives. The cells were exposed to a 1 mM concentration of Compounds 1 and 2. Fig. 22: Peripheral blood mononuclear cells and Superantigen in Ex Vivo 10 medium were exposed to either benzaldehyde, deuterated benzaldehyde, Compound 2 or zilascorb( 2 H). The proliferation of peripheral blood mononuclear cells was measured as incorporation of tritiated thymidine at different drug concentrations. Fig. 23: NMRI mice were infected i.p. with spleen invading Friend erythroleukemia virus. Infected- and uninfected mice were treated i.p. daily with 5 mg/kg of either Compound 2 or Compound 5. After treatment for 19 days, spleens were dissected out and weighted. Fig. 24: The effect of Compound 1 , 2 and 5 on the liver invasion of human colorectal tumour, C170HM2 is shown. Fig. 25: Cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (O) or Compound 13 (•) is shown. Fig. 26: Cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (O) or Compound 14 (•) is shown. Fig. 27: Rate of protein synthesis of human cervix carcinoma cells, NHIK 3025, treated with Compound 1 or Compound 21 as measured by amount of incorporated [ 3 H]-valine during a pulse period of lh starting either immediately following addition of test compound (closed symbols) or starting 2h later (open symbols). Fig. 28: Rate of protein synthesis of human cervix carcinoma cells, NHIK 3025, treated with Compound 2 or Compound 22 as measured by amount of incoφorated [ 3 H]-valine during a pulse period of lh starting either immediately following addition of test compound (closed symbols) or starting 2h later (open symbols). Fig. 29: Cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (•) or Compound 21 (O) is shown. Fig. 30: Cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 2 (O) or Compound 22 (A) is shown. Fig. 31: Cell survival as measured by colony-forming ability for human breast carcinoma cells, T47-D, after treatment for 20h with either L-glucose (•) or Compound 21 (O) is shown. Fig. 32: Airway responsiveness 24 hours after exposure to aerosolized methacholine in ovalbumin-sensitized mice challenged with saline (open bars and horizontally striped bars) or ovalbumin (solid bars and vertically striped bars) and treated with solvent solution or Compound 2. Results are expressed as arithmetic average ±SEM (n=9 per group). Fig. 33: Number of neutrophil cells recovered 24 hours after the last saline (open bars) or ovalbumin (solid bars) challenge in broncho-alveolar fluid of ovalbumin-sensitized mice, treated with solvent solution or Compound 2. Results are presented as arithmetic average ±SEM (n=9 per group). Preparation As is well known, aldehydes undergo acid facilitated condensation reactions with alcohols to generate acetals. Water is concomitantly formed as a co-product. The reaction is reversible, and in solution, an equilibrium mixture of aldehyde/alcohol and acetal/water is formed. The position of the equilibrium will mainly be determined by the reactivity and concentration of each species. In order to force the reaction towards completion, one of the products (acetal or water), is normally removed from the reaction mixture. In the present patent application, various sugars, deoxysugars and aminosugars are condensed with aldehydes or aldehyde equivalents to form suger-acetal derivatives. Particularly preferred is a re-acetalisation strategy, where the aldehyde protected as its dimethyl acetal is used instead of the aldehyde itself. Methanol is then formed as co-product. The reaction mixture is moderately heated at reduced pressure to remove the methanol once it is formed. In most cases, these reaction conditions will drive the equilibrium smoothly in favour of the acetal. Acetalisation of sugars will normally lead to mixtures of regio- and stereo isomers. Ring contraction transformations may also occur, leading to mixtures of pyranoses and furanoses, and, in some cases, di-acetalisation adducts are formed. As a consequence, unless protection strategies are applied, very complex reaction mixtures are often encountered. However, surprisingly pure product fractions were prepared following appropriate work-up, especially by using liquid chromatography. Identification of the products were achieved by using GC-MS-spectroscopy and various NMR techniques. The specific reaction conditions, solvent and catalyst used will in each individual case depend on the solubility and reactivity of the reactants and of the properties of the product. The catalyst may be a mineral acid, e.g. sulphuric acid, an organic acid, e.g. pαrα-toluene sulfonic acid, an acidic ion exchanger resin, e.g. Amberlyst 15, a Lewis acid mineral clay, e.g. Montmorillonite K-10 or a resin supported super acid, e.g. Nafion NR 50. The reaction may conveniently be carried out in a dipolar, aprotic solvent such as dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl pyrrolidone, dimethoxyetane or the like. Rαrα-toluene sulfonic acid in dimethyl formamide constituted the preferred and most applied reaction condition. The compounds of formula (I) wherein L is deuterium may be prepared as described above, but starting with the dimethyl acetal of an aldehyde which is deuterated in the formyl position. The preparation of deutero-benzaldehyde may be performed by a modified Rosenmund reduction using D 2 gas in a deuterated solved, as described in EP 0 283 139 Bl. Deuterated benzaldehyde derivatives with substituents in the phenyl ring may be prepared according to examples given in EP 0 493 883 Al and EP 0 552 880 Al. The following examples are illustrative of how the compounds of the present invention may be prepared. Compound 1 : 4.6-O-Benzylidene-D-glucopyranose This prior art compound was prepared as described for compound 2, starting with undeuterated benzaldehyde dimefhylacetal. The identity was confirmed by 'H NMR spectroscopy in DMSO-d 6 : δ rel. to TMS: 7.58-7.29 (5H, m, Ar-H), 6.83 (0.4H, d, OH-l-β), 6.60 (0.6H, d, OH-l-α), 5.61 (IH, s+s, acetal-H), 5.25 (0.4H, d, OH-3-β), 5.21 (0.4H, d, OH-2-β), 5.62 (0.6H, d, OH-3-α), 5.00 (0.6H, H-l-α), 4.82 (0.6H, d, OH-2-α), 4.49 (0.4H, t, H-l-β), 4.18-4.02 (IH, m, H-6'-α+β), 3.89-3.77 (0.6H, m, H-5-α), 3.75-3.57 (1.6H, m, H-6"-α+β and H-3-α), 3.45-3.27 (2.5H, m, H-3-β, H-4-α+β, H-5-β and H-2-α) and 3.11-3.00 (0.4H, m, H-2-β). Compound 2: 4.6-O-(Benzylidene-dι)-D-glucopyranose Benzaldehyde-di was prepared and converted to benzaldehyde dimethylacetal-di as described in EP 0 283 139 Bl. The preparation of 4,6-O-(benzylidene-dι)-D-glucopyranose is also described in EP 0 283 139 Bl, but the compound was this time prepared according to an alternative procedure with priority given to achieving high purity: D(+)-Glucose (706 g, 3.92 mol), benzaldehyde dimethylacetal-d, (571 g, 3.73 mol), dry DMF (1.68 kg) and pαrα-toluene sulfonic acid (4.5 g, 24 mmol) were mixed in a dry distillation apparatus connected to a vacuum pump through a cold reflux condenser. The mechanical stirred mixture was warmed to max. 69°C at 30 Torr to distil off methanol and after 2 hours, 235 g was collected. The reflux condenser was then shut off and the temperature increased to max 73°C in order to distil off DMF. After 2 more hours, an additional amount of 1385 g was collected and the distillation interrupted. The residue was cooled to approx. 40°C and ice/water (2.9 L) added within 5 min. The temperature dropped below 0°C and a precipitate was formed, partly as big lumps. The mixture was transferred to a beaker and additional 8-9 L ice/water added in order to make the lumps fell apart and form a suspension. The suspension was filtered on two notches and the two filter cakes left over night on the filters with water jet vacuum connected, each filter cake being flushed with N 2 via an inverted funnel. The filter cakes were spread on two boards and dried at 32°C for 20 hours in a vacuum oven. The vacuum was first set at 13 mbar, then regulated down to 1 mbar. The crude product was recrystallised (in order to remove di-benzylidene acetals) and water-washed (to remove DMF and glucose) until these contaminants were eliminated. Accordingly, the crude product (500 g) was dissolved in hot dioxane (800 ml) and the solution added via a folded filter to boiling chloroform (9 L). The solution was allowed to cool, first to ambient temperature, then in an ice bath overnight. The precipitate was filtered off, dried for 2 hours on the filter (flushing with N 2 as described previously) and dried further overnight at 31°C in vacuo on a rotavapor. The product (142 g) was suspended in ice/water (1 L), filtered on a nutch (washing with 200 ml ice/water) and dried on the filter overnight as described previously. It was then grounded, sieved (0.5 mm grid size) and dried in vacuo for 5 hours at 31 °C on a rotavapor. The product (96 g) once again was suspended in ice/water (500 ml), filtered (washing with 150 ml ice/water) and dried (7 hours under N 2 flush). It was finally grounded on a mortar, sieved (0.5 mm) and dried in a vacuum oven. The product was a white, finely divided powder of high purity, as analysed on HPLC. The yield was 95 g, 10% of the theoretical. NMR in DMSO-d 6 indicated an α to β anomeric ratio of approx. 7:3. Η- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 7.55-7.28 (5.00H, m, Ar-H), 6.85 (0.27H, d, OH-l-β), 6.58 (0.71H, d, OH-l-α), 5.24 (0.27H, d, OH-3-β), 5.19 (0.28H, d, OH-2-β), 5.61 (0.71H, d, OH-3-α), 4.99 (0.72H, H-l-α), 4.82 (0.71H, d, OH-2-α), 4.48 (0.29H, t, H-l-β), 4.20-4.04 (1.04H, m, H-6'-α+β), 3.88-3.73 (0.78H, m, H-5-α), 3.73-3.56 (1.72H, m, H-6"-α+β and H-3-α), 3.46-3.21 (2.61H, m, H-3-b, H-4-α+β, H-5-β and H-2-α) and 3.09-2.99 (0.28H, m, H-2-β); 137.881, 128.854, 128.042, 126.435 (Ar-C), 100.462 (acetal-C), 97.642 (C-l-β), 93.211 (C-l-α), 81.729 (C-4-α), 80.897 (C-4-β), 75.796 (C-2-β), 72.906 (C-2-α and C-3-β), 69.701 (C-3-α), 68.431 (C-6-α), 68.055 (C-6-β), 65.810 (C-5-β) and 62.032 (C-5-α). Compound 3: 4.6-O-Benzylidene-D-galactopyranose D(+) Galactose (15.0 g, 0.083 mol) and dry DMF (80 ml) were mixed with stirring at 50°C in a distillation apparatus. To the suspension thus formed, benzaldehyde dimethylacetal (12.2 g, 0.083 mol) and pαrα-toluene sulfonic acid (0.14 g) were added and methanol/DMF slowly distilled off with a water jet. After 3 hours, most of the galactose was consumed and the remaining DMF removed on a rotavapor connected to a vacuum pump. The residue, which formed a very viscous syrup, was purified on a Lobar C RP-8 column eluting with methanol/water 1:1. The product fractions were freeze dried. GC of the TMS derivatives showed the product to consist mainly of two isomers. On the basis of 'H-, 13 C-, COSY-, DEPT- and C-H correlation NMR spectra, the product was identified as the α and β anomers of the title compound. Η- and 13 C NMR (D 2 O), δ rel. to TMS: 7.49-7.27 (5H, m, Ar-H), 5.57 (IH, s, acetal-H), 5.22 (0.5H, d, H-l-α), 4.56 (0.5H, d, H-l-β), 4.23+4.18 (0.5H+0.5H, d+d, H-4-α+β), 4.14-3.98 (2H, m, H-6-α+β), 3.94-3.79 (1.5H, m, H-2-α, H-3-α and H-5-α), 3.69-3.49 (1.5H, m, H-2-β, H-3-β and H-5-β); 137.422, 129.981, 128.902, 126.639 and 126.590 (Ar-C), 101.325 (acetal-C), 96.540 (C-l-β), 93.161 (C-l-α), 76.581 (C-4-α), 76.093 (C-4-β), 71.889 + 71.802 (C-2-β+C-3-β), 69.404 (C-6-α), 69.182 (C-6-β), 68.566 + 68.057 (C-2-α + C-3-β), 66.759 (C-5-β) and 62.886 (C-5-α). Compound 4: Methyl 4.6-O-Benzylidene-α-D-mannopyranoside Methyl-α-D-mannopyranoside (18.1 g, 0.093 mol), benzaldehyde dimethylacetal (21.0 g, 0.138 mol) and dry DMF (90 ml) were mixed with stirring at 50-55°C in a distillation apparatus. Rαrα-toluene sulfonic acid (ca. 0.1 g) was added and 10 min. thereafter a water jet was connected to distil off methanol. After 4 hours, the reaction mixture was evaporated to form a white solid. The residue was washed with dibutyl ether, filtered and the filter cake dissolved in acetonitrile. A precipitation started and the mixture left in a refrigerator for 5 days. Thereafter, the precipitation was filtered off and the filtrate evaporated. The residue was purified on a Lobar C RP-8 column, eluting with 30 % acetonitrile in water. Product fractions from 4 separate runs were freeze dried and combined. GC analysis of the TMS derivatives indicated the product to consist of 95 area % monoacetals. The monoacetals in turn consisted of 4 peaks integrating for 0.4, 3.2, 94.1 and 2.4 area %, respectively. On the basis of 'H-, I3 C-, COSY-, DEPT- and C-H correlation NMR spectra, together with GC/MS spectroscopy, the dominating species was identified as the title compound. Η- and 13 C NMR (aceton-d 6 ), δ rel. to TMS: 7.54-7.30 (5H, m, Ar-H), 5.60 (IH, s, acetal-H), 4.71 (IH, s, H-l), 4.34 (IH, broad s, OH), 4.22-4.02 (2H, m+broad s, H-6'+OH), 3.94-3.82 (3H, m, H-2, H-3 and H-4), 3.80-3-60 (2H, m, H-5+H-6") and 3.39 (3H, s, CH 3 ); 139.264, 129.396, 128.662 and 127.211 (Ar-C), 102.825 (C-l), 102.468 (acetal-CJ, 79.888 (C-4), 72.090 (C-3), 69.308 (C-6), 69.127 (C-2), 64.363 (C-5) and 54.921 (CH 3 ). Compound 5: 4,6-O-(Benzylidene-dι)-2-deoxy-D-glucopyranose Benzaldehyde-di was prepared and converted to benzaldehyde dimethylacetal-di as described in EP 0 283 139 B 1. 2-Deoxy-D-glucose (10 g, 60.9 mmol), dry DMF (35 ml), benzaldehyde dimethylacetal-di (11.7 g, 76.4 mmol) and pαrα-toluene sulfonic acid (70 mg, 0.37 mmol) were mixed under N 2 to give a white slurry. By warming to 45-50°C, a colourless solution was formed within 1/2 hour. A vacuum pump was connected to remove methanol through a cooled column (to prevent loss of benzaldehyde dimethylacetal-di). The pressure was regulated stepwise from 70 mbar down to 20-30 mbar during 4.5 hours and the temp, was maintained at 40-45°C. Thereafter the distillation was interrupted, the apparatus rebuilt without the column and DMF removed by short path distillation at 50-55°C, max. vacuum. The residue was a slightly yellow syrup. 1/4 of the syrup was dissolved in slightly alkaline (NaHCO 3 ) methanol/water 60/40 and purified on a Merck LiChroprep RP-8 reversed phase column eluting with methanol/water 60/40. Product fractions were concentrated to remove methanol and freeze dried to give a white, fluffy solid. Products from four separate runs were combined to give 3.5 g, 23 % of the theoretical yield. GC analysis of the TMS-derivatives and NMR spectroscopy proved the product to consists of a 1:1 mixture of the α and β anomers. Η- and 13 C NMR (DMSO-d 6 ), δ (ppm) rel. to TMS: 7.52-7.28 (m, 5H, Ar-H I+II), 6.9-6.65 (broad s, 1/2 H, OH-1 II), 6.55-6.32 (broad s, 1/2 H, OH-1 1), 5.25-5.12 (m, 1 H, OH-3 II and H-l I), 5.12-5.0 (d, 1/2 H, OH-3 II), 4.84-4.73 (dd, 1/2 H, H-l II), 4.20-4.02 (m, IH, H-6 I+II), 3.98-3.73 (m, IH, H-3 I and H-5 I), 3.73-3.58 (m, 1.5H, H-6' I+II and H-3 II), 3.42-3.18 (2.5 H, H-4 I+II and H-5 II and H,O), 2.10-1.86 (m, IH, H-2 I+II) and 1.62-1.34 (m, IH, H-2' I+II); 137.979, 137.926, 128.841, 128.036 and 126.432 (Ar-C I+II), 101.5-100.0 (acetal-C I+II), 94.057 and 91.424 (C-1 I+II), 83.916 and 83.093 (C-4 I+II), 68.374 and 68.119 (C-6I+II), 66.889, 66.092, 64.174 and 62.604 (C-3 I+II and C-5 I+II) and 41.932 and 40.051 (C-2 I+II). Compound 6: 4,6-0- (4-Carbomethoxybenzylidene)-D-glucopyranose Methyl 4-formylbenzoate (100 g, 0.609 mol), methanol (91.5 g, 2.86 mol), trimethyl ortoformate (71 g, 0.67 mol) and cone, hydrochloric acid (165 μl) were mixed in a 500 ml three-necked flask. The slurry transformed into a slightly yellow solution within few minutes and the temp, spontaneously increased from 15°C to 30°C. After stirring for 15 min., the reaction mixture was refluxed at 58°C for another 25 min. and then cooled to 10°C (ice/water). An alkaline solution was made by dissolving KOH (8.3 g) in metanol (53 ml) and 7 ml of the solution added to the reaction mixture. After stirring at 10°C for 25 min., the reactor was re-built for short path distillation and all volatiles removed in vacuo (water jet). The distillation was thereafter continued with a vacuum pump and a colourless oil collected at 112-114°C/0.5 mbar. The oil transformed into a colourless solid, m.p. 32-33°C, and was identified by NMR to be methyl 4-formylbenzoate dimethylacetal. The yield was 108.75 g, 85 % of the theoretical. D(+)-glucose (8.0 g, 44.4 mmol), dry DMF (25 ml), methyl-4-formylbenzoate dimethylacetal (10.4 g, 49.5 mmol) and pαrα-toluene sulfonic acid were mixed at 50°C under N 2 to give a white suspension. The apparatus was connected to a vacuum pump through a vertical condenser and evaporation of methanol started at 80-100 mbar, 55°C. The vacuum was gradually lowered to 40 mbar, maintaining the temp, at 55-60°C. The reaction mixture gradually clarified and finally became transparent. After 8 hours the distillation was interrupted and the apparatus rebuilt for short path distillation of DMF. The residue was a slightly yellowish syrup. The syrup was dissolved in a warm solution of 100 mg NaHCO 3 in 20 ml methanol and 8 ml water and precipitated by adding 100 ml ethylacetate. The precipitate was isolated from the mother liquor by filtration, washed with cold water (4 x 15-20 ml) and transferred to a rotavapor flask. Humidity was removed by adding ethylacetate and evaporating twice. The product was finally dried under high vacuum. More precipitate was filtered off from the mother liquor, washed and dried to give a second crop. The two crops were combined to give 1.94 g pure product, 13 % of the theoretical yield. GC analysis of the TMS-derivatives showed two isomers in the ratio 2: 1. Η- and 13 C NMR (DMSO-d 6 ), δ (ppm) rel. to TMS: 7.99 and 7.61 (dd, 2+2H, furfuryl-H), 6.87 (d, 0.67H OH-1 II), 6.59 (d, 0.28H, OH-1 I), 5.68 (s+s, IH, acetal-H I+II), 5.29 (d, 0.68H, OH-3 II), 5.21 (d, 0.67H, OH-2 II), 5.16 (d, 0.3 IH, OH-3 I), 5.00 (t, 0.30H, H-l I), 4.85 (d, 0.28H, OH-2 I), 4.48 (t, 0.73H, H-l II), 4.25-4.08 (m, 1.14H, H-6), 3.95-3.77 (m, 3.43H, OCH3 and H-5 I), 3.78-3.59 (m, 1.40H, H-3 I and H-6'), 3.49-3.23 (m, 3.59H, H-4 I and II, H-5 II, H-2 I and H-3 II), 3.10-2.98 (m, 0.72H, H-2 II); 165.978, 142.553, 142.553, 129.959,129.067, 126.763, 99.982, 99.812, 97.661, 93.238, 81.794, 81.794, 80.963, 75.808, 72.902, 69.658, 68.487. 68.110, 65.714, 61.952 and 52.253. Compound 7: 4.6-O-Benzylidene-2-deoxy-D-glucopyranose 12-Deoxy-D-glucose (10.0 g, 60.9 mmol), dry DMF (34 ml), benzaldehyde dimethylacetal (11.6 g, 76.2 mmol) and p rα-toluene sulfonic acid (70 mg, 0.37 mmol) were mixed under N 2 to give a white slurry. The reaction mixture was stirred at room temp, for 30 min. and by warming to 45-50°C, the solid gradually dissolved. A vacuum pump was connected to remove methanol through a cooled column (to prevent loss of benzaldehyde dimethylacetal) and the reaction continued for 4.5 hours. Thereafter the distillation was interrupted, the column removed and DMF distilled off through a short path at 50-55°C, max. vacuum. The residue was a slightly yellow syrup. The syrup was dissolved in slightly alkaline (NaHCO 3 ) methanol/water 60/40 and purified on a Merck LiChroprep RP-8 reversed phase column, eluting with methanol/water 60/40. Product fractions were concentrated to remove methanol and freeze dried to give a white, fluffy solid. Products from four separate runs were combined to give 3.18 g, 21 % of the theoretical yield. GC analysis of the TMS-derivatives and NMR spectroscopy proved the product to consists of a 1:1 mixture of the α and β anomers. Η NMR (DMSO-d 6 ), δ (ppm) rel. to TMS: 7.52-7.30 (m, 5H, Ar-H I+II), 6.85-6.68 (broad s, 1/2 H, OH-1 II), 6.50-6.35 (broad s, 1/2 H, OH-1 1), 5.61 (s+s, IH, acetal-H I+II), 5.23-5.12 (m, 1 H, OH-3 II and H-l I), 5.12-5.02 (d, 1/2 H, OH-3 II), 4.84-4.74 (dd, 1/2 H, H-l II), 4.20-4.04 (m, IH, H-6 I+II), 3.98-3.74 (m, IH, H-3 I and H-5 I), 3.74-3.57 (m, 1.5H, H-6' I+II and H-3 II), 3.42-3.18 (2.5 H, H-4 I+II and H-5 II and EbO), 2.08-1.88 (m, IH, H-2 I+II) and 1.62-1.32 (m, IH, H-2' I+II). Compound 8: 2-Acetamido-4,6-O-benzylidene-dι-2-deoxy-D-glucopyranose Benzaldehyde-di was prepared and converted to benzaldehyde dimethylacetal-di as described in EP 0 283 139 Bl. Benzaldehyde dimethylacetal-d i (8.7 g, 56.8 mmol), N-acetyl-D-glucosamine (10.0 g, 45.2 mmol), dry DMF (30 ml) and pαrα-toluene sulfonic acid (88 mg, 0.46 mmol) were mixed under N 2 to give a white suspension. The reaction mixture was stirred at 50°C for 45 min, then a vacuum pump was connected through a vertical condenser and the reaction continued for 2 hours at 55°C/60-70 mbar. The apparatus was rebuilt to remove DMF through a short path and the distillation continued at 55-60°C, max. vacuum for 1 more hour. The residue was a yellow-white, soft solid. A solution was made by mixing NaHCO 3 (150 mg) in 30 ml methanol/water (3:2) and the residue neutralised by adding the solution. The creamy slurry thus formed was filtered, washing 2-3 times with a 1 % NaHCO 3 solution and several times with ether. The product was analysed to be sufficiently pure (GC) and dried in vacuo. The yield was 8.8 g, 63 % of the theoretical. GC analysis of the TMS derivatives indicated a 1:1 isomeric mixture. NMR spectroscopy in DMSO-d 6 solution identified the product as a 3: 1 anomeric mixture. 'H- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 7.83 (s+s, IH, NH) 7.51-7.28 (m, 6H, Ar-H), 7.0-6.2 (broad s, IH, OH-1), 5.65-5.05 (broad s, IH, OH-3), 4.99 (d, IH, H-l I), 4.61 (d, 0.3H, H-l II), 4.21-4.03, 3.92-3.67 and 3.51-3.22 (m, 6H, H-2, H-3, H-4, H-5 and H-6) and 1.85 (s+s, 3H, CH3); 169.452 (C=O), 137.818, 128.869, 128.035 and 126.438 (Ar-C), 100.505 (acetal-C), 96.056, 91.500, 82.471, 81.505, 70.549, 68.300, 67.961, 67.218, 65.906, 62.123, 58.038, 54.790 (sugar-C) and 23.123 and 22.674 (CH3). Compound 9: 2-Acetamido-2-deoxy-4.6-O-(3-nitrobenzylidene)-D-glucopyranose 3-Nitrobenzaldehyde (100 g, 0.66 mol), methanol (99 g, 3.1 mol), trimethyl ortoformate (77.3 g, 0.73 mol) and cone, hydrochloric acid (165 μl) were mixed in a 500 ml three-necked flask to form a yellow slurry which transformed into a solution within 5 min. The reaction mixture was refluxed at ~ 50°C for 15 min. and then cooled with ice/water to 10 °C. KOH (2.5 g) was dissolved in methanol (16 ml), and the reaction mixture quenched by adding 6.6 ml of this solution. Stirring was continued for 15 min and the reactor re-built for short path vacuum distillation. Volatile material (CH 3 OH + HCOOCH 3 ) was distilled off in a water jet, the distillation interrupted and a vacuum pump connected. The distillation was then continued and a yellow oil distilled off at 93 - 97.5 °C/20 mbar. The oil was identified by NMR to be 3-nitrobenzaldehyde dimethylacetal of high purity. The yield was 127 g, 97.6 % of the theoretical. 3-Nitrobenzaldehyde dimethylacetal (5.5 g, 0.028 mol), N-acetyl-D-glucosamine (5.0 g, 0.023 mol), pαrα-toluene sulfonic acid (50 mg, 0.263 mmol) and dry DMF (15 ml) were mixed with stirring at 50°C to form a slightly yellow suspension. After 1/2 hour, a vacuum pump was connected and the reaction continued at 56°C/50 mbar for 11 hours. The reaction mixture was evaporated and the residue partitioned between a small volume of slightly alkaline (NaHCO 3 ) water and chloroform. The water phase (forming a 5 cheese-like suspension) was re-extracted twice with chloroform and filtered, washing several times with water and ether. The product was dried in vacuo to form a slightly brownish powder. The yield was 570 mg, 7 % of the theoretical. GC analysis of the TMS derivatives indicated the product to consist of two isomers in a 10 2: 1 ratio. NMR spectroscopy identified the product as a mixture of α- and β anomers. Η- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 8.4-8.1 (m, 2H, Ar-H), 8.05-7.79 (m, 2H, Ar-H), 7.79-7.60 (t, IH, NH), 6.80 (d, IH, OH-1), 5.81 (s+s, IH, acetal H), 5.30 and 5.18 (s+s, 1/2 H + 1/2 H, H-l), 4.30-4.10, 3.93-3.3 (m, 6H, H-2 - H-6) and 1.85 (d, 3H, CH3); 169.331 (C=O), 147.490, 139.544, 133.018, 129.862, 123.732, 120.884 (Ar-C), 99.000, 15 98.806 (acetal-C), 95.924, 91.406, 82.433, 81.454, 70.320, 68.240, 67.907, 67.020, 65.574, 61.833, 57.875, 54.609 (sugar-CJ, 23.014 and 22.557 (CH3). Compound 10: 4.6-O-(Benzylidene-dι)-D-galactopyranose 20 Benzaldehyde-di was prepared and converted to benzaldehyde dimethylacetal-d ι as described in EP 0 283 139 Bl. D(+)-Galactosel5.0 g,0.0833 mol) and dry DMF (80 ml) were st red in a distillation apparatus at 45°C. Benzaldehyde dimethylacetal-d i (12.8 g, 0.0836 mol) and pαrα-toluene 25 sulfonic acid (0.14 g) were added and methanol and DMF slowly distilled off in vacuo (water jet). After 3 hours, a vacuum pump was connected and the remaining DMF distilled off. Portions of the residue was dissolved in methanol/water (1:1) containing NaHCO 3 (11 mg/ml) and purified on a Lobar C RP-8 column, eluting with methanol/water (1:1). Product fractions from 7 individual runs were freeze dried and combined to form a 30 white, fluffy product. The yield was 6.62 g, 30 % of the theoretical. GC- and NMR analysis showed the product to consist of a 1: 1 anomeric ratio. 'H- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 7.52-7.30 (m, 5H, Ar-H), 6.62 (0.5H, d, OH-l-β), 6.32 (0.5H, d, OH-l-α), 5.05 (0.5H, t, H-l-α), 4.85+4.69+4.49 (1H+0.5H+0.5H, m+d+d, OH-2+OH-3), 4.35 (0.5H, t, H-l-β), 4.12-3.92+3.81-3.71+3.69-3.59 +3.49-3.39+3.39-3.28 (3H+1H+0.5H+1H+2H m+m+m+m+m, H-2-H-6+H 2 O); 138.753, 138.690, 128.607, 128.319, 127.913 and 126.3 (Ar-C), 99.345 (acetal-C), 97.307 and 93.178 (C-1), 76.738 and 76.158 (C-4), 72.101, 71.605, 68.947, 68.862 , 68.486 and 67.730 (C-2, C-3 and C-6) and 65.829 and 62.068 (C-5). Compound 11: 4,6-O-(Benzylidene-dι)-D-mannopyranose Benzaldehyde-di was prepared and converted to benzaldehyde dimethylacetal-di as described in EP 0 283 139 Bl. D(+)-Mannose (15.0 g, 0.0833 mol) and dry DMF (70 ml) were sthred in a distillation apparatus at 40°C. Benzylidene dimethylacetal-di and pαrα-toluene sulfonic acid (0.14 g) were added to form a clear solution. A vacuum pump was connected and methanol and DMF slowly distilled off at 70-20 mbar, 45-50°C. After 3 hours, the remaining DMF was distilled of at max. vacuum, leaving a slightly yellowish syrup. The residue was washed repeatedly with ether in order to remove lipophilic species. Portions of crude product were dissolved in slightly alkaline (NaHCO 3 ) methanol/water (3:2) and purified on a Lobar C RP-8 column, eluting with methanol/water (3:2). GC of the TMS derivatives indicated the product to consist of 4 isomers in the ratio 10:3:1:4. It was re-eluted with methanol/water (1:4) to obtain a white, fluffy product consisting of just 2 isomers in the ratio 70/30, as analysed by GC. The yield was 1.42 g, 6.4 % of the theoretical. On the basis of Η-, 13 C-, COSY-, DEPT- and C-H conelation NMR, the chemical structure was confirmed and the α- and β anomers found to equilibrate at a 1:8 ratio. 'H- and 13 C NMR (DMSO-d 6 ) of predominating isomer, δ rel. to TMS: 7.5-7.28 (m, 5H, Ar-H), 6.56 (d, IH, OH-1), 5.0-4.85 (m, 3H, H-l, OH-2 and OH-3), 4.10-4.02 (m, IH, H-6), 3.63-3.40 (m, 5H, H-2, H-3, H-4, H-5 and H-6'); 138.045, 128.825, 128.029, 126.438 (Ar-C), 100.802 (acetal-C), 95.233 (C-1), 78.987 (C-4), 72.032 (C-3), 68.317 (C-6), 67.252 (C-2), 63.495 (C-5). Compound 12: 2-Acetamido-4.6-O-benzylidene-2-deoxy-α-D-galactopyranose Benzaldehyde dimethylacetal (2.0 ml, 14 mmol) followed by αrα-toluene sulfonic acid monohydrate (15 mg) were added to a stirred suspension of N-acetyl-D-galactosamine (1.50 g, 6.77 mmol) in acetonitrile (37 ml). The reaction mixture was then lowered into a warm (60°C) oil bath and stirced under nitrogen for 3 h, during which time a thick white precipitate was seen to form. The reaction mixture was then filtered and the solid washed with cold dichloromethane (approx. 2 ml) followed by continued suction filtration under a stream of nitrogen. The white powder was then placed in a pre- weighed glass vial and left under vacuum (0.06 mbar) over 72 h to give the pure desired product as only the α-isomer (1.74 g, 83 %). Η NMR δ H (300 MHz; d 6 -DMSO) 1.83 (3H, s, CH 3 ), 3.80-4.17 (6H, m, H-2, H-3, H-4, H-5 and H-6), 4.65 (IH, d, OH-3), 5.06 (IH, t, H-l), 5.59 (IH, s, ArCH), 6.52 (IH, d, OH-1), 7.33-7.55 (5H, m, ArH) and 7.69 (IH, d, NH); 13 C NMR δ c { 'H}(75 MHz; D6-DMSO) 23 (CH 3 ), 50, 62, 65, 69 and 76 (C-2, C-3, C-4 C-5 C-6), 91 (C-1), 100 (ArCH), 126, 128, 128 and 138 (arom. C) and 170 (C=O). Compound 13: 4,6-O-(3-Nitrobenzylidene)-D-glucopyranose 3-Nitrobenzaldehyde dimethylacetal was prepared as described for Compound 9. 3-Nitrobenzaldehyde dimethylacetal (21.9 g, 0.11 mol), D(+)-glucose (16.0 g, 0.09 mol), pαrα-toluene sulfonic acid (100 mg, 0.5 mmol) and dry DMF (50 ml) were mixed under N 2 and stined at 58°C for 25 min. A vacuum pump was connected and methanol and DMF slowly distilled off via a cooled column at 55-60°C, 30-40 mbar for 4 h, 15 min. The apparatus was rebuilt to remove most of the DMF through a short path and the distillation continued for 1.5 h. The residue was a slightly yellow syrup. The syrup was dissolved in slightly alkaline (NaHCO 3 ) methanol/water 60:40 and purified on a Lobar C RP-8 column, eluting with methanol/water 60:40. Product fractions were evaporated (to remove methanol), freeze-dried and combined to give 5 g of a white, fluffy solid. The product was re-purified eluting with methanol/water 40:60 to give the title compound of sufficient purity. The yield was 3.3 g, 12 % of the theoretical. GC indicated the product to consist of two isomers in a 70:30 ratio. Η NMR (DMSO-d 6 ), δ rel. to TMS: 8.33-7.63 (5H, m, Ar-H), 6.89+6.60 (IH, d+d, OH-1-I+II), 5.78 (IH, s+s, acetal-H- I+II), 5.34 (0.65H, d, OH-3-II), 5.75+5.71 (1.12H, d+d, OH-2-II + OH-3-I), 4.99 (0.56H, m, H-l -I), 4.88 (0.32H, OH-2-I), 4.49 (0.74H, m, H-l -II), 4.28-4.12 (IH, m, H-6'-I+II), 3.85-3.53 (2.27H, m, H-3-I, H-5-I and H-6"-I+II), 3.49-3.32 (2.58H, m, H-2-I, H-3-II, H-4-I+II and H-5-II) and 3.12-2-98 (0.85H, m H-2-II). Compound 14: 4,6-O-(2-Hydroxybenzylidene-D-glucopyranose 2-Hydroxybenzaldehyde (16.0 g, 0.13 mol), D-glucose (23.6 g, 0.13 mole) and para- toluene sulfonic acid (catalytic amount) were mixed in DMF (100 ml). The mixture was heated to about 60 °C for 0.5 h to give a solution. The reaction was monitored by TLC analysis (silica gel, ethyl acetate). After 20 h at 20 °C the mixture was heated twice to 60 °C for 1 h and then evaporated at 60 °C at reduced pressure to remove most of the DMF. Ethyl acetate (approx. 100 ml) was added to give a precipitate. The solution was decanted off, analysed by TLC and evaporated at reduced pressure to give an oil. The oil was dissolved in ethyl acetate, silica gel (120 g, 200-500 μm) added and the solvent evaporated. About half of the product was chromatographed on silica gel (550 ml, 30-60 μm) with ethyl acetate as eluent. Fractions of 100 ml were collected and fr.15 to 25 were evaporated at reduced pressure to give an oil (3.4 g), impured by substantial amounts of DMF. The product, only slightly soluble in chloroform, was precipitated by addition of about 20 ml of the same solvent. Washing with chloroform and drying gave a solid (1.86 g). The rest of the product was chromatographed and precipitated accordingly to give 2.43 g and further 1.6 g was recovered from the mother liquors by precipitation. The total yield was 5.85 g, 16 % of the theoretical. According to NMR and TLC analyses the product was impured by a few percent of 2-hydroxybenzaldehyde and glucose. Chromatography, as above, gave a product essentially free from impurities. NMR spectroscopy showed the product to consist of a mixture of α and β anomers. In DMSO-d 6 , the anomeric ratio was initially α/β = 2:1, but 5 changed over time. Also GC spectroscopy of the silylated derivatives displayed two peaks in a 2:1 ratio. 'H- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 9.50 (s, IH, Ar-OH), 7.30 (m, IH, Ar-H-6), 7.09 (m, IH, Ar-H-4) 6.80-6.68 (m, 2.34H, Ar-H-3 + Ar-H-5) + OH-l-β), 6.48 (d, 0.67H, 10 OH-l-α), 5.71 (s, acetal-H-α+β), 5.10 (t, 0.65H, OH-2-β + OH-3-β), 4.97 (d, 0.63H, OH-3-α), 4.90 (t, 0.66H, H-l-α), 4.71 (d, 0.65H, OH-2-α), 4.39 (t, 0.39H, H-l-β), 4.10-3.93 (m, 1.13H, H-6'-α+β), 3.80-3.67 (m, 0.71H, H-5-α), 3.60-3.45 (m, 1.73H, H-3-α and H-6"-α+β), 3.35-3.14 (m, 3.31H, H-4-α+β, H-2-α, H-3-β, H-5-β and l O), 3.00-2.95 (m, 0.42, H-2-β); 154.72, 154.69, 130.11, 127.85, 127.77, 124.44, 124.38, 15 118.97 and 115.69 (Ar-C), 97.95 (C-l-β), 96.95 and 96.87 (acetal-C), 93.50 (C-l-α), 82.35 (C-4-α), 81.52 (C-4-β), 76.04 (C-2-β), 73.32 (C-3-β), 73.19 (C-2-α), 70.04 (C-3-α), 68.98 (C-6-α), 68.61 (C-6-β), 66.24 (C-5-β) and 62.46 (C-5-α). Compound 15: 2-Deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose 20 A catalytic amount of pαrα-toluene sulfonic acid was added to 2-hydroxybenzaldehyde (10.7 ml, 0.100 mol) and trimethyl ortoformate (11.0 ml, 0.100 mol). After 60 min., 2-deoxy-D-glucose (16.4 g, 0.100 mol) and DMF (300 ml) were added and the mixture heated briefly to about 60°C. TLC analysis indicated the presence of product after 10 25 minutes and a small amount of pyridine was added after 25 h. A sample was withdrawn and cromatographed (ethyl acetate/methanol 9:1) to give impure fractions. Fractions with fairly pure product were collected after chromatography of a small amount with heptane/ethyl acetate (1:4). The rest of the reaction mixture was evaporated under vacuum, the residue dissolved in ethyl acetate, silica gel (200-500 μm) added and the 30 solvent evaporated in vacuo. Chromatography (heptane/ethyl acetate 1:4) yielded ca. 2 g product with moderate purity. The modest yield may be suspected as a result of unnecessary long reaction time and the preparation was repeated, with addition of pyridine after 2.5 h. Work-up and chromatography as above gave 2.4 g of impured product. The collected products were mixed and re-chromatographed (heptane/ethyl acetate 1 :4) to give a white solid. The yield 5 was 4.1 g, 7 % of the theoretical. NMR analysis showed a clean spectrum of the expected product, but also signals from a few percent of impurities (signals around 1 ppm; possibly impurities introduced via solvents). Attempts to purify the product by repeated chromatography resulted in substantial loss of material and merely 1.2 g was finally isolated. NMR spectroscopy indicated the α:β ratio to be approximately 1:1. 10 'H- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS: 9.56 (s, IH, Ar-OH), 7.41-7.29 (m, IH, Ar-H), 7.18-7.06 (m, IH, Ar-H), 6.86-6.70 (m, 2.54H, Ar-H + OH-l-β), 6.40 (d, 0.50H, OH-l-α), 5.83 and 5.80 (s + s, IH, acetal-H), 5.17 (t, 0.51H, H-l-α), 5.11 (d, 0.46H, OH-3-β), 5.03 (d, 0.50H, OH-3-α), 4.79 (t, 0.46H, H-l-β), 4.14-3.95 (m, 1.25H, H-6-α+β) 15 + EtOAc), 3.91-3.72 (m, 1.1 IH, H-3-α + H-5-α), 3.72-3.57 (m, 1.48H, H-3-β + H-6'-α+β), 3.36-3.16 (m, 1.39H, H-4-α+β, H-5-β + H 2 O), 2.05-1.86 (m, 0.93H, H-2-α+β + EtOAc) 1,63-1.47 (m, 0.51H, H-2'-α) and 1.47-1.32 (m, 0.48H, H-2'-β); 154.71 and 154.66 (Ar-C-OH), 130.09, 127.88, 127.78, 124.54, 124.48, 118.96, 118.93, 115.67 (Ar-C , 97.06 and 97.00 (acetal-C), 94.36 (C-l-β), 91.71 (C-l-α), 84.52 and 83.70 (C-4), 20 68.92 and 68.68 (C-6), 67.24 (C-3-β), 66.52 (C-5-β), 64.50 (C-3-α), 63.03 (C-5-α) and 42.29 (C-2). Compound 16: 2- Acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose 25 To 2-hydroxybenzaldehyde (10.7 ml, 0.100 mol) and trimethyl ortoformate (11.0 ml, 0.100 mol) was added a catalytic amount of p rα-toluene sulfonic acid. The temperature spontaneously raised to ca. 60 °C and the mixture was set aside for ca. 2 h. before addition of N-acetyl glucosamine (20.3 g, 0.092 mol) and DMF (150 ml). The reaction mixture was stirred for 30 min. at 20 °C and then briefly heated to 50 °C. Most of the N-acetyl 30 glucosamine was dissolved and TLC-analysis indicated substantial conversion to anticipated product. The reaction mixture was again briefly heated to ca. 50 °C and volatile components evaporated at 20 °C/ 15 mmHg. The slightly turbid raction mixture was kept at 20°C for 4 days. A small amount of pyridine was added and most of the solvents evaporated at 60 °C/15 mmHg to give an oil. The oil was added to ethyl acetate (350 ml), giving a small amount of precipitate, and the decanted solution was evaporated together with silica gel (200 g, 200-500 μm). 5 A minor part of the product was chromatographed on silica (550 ml, 30-60 μm), eluting with ethyl acetate and collecting 100 ml fractions. After fraction 58, the eluent was changed to ethyl acetate/methanol 9:1 and the product collected within the next 20 fractions. Evaporation of the product fractions gave 3.3 g of a solid. The rest of the 10 product was chromatographed on silica gel with ethyl acetate/methanol 9:1 to give further 21 g of solid product. DMF was removed by stirring the finely divided product with ethyl acetate (200 ml) for 2 h. Filtration, washing with ethyl acetate and drying gave 16.7 g pure product, 56 % of the theoretical yield. GC analysis of the silylated derivatives showed a 5: 1 preponderance of one of the isomers. NMR analysis in DMSO-d 6 showed 15 the β isomer to exist in 4-5 fold excess over the α isomer. Η- and 13 C NMR in (DMSO-d 6 ), δ rel. to TMS: 9.59 (s, IH, Ar-OH), 7.80 (d, IH, NH), 7.38 (t, IH, Ar-H), 7.17 (t, IH, Ar-H), 6.86-6.72 (m, 3H, Ar-H and OH-l-α+β), 5.82 (s+s, IH, acetal-H), 5.17 (d, 0.22H, OH-3-β), 5.10-4.98 (m, 1.54H, OH-3-α and H-l-α), 4.61 (t, 20 0.21H, H-l-β), 4.17-4.10 (m, 0.24H, H-6'-β), 4.10-4.03 (m, 0.78H, H-6'-α), 3.90-3.80 (m, 0.80H, H-5-α), 3.79-3.61 (m, 2.53H, H-6"-α+β, H-3-α and H-2-α), 3.61-3.53 (m, 0.26H, H-3-β) and 3.46-3.28 (m, 3.58H, H-2-β, H-4-α+β, H-5-β and l O); 169.81, 169.77 (C=O), 154.70, 130.15, 127.86, 127.75, 124.41, 124.36, 118.97 and 115.70 (Ar-Q, 97.00 and 96.86 (acetal-C), 96.34 (C-l-β), 91.81 (C-l-α), 83.08 and 82.12 (C-4), 70.92 and 25 67.58 (C-3), 68.86 and 68.52 (C-6), 66.34 and 62.58 (C-5), 58.33 and 55.08 (C-2), 23.46 and 23.00 (CH 3 ). Compound 17: 4,6-O-(2-Hvdroxybenzylidene)-D-galactopyranose 30 A catalytic amount of pαrα-toluene sulfonic acid was added to 2-hydroxybenzaldehyde (10.7 ml, 0.100 mol) and trimethyl ortoformate (11.0 ml, 0.100 mol). After st ring for 60 min., D-galactose (18.0 g, 0.100 mol) and DMF (300 ml) were added and the reaction mixture heated briefly to about 60 °C. The reaction mixture was homogeneous within a few min. and the presence of product evident from TLC analysis. A small amount of pyridine was added after 20 h., most of the solvent removed, and the residue applied on silica gel as described previously. Column chromatography (ethyl acetate/methanol 9:1) gave high yield of the desired product (ca. 17 g), impured only by DMF. Repeated chromatography gave 4.9 g pure product, together with ca. 10 g impured by a few percent DMF. NMR spectroscopy showed the α to β ratio to be 77:23. Also GC analysis of the silylated derivatives showed two peaks in a similar ratio. 'H- and I3 C NMR (DMSO-d 6 ), δ rel. to TMS: 9.28 (s, IH, Ar-OH), 7.43-7.34 (m, IH, Ar-H), 7.19-7.13 (m, IH, Ar-H), 6.85-6.76 (m, 2H, Ar-H), 6.63 (d, 0.23H, OH-l-β), 6.30 (d, 0.76H, OH-l-α), 5.75 (s, IH, acetal-H), 5.06 (t, 0.76H, H-l-α), 4.84 (d, 0.23H, OH-2-β), 4.79 (d, 0.22H, OH-3-β), 4.60 (d, 0.76, OH-3-α), 4.54 (d, 0.78, OH-2-α), 4.34 (t, 0.23H, H-l-β), 4.13-3.87 (m, 3H, H-4-α+β and H-6-α+β), 3.79-3.70 (m, 1.55H, H-3-α and H-5-α), 3.66-3.59 (m, 0.78H, H-2-α), 3.45-3.36 (m, 0.49H, H-3-β and H-5-β) and 3.36-3.27 (m, 0.95H, H-2-β and HzO); 154.76, 154.70, 129.96, 128.08, 128.03, 125.18, 125.06, 118.95, 118.88 and 115.69 (Ar-C), 97.57 (C-l-β), 96.68 and 96.49 (acetal-C), 93.49 (C-l-α), 77.19 and 76.62 (C-4), 72.36 and 71.88 (C-2-β and C-3-β), 69.30 and 69.19 (C-6), 68.79 and 67.99 (C-2-α and C-3-α), 66.10 and 62.33 (C-5). Compound 18: 2-Deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose A catalytic amount of pαrα-toluene sulfonic acid was added to 2-hydroxybenzaldehyde (0.65 ml, 6.1 mmol) and trimethyl ortoformate (0.63 ml, 6.1 mmol). After 1 h., 2-deoxy-D-galactose (1 g, 0.61 mmol) and DMF (25 ml) were added and the mixture heated briefly to about 60 °C to give a homogeneous solution. TLC analysis indicated formation of product within 10 min. Pyridine was added after 2.5 h. and work-up performed as above. Chromatography with ethyl acetate gave poor separation and the eluent was changed to ethyl acetate/methanol 95:5 to give 98 mg (6 %) of fairly pure product. NMR spectroscopy indicated the presence of two isomers in a 3:2 ratio. 'H NMR (DMSO-d 6 ), δ rel. to TMS: 9.26 (s, IH, Ar-OH), 7.48-7.37 (m, IH, Ar-H), 7.23-7.10 (m, IH, Ar-H), 6.86-6.73 (m, 2H, Ar-H), 6.62 (d, 0.31H, OH-l-β), 6.21 (d, 0.48H, OH-l-α), 5.80 (s, IH, acetal-H), 5.31 (s, 0.49H, H-l-α), 4.78 (d, 0.31H, OH-3-β), 4.67 (d, 0.94H, OH-3-α + H-l-β), 4.07-3.79 (m, 3.49H, H-4-α+β, H-6-α+β + H-3-α), 3.70 (m, 0.95H, H-5-α + H-3-β), 3.33 (m, H-5-β + H 2 O), 1.89-1.77 (m, 0.53H, H-2-α), 1.77-1.62 (m, 0.90H, H-2-β + H-2'-β) and 1.72-1.51 ( m, 0.53H, H-2'-α); 154.79 and 154.76 (Ar-C-OH), 129.96, 128.12, 125.24, 125.15, 118.94, 118.88 and 115.69 (Ar-C), 96.62 and 96.45 (acetal-C), 94.21 (C-l-β), 91.66 (C-l-α), 75.80 and 74.71 (C-4), 69.86 and 69.61 (C-6), 67.47 (C-3-β), 66.35 (C-5-β), 63.43 (C-3-α), 62,38 (C-5-α) and 37.09 and 34.23 (C-2). Compound 19: 2-Acetamido-2-deoxy-4.6-O-(2-hydroxybenzylidene)-D-galactopyranose A small amount of /_?αrα-toluene sulfonic acid was added to 2-hydroxybenzaldehyde (0.48 ml, 4.5 mmol) and trimethyl ortoformate (0.47 ml, 4.5 mmol). After 60 min., N-acetyl galactosamine (1.0 g, 4.5 mmol) and DMF (25 ml) were added and the reaction mixture heated briefly to 50 °C to give a homogeneous solution. The presence of product was indicated by TLC analysis after 15 min. A small amount of pyridine was added after 2.5 h. and most of the DMF evaporated at reduced pressure. The product was applied on silica gel as described previosly and chromatographed with ethyl acetate/methanol 9:1 to give 444 mg (30 %) of the title compound. NMR- spectroscopy showed the compound to excist predominently as one isomer, probably the α isomer. 'H- and 13 C NMR (DMSO-d 6 ), δ rel. to TMS (predominant isomer): 9.34 (s, IH, Ar-OH), 7.63 (d, IH, NH), 7.47-7.39 (m, IH, Ar-H), 7.21-7.14 (m, IH, Ar-H), 6.87-6.79 (m, 2H, Ar-H), 6.52 (d, 0.96H, OH-1), 5.80 (s, IH, acetal-H), 5.08 (t, 0.97H, H-l), 4.58 (d, IH, OH-3), 4.12 (d, IH, H-4), 4.08-3.98 (m, 2H, H-2 + H-6), 3.98-3.89 (m, IH, H-6'), 3.89-3.79 (m, IH, H-3), 3.78 (s, IH, H-5) and 1.83 (s, 3H, CI ); 169.92 (C=O), 154.69 (Ar-C-OH), 130.00, 128.05, 125.15, 118.98 and 115.68 (Ar-C), 96.40 (acetal-C), 91.72 (C-1), 76.45 (C-4), 69.37 (C-6), 65.75 (C-3), 62.27 (C-5), 50.57 (C-2) and 23.09 (CH 3 ). Compound 20: 4,6-O-(2-Hydroxybenzylidene)-D-mannopyranose A catalytic amount of pαrα-toluene sulfonic acid was added to 2-hydroxybenzaldehyde (10.7 ml, 0.100 mol) and trimethyl ortoformate (11.0 ml, 0.100 mol). After 60 min. D-mannose (18 g, 0.100 mol) and DMF (300 ml) were added and the reaction mixture heated briefly to about 60 °C. The reaction mixture was almost homogeneous after 20 min. and TLC analysis indicated the presence of product. After 2.5 h., a small amount of pyridine was added and most of the DMF evaporated at reduced pressure. The residue was dissolved in ethyl acetate (a small amount of methanol was added to get a homogeneous system), silica gel (200-500 μm) added and the solvents evaporated in vacuo. A small amount of the crude product was chromatographed (ethyl acetate/methanol 9:1) and the identity of the product confirmed by NMR analysis. The rest of the crude mixture was chromatographed to give 7.7 g product, impured by large amounts of DMF. Attempts to remove DMF by stirring the product with chloroform followed by filtration gave 7.1 g of a solid product containing ca. 20 mol % DMF. The product was stirred for 20 h. with ca. 300 ml ethyl acetate and filtered to give 1.7 g of slightly reddish crystals, essentially free from DMF. Chromatography gave a DMF-free but slightly discoloured product. The filtrate was evaporated and the residue purified by chromatography to give additional 3.5 g of the product. The total isolated yield was 4.7 g, 16 % of the theoretical. NMR- spectroscopy showed the compound to excist predominently as the α isomer (α:β ~ 85: 15). 'H- and 1 C NMR (DMSO-d 6 ), δ rel. to TMS (predominant isomer): 9.51 (s, IH, Ar-OH), 7.42-7.29 (m, IH, Ar-H), 7.22-7.11 (m, IH, Ar-H), 6.83-6.72 (m, 2H, Ar-H), 6.52 (d, 0.73H, OH-1), 5.79 (s, 0.72, acetal-H), 4.96-4.79 (m, 2.88H, H-l, OH-2 + OH-3), 4.04-3.98 (m, 0.58H, H-6)3.83-3.68 (m, 2.52H, H-3, H-4 + H-5) and 3.68-3.54 (m, 2.84H, H-2 + H-6'); 154.65 (Ar-C-OH), 130.07, 127.84, 124.56, 118.92 and 115.69 (Ar-C), 97.29 (acetal-C), 95.51 (C-1), 79.55 (C-4), 72.38 (C-2), 68.88 (C-6), 67.53 (C-3) and 63.87 (C-5). Compound 21: 4.6-O-Benzylidene-L-glucopyranose L(-)-Glucose (5.0 g, 27.8 mmol), benzaldehyde dimethylacetal (4.66 g, 30.6 mmol) and p rα-toluene sulfonic acid (32 mg, 0.17 mmol) were mixed in dry DMF (20 ml) in a distillation apparatus. A water pump was connected through a short path to remove methanol and DMF in vacuo. The colourless suspension dissolved within 1/2 h at 55 °C and the resulting solution stined at 120 mbar for 1/2 h while gradually increasing the temperature to 65 °C. The vacuum was increased to maximum and the reaction mixture evaporated further for 45 min. The temp, increased to 75 °C at the end of the destination. The residue was a slightly yellowish sirup, which was neutralised by adding NaHCO 3 (29 mg) and allowed to cool. The crude product was dissolved in methanol (10 ml) and purified on a reversed phase RP-8 column, eluting with methanol/water 1:1. Product fractions were combined and evaporated to remove methanol. The residual solution was further diluted with water and freeze dried. White, fluffy solid from three separate runs were collected to yield a total of 2.42 g, 32.5 % of the theoretical. GC chromatography of silylated samples indicated the product to consist of two isomers (α and β anomers) in a 35/65 ratio. The 'H NMR shifts in DMSO-d 6 were similar to those of 4,6-O-benzylidene-D-glucopyranose: 7.51-7.30 (5H, m, Ar-H), 6.86 (0.6H, broad s, OH-l-β), 6.58 (0.3H, broad s, OH-l-α), 5.58 (0.9H, s+s, acetal-H-α+β), 5.23 (0.7H, d, OH-3-β), 5.20 (0.6H, d, OH-2-β), 5.11 (0.4H, d, OH-3-α), 5.00 (0.4H, H-l-α), 4.82 (0.3H, d, OH-2-α), 4.47 (0.7H, d, H-l-β), 4.21-4.08 (IH, m, H-6'-α+β), 3.87-3.73 (0.4H, m, H-5-α), 3.73-3.59 (1.3H, m, H-6"-α+β and H-3-α), 3.46-3.22 (3.7H, , H-3-β, H-4-α+β, H-5-β and H-2-α) and 3.09-2.99 (0.6H, m, H-2-β). Compound 22: 4.6-O-(Benzylidene-dι)-L-glucopyranose L-Glucose (5.14 g, 28.6 mmol) was warmed in DMF (20 ml) to 95 °C until a clear solution was formed. The reaction flask was then transfened to a water bath at 65 °C and pαrα-toluene sulfonic acid (33 mg, 0.17 mmol) was added. Benzylidene dimethyl acetal-di (4.7 ml, 31 mmol) was then added dropwise by syringe over 20 minutes to the stirred glucose solution under a regulated water pump vacuum of 80 mbar. The DMF was then evaporated under vacuum (2 mbar) at 65 °C to give a very pale yellow oil to which was added NaHCO 3 (345 mg) followed by stirring for 5 minutes. Warm water (67 °C, 15 ml) was added with stirring (magnetic bead) to the oil at 65 °C and then the flask was shaken in the warm water bath until the oil appeared to have dissolved. The reaction flask was then placed under a stream of cold water for approx. 5 minutes. After only one or two minutes an amorphous mass formed. The aqueous mixture was placed in an ice-water bath and left to stand for 40 minutes. A white precipitate formed during this time which was isolated by vacuum filtration (decanted from the amorphous material), washed with cold spring water (25 ml) followed by cold wø-propanol (5 °C, 2 x 5 ml) and dried under a stream of nitrogen to give 1.85 g of a dry white powder. This product was silylated and analysed by gas chromatography and appeared to be 99% pure desired product. Η NMR, δ (DMSO-d 6 ) rel. to TMS: 7.55-7.25 (m, 5H, Ar-H), 6.85 (s, 0.48 H, OH-l-β), 6.55 (s, 0.33H, OH-l-α), 5.25 (d, 0.48 H, OH-3-β), 5.20 (d, 0.49 H, OH-2-β), 5.10 (d, 0.35 H, OH-3-α), 4.98 (d, 0.35 H, H-l-α), 4.82 (d, 0.34 H, OH-2-α), 4.48 (d, 0.51 H, H-l-β), 4.20-4.05 (m+m, 0.53 H +0.42 H, H-6' α+β), 3.85-3.73 (m, 0.44 H, H-5-α), 3.72-3.57 (m, 1.27 H, H-6"-α+β and H-3-α), 3.45-3.20 (m, 7.8 H, H-3-β, H-4-α+β, H-5-β and H-2-α) and 3.10-2.98 (m, 0.56 H, H-2-β). Compound 23: 4.6-O-(2-Acetoxybenzylidene)-D-glucopyranose 2-Acetoxybenzaldehyde is prepared, either by acetylation of 2-hydroxybenzaldehyde or by reduction of 2-acetoxybenzoyl chloride. A catalytic amount of p rα-toluene sulfonic acid is added to an equmolar mixture of 2-acetoxybenzaldehyde and trimethyl ortoformate. After stining for 1 h., an equal molar amount of D-glucose and DMF are added and the mixture heated to about 60 °C. The conversion is followed by TLC chromatography and when an equilibrium is reached, the reaction is quenched by the addition of a small amount of pyridine. Most of the DMF is evaporated at reduced pressure and the residue applied on silica as described previously. This is purified by chromatography, the product fractions isolated and evaporated and the compound analysed by NMR spectroscopy. Compound 24: 4,6-O-(2,3-Dihydroxybenzylidene)-D-glucopyranose The title compound is prepared and purified as described previously, starting from 2,3-dihydroxybenzaldehyde. The identity is confirmed by NMR spectroscopy. Biological Experiments 10 Example 1 Biological materials and methods used to demonstrate the effect- 15 Cell Culturing Techniques Human cells, NHIK 3025, originating form a cervical carcinoma in situ (Nordbye, K., and Oftebro, R. Exp. Cell Res., 58: 458, 1969, Oftebro R., and Nordbye K., Exp. Cell Res., 58: 20 459-460, 1969) were cultivated in Eagel's Minimal Essential Medium (MEM) supplemented with 15% foetal calf serum (Gibco BRL Ltd). Human breast carcinoma cells, T-47D, (Keydar, I. et al., Eur. J. Cancer, vol 15, pp. 659-670, 1979) were cultivated in medium RPMI-1640 supplemented with 10% foetal calf serum, 0.2 u/ml insulin, 292 mg/ml L-glutamine, 50 u/ml penicillin, 50 mg/ml streptomycin. The cells are routinely 25 grown as monolayers at 37°C in tissue culture flasks. In order to maintain cells in continuos exponential growth, the cells were trypsinised and recultured three times a week. 30 Cell Survival Cell survival was measured as the colony forming ability. Before seeding, the exponentially growing cells were trypsinised, suspended as single cells and seeded directly into 5 cm plastic dishes. The number of seeded cells was adjusted such that the number of surviving cells would be approximately 150 per dish. After about 2 h incubation at 37°C, the cells had attached to the bottom of the dishes. Drug treatment was then started by replacing the medium with medium having the desired drug concentration. Following drug treatment the cells were rinsed once with warm (37°C) Hank's balanced salt solution before fresh medium was added. After 10 to 12 days at 37°C in a CO2-incubator, the cells were fixed in ethanol and stained with methylene blue before the colonies were counted. Fig. 1-3 show cell surviving fraction for NHIK 3025-cells treated for 20 hours with either Compound 8 and 9 (Fig. 1), Compound 5 and 7 (Fig. 2) or Compound 12 (Fig. 3). The data indicate that all compounds induce cell inactivation in a drug dose range similar or better to that of zilascorb( 2 H) (Pettersen et al., Anticancer Res. vol. 11, (1991), pp. 1077-1082). It can be seen from Fig. 4 that Compound 2 incuces greater cell inactivation than Tucaresol. Example 2 Protein Synthesis The rate of protein synthesis was calculated as described previously (Ronning, O. W. et al., J. Cell Physiol., 107: 47-57, 1981). Briefly, cellular protein was labelled to satuarion during a minimum 2 day preincubation with [ 14 C]valine of constant specific radioactivity (0.5 Ci mol). In order to keep the specific radioactivity at a constant level, a high concetration of valine (1.0 mM) was used in the medium. At this concetration of valine, the dilution of [ 14 C]valine by intracellular valine and proteolytically generated valine will be negligible (Ronning, O. W., et al, Exp. Cell Res. 123: 63-72, 1979). The rate of protein synthesis was calculated from the incorporation of [ 3 H] valine related to the total [ 14 C]radioactivity in protein at the beginning of the respective measurement periods and expressed as percentage per hour (Ronning, O. W. et al., J. Cell Physiol., 107: 47-57, 1981). It can be seen from Fig. 5 that Compound 2 induces greater protein synthesis inhibition than Tucaresol. Example 3 Experiments on human xeno grafts in nude mice Drugs were tested in the treatment of three human cancer xenografts implanted into female, athymic mice. The cell lines used are SK-OV-3 ovarian carcinoma, A-549 lung carcinoma and Caco-2 colorectal carcinoma. They were purchased from the American Type Culture Collection and cultivated shortly in vitro before being implanted into nude mice. The tumour lines were passaged as s.c. implants in nude mice. Mice which should be used in experiments were 8-9 weeks of age at the time of tumour implantation. Small tumour pieces were implanted s.c. on the left flank of the animals. Animals with growing tumours (tumour volumes 25-110 mm 3 ) were randomly assigned to drug-treated or control groups, with the average tumour size among the groups being approximately equal. The antitumour activity was measured by tumour volume growth curves and histological evaluation of some tumours. During treatment tumours were measured 2 times a week by measuring two perpendicular diameters using calipers. Tumour volume was estimated by the formula: volume = (length x width 2 )/2. The tumour volume growth curves were generated by standardising the tumour sizes in the different groups by obtaining relative tumour volume (RV) calculated by the formula RV = Vx/Vl, where Vx is the tumour volume at day x and VI is the initial volume at the start of the treatment (day 1), and plotting the mean volume with standard enors for each treatment group as a function of time. An exponential curve was fitted to the relative tumour volume growth data and the interval during which the tumour volume in each group increased to twice its volume, tumour volume doubling time (TD), was determined from the fitted curve (loge2/&, where k is the estimated rate constant for the process.) Histological evaluation was based on macroscopic examination of the tumour and light microscopic examination of small tumour sections (6-8 mm thick) embedded in paraffin and stained with hematoxylin and eosin. In the table 1 tumour volume doubling time (TD) in human tumour xenografts grown in nude mice, treated daily i.v. with drugs and doses as indicated, are shown. Table 1: ^significant difference between treated group and control group, p<0.05. In Fig. 6 mean tumour growth curves of the tumour line SK-OV-3 ovarian carcinoma xenograft implanted in nude mice, where the mice were treated daily with 1 mg/kg and 7.5 mg/kg of Compound 8 are shown. The curves show a significant growth inhibitory effect for both doses. Fig. 7-12 show microscopic photographs of tumours from each group. These photographs indicate a general finding of this compound, namely that there is a difference with respect to tumour cell necrosis between control tumours and those treated with Compound 8. Since the treated tumours are necrotized by the treatment the drug effects are in reality even stronger than that shown by the growth curves. Example 4 Multicellular spheroids and activation of retinoblastoma protein (pRB) Spheroids were initiated by transferring suspended single cells to a 25 cm 2 tissue culture flask containing 12 ml of medium. The flask was then placed on a tilting board (MIXER 440, Swelab Instrument) inside a walk-in incubator room at 37 °C. Tilting rate was adjusted to 10 tilts per 18 s. During tilting the suspended cells were prevented from attaching to the bottom of the flask. Instead many cells were able to attach to each other forming small aggregates of cells containing typically 50-100 cells each after about 24 h tilting. The small aggregates were then transferred to another 25 cm 2 tissue culture flask. In this case the bottom of the flask was on beforehand covered (i.e. coated) with a thin layer of 1.3% sterilised agar (Bacto-Agar, Difco Laboratories, USA). The cell aggregates sedimented on top of the agar layer and were unable to attach to this. The cells within the aggregates, however, attached to each other, started cell division. After 1 week the aggregates had doubled their volume several times and had become rounded like spheroids. During this period medium was changed 3 times per week and the spheroids were transfened to new agar-coated flasks once each week. When spheroids had reached a size of about 400 μm in diameter (after 2 to 3 weeks cultivation) they were transferred to small micro wells, with 1 spheroid per well together with 1 ml medium. It was made sure that all selected spheroids were of about the same size. The wells were also coated with agar in order to avoid attachment of spheroids to the bottom of the wells. The various wells were supplemented with new medium containing the test substance in the chosen concentration and thereafter the diameter of each individual spheroid was measured once each day. This was done by microscopy, using phase contrast optics and a grating of known line separation in one of the oculars (distance between two neighbouring lines. In each group there were 8-12 parallel spheroids. Relative spheroid volume (volume at day n divided by volume at day 1) was calculated for each individual spheroid each day and growth cures were plotted with mean relative volume for all spheroids in a group as a function of time after start of treatment. In the table 2 T-47D spheroid volume doubling time (TD) treated for 259 hours with Compound 8 at doses indicated, are shown. Table 2 shows volume doubling times of spheroids of T-47D-cells either untreated (dose = OmM) or treated continuously with 0.1 or 1.0 mM Compound 8 in the medium. Compound 8 is shown to increase the spheroid doubling times (i.e. inhibiting spheroid growth) in a dose-dependent manner, since the effect is clearly stronger with 1.0 mM than with 0.1 mM of the drug. Table 2: * significant difference between treated group and control group p<0.05. In Fig. 13 mean spheroid volume growth curves of cell line T-47D breast carcinoma where the spheroids were treated with 0.1 mM and 1.0 mM Compound 8 dissolved in medium, are shown. With NHIK 3025-cell spheroids the increase with time of spheroid volume was not found to be reduced in the same manner as was found with T-47D cell spheroids of. Instead the spheroids treated with Compound 8 disintegrated after relatively short time treatment (7 to 10 days). In order to elucidate the reason for this strong effect we performed an experiment treating spheroids of NHIK 3025-cells for only 4 days and then preparing histological sections of the spheroids. The results of this experiment is shown in Fig. 14. Fig. 14 shows microscopic photographs of sections of 3 differently treated NHIK 3025 cell spheroids, one untreated control (A), one treated with 0.1 mM Compound 8 for 4 days (B) and one treated with 1.0 mM Compound 8 for 4 days (C). Spheroids were fixed in 4% formaldehyde and embedded in paraffin before 6mm thick sections were made and stained with haematoxylin and eosin. Both spheroids treated with Compound 8 show considerable central areas where the cells have an appearance indicating that they are in apoptosis. Apoptotic figures were not found in any of the control spheroids, but was widespread in the Compound 8-treated spheroids. In both types of cells treated with Compound 8 there is a clear drug effect although different in the one cell type as compared to the other. In spheroids of T-47D cells there is a reduced volume growth in drug-treated spheroids which is drug-dose dependent. In spheroids of NHIK 3025 cells there is no reduction in spheroid volume growth due to the drug treatment, rather the volume increases faster in treated spheroids as compared to control spheroids over a period of 9 days. However, in these spheroid there is a substantial fraction of cells undergoing apoptosis in the drug-treated spheroids, so that debris from dead cells in this case constitutes much of the spheroid volume. The rapid increase in volume for these spheroids is probably due to changes in osmotic pressure following lysis of cell fragments. Due to the swelling these spheroids became unstable and disintegrated after about 9 days. The reason for the difference in response between the two cell types can not be stated with certainty. There is, however, an important genetical difference between the two cell types with respect to regulation of cell growth and -proliferation which may be part of the reason for the difference. T-47D cells express functional pRB, the retinoblastoma protein, which is a normal tumour suppressor gene that is important in regulating cell-cycle progression in normal cells. This gene is often defect in cancer cells, and NHIK 3025 cells are among those with a defect pRB-function. We have observed that pRB may be activated to arrest cells under conditions of stress even when cells have entered the S-phase of the cell cycle, indicating that this gene may protect cells against the inactivating effects of a stress in combination with DNA-synthesis (see Amellem, Sandvik, Stokke and Pettersen, British Journal of Cancer 77 (1998) 862-872). In the present study the benzaldehyde derivative acts as a growth-inhibitory stress influence. Thereby it is possible that The T-47D-cells are protected by their functional pRB, and therefore do not induce apoptosis whereas NHIK 3025-cells having a defect pRB-function are unable to avoid apoptotic death. In order to test activation of pRB we used two different cell types which both have a normal expression of pRB, T-47D- and MCF-7-cells. The nucleii-bound pRB-protein was measured by means of flow cytometry. Coincident measurement of DNA was also performed and data were presented as two-parametric DNA versus pRB -histograms. Fixation and staining methods were performed as described by Amellem, Sandvik, Stokke and Pettersen, British Journal of Cancer 77 (1998) 862-872. Briefly, detergent-extracted cells were prepared by resuspending cells in 1.5 ml of low-salt detergent buffer. The extracted nucleii were fixed in 4% paraformaldehyde for lh before pRB was bound with the PMG3-245 monoclonal antibody (Pharmingen) which recognise both the under- and hyperphosphorylated forms of the protein. The pRB antibody was streptavidin-FITC-stained and DNA was stained with Hoechst 33258. The nucleii were measured in a FACStart plus flow cytometer (Becton-Dickinson) equipped with two argon lasers (Spectra Physics) tuned to 488 nm and UV respectively. The data of Fig. 15-18 show the fraction of nuclei within each of the interphase stages, Gl, S and G2, having the RB -protein bound in the nucleus following treatment with Compound 8. When bound this way pRB is considered to regulate cells out of the cell cycle, i.e. to take over cell-cycle control, (see Amellem, 0., Stokke, T., Sandvik, J.A. & Pettersen, E.O.: The retinoblastoma gene product is reversibly dephosphorylated and bound in the nucleus in S and G2 phase during hypoxic stress. Exp. Cell Res. 227 (1996) 106-115.) Data are shown for two types of human breast cancer cells, MCF-7 (Fig. 15 and 16) and T-47D (Fig. 17 and 18) and for drug treatment times of 24h (Fig. 15 and 17) and 48h (Fig. 16 and 18). For both cell types Compound 8 at concentrations above 0.5 mM induces increased fractions of nuclei with bound pRB in all interphase stages. The effect increases with increasing treatment time, and is thus far more pronounced after 48 than after 24h of treatment. This is taken to indicate that the substance activates cell-cycle regulatory action by pRB, resulting in reduced cell-cycle progression. The drug dose dependence is complicated, however, showing a maximum effect for Compound 8 doses around 1 mM and a decrease for higher drug doses. Thus, we see a bell-shaped dose response curve in much the same way as was shown for Compound 10 in the animal experiment on SK-OV-3 xenograft in nude mice (see table 1). Although it is so far not known why the pRB -activation is reduced for Compound 8 doses above 1 to 1.5 mM it is interesting to notice that we have found a relatively strong protein synthesis inhibition with this drug at these doses. Following 24 h treatment of NHIK 3025-cells with 1.5 mM Compound 8 the rate of protein synthesis is 70 % of that of control cells (see Fig. 19). In Fig. 20 it is shown that protein synthesis following 24h treatment with either 1.5 or 2.5 mM Compound 8 is 75 or 50% respectively, but increases back to normal in about 6h after removal of the drug. Possibly cell-cycle inhibition that inevitably follow as a result of the reduced protein synthesis inhibition (see Rønning, 0.W., Lindmo, T., Pettersen, E.O. & Seglen, P.O.: Effect of serum step-down on protein metabolism and proliferation kinetics of NHIK 3025 cells. J. Cell Physiol. 107 (1981) 47-57.) is in itself over-ruling the regulatory effects of pRB at concentrations in the range 1.5 to 2.5 mM. Example 5 Cell adhesion measurements Cell adhesion forces were measured using the manipulation force microscope (G. Sagvolden. Manipulation force microscope. Ph.D. thesis, University of Oslo, 1998, and G. Sagvolden, I. Giaever and J. Feder. Characteristic protein adhesion forces on glass and polystyrene substrates by atomic force microscopy. Langmuir 14(21), 5984-5987, 1998.). Briefly, NHIK 3025 carcinoma cells were cultured in CO 2 -independent medium containing 15% fetal calf serum. The cells were exposed to a 1 mM concentration of Compound 1 or Compound 2 for 20 hours before they were released from the cell culture flasks using trypsin. The cells were kept in suspension, and seeded in medium with Compound 1 or Compound 2 on polystyrene tissue culture substrates 90 minutes after the trypsin reaction had been stopped. The cell-substrate adhesion forces were measured by displacing cells using an inclined atomic force microscope cantilever acing as a force transducer. One cell was displaced at a time and each cell was displaced only once. The maximal force exerted on each cell was recorded as a function of the time since the cells were seeded on the substrate. The median force of a group of 19 measurements is shown as a function of the mean time for cells exposed to Compound 1 or Compound 2 in Fig. 21, together with the adhesion forces of cells not exposed to these compounds. Compound 2 shows a large effect in reducing the adhesion force at this concentration, while Compound 1 shows no significant response. The effect of the compound is mainly to reduce the adhesion force of the cells, but not the time course of adhesion. The reduced ability to attach to the substrate may be related to the blocking of integrin-mediated anchorage of the cells. It has been shown that such blocking may induce programmed cell death in both hepatoma and melanoma cancers. (Paulsen JE, Hall KS, Rugstad HE, Reichelt KL and Elgjo K, The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglytamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into buffalo rats and athymic mice. Cancer Res. 52 (1992) 1218-1221. and Mason MD, Allman R, and Quibell M, "Adhesion molecules in melanoma - more than just superglue?" J. Royal Soc. Med. 89 (1992) 393-395.) The adhesion force between NHIK 3025 cells and the substratum was measured after pre-incubation of the cells in solutions of Compounds 1 and 2. Even at 1 mM concentration, an astonishing D-isotope effect was shown. Surprisingly, Compound 2 significantly reduced the adhesion force to 1/3 relative to control, whereas Compound 1 did not lead to significant reduction. The inventors believe that Compound 2 may have interfered with the biosynthesis of integrins, reducing the cell's ability to attach to the substratum. Integrins are structural trans-membrane proteins crucial for binding cells to the extracellular matrix and for cell-cell interactions. Inhibiting the function of the integrins could thus directly affect the metastasising ability of cancer cells. The experiment indicate that integrines could be especially sensitive to protein synthesis inhibition. Thus, Compound 2 could well be used for prevention of metastatic processes in cancer development. Example 6 Experiments with Compound 2 and Compound 5 in NMRI mice infected with FRIEND erythroleucaemia virus (FLV). Virus: Eveline cells were supplied by prof. Gerhard Hunsman, Munich. We have shown that this virus, which originally was used as a source of Friend helper virus, contain a defect virus of the same size as Spleen Focus Forming Virus (SFFV) which induces erythroleukaemia in NMRI mice after a delay of 4-8 weeks. 10 Mice: NMRI mice came from old Bomholt Farm, Denmark, and were purchased via SIFF. The mice were received on May 6th and entered into the experiment on May 11th. They were then infected with 50 microlitres supernatant from Eveline culture, intraperi tonally. After 24 hours the treatment was started. Compound 2 and Compound 5 were dissolved in 15 sterile isotonic glycerol solution in a concentration conesponding to 5 mg per kg when giving 50 microlitres intraperi tonally. The experiment was set up as follows: 20 10 mice uninfected control 10 mice infected control 5 mice uninfected, treated with Compound 2 10 mice infected, treated with Compound 2 5 mice uninfected, treated with Compound 5 25 10 mice infected, treated with Compound 5 The mice were given injections intraperitonally once daily for 19 days. From June 1st till June 16th, when they were sacrificed, no treatment was given. On June 16th, the mice were sacrificed. Blood was withdrawn (for future analysis). The spleen was removed and 30 weighed (see table 3 below). One bit of the spleen was frozen in nitrogen for the purpose of cutting thin slices and one bit was formaline fixated. Table 3: The results can also be seen in Fig. 23. As one can see, there is a significant difference in spleen weights in infected animals compared to uninfected controls. Weights of uninfected animals treated with Compound 2 or with Compound 5 are above the weights of uninfected controls, even if this is not significant. One notices that infected animals which were treated with Compound 2 actually have a lower average spleen weight compared to uninfected animals which were treated similarly (here, it is assumed that the outcome stems from one animal in the control group having a comparatively big spleen). A histological examination revealed that the uninfected controls have a normal spleen anatomy. All animals in the infected untreated group have invasion of pathological leukaemia cells in the red pulpa. The spleens, both from the uninfected Compound 2 - and Compound 5 - treated animals, have hypertrofic germinal centra, which are interpreted as an expression of immune stimulation. One does not find leukemic changes in spleens from the Compound 2 - treated infected group. In the Compound 5 - treated group, the animal with the biggest spleen (308 g) had leukemic changes while all in the infected control group had leukemic changes. The results are encouraging taking into consideration the aggressive nature of FLV in mice and also when one compares the effect with that seen with azidothymidine and other anti-virus treatment. Example 7 Proliferation of peripheral blood mononuclear cells The inventors performed an experiment where peripheral blood mononuclear cells were exposed to Superantigen together with benzaldehyde, deuterated benzaldehyde, Compound 2 or zilascorb( 2 H). Superantigen is used as a very active standard for proliferation of T-cells and is presented via antigen presenting cells to T-cells. The experiment demonstrated (see figur 22) that by adding benzaldehyde, deuterated benzaldehyde or Compound 2, the proliferation of peripheral blood mononuclear cells was increased significantly in a bell-shaped, dose-dependent manner, whereas very little effect was observed with zilascorb( 2 H). The fact that we are able to increase the proliferation signal from the Superantigen indicates that the compounds act by additional co-stimulatory effects on the T-cells. Example 8 Effect on liver invasive colorectal cancer in nude mice Material and Procedures The cell line evaluated, C170HM2, is an established human colorectal cell line (S.A.Watson et al., Eur.J.Cancer 29A (1993), 1740-1745) and was derived originally from a patient's primary tumour. C170HM2 cells were maintained in vitro in RPMI 1640 culture medium (Gibco, Paisley, UK) containing 10% (v/v) heat inactivated foetal calf serum (Sigma, Poole, UK) at 37°C in 5% C0 2 and humidified conditions. Cells from semi-confluent monolayers were harvested with 0.025% EDTA and washed twice in the culture medium described above. C170HM2 cells harvested from semi-confluent cell monolayers were re-suspended at lxl0 6 /ml of sterile phosphate buffered saline, pH 7.4 [PBS] and injected in a 1 ml volume into the peritoneal cavity of 20 MF1 male nude mice (bred within the Cancer Studies Unit at the University of Nottingham). Mice were identified by an electronic tagging system (RS Biotech DL2000 Datalogger). On day 10 following cell injection, the mice were randomly assigned to alter a placebo control group or experimental groups;- Group 1 : Compound 1 5 mg/kg 30 mg/kg 90 mg/kg Group 2: Compound 2 5 mg/kg 30 mg/kg 90 mg/kg Group 3: Compound 5 20 mg/kg 40 mg/kg 90 mg/kg The drugs were dosed intravenously (iv) from day 10 and continue until therapy termination. The experiment was terminated at day 40 post cell implantation. Mice were weighed at regular intervals throughout the pilot study. At termination the liver was exposed, and visible liver tumours were counted and their total cross-sectional area measured. The tumours were also photographed. No liquefaction of the tumours had occuned, thus they were dissected free from the normal liver tissue, weighed and fixed in formal saline. Peritoneal nodules were dissected free and the cross-sectional area and weight measured. Detailed pathological assessment of the tumours was performed. The effect of Compound 1, 2 and 5 on the liver invasion of the human colorectal tumour, C170HM2 is shown in Fig. 24. Example 9 Biological effects of Compound 13 compared with Compound 1 Cell Survival Fig. 25 shows cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (O) or Compound 13 (•). Cells were treated in open plastic Petri dishes incubated in CO 2 -incubators at 37°C. The plotted survival values represent mean values from 5 simultaneously and similarly treated dishes. Standard enors are indicated by vertical bars in all cases where they exceed the size of the symbols. The data indicate that Compound 13 induce roughly a 10 times stronger inactivating effect than Compound 1 on a dose basis. Example 10 Biological effects of Compound 14 compared with Compound 1 Cell Survival Fig. 26 show cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (O) or Compound 14 (•). Cells were treated in open plastic Petri dishes incubated in CO 2 -incubators at 37°C. The plotted survival values represent mean values from 5 simultaneously and similarly treated dishes. Standard enors are indicated by vertical bars in all cases where they exceed the size of the symbols. The data indicate that the two compounds induce similar inactivating effect over the whole concentration range up to 12 mM. Example 11 Biological effects of Compounds 21 and 22 compared with Compounds 1, 2 and L- glucose Protein Synthesis Fig. 27 show rate of protein synthesis of human cervix carcinoma cells, NHIK 3025, as measured by amount of incorporated [ 3 H]-valine during a pulse period of lh starting either immediately following addition of test compound (closed symbols) or starting 2h later (open symbols). Test compounds, Compound 1 and Compound ' 21, were present from time zero to the end of the pulses. Cells were pre-labeled with [ 14 C]-valine for at least 4 days in order to have all cellular protein labeled to saturation. Incorporated amount of [ 3 H] was related to incorporated amount of [ 14 C] so that protein synthesis was calculated as per cent of the total amount of protein in the cells. Rate of protein synthesis is given as per cent of that in an untreated control. The plotted values for protein synthesis represent mean values from 4 simultaneously and similarly treated wells. Standard enors are indicated by vertical bans in all cases where they exceed the symbols. The data indicate that Compound 1 induces a protein synthesis inhibition which increases linearly with increasing concentration of drug while little or no effect is seen by Compound 21. Fig. 28 show rate of protein synthesis of human cervix carcinoma cells, NHIK 3025, as measured by amount of incorporated [ 3 H] -valine during a pulse period of lh starting either immediately following addition of test compound (closed symbols) or starting 2h later (open symbols). Test compounds, Compound 2 and Compound 21, were present from time zero to the end of the pulses. Cells were pre-labeled with [ 14 C]-valine for at least 4 days in order to have all cellular protein labeled to saturation. Incorporated amount of [ H] was related to incorporated amount of [ 14 C] so that protein synthesis was calculated as per cent of the total amount of protein in the cells. Rate of protein synthesis is given as per cent of that in an untreated control. The plotted values for protein synthesis represent mean values from 4 simultaneously and similarly treated wells. Standard enors are indicated by vertical bans in all cases where they exceed the symbols. The data indicate that both Compound 2 and Compound 22 induces an effective inhibition of protein synthesis at about the same level for both compounds. Both these two deuterated compounds are more effective than the corresponding undeuterated compounds shown in Fig. 27. Cell Survival Fig. 29 show cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 1 (•) or Compound 21 (O). Cells were treated in open plastic Petri dishes incubated in CO 2 -incubators at 37°C. The plotted survival values represent mean values from 5 simultaneously and similarly treated dishes. Standard enors are indicated by vertical bans in all cases where they exceed the size of the symbols. From the data the dose response curves follow different shapes for the two compounds, indicating that Compound 21 is more effective than Compound 1 in inactivating cells at low compound-concentrations. The differences in curve shapes indicate different mechanisms of cell inactivation for these two drugs. Fig. 30 show cell survival as measured by colony-forming ability for human cervix carcinoma cells, NHIK 3025, after treatment for 20h with either Compound 2 (O) or Compound 22 (A). Cells were treated in open plastic Petri dishes incubated in CO 2 -incubators at 37°C. The plotted survival values represent mean values from 5 simultaneously and similarly treated dishes. Standard enors are indicated by vertical bans in all cases where they exceed the symbols. Compound 22 is more effective than Compound 2 in inactivating cells, particularly in the low-dose region. For example is cell survival down to 50% following treatment with 0.5 mM of Compound 22 and 4 mM of Compound 2 respectively, indicating an 8-fold higher inactivating efficiency of Compound 22 compared to Compound 2 at this particular effect level. At a survival level of 10 % the difference is much smaller. Fig. 31 show cell survival as measured by colony-forming ability for human breast carcinoma cells, T47-D, after treatment for 20h with either L-glucose (•) or Compound 21 (O). Cells were treated in open plastic Petri dishes incubated in CO 2 -incubators at 37°C. The plotted survival values represent mean values from 5 simultaneously and similarly treated dishes. Standard enors are indicated by vertical bans in all cases where they exceed the symbols. The data indicate that L-glucose has little or no effect on cell survival for concentrations up to at least 10 mM, the highest dose tested. Compound 21 also has little effect on these cells for concentrations up to 2 mM, but induces considerable inactivating effect for higher concentrations and only one of 1000 cells survive 20h in presence of 8 mM of this compound. Conclusion Both the two L-glucopyranose derivatives tested (Compounds 21 and 22) inactivate cells more effectively than the conesponding D-glucopyranose derivatives (Compounds 1 and 2). L-glucose alone, however, does not induce any significant cell inactivating effect for concentrations tested here. Thus, it is in the context of a benzylidene derivative this increased effect of L as compared to D glucose is found. Example 12 Testing of the effect of Compound 2 in ova-sensitized and challenged animals. Male Balb/C mice of 6 weeks old were sensitized with 7 i.p. injections of 10 μg ovalbumin in 0,5 ml saline on alternate days. Three weeks after the last injection, the mice were exposed to 8 ovalbumin ( 2 mg/ ml ) or 8 saline aerosols on consecutive days, 1 aerosol per day for 5 minutes. Two days prior to the first ovalbumin alt. saline injection treatment with Compound 2 was started, 5 mg per kg given daily i.p, for a period of 10 days, nine animals given ovalbumin and nine animals given saline, the control groups were given saline. 24 hours post the last exposure, airway hypenesponsiveness in response to metacholine was measured in vivo using BUXCO set-up. After measuring in the BUXCO, the mice were put down, lungs lavaged and the isolated cells washed, counted and differentiated. Blood was taken to isolate serum for determination of total and ova-specific IgE-levels. Thoracic lymph nodes were isolated from paratracheal and parabronchial region for determination of IFN-gamma, IL-4, IL-5 and IL-12. The experiment contained 9 animals per group. The number of cells (Fig. 32) in saline treated or ovalbumine sensitized mice were not affected by Compound 2 treatment, and there was no difference in the count of the macrophages, the lymphocytes or the eosinophils between the two groups. Astonishingly, we found that the influx of neutrophils was inhibited by the Compound 2 treatment (Fig. 33). The number of neutrophils in the lung lavage is the same for the control and the ovalbumin sensitized animals treated with Compound 2, whilst the number of neutrophils increases in ovalbumine sensitized animals treated with saline. To our knowledge no other drug exert this kind of effect. The inhibition of the neutrophil influx could be of great value to medicine, as the tissue damage caused by neutrophil released lysosomal enzymes are thought to be of great importance in lung emphysema (also induced by smoking), in occupational asthma, inflammatory bowl diseases (like Morbus Crohn and Ulcerous colitt), rheumatoid arthritis and similar immunic disorders. This is a very surprising observation. Conclusions The benzaldehyde derivatives of this invention react with certain groups on the cell surface, e.g. with free amino groups to form Schiff s bases. As many cell processes, like protein synthesis, cell cycle, immune response etc. are controlled by signals from the cell-surface, these bindings will alter the behaviour of the cell. We have also shown that the benzaldehyde complex of the cell surface change the adhesion characteristics of the cell. We have shown that the compounds of this invention can be useful in new therapies to combat cancer, auto immune diseases, viral infections and possibly also infections of other microorganisms. We have found that the hexose derivatives of benzaldehydes are surprisingly more effective than derivatives of other carbohydrates in treating cancer in certain organs like liver, kidney and lung. We believe that this phenomenon is connected with receptor affinity of these organs to the sugar moiety of the derivatives. Administration The pharmaceutical compositions according to the present invention may be administered in anti-cancer treatment, anti-viral treatment or in treatment of diseases which arise due to abnormally elevated cell proliferation and/or for combating auto immune diseases. This pharmaceutical compositions may also be administered as immunopotentiators. For this purpose the compounds of formula (I) may be formulated in any suitable manner for administration to a patient, either alone or in admixture with suitable pharmaceutical caniers or adjuvants. It is especially prefened to prepare the formulations for systemic therapy either as oral preparations or parenteral formulations. Suitable enteral preparations will be tablets, capsules, e.g. soft or hard gelatine capsules, granules, grains or powders, syrups, suspensions, solutions or suppositories. Such will be prepared as known in the art by mixing one or more of the compounds of formula (I) with non-toxic, inert, solid or liquid carriers. Suitable parental preparations of the compounds of formula (I) are injection or infusion solutions. When administered topically the compounds of formula (I) may be formulated as a lotion, salve, cream, gel, tincture, spray or the like containing the compounds of formula (I) in admixture with non-toxic, inert, solid or liquid carriers which are usual in topical preparations. It is especially suitable to use a formulation which protects the active ingredient against air, water and the like. The preparations can contain inert or pharmacodynamically active additives. Tablets or granulates e.g. can contain a series of binding agents, filler materials, carrier substances and/or diluents. Liquid preparations may be present, for example, in the form of a sterile solution. Capsules can contain a filler material or thickening agent in addition to the active ingredient. Furthermore, flavour-improving additives as well as the substances usually used as preserving, stabilising, moisture-retaining and emulsifying agents, salts for varying the osmotic pressure, buffers and other additives may also be present. The dosages in which the preparations are administered can vary according to the indication, the mode of use and the route of administration, as well as to the requirements of the patient. In general a daily dosage for a systemic therapy for an adult average patient will be about 0.01 -500mg/kg body weight once or twice a day, preferably 0.5-100 mg/kg body weight once or twice a day, and most prefened 1-20 mg/kg weight once or twice a day. If desired the pharmaceutical preparation of the compound of formula (I) can contain an antioxidant, e.g. tocopherol, N-methyl-tocopheramine, butylated hydroxyanisole, ascorbic acid or butylated hydroxy toluene.

Claims: CLAIMS 1. Use of a benzaldehyde derivative of formula I: (I) wherein L is H or D; Ar is phenyl or substituted phenyl with 1-3 substituents, the substituents which are the same or different, are selected from the group comprising alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms, phenyl, halogen, nitro, cyano, NH 2 , NHR 1 , N(R') 2 , NHC(O)R' or N[C(O)R'] 2 wherein R 1 which is the same or different, is alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms, OR 2 or OC(O)R 2 wherein R 2 is H, D, alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms, SR 2 , CA(OR 1 ) 2 or CA[OC(O)R 1 ] 2 wherein A is H or D, C(O)R 2 , COOR 3 wherein R 3 is H or alkyl with 1-20 carbon atoms, or fluoroalkyl with 1-6 carbon atoms or CON(R 3 ) 2 wherein R 3 is the same or different; Y is selected from the atoms or groups comprising H, D, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms, fluoro, chloro, nitro, OR 2 , OC(O)R 2 , SR 2 , NH 2 , NHR 1 , N(R' ) 2 wherein R 1 is the same or different, NHC(O)R > or N[C(O)R'] 2 wherein R 1 is the same or different; R is H, D, alkyl with 1-20 carbon atoms, cycloalkyl with 3-6 carbon atoms, fluoroalkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms, alkynyl with 2-6 carbon atoms; with the proviso that 4,6-O-benzylidene-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-glucopyranose, 4,6-benzylidene-D-allose and derivatives of 4,6-benzylidene-D-allose are excluded, or any stereoisomer thereof, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of cancer. 2. Use according to claim 1 of 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-0- (4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of cancer. 3. Use according to claim 1, of 4,6-O-benzylidene-L-glucopyranose and/or 4,6-O-(benzylidene-dι)-L-glucopyranose or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of cancer. 4. Use according to claim 1, of a benzaldehyde derivative of formula I, with the proviso that 4,6-O-(benzylidene-dι)-D-glucopyranose, 4,6-O-benzylidene-L-glucopyranose and 4,6-O-(benzylidene-dι)-L-glucopyranose are excluded, or any stereoisomer thereof, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for prophylactic treatment of cancers induced by viruses like hepatitis B and C, oncogene papilloma viruses and other oncogene viruses. 5. Use according to claim 4, of 4,6-O-benzylidene-D-glucopyranose, 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for prophylactic treatment of cancers induced by viruses like hepatitis B and C, oncogene papillioma viruses and other oncogene viruses. 6. Use of a benzaldehyde derivative of formula I, or any stereoisomer thereof, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of infections caused by virus, protozoa, fungi and other microorganisms via alteration of the immune system. 7. Use according to claim 6, of 4,6-O-benzylidene-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-glucopyranose, 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of infections caused by virus, protozoa, fungi and other microorganisms via alteration of the immune system. 8. Use according to claim 6 or 7, of 4,6-O-benzylidene-L-glucopyranose and/or 4,6-O-(benzylidene-dι)-L-glucopyranose or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of infections caused by virus, protozoa, fungi and other microorganisms via alteration of the immune system. 9. Use of a benzaldehyde derivative of formula I, or any stereoisomer thereof, or a pharmaceutical acceptable salt thereof, with the proviso that 4,6-O-benzylidene-D-glucopyranose and 4,6-O-(benzylidene-dι)-D-glucopyranose are excluded, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of diseases arising from an abnormally elevated cell proliferation. 10. Use according to claim 9, of 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of diseases arising from an abnormally elevated cell proliferation. 11. Use according to claim 9, of 4,6-O-benzylidene-L-glucopyranose and/or 4,6-O-(benzylidene-dι)-L-glucopyranose or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of diseases arising from an abnormally elevated cell proliferation. 12. Use of a benzaldehyde derivative of formula I, or any stereoisomer thereof, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of auto immune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus erythematosis, acne, Bechterew's arthritis, progressive systemic sclerosis (PSS), seborrhea and other auto immune disorders like Ulcerous colitt and Morbus Crohn. 13. Use according to claim 12, of 4,6-O-benzylidene-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-glucopyranose, 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of auto immune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus erythematosis, acne, Bechterew's arthritis, progressive systemic sclerosis (PSS), seborrhea and other auto immune disorders like Ulcerous colitt and Morbus Crohn. 14. Use according to claim 12 or 13, of 4,6-O-benzylidene-L-glucopyranose and/or 4,6-O-(benzylidene-dι)-L-glucopyranose or a pharmaceutical acceptable salt thereof, for the manufacture of a therapeutical agent for the prophylaxis and/or treatment of auto immune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus erythematosis, acne, Bechterew's arthritis, progressive systemic sclerosis (PSS), seborrhea and other auto immune disorders like Ulcerous colitt and Morbus Crohn. 15. A benzaldehyde derivative useful as a therapeutic agent wherein the benzaldehyde derivative is 4,6-O-benzylidene-D-galactopyranose, methyl 4,6-O-benzylidene-α-D-mannopyranoside, 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-d i )-2-deoxy-D-glucopyranose, -acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, ,6-O-(benzylidene-dι)-D-galactopyranose, ,6-O-(benzylidene-dι)-D-mannopyranose, -acetamido-4,6-O-benzylidene-2-deoxy-α-D-galactopyranose, ,6-O-(3-nitrobenzylidene)-D-glucopyranose, ,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose and/or 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof. 16. A pharmaceutical composition comprising a benzaldehyde derivative according to any preceding claim, and a pharmaceutically acceptable canier, diluent and/or excipient. 17. A process for manufacture of a pharmaceutical composition, which comprises the step of incorporating a benzaldehyde derivative as defined in any preceding claim, together with a pharmaceutically acceptable carrier, diluent and/or excipient. 18. A benzaldehyde derivative defined as 4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 4,6-O-(4-carbomethoxybenzylidene)-D-glucopyranose, 4,6-O-benzylidene-2-deoxy-D-glucopyranose, 2-acetamido-4,6-O-(benzylidene-dι)-2-deoxy-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(benzylidene-dι)-D-galactopyranose, 4,6-O-(benzylidene-dι)-D-mannopyranose, 4,6-O-(3-nitrobenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-glucopyranose, 4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 2-acetamido-2-deoxy-4,6-O-(2-hydroxybenzylidene)-D-galactopyranose, 4,6-O-(2-hydroxybenzylidene)-D-mannopyranose, 4,6-O-(2-acetoxybenzylidene)-D-glucopyranose, 4,6-O-(2,3-dihydroxybenzylidene)-D-glucopyranose, or the conesponding L-sugar isomers, or a pharmaceutical acceptable salt thereof.

Inventors: BOERRETZEN BERNT, DUNSAED CAMILLA BRUNO, LARSEN ROLF OLAF, MOEN VIDAR, PETTERSEN ERIK OLAI, SAGVOLDEN GEIR, BOERRETZEN, BERNT, DUNSAED, CAMILLA, BRUNO, LARSEN, ROLF, OLAF, MOEN, VIDAR, PETTERSEN, ERIK, OLAI, SAGVOLDEN, GEIR
Applicants: BOERRETZEN BERNT, DUNSAED CAMILLA BRUNO, LARSEN ROLF OLAF, MOEN VIDAR, NORSK HYDRO AS, PETTERSEN ERIK OLAI, SAGVOLDEN GEIR, BOERRETZEN, BERNT, DUNSAED, CAMILLA, BRUNO, LARSEN, ROLF, OLAF, MOEN, VIDAR, NORSK HYDRO ASA, PETTERSEN, ERIK, OLAI, SAGVOLDEN, GEIR
Application year: 2000
Main classification: A61K31
IPC codes: A61K31, A61P1, A61P17, A61P19, A61P29, A61P31, A61P33, A61P35, A61P37, A61P43, C07H9, C07H15