FR2701950A1 - Synthesis of new disaccharides associating two derivatives of oses or of itols by means of a spacing arm, products obtained and applications, for example, as medication or surfactant - Google Patents

Abstract

We have prepared new disaccharide compounds associating by glycoside linkage or otherwise, two derivatives of oses or of itols A and B in the form of diether between sites chosen in advance, by means of a divalent radical R, of formula I: The process for the synthesis of these compounds includes especially the attack of a derivative of the unit A in alcoholate form on a reactant X-R1-X producing the intermediate A-R1-X which subsequently is subjected to attack of a derivative of the unit B in alcoholate form. The products obtained bear, respectively, 0 to 4 (n) groups ZIFI on the unit A and 0 to 4 (n') groups ZJGJ on the unit B, as well as a modulable number of free OH groups which may vary from 0 to 4 (p) on the unit A and from 0 to 4 (p') on the unit B. Surface-active and biological properties revealed by the products obtained are described with a view to applications as surface agents, catalysts for bleaching agents, calcium antagonist medications and antitumour medications.

Description

The present invention relates to the preparation of new disaccharide compounds associating two derivatives of monosaccharides A and B at sites selected in advance, via a carbon group R. It also concerns the new products obtained by this process and their applications as surfactant molecules, or as catalysts for bleaching agents, or as drugs, or as pesticides, or as chelants, or more generally as vectors of active biological principles; according to general formula I

 It is known that the most widespread natural or synthetic disaccharide compounds have structures that combine, by glycosidic junction, two identical monosaccharide units, for example maltose (glucose (1 → 4 ') glucose) or different ones, for example sucrose (glucose (1-> 1 ') fructose). It is also known that the direct functionalization (without prior protection) of the disaccharide compounds leads to mixtures of mono and polyfunctional isomers.

 One of the aims of the present invention is to describe the process for the synthesis of disaccharide compounds with or without glycoside junction, corresponding to the general formula I, from the same or different derivatives of oses or itols A and B.

 In these new compounds, A and B may be hexoses, pentoses, pentitols or glycerol or acetalized or etherified derivatives of these polyhydroxylated molecules. The junction between the two derivatives A and B can be in the form of diether between sites of A and B chosen in advance, and a bivalent carbonaceous group R.

 The units A and B may respectively carry a number n of groups (ZiFi) and n 'of group (ZjGj), n and n' being between 0 and 4. Fi and Gj may be derivatives of oses or itols acetalized or otherwise, functionalized or not, chosen for example from derivatives of hexoses, pentoses, pentitols and glycerol, or biologically active principles, or hydrophobic carbon chains or a protective group. The groups Fi may be identical or different, i ranging from 0 to n, as well as the groups Gj, j varying from 0 to n '. The carbon chain as a hydrophobic pole may be chosen for example from: a saturated or unsaturated, cyclic or non-branched or unbranched chain having at least seven carbon atoms. The protective group may be chosen, for example, from benzyl or allyl. The biologically active principles ZiFi and / or ZjGj may or may not be released in vivo from the disaccharide substrates.

 The groups Fi and Gj are grafted onto sites chosen in advance, by means of the respective atoms or groups of atoms Z1 and Zj. The atoms or groups of atoms Z1 may be identical or different, as may the atoms or groups of atoms. groups of atoms Zj, i and j respectively varying from 0 to n and from 0 to n ', with n and n' between 0 and 4. Zi and Zj are chosen for example from an oxygen atom, an atom of sulfur, or a carboxyl group.

 The numbers of free OH groups p and p 'carried respectively by A and B are between 0 and 4.

 The sum n + p of groups ZiFi and free OH groups on unit A is between 2 and 4.

 The sum n '+ p' of groups ZjGj and free OH groups on unit B is between 2 and 4.

The carbon group R, in the compounds corresponding to the formula
I, may be an alkylene group whose carbon number is between 1 and 20, or a bivalent saturated or unsaturated radical, branched or unbranched, cyclic or otherwise, bearing or not functional groups or groups of heteroatoms.

 The process according to the present invention consists in the synthesis of the compounds corresponding to formula I, according to steps a to g and subsequent, of scheme 1, illustrated for example from acetalized derivatives A = B of Dglucose.

Schema 1

<SEP> O <SEP> O <SEP> O
<tb> D-glucose <SEP> a <SEP>#<SEP>#<SEP> b <SEP>#<SEP>#<SEP> c2 <SEP>#<SEP>#
####
## EQU1 ##
<tb><SEP> O # <SEP>#O<SEP>#O
<tb><SEP>#<SEP> O
<tb><SEP> 1 <SEP>#<SEP> 2 <SEP>#<SEP> 3 '
<tb><SEP> c3 <SEP> c1
<tb><SEP>#
<tb><SEP>c'3
<tb><SEP> O <SEP> O <SEP> HO <SEP> HO
<tb><SEP> O <SEP> R '# OH <SEP>### O <SEP> O <SEP>#<SEP>#<SEP>#
<tb>#<SEP>## O <SEP> C <SEP> O <SEP>#<SEP>#<SEP>#O<SEP> O <SEP>#O<SEP> d1a <SEP> HO # <SEP> HO <SEP> O
## EQU1 ## O #
####
<tb><SEP> O <SEP> O <SEP> O #
<tb><SEP> 3 "<SEP> 3 <SEP> 3a
<tb>#(FjZj;;<SEP> GjZ ';<SEP> d2a # <SEP> e2 # <SEP>#
<tb><SEP> e1
<tb><SEP> HO <SE> O <SEP> O
####
#####
<tb> HO # O - ###
<tb><SEP>#O<SEP> O # <SEP> O # <SEP> O <SEP> O #
<tb><SEP> O #
<tb><SEP> 3 "to <SEP> 4 '<SEP># i3 <SEP># i1 <SEP> 4
<tb><SEP> HO <SEP> HO <SEP> F1Z1 <SEP>G1Z'1
<tb><SEP>#<SEP>#<SEP>#<SEP>#
<tb><SEP># O # OH <SEP>## O <SEP> HO ## O <SEP> HO # O <SEP>F2Z2;<SEP>G2Z'2
<tb><SEP>## O-CmH2m-O <SEP>#OH<SEP> O-CmH2m-O # O <SEP>#<SEP>#
<tb><SEP> HO <SEP> HO # <SEP> O #
<tb><SEP> OH
<tb><SEP> 3b <SEP> 5a
<tb> HO # <SEP> R '# OH <SEP> HO
<tb><SEP>#O<SEP> C <SEP># O # <SEP>#<SEP>#
<tb><SEP> HOO-CmH2 # <SEP># CmH2m-O <SEP>#OH
<tb><SEP> HO # OH
<tb><SEP>#<SEP> AcO # <SEP> O <SEP> AcO <SEP> F1Z1 <SEP> O <SEP>G1Z'1
<tb><SEP> FjZj: <SEP> GjZ) <SEP>#<SEP># -OAc <SEP>#O<SEP>#<SEP># -OH <SEP>#
#####
<tb><SEP> AcO # <SEP> OAc <SEP> HO <SEP> HO # <SEP># -OH <SEP>FjzJ;<SEP> GzZj
<tb><SEP>#<SEP>#
<tb><SEP> OH
<Tb>
Step a: protecting units A and B leading in one or more steps to type 1 compounds having a single free OH group.

 When the starting units A and B are hexoses, pentoses, pentitols or glycerol, the protection may be, for example, in the form of acetalized derivatives or ethers, prepared according to the methods described in the literature.

 The carbohydrate units A and B may also be protected as monoacetalised derivatives bearing previously defined groups, ZiFi and ZjGj. Step b: etherification of the compound of type 1, derived from unit A, by a bifunctional derivative X-R1 -X to type 2 compounds in which unit A bears the group O - R1 - X. This reaction can be carried out in the presence of a base in a polar solvent.

 The bifunctional derivative X-R 1 -X bears two leaving groups X chosen for example from chloride, bromide, iodide, mesylate, tosylate, brosylate, triflate; R1 may be an alkylene group whose carbon number is between 1 and 20, or a bivalent saturated or unsaturated radical, branched or unbranched, cyclic or otherwise, bearing or without functional groups or heteroatoms .

 The base may be chosen for example from LiOH, NaOH, KOH or, for example, an alkaline hydride, or for example an alcoholate.

The polar solvent may be, for example, selected from DMSO, DMF,
HMPA, employed alone or in combination with an apolar solvent selected, for example, from hexane, benzene, toluene.

 During the etherification step, the compounds of type 2 can lead in situ, on the one hand, to the symmetrical disaccharide derivatives of type Q with A = B, according to step c1, and / or on the other hand, to the products type 3 elimination by action of the base present in the medium, according to step c2.

 The relative proportions of the monoetherified and symmetrical disaccharide type 2 products can be modulated according to the initial concentrations of substrate 1 and X - R1 - X reagent.

Step cI: etherification of the compound of type a by the free OH group of unit B in alcoholate form, to give the disaccharide derivative of type a, symmetrical for A = B or asymmetric for A * B, with R = R1 .

 This step can be carried out in the same solvents and with the same bases as in step b of the present process according to the invention.

Step c2: Formation of the 3 'compound by elimination reaction on the z-type compound in the presence of a base.

 This step can be carried out by preferably choosing the leaving group X, for example, from chloride, bromide, iodide, with the same solvents and with the same bases as in step b of the present process according to the invention, or with hydroxylated bases in pure aprotic or hydroxylated solvents or in water-alkanol mixtures.

Step c3 and C'3: Formation of the Type 3 Symmetric Disaccharide Compound by the Transformation of the Type Z Compound into an Organometallic Compound (Step c3) followed by the Condensation of this Compound on a R'COOR "Ester or on a Halide R'COX 'acyl in an anhydrous aprotic solvent (step C'3) which leads to the symmetrical disaccharide compound of type 3 "with A = B and R =
R1-C (OH, R ') - R1.

 The organometallic derivative can be obtained, for example, by the action of magnesium or lithium on compounds of type 2 bearing a leaving group X in the form of, for example, chloride, bromide or, better still, iodide.

 The radical R 'of the ester or of the acyl halide may be a saturated or unsaturated, cyclic or non-branched or unbranched hydrocarbon chain, whether or not comprising heteroatoms, comprising 1 to 20 carbon atoms.

 The radical R "of the ester R'-COOR" may be of the same nature as R 'or better still the methyl or ethyl radical.

 The halogen atom X 'of the acyl halide may be, for example, chlorine or bromine.

 The anhydrous aprotic solvent may be an alkane, an aromatic hydrocarbon, a cyclic or acyclic ether, a tertiary amine, or a mixture of these solvents, or better, THF.

Steps dia, dlb, d2a, d2b: deprotection of compounds of type 3 and & respectively leading to products of type or 3k and type 4 or
Partial deprotection of hydroxylated sites of units A and / or B, according to steps d1a and d2a, respectively leads to products of type 3a and
3 ".

The total deprotection of hydroxylated sites of units A and B, according to steps dlb and d2b, respectively leads to products of type ak and
When the protective groups are acetals, these deprotections can be carried out by acidocatalysis in a pure hydroxylated solvent, chosen from water or alkanol, or in a water-solvent mixture, the cosolvent possibly being an alkanol such as, for example, methanol, ethanol or else a non-protic solvent such as, for example, dioxane or THF. The acidocatalysis can be carried out in a homogeneous phase, in the presence of an organic or inorganic acid or in a heterogeneous phase in the presence of an acidic resin.

 The selectivity of the deprotection is governed by the conditions of acidity, temperature and duration. The operating conditions will be adapted to control the degree of deprotection of units A and B.

 Steps e1 and e2: activation of compounds of type 4 and 4 for subsequent functionalization by regiospecific introduction of a leaving group X chosen for example from chloride, bromide or iodide, or else chosen for example from mesylate, tosylate> nosylate or triflate or by formation of an anhydro derivative of type 4 or a sulphito derivative or sulfato o type. The anhydro derivative of type 4 is obtained from compounds of type 4 and 4 activated by the leaving group X as defined above and having a free OH, by trans-elimination in the presence of a base. The base may be chosen from, for example, LiOH, NaOH, KOH or an alcoholate. The sulfite and sulfato derivatives of type 4 'are obtained respectively by the action of thionyl chloride and sulfuryl chloride on compounds of type 4 and 4 having two free OHs, in a solvent in the presence of a base. The solvent may be a saturated or aromatic hydrocarbon or any other non-hydroxylated solvent. The base may be chosen from pyridine or any other tertiary amine such as triethylamine for example.

Stage f: Regiospecific Grafting of F1Z1 and / or G1Z'1 Groups on Type 4 Intermediate, to Lead to XL-Type Products
The previously defined F1Z1 and G1Z'1 groups can be grafted onto the type 4 derivatives in the form of an alcoholate by adding a hydroxyl compound in the presence of a base in an aprotic solvent. The hydroxylated compound may be an alcohol having a number of carbon atoms of between 1 and 20 or a monosaccharide, itol or glycerol derivative carrying a single free OH. The base and the solvent may be chosen from those defined in step b according to the present process.

 The previously defined F1Z1 and G1Z'1 groups may be grafted onto the type 4 derivatives in the form of a thiol in an apolar solvent which may be a saturated or aromatic hydrocarbon. The grafting in thiol form may be favored by a Lewis acid such as, for example, the lithium ion in the form of, for example, lithium chloride.

 The same grafting can be carried out under the above conditions, from the Q-type compounds after activation under the conditions of step el of the present process.

 The f1 step can be followed in all cases of grafting, on sites carrying a free OH group, F2Z2 and / or G2Z'2 groups as previously defined. These graftings can be carried out in the form of an ether under the conditions of stage b of the present process according to the invention or in the form of an ester under the conditions of stage f 2 of the present process according to the invention, or still in the form of thioether, after activation of the free OH group.

Step f2: regioselective grafting of FlZ1 and / or G1Z'1 groups on the products of type 3a, to lead to type 4 products.

The groups F1Z1 and / or G1Z'1 can be grafted directly in the form of O-acyl groups by action of an acid chloride on the OH primary site or sites of the compounds of type 4, in an aprotic solvent in the presence of a base. The acid chloride may contain 1 to 20 carbon atoms; the solvent may be a saturated or aromatic hydrocarbon such as toluene for example; the base may be pyridine or any other tertiary amine such as triethylamine for example. Step f2 can be followed in all cases by the introduction on the sites carrying a free OH group, F2Z2 and / or G2Z'2 groups in ester form which are identical or different from
F1Z1 and / or G1Z'1.

 The same grafting can be carried out under the above conditions, starting from the compounds of type 4.

Step f3: regiospecific grafting of groups F1Z1 and / or G1Z'1 on the intermediate 4 ', to lead to XL type products
The previously defined groups F1Z1 and / or G1Z'1 can be grafted as an O-acyl group by adding a carboxylic acid salt to the type intermediate in a solvent defined in step b of the present process. The carboxylic acid may have a number of carbon atoms of between 1 and 20.

 The same grafts can be made from compounds of type 4, under the above conditions, after activation according to step e2 in the form of derivatives similar to 4 '.

 Step f3 can be followed in all cases of grafting, on sites carrying a free OH group, F2Z2 groups and / or G2 Z'2 as previously defined. These graftings may be carried out in the form of an ether under the conditions of stage b of the present process according to the invention or in the form of an ester under the conditions of stage f 2 of the present process according to the invention, or still in the form of thioether, after activation of the free OH group.

Step f4: Peracetylation of Type 3b Compounds to Lead to 5'b Products
The peracetylation can be carried out with acetic anhydride or with acetyl chloride in an aprotic solvent in the presence of a base; the solvent may be an aromatic hydrocarbon such as toluene for example; the base may be pyridine or any other tertiary amine such as triethylamine, for example; the base can be used in excess, to constitute 50 to 80% of the medium. The peracetylation can also be carried out with the anhydride-acetic acid mixture sodium acetate in saturated aqueous solution.

 The peracetylation can also be carried out under the above conditions on the compound of tpe 3 "k.

Stage g: total deprotection followed or not by new grafting.

 The total deprotection of the compounds of type 4, carrying F1Z1 and / or G1Z'1 groups as well as the deprotection of their homologues described in steps f1, 2 and f3, carrying groups F2Z2 and / or G2Z'2, can be carried out under the conditions defined in steps dlb and d2b of the present process according to the invention. The products of type ak and 3 "k are then obtained, as well as their homologues carrying group F2Z2 and / or G'2Z'2.

The total deprotection can be followed in all the cases of the grafting, on the sites carrying a free OH group, of groups F3Z3 and F4Z4 and / or
G3Z'3 and G4Z'4, as previously defined, under the same conditions as those used for grafting F1Z1 and G1Z'1 or F2Z2 and G2Z'2.

 The compounds obtained according to the process according to the present invention are intended for use as surfactants or as medicaments, or as pesticides or more generally as vectors of biological active principles, or as catalysts for bleaching agents.

 In addition to the preceding provisions, the invention also comprises other provisions, which will emerge from the description which follows. It should be understood, however, that this description and the examples which it contains are given solely by way of illustration of the subject of the invention of which they in no way constitute a limitation.

EXAMPLE 1 Synthesis of Disaccharide Compounds from A = B = D-Glucose, of 3,3'-OR-bis (6-Z1F1-monoacetoneglucose) Structure and Corresponding Partially or Completely Deprotected Derivatives, of Type:
31a and 31b, 3 "1a, 3111b with R = -CH2-; -n-C4H8-; -n-C8H16-; -n-C10H20-; -n-C4H8-C (OH, C7H15) -n-C4H8 -etZ1F1 = Z1G1 = OH
- 51a1> with R = -n-C4H8- and Z1F1 = Z'1G1 = On-octyl
- 51a2 and 51b2> with R = -n-C4H8- and Z1F1 = Z'1G1 = On-dodecyl
- 51a3, with R = -CH2-; -n-C4H8- and Z1F1 = Z'1G1 = O-butanoyl
- 51a4 and 51b4, with R = -CH2- ;; -n-C4H8- and Z1F1 = Z'1G1 = O-lauroyl
-31 "a and 31" b, with R = -N-C4H8-C- (OH-C7H15) -N-C4H8 and Z1F1 = Z'1G1 = OH
Step a: Preparation of diacetoneglucose 1
Diacetone glucose was prepared by reacting D-glucose monohydrate in acetone in the presence of H 2 SO 4 under the conditions of the FR patent. 8915995.

Step b: Preparation of 3-O - [(α-bromo) -R] -1,2: 5,6-di-O-isopropylidene-α-D-glucofuranose, of structure 2p (R = -n) -C4H8 -); 21 &gamma; (R = n-C8H16-) 216 (R = -N-C10H20-)
To a solution containing 650 ml of toluene-DMSO (90:10, v / v) is added, with stirring at room temperature, 65 g (0.385 mol) of diacetoneglucose 1, 0.30 mol of 1α-dibromoalkane. 33.5 g (0.60 mol) of powdered potash and 25 g of Na 2 SO 4. When almost all of the 1α-dibromoalkane has disappeared, 250 ml of saturated aqueous NH 4 Cl solution are added. The organic phase is decanted and the aqueous phase is taken up twice with 50 ml of toluene. The combined organic phases are washed with a saturated aqueous solution of NaCl and then evaporated under reduced pressure. The products are purified on silica gel with the hexaneacetone gradient.

The distribution of the products of type 21, 31, 3'1 at the end of the reaction (disappearance of l, m-dibromoalkane) is given in Table 1 below:
Table 1

<tb><SEP> R <SEP> time (h) <SEP><SEP> distribution of <SEP> products
<tb><SEP> 21 <SEP> 31 <SEP>3'1
<tb><SEP> -C4H8- <SEP> (21 <SEP>) <SEP> 5 <SEP> 87.5 <SEP> 9 <SEP> 3.5
<tb><SEP> -C8H16- <SEP> (21) <SEP> 6 <SEP> 82 <SEP> 13 <SEP> 5
####
<Tb>
The yields, physical constants and elemental analyzes of the type 21 products after purification are given in Table 2 below:
Table 2

<tb> Basic SEP Analysis
<tb><SEP> Calculated <SEP> Found
<tb><SEP> R <SEP> Yield (%) <SEP>[&alpha;] D25CHCl3 <SEP> C (%) <SEP> H (%) <SEP> Br (%) <SEP> C (%) <SEP> H (%) <SEP> Br (%)
<tb><SEP> -C4H8- (21ss) <SEP> 45 <SEP> -24.6 (c = 1.05) <SEP> 48.62 <SEP> 6.84 <SEP> 20.23 <SEP > 49.06 <SEP> 7.23 <SEP> 20.19
<tb><SEP> -C8H16- (21 &gamma;)<SEP><SEP> 53 <SEP> -19.8 (c = 1.1) <SEP> 53.10 <SEP> 8.02 <SEP> 17 , 66 <SEP> 53.48 <SEP> 7.81 <SEP> 17.45
<tb><SEP> C10H20- (21 &gamma;)<SEP><SEP> 43 <SEP> -16.9 (c = 1.2) <SEP> 55.11 <SEP> 8.20 <SEP> 20, 02 <SEP> 55.85 <SEP> 8.25 <SEP> 19.19
<Tb>
Step: Preparation of 3,3'-OR-bis [1,2,5,6-di-O-iso-propylidene-alpha]
D-glucofuranose], of structure 31a (R = -CH2-) 31p (R = -n-C4H8-); 317 (R = -N-C8H16 -); 31 # (R = -N-C10H20-)
In order to increase the proportion of type 9 product that is formed under the conditions of step b of the present example according to the invention, we modified the conditions of step b by increasing the polarity of the solvent and doubling the proportions of compound 1 and potash as follows:
To a solution containing 130 ml of toluene - DMSO (80 :: 20, v / v), 13 g (50 mmol) of diacetoneglucose 1, 30 mmol of 1, # - dibromoalkane or ClCH 2 Cl are added with stirring at room temperature, 6.7 g (0.12 mol) of powdered potash and 3.3 g of anhydrous Na 2 SO 4. After 16 hours, the products are extracted and purified under the conditions of step b of the present example according to the invention.

The distribution of the products of type 21, 31, 3'1, at the end of the reaction (disappearance of the 1, # -dibromoalkane) is given in Table 3 below:
Table 3

<tb><SEP><SEP> Distribution of <SEP> Products
<tb><SEP> R <SEP> time <SEP> (h) <SEP> Progress <SEP> S <SEP>
<tb><SEP> 3i <SEP> 21 <SEP> 3? i <SEP>
<tb><SEP> -CH2- <SEP> (31a) <SEP> 16 <SEP> 100 <SEP> 100 <SEP> 0 <SEP> 0
<tb><SEP> 16 <SEP> 56 <SEP> 88 <SEP> 2 <SEP> 10
<tb><SEP> -C4H8- (31ss)
<tb><SEP> 65 * <SEP> 90 <SEP> 85 <SEP> 15 <SEP> 0
<tb><SEP> -C8H16- <SEP> (31 &gamma;;)<SEP><SEP> 16 <SEP> 92 <SEP> 72 <SEP> 8 <SEP> 20
<tb> -CloH20- <SEP> (318) <SEP> 16 <SEP> 88 <SEP> 70 <SEP> 7 <SEP> 23
<Tb>
* with 1,4-di-O-mesylbutane instead of 1,4-dibromobutane
The yields, physical constants and elemental analyzes of the after-purification products are given in Table 4 below:
Table 4

<tb><SEP> Basic SEP Analysis
<tb><SEP> Calculated <SEP> Found
<tb><SEP> R <SEP> Yield% <SEP> [a] D25 <SEP> CHCl3 <SEP> C% <SEP> H% <SEP> C% <SEP> H%
<tb><SEP> -CH2- <SEP> (31 &alpha;)<SEP><SEP> 87 <SEP> + <SEP> 30.7 <SEP> (c = 1.4) <SEP> 59.98 <MS> 8.05 <SEP> 60.08 <SEP> 8.10
<tb><SEP> 45
<tb> -C4H8- (31ss) <SEP> 75 * <SEP> -34.2 (c = 1.0) <SEP> 58.52 <SEP> 8.07 <SEP> 58.59 <SEP> 8 13
<tb><SEP> -C8H16- (31 &gamma;;)<SEP><SEP> 71 <SEP> -29.2 (c = 1.2) <SEP> 60.93 <SEP> 8.62 <SEP> 61.05 <SEP> 8.61
<tb><SEP> -C10H20- <SEP> (31O) <SEP> 63 <SEP> - <SEP> 26.7 <SEP> (c = 1.5) <SEP> 61.98 <SEP> 8, 87 <SEP> 62.23 <SEP> 9.00
<Tb>
* with 1,4-di-O-mesylbutane instead of 1,4-dibromobutane
Retape c2: Preparation of 3-0 - [(O-1) alkene] -1,2,5,6-di-O -isopropylidene-α-D-glucofuranose, structure 3'1ss (R = - C2H4-CH = CH 2)
To a solution containing 50 ml of toluene-DMSO (90:10, v / v) was added with stirring at room temperature, 5g (0.011 mol) of compound 21ss (R = -n-C4H8), 0.15g (0.026). mole) sprayed potash.After 16 hours of reaction at 60 C, less than 5% of product remains 21ss, 3'1ss elimination product is isolated pure under the conditions of extraction and purification of step b of the present example according to the invention, with a yield of 80%.

[&alpha;] D25 = -28.4 (c = 1.2; CHCl3)
Steps c3 and c'3: Preparation of 3,3'-OR-bis (diacetoneglucose) of Structure 3 "1 (R = -N-C4H8-C (OH, C7H15) -N-C4H8-)
In a three-necked flask equipped with a condenser is placed 20 mT of anhydrous THF, 1.93 g (80 mmol) of magnesium chips, an iodine crystal and added slowly using a light bulb. bromine, 29.8 g (76 mmol) of 3-O- (4'-bromobutyl) diacetoneglucose 21ss dissolved in 100 ml of anhydrous THF. The mixture is then heated under reflux (700 ° C.) for 4 hours (disappearance of magnesium). 0.70 g (49 mmol) of n-octanoyl chloride dissolved in 10 mT of toluene are then added dropwise to the dropping funnel.
Anhydrous THF and the reflux is maintained for 20 hours. The reaction medium is hydrolysed with aqueous NH4Cl. The aqueous phase is extracted twice with 30 mT of toluene. The organic phases are combined and dried over anhydrous Na 2 SO 4 and evaporated under reduced pressure. analysis
HPLC of the crude obtained (27.9 g) shows, after the signal of the octanoic acid, 5 signals A, B, C, D and E of relative intensities:
(A) / (B) / (C) / (D) / (E) = 52/13 / 17.5 / 6 / 12.5.

After fractionation of the crude on silica gel with the hexaneacetone gradient, the following are collected:
- 14 g of product mixture corresponding to the signals B, C and D in the proportions 36/48/16 respectively. According to the NMR analysis, B corresponds to the product 3'1ss, C corresponds to 3-O-butyl diacetoneglucose resulting from the hydrolysis of the corresponding organomagnesium and D corresponds to 3,3'-O-octylene bis (diacetoneglucose ) 31y resulting from the Wurtz type reaction undergone by the organomagnesium.

 - 12 g (yield: 44%) of a product corresponding to the signal A whose structure is that of compound 3 "1 (NMR Table 5).

[&alpha;] D25 = -23.2 (c = 1.2; CHCl3)
Elemental analysis
C% H%
Calculated 63.33 9.23
Found 63.17 9.45
Table 5: 13 C-NMR of the compound 3 "1 of 3,3'-OR-bis (diacetoneglucose) structure with (R = -N-C4H8-C (OH, C7H15) -N-C4H8-)

<tb><SEP> 13C <SEP># (ppm)
<tb><SEP> C1 <SEP> 105.2
<tb><SEP> C2 <SEP> 82.4
<tb><SEP> C3 <SEP> 82.1
<tb><SEP> C4 <SEP> 81.0
<tb><SEP> 72.5
<tb><SEP> C6 <SEP> 67.1
<tb><SEP> 4 <SEP> x <SEP> CH3 <SEP> 26.8-25.4
<tb> 2 <SEP> x <SEP> C <SEP> (iso) <SEP>111.6;<SEP> 108.9
<tb><SEP> C &alpha;<SEP> 70.2
<tb><SEP> Css <SEP> 30.2
<tb><SEP> C &gamma;<SEP><SEP> 29.3
<tb><SEP> C <<SEP> 38.9
<tb><SEP> C <SEP> (OH) <SEP> 74.0
<tb><SEP>C'1<SEP> 39.0
<tb><SEP>C'2<SEP> - <SEP>C'6<SEP> 31.8 <SEP> - <SEP> 19.8
<tb><SEP> CH3 <SEP> 14.0
<Tb>
Steps d1a and d2a: Preparation of 3,3'-OR-bis- [1,2-O-isopropylidene-α-D-glucofuranose], of structure 31a &alpha; (R = -CH "-); 31ass (R = - n-C4H8-); 31a-gamma (R = -N-C8H16-); 31a <(R = -N-C10H20-) and 3 "1ass (R = -N-C4H8-C (OH, C7H15) -n- C4H8
In a 50 ° C. thermostatic flask containing 90 ml of ethanol 95 with sulfuric acid [H +] = 0.1N, 10 g of 3,3'-OR-bis (diacetoneglucose) of type 31 are reacted with stirring. 3 "1, the reaction is followed by
HPLC. After a degree of progress greater than 85%, the solution is neutralized by the corresponding amount of sodium hydroxide. After filtration and evaporation under reduced pressure, pure 3,3'-OR-bis (monoacetoneglucose) is isolated by gel fractionation. of silica with the hexane-acetone gradient.

Table 6

<tb><SEP> Analysis <SEP> Elementary
<tb><SEP> Calculated <SEP> Found
<tb><SEP> R <SEP>% Av. <SEP> Yield (%) <SEP>[&alpha;] D25CHCl3 <SEP><SEP> C (%) <SEP> H (%) <SEP> C (%) <SEP> H (%)
<tb><SEP> -CH2- (31a &alpha;)<SEP><SEP> 88 <SEP> 77 <SEP> -17.0 <SEP> 42.43 <SEP> 7.13 <SEP> 42.56 <SEP> 7.25
<tb><SEP> -C4H8- (31ass) <SEP> 93 <SEP> 77 <SEP> -34.2 <SEP> 53.40 <SEP> 7.75 <SEP> 53.20 <SEP> 8, 18
<tb><SEP> -C8H16- (31a &gamma;;)<SEP><SEP> 82 <SEP> 60 <SEP> -33.3 <SEP> 56.71 <SEP> 8.42 <SEP> 56.12 <SEP> 8.52
<tb><SEP> -C10H20- (31a <) <SEP> 88 <SEP> 65 <SEP> -36.4 <SEP> 58.12 <SEP> 8.71 <SEP> 58.79 <SEP> 8 96
<tb> -N-C4H8-C (OH, C7H15) -C4H8
<tb><SEP> (3 "1a) <SEP> 95 <SEP> 59 <SEP> +19.0 <SEP> 60.16 <SEP> 9.20 <SEP> 60.09 <SEP> 9.40
<Tb>
The partial deprotection according to the dla and d2a steps was also carried out in a heterogeneous phase at 600 ° C. by placing the solution of the α1 and β1 products in ethanol at 95 in the presence of 10 H + amberlite resin at a concentration of 10 g. substrate and 15 g of resin in 100 ml solvent The reaction continued up to 90% advancement yields similar to those of the previous method.

Steps dlb and d2b: Preparation of 3,3'-OR-bis- (D-glucose),
structure 31bss (R = -N-C4H8-); 31b &gamma; (R = n-C8H16-); 31b <(R = -n-C10H20
) .And (R = n-C4H8-C (OH, C7H15) -C4H8-)
In a 70 C thermostated flask containing 100 mT of mixture
dioxane-water (80:20, v / v), with [H + J = 1.0 N (H2SO4), reacting under
stirring, 10 g of compound ai or 3 "1. When the progress of the reaction
reaches 95%, the solution is neutralized by the quantity of soda
corresponding. After filtration and evaporation under reduced pressure,
isolated by fractionation on silica gel with the hexane-acetone gradient,
products 31b and 3 "1b pure. Physical constants and yields
are shown in Table 7 below:
Table 7

<tb><SEP> Analysis <SEP> Elementary **
<tb> Calculate + H2O <SEP> Found
<tb><SEP> R <SEP> time (min) <SEP> Yield (%) <SEP> C (%) <SEP> H (%) <SEP> C (%) <SE> H (%)
<tb> -C4H8- (31bss) <SEP> 80 <SEP> 78 <SEP> 44.49 <SEP> 7.45 <SEP> 44.96 <SEP> 7.45
<tb><SEP> -C8H16- (31b &gamma;)<SEP><SEP> 80 <SEP> 59.5 <SEP> 49.17 <SEP> 8.25 <SEP> 49.36 <SEP> 8.22
<tb><SEP> -C10H20- (31b <) <SEP> 80 <SEP> 57 <SEP> 51.15 <SEP> 8.58 <SEP> 52.69 <SEP> 8.49
<tb><SEP> -n-C4H8-C (OH, C7H15) -C4H8
<tb><SEP> (3 "1b) * <SEP> 120 <SEP> 57 <SEP> - <SEP> - <SEP> - <SEP>
* mixture of product 3 "lb and dehydration product in proportions 60:40
** Elemental analysis is close to the monohydrate form
Step el: Preparation of 3,3'-OR-bis (5 (5,6-anhydro monoacetone glucose) of structure 41ss (R = -N C4Hg-)
The product 31ass is trasformed to 3,3-OR-bis (6-O-tosylmonoacetone glucoside) by reacting it with 2 equivalents of tosyl chloride in toluene-pyridine solvent (50:50, v / v) to +5 " C for 48 h.

The ditosylate obtained pure with a yield of 65% is treated with a
0.2 N sodium hydroxide solution, 4 equivalents per mole, in solution
in dioxane-water (90:10, v / v), at 20 ° C. for 60 minutes. After
extraction and purification, the product 41b is isolated pure with a yield of
90% relative to the precursor ditosylate.

[&alpha;] D25 = 61.90 (c = 1.6, CHCl3)
Elemental analysis
C% H%
Calculated 57.64 7.47
Found 57.45 7.62
Step e2: Preparation of 3,3-OR-bis (5,6-sulfinyl-monoacetone glucose) of structure 4'1ss (R = -n-C4Hg-)
In a flask containing 50 ml of ethyl acetate, 3 g (0.03 mol) of triethylamine and 5 g (0.01) of 3X product, 4.8 g (0.04 mol) of chloride are slowly added. of thionyl, with stirring at room temperature.

After 4 hours of reaction, the product is extracted by filtration of triethylamine hydrochloride, evaporation of the solvent and purification on silica gel with the hexane-acetone gradient. 4.2 g (Yield = 71%) of the pure product 4'1ss.

[a] D25 - 76.50 (c = 1.6, CHCl3)
Step f1: Preparation of 3,3'-O-butylene-bis- (6-O-dodecyl monoacetone glucose) of structure 51ass1 (R = -n-C4H8-; Z1F1 = Z'1G1 = On-octyl) and 51aD2 ( R = -N-C4H8-; Z1F1 = Z'1G1 = On-ododecyl).

In a flask containing 50 ml of the toluene-DMSO mixture (50:50, v / v), 5.6 g (0.1 mole) of pulverized potash and 0.05 mole of n-alkanol, the mixture is poured with stirring at 40 ° C. 4.6 g (0.01 mole) of compound 41ss The reaction is continued for 20 hours (total disappearance of the product 4g). After extraction and fractionation on silica gel under the conditions of steps b and c of the present example according to the invention, the following are isolated: - the residual n-alkanol, - the condensation products of compound 41ss, - the expected diethers 51ass1 ( Yield 40%) and 51ass2 (Yield 42%) pure from the NMR spectra (Table 8):
For 51ass1:
[&alpha;] D25 -28.30 (c = 1.0; CHCl3)
Elemental analysis
C% H%
Calculated 63.48 9.81
Found 63.69 9.70
For 51ass2 :: [&alpha;] D25 = -25.7 (c = 1.0; CHCl3)
Elemental analysis
C% H%
Calculated 66.47 10.43
Found 66.22 10.61
Table 8: 13 C-NMR of the compounds 51ass1 and 51ass2 of structure 3,3'-Obutylene-bis (6-On-alkyl monoacetoneglucose)

<tb><SEP> 13C <SEP><(ppm)<SEP> 13C <SEP><(ppm)
<tb><SEP> C1 <SEP> 105.0 <SEP> Z1F1 = Z'1G1 = On-CnH2n + 1
<tb><SEP> C2 <SEP> 82.4 <SEP> C '&alpha;<SEP> 70.1
<tb> C3 <SEP> 82.2 <SEP>C'ss<SEP> 31.8
<tb><SEP> C4 <SEP> 79.7 <SEP> nxCH2 <SEP> 29.5-22.5
<tb><SEP> C5 <SEP> 67.6 <SEP> CH3 <SEP> 13.9
<tb><SEP> C6 <SEP> 72.5 <SEP> R <SEP> = <SEP> -C4H8
<tb><SEP> 2XCH3 <SEP> 26.1, <SEP> 26.6 <SEP> C &alpha;<SEP> 71.5
<tb><SEP> C (iso) <SEP> 111.4 <SEP> Css <SEP> 26.3
<Tb>
Step f2: Preparation of 3,3'-OR-bis (6-On acyl monoacetone
glucose type 5a and structure 1a &alpha; 3 and 51 &alpha; 4 (R = -CH2-; Z1F1 = Z'1G1
= On-butanoyl and Z1F1 = Z'1G1 = On-lauroyl) and 51ass3 and 51ass4 (R =
-C4H8; Z1F1 = Z'1G1 = On-butanoyl and Z1F1 = Z'1G1 = On-lauroyl).

 In a flask containing 70 ml of anhydrous acetone, 0.012 mole of product of type aa and 3.6 g (36 mmol) of TEA, 36 mmol of acyl chloride dissolved in 30 ml of acetone are added dropwise. After 200 min.

stirring at room temperature, the progress relative to the product 3a reaches 90%. The triethylammonium hydrochloride formed is filtered and the filtrate evaporated under reduced pressure gives a syrupy residue which is fractionated on silica gel with the hexane-acetone gradient. The results are given in Table 9.

Table 9

<SEP> Analysis <SEP> Elementary
<tb><SEP> Calculated <SEP> Found
<tb><SEP> Acyl <SEP> R <SEP> Yield (%) <SEP>[&alpha;] D25CHCl3 <SEP><SEP> C (%) <SEP> H (%) <SEP> C (%) <SEP> H (%)
<tb><SEP> Butanoyl <SEP> -CH2- (51a &alpha; 3) <SEP> 70 <SEP> -49.6 (c = 21.2) <SEP> 54.72 <SEP> 7.48 <SEP > 54.88 <SEP> 7.39
<tb> -C4H8- (51ass3) <SEP> 65 <SEP> -25.6 (c = 1.0) <SEP> 56.77 <SEP> 7.82 <SEP> 57.09 <SEP> 7, 82
<tb><SEP> Lauroyl <SEP> -CH2- (51a &alpha; 4) <SEP><SEP> 76 <SEP> -47.2 (c = 1.8) <SEP> 63.21 <SEP> 9, 38 <SEP> 63.29 <SEP> 9.42
<tb> -C4H8- (51ass4) <SEP> 70 <SEP> -24.9 (c = 1.1) <SEP> 64.31 <SEP> 9.62 <SEP> 64.26 <SEP> 9, 36
<Tb>
The 13C NMR spectra conforming to compounds of type 51a &alpha;; 4 and are are given in Table 10, the spectra of homologs 51a &alpha; 3 and are identical.

Table 10; 13C NMR of Compounds 51a &alpha; 4 & 51a &alpha; 4 of Structure 3.3 '
OR-bis (6-O-lauroyl monoacetoneglucose)

<tb><SEP> 13C <SEP><(ppm)<SEP> 13C <SEP><(ppm)
<tb><SEP> C1 <SEP> 105.0 <SEP> Z1F1 = Z'1G1 = OCOC11H2
<tb><SEP> C2 <SEP> 82.6 <SEP> C = P <SEP> 174.4
<tb><SEP> C3 <SEP> 81.9 <SEP> C '&alpha;<SEP><SEP> 34.1
<tb><SEP> C4 <SEP> 79.1 <SEP> 9XCH2 <SEP> 31.8-22.6
<tb><SEP> C5 <SEP> 67.7 <SEP> CH3 <SEP> 14.0
<tb><SEP> C6 <SEP> 66.5 <SEP> R = -C4H8- <SEP>
<tb> 2 <SEP> x <SEP> CH3 <SEP> 26.2 <SEP>, 26.7 <SEP> Ca <SEP> 70.0
<tb><SEP> C <SEP> (iso) <SEP> 111.7 <SEP> Css <SEP> 26.3
<tb><SEP> R <SEP> = <SEP> -CH2
<tb><SEP> Ca <SEP> 91.8
<Tb>
Step: Preparation of 3,3'-OR-bis (6Z1F1 (Z'1G1) -D-glucose) of type 51b and structure:
51bss2 (R = -C4H8-; Z1F1 = Z'1G1 = On-dodecyl)
51bss4 (R = -C4H8-; Z1F1 Z'G1 = = On-lauroyl).

In a thermostatically controlled flask at 300 ° C. containing 40 ml of dioxane and 5 g of product 51 a, 15 ml of aqueous solution of concentrated HCl (11N) are added with stirring. When the progress reaches 90%, it is neutralized by
Solid NaHCO3. The crude product obtained after filtration, rinsing the precipitate with dioxane, evaporation of the organic phases, is purified on silica gel with the hexane-acetone gradient. The results are given in Table 11 below:
Table 11

<tb><SEP> Analysis <SEP> Elementary <SEP> (*:
<tb><SEP> Calculated <SEP> (+ H20, <SEP> Found
<tb><SEP> R <SEP> time (h) <SEP> Yield (%) <SEP> C (%) <SEP> H (%) <SEP> C (%) <SEP> H (%)
<tb><SEP> -C4H8- (51bss2) <SEP> 10 <SEP> 85 <SEP> 62.63 <SEP> 10.25 <SEP> 62.63 <SEP> 10.26
<tb><SEP> Z1F1 = Z'G = On-C12H25
<tb><SEP> -C4H8- (51Bss4) <SEP> 55 <SEP> 60 <SEP> 60.28 <SEP> 9.62 <SEP> 59.75 <SEP> 9.35
<tb> Z1F1 = Z'1G1 = O-COC11H23
<tb> * Elemental analysis is consistent with the monohydrate form
The NMR spectra confirm the total deprotection of the acetal sites but the saccharide units coexist in pyranic and furanic form, with the anomeric OH groups in the α and σ positions.

Example 2 Synthesis of Disaccharide Compounds from A = B =
D-galactose, D-xylose, D-xylitol and glycerol, of structure according to general formula I, of type:
32, 32b, 3 "2 and 2b with A = B = D-galactose; R = -CH2-; -n-C4Hg-; -n-C8H16-; - n-C10H20-; - n-C4H8-C ( OH, C7H15) -C4H8- and Z1F1 = Z'1G1 = OH
33 with A = B = D-xylose; R = -N-C4Hg-; Z1F1 = Z'1G1 = O-allyl, Obenzyl.

34, 34b and 5'4b with A = B = D-xylitol; R = -CH2-; ZiFi = Z'jGj = OH and
ZiFi = Z'jGj = O-acetyl.

35, 35b and 5'5b with A = B = glycerol; R = -CH2-; ZiFi = Z'jGj = OH and
ZiFi = Z'jGj = O-acetyl.

 Etaoea: Preparation of type I compounds in which unit A has only one free OH.

 D-galactose and D-xylitol were converted into diacetals and glycerol into monoacetal by treating them with acetone in the presence of H 2 SO 4 under the conditions of patent FR 8915995.

The protection of D-xylose, preceding step b, proceeds in the following sequence:
- formation of diacetonexylose under the preceding conditions, preparation of 1,2-O-isopropylidene-α-D-xylofuranose under the conditions of step dla of Example 1 according to the present invention and synthesis of the corresponding 3,5-anhydro derivative under the conditions of step el of Example 1 according to the present invention;
nucleophilic addition of the allyl or benzyl alcoholate to the 3,5-anhydro derivative under the conditions of step f1 of Example 1 according to the present invention, resulting in 5-O-allyl and 5- O -benzyl-1,2-O-isopropylidene aD-xylofiiranose type i.

Step c1: Preparation of Type 3 Compounds
- A = B = D-galactose, of structure 6,6'-OR-bis (diacetonegalactose): 32 &alpha; (R = -CH2-); 32ss (R = -n-C4H8-); 32 &gamma; (R = - n-C8H16); 32 <(R = -N- C10H20-);
-A = B = D-xylose, of structure 3,3'-OR-bis (5-Z1F1-monoacetonexylose):
33ss1 (R = -N-C4H8-; Z1F1 = Z'1G1 = O-allyl) and
33ss2 (R = n-C4H8-; Z1F1 = Z'1G1 = O-benzyl),
- A = B = D-xylitol, of structure 1, the-OR-bis (diacetonexylitol):
34a (R = -CH2-),
- A = B = glycerol, of structure 1, the-OR-bis (solketal):
35a (R = -CH2-),
These products are prepared under the conditions of step c1 of Example 1 according to the present invention, by reacting 2 equivalents of compound of type 1 with one equivalent of compound X-CmH2m-X.The results are given in FIG. Table 12 below:
Table 12

<tb><SEP> A = B <SEP> R <SEP> X <SEP> time (0C) <SEP> urea <SEP> (h) <SEP> Avab * (%) <SEP> Yield <SEP> % <SEP>[&alpha;] 25D <SEP> CHCL3
<tb><SEP> -CH2- <SEP> C1 <SEP> 120 <SEP> 22 <SEP> 82 <SEP> 70 <SEP> 77.4 <SEP> (c = 1.1) <SEP>
<tb><SEP> -C4H8- <SEP> 16 <SEP> 60 <SEP> 55 <SEP> -76.0 <SEP> (c = 1.2)
<tb> D-galactose <SEP> -C8H16- <SEP> Br <SEP> 20 <SEP> 25 <SEP> 90 <SEP> 65 <SEP> -62.4 (c = 1.3)
<tb><SEP> -C10H20- <SEP> 25 <SEP> 85 <SEP> 60 <SEP> 61.2 <SEP> (c = 1.2)
<tb><SEP> 65 <SEP>. <SEP> 80 <SEP> 70 <SEP> -52.90 <SEP> (c = 0.8)
<tb><SEP> D-xylose <SEP> -C4H8- <SEP> OMs <SEP> 20
<tb><SEP> 65 <SEP> 70 <SEP> 65 <SEP> -55.4 <SEP> (c = 1.7)
<tb><SEP> D-xylitol <SEP> CH2 <SEP> Cl <SEP> 120 <SEP> 2 <SEP> 97 <SEP> 93 <SEP> +9.30 <SEP> (c = 1.2)
<tb><SEP> glycerol <SEP> -CH2- <SEP> C1 <SEP> 120 <SEP> 0.25 <SEP> 100 <SEP> 90
<tb> * in relation to the disappearance of A
Steps c3 and c'3. Preparation of 6,6-OR-bis (diacetonegalactose) of Structure 3 "2 (R = -N-C 4 H 8 -C (OH, C 7 H 15) -N-C 4 H 8 -)
The compound of structure 3 "2 was prepared with a yield of 45% under the conditions of steps c3, c'3 of Example 1 according to the present invention. The reaction was carried out with the compound 6-O- [ (4'-bromo) -butyl] diacetonegalactose type a obtained under the conditions of step b of
Example 1 according to the present invention.

[&alpha;] D25 = -52.0 (c = 1.2; CHCl3)
Elemental analysis
C% H%
Calculated 63.33 9.23
Found 62.68 9.12
Steps d1b and d2b: preparation of compounds of type 3b and 3'1)
- A = B = D-galactose, of structure 6,6'-OR-bis (D-galactose):
32bss (R = -N-C4H8-); 32b (R = -N-C8H16-); 32b8 (R = -N-C10H20-) and 3 "2b (R = -N-C4H8-C (OH, C7H15) -N-C4H8-))
- A = B = D-xylitol, of structure 1, the-OR-bis (D-xylitol):
34ba (R = -CH2-),
- A = B = glycerol, of structure 1, the-OR-bis (glycerol):
35ba (R = -CH2-).

These products are obtained under the conditions of the dlb and d2b stages of Example 1 according to the present invention, starting from the Q and 32 type precursors. The results are given in Table 13 below:
Table 13

<tb><SEP> A = B <SEP> R <SEP> Yield%
<tb><SEP> -C4H8- <SEP> (32bp) <SEP> 76
<tb><SEP> -C8H16- <SEP> (32by) <SEP> 70
<tb> D-galactose <SEP> -C10H20- <SEP> (32b6) <SEP> 72
<tb><SEP> -n-C4H8-C (OH, C7H15) C4H8- (3 "2b) <SEP> 70 *
<tb><SEP> D-xylitol <SEP> -CH2- <SEP> (34b) <SEP> 80
<tb><SEP> glycerol <SEP> -C :: H2- <SEP> (35b) <SEP> 85
<Tb>
* mixture of 3 "2b product and dehydration product, in the 60/40 poportions
Steps f4 preparation of compounds of type 5'b
- A = B = D-xylitol, of structure 1, the-OR-bis (peracetyl D-xylitol):
5'4b &alpha; (R = -CH2-, ZiFi = Z'jGJ = O-acetyl, n = n '= 4),
- A = B = glycerol, of structure 1, the-OR-bis (peracetyl glycerol):
5'5b &alpha; (R = -CH2-, ZiFi = Z'jGg = O-acetyl, n = n '= 2).

Peracetylation was performed using three methods:
I - Stirring addition of n + n 'equivalents of acetic anhydride to 10 g of type 3b product in solution in SO niL triethylaminetoluene solvent (50:50, v / v) at 700C for one hour.

 II- Stirring addition of n + n equivalents of acetyl chloride to 10 g of product of type 3b in solution in 50 mL of pyridinetoluene solvent (50:50, v / v) at room temperature for one hour.

 III- Stirring addition of n + n 'equivalents of acetic anhydride to 10 g of product type 3b in solution in 50 mL of water saturated with sodium acetate, at 100 C for one hour.

 After extraction of the products with toluene and evaporation, the pure products 5'4ba and 5'5ba are isolated on silica gel with the hexaneacetone gradient. The results are given in Table 14.

Table 14

<SEP> method <SEP> I <SEP> method <SEP> II <SEP> method <SEP> III
<tb><SEP> A <SEP> = B <SEP> Yield <SEP>% <SEP> Yield <SEP>% <SEP> Yield <SEP>% <SEP><SEP> FalD25 <SEP> (CHCl3) <September>
<tb> D-xylitol <SEP>(5'4b&alpha;)<SEP>)<SEP> 70 <SEP> 75 <SEP> 60 <SEP> +9.3 <SEP> (c = 1.2)
<tb> glycerol <SEP>(5'5ba<SEP>)<SEP> 75 <SEP> 80 <SEP> 65
<Tb>
Example 3 Synthesis of disaccharide compounds from A = glucose and B = D-galactose and D-fructose, of structure 3-O - [(# -R) -N'-O-diacetal BJ diacetoneglucose and their functionalized derivatives, partially or totally deprotected, of type:
31: 2 and 31: 2a with B = D-galactose, R = -N-C4H8-; n-C8H16-; -not
C10H20- and Z1F1 = Z2F2 = OH
31: 6 and 31: 6a with B = D-fructose, R = -n-C4H8-; -N-C8H16-; -n CloH20- and Z1F1 Z2F2 = OH
51: 2a with B = D-galactose, R = -n-C4H8- and Z1F1 = -n-dodecyl
51: 2b with B = D-galactose, R = -n-C4H8- and Z1F1 = -n-dodecyl and
Z2F2 = Z3F3 = Z4F4 = Z'jGj = OH
Etaoea: Preparation of type 1 compounds in which unit B has only one free OH.

The diacetal of fructose is in the form 2,3: 4,5-di-O-isopropylidene a
D-fructopyranose. has been prepared under the conditions of patent FR 8915995, as the diacetal of D-galactose and other di-O-acetals described in Examples 1 and 2 of the present process according to the invention.

Step cI: Preparation of 31: 2 and 31: 6 compounds
- A = D-glucose, B = D-galactose of structure 3-O - [(# -R) -6'-O-diacetonegalactose] diacetoneglucose:
31: 2ss (R = -N-C4H8-); 31: 2 &gamma; (R = n-C8H16-); 31: 2 # (R = -N-C10H20-);
- A = D-glucose, B = D-fructose of structure 3-O - [(# -R) -1'-O-diacetonefructose] diacetoneglucose:
31: 6ss (R = -N-C4H8-); 31: 6 &gamma; (R = n-C8H16-); 31: 6 (R = -N-C10H20-);
These products were prepared under the same temperature, solvent and base conditions as in step b of Example 1 of the present process by reacting mole to mole the diacetal type 1 galactose or fructose on the derivative. type 2 glucose prepared under the conditions of step b of Example 1 of the present process according to the invention. The results are given in Table 15.

Table 15

<tb><SEP> Basic SEP Analysis
<tb><SEP> Calculated <SEP> Found
<tb><SEP> B <SEP> m <SEP> Product <SEP> Yield% <SEP>[&alpha;] D25 <SEP><SEP> CHCl3 <SEP> C% <SEP> H% <SEP> C % <SEP> Hio <SEP>
<tb><SEP> 31: 2ss <SEP> 61 <SEP> -50.0 <SEP> (c = 1.0) <SEP> 58.52 <SEP> 8.07 <SE> 58.80 <SEP > 8.19
<tb> Dagal60H <SEP> 8 <SEP> 31: 2y <SEP> 52 <SEP> -48.3 <SEP> (c = 1.1) <SEP> 59.95 <SEP> 8.70 <SEP> 60.15 <SEP> 8.90
<tb><SEP> 10 <SEP> 31:26 <SEP> 58 <SEP> -40.9 <SEP> (c = 1.2) <SEP> 61.98 <SEP> 8.87 <SEP> 61 , 05 <SEP> 8.61
<tb><SEP> 4 <SEP> 31:60 <SEP> 48 <SEP> -32.1 <SEP> (c = 1.3) <SEP> 58.52 <SEP> 8.07 <SEP> 58 , 77 <SEP> 8.12
<tb> afrulOH <SEP> 8 <SEP> 31 :: 6y <SEP> 53 <SEP> -30.0 <SEP> (c = 1.3) <SEP> 59.95 <SEP> 8.70 <SEP > 60.95 <SEP> 8.57
<tb><SEP> 10 <SEP> 31:66 <SEP> 42 <SEP> -28.8 <SEP> (c = 1.2) <SEP> 61.98 <SEP> 8.87 <SEP> 62 , 01 <SEP> 8.95
<Tb>
Step dla: Preparation of compounds of type 31a and 31: 6a.

- A = D-glucose, B = D-galactose structure 3-O - [(# -R) -6'-O-diacetonegalactose] monoacetoneglucose:
31: 2ass (R = -N-C4H8-);
- A = D-glucose, B = D-fructose of structure 3-O - [(oe-R) -1'-O-diacetonefructose] monoacetoneglucose:
31: 6ass (R = -N-C4H8-);
These products were prepared under the conditions of step dla of Example 1 of the present process according to the invention which makes it possible to selectively release the OH groups from the CS and C-6 sites of the unit A = glucose.

The results are given in Table 16.

Table 16

<tb><SEP> Basic SEP Analysis
<tb><SEP> Calculated <SEP> Found
<tb><SEP> B <SEP> Product <SEP> Yield <SEP> (%) <SEP>[&alpha;] D25 <SEP> CHCl3 <SEP> C (%) <SEP> H <SEP> (%) <SEP> C <SEP> (%) <SEP> H <SEP> (%)
<tb> DAGal6OH <SEP> 31: 2ass <SEP> 83 <SEP> -47.6 <SEP> (c = 1.4) <SEP> 56.17 <SEP> 7.92 <SEP> 55.81 <SEP> 8.01
<tb> DAFuOHOH <SEP> 31: 6ass <SEP> 73 <SEP> -38.3 <SEP> (c = 1.3) <SEP> 56.92 <SEP> 7.92 <SEP> 56.27 <SEP> 7.96
<Tb>
Step el: Preparation of the compound 3-O - [(# -R) -6'-O-diacetonegalactose] 5,6-anhydro monoacetoneglucose, of structure 41: 2ss (R = -N-C4H8-);
The product 31 :: 2ass is converted to 3-O - [(o) -R) -6'-O-diacetone galactosel 6-O-tosyl monoacetoneglucose by reacting it with 1.1 equivalent of tosyl chloride under the conditions of step el of example 1 according to the present invention. The tosylate obtained with 60% yield is converted into anhydro derivative 41: 2ss under the same solvent and base conditions as in the step el of Example 1 according to the present invention. The compound 41:23 is isolated after the extraction and purification operations with a yield of 90% relative to the precursor tosylate.

[&alpha;] D25 -56.50 (c = 1.2; CHCl3)
Fil Step Preparation of the compound 3-O - [(# -R) -6'-O-diacetonegalactose] 6-On-dodecyl monoacetoneglucose, of structure 51: 2ass (R = -N-C4H8-
Z1F1 = On-dodecyl);
This product was prepared under the same temperature, solvent and base conditions as in step f of Example 1 of the present process by reacting 2.5 moles of n-dodecanol with one mole of anhydro derivative 41: 2B. Isolation after extraction and purification on silica gel with the hexane-acetone gradient, the compound 51: 2ass with a yield of 40%.

[a] D25 - 37.40 (c = 1.0; CHCl3)
Elemental analysis
C% H%
Calculated 63.22 8.94
Found 63.02 9.21
Step g: Preparation of the compound 3-OL (-R) -6'-OD-galactose, 6-O-ndodecyl D-glucose, of structure 51: 2bss (R = -N-C4H8-; Z1F1 = On-dodecyl) and Z2F2 = Z3F3 = Z4F4 = Z'jGj = OH)
This product was prepared under the same conditions of temperature, solvent and acidity as in step g of Example 1 of the present process according to the invention. Compound 51: 2bss is obtained with a yield of 80%.

Elemental analysis
C% H%
Calculated 57.71 9.34
Found 57.53 9.38
Example 4: Surfactant Properties
The compounds having, according to the general formula I according to the present invention, a number of free OH groups p + p 'of between 2 and 8 and bearing groups ZiFi and / or ZjGj, in which Fi and Gj have a hydrocarbon chain of more than 7 carbon atoms and / or whose radical R has more than 7 carbon atoms, have revealed surfactant properties.

 These compounds, such as those described in particular in Examples 1, 2 and 3 according to the present invention, are characterized by a lowering of the surface tension of water at 25 ° C. to 30-35 mN / m with critical micellar concentrations ( CMC) between 10-4 M and 5.10-4 M.

When the number of free OH groups p + p 'is between 2 and 4, as for example for the compounds:
-31a &gamma; or 31a # or 3 "1a (A = B = D-glucose; R = -n-C8H15-; -n-C10H20-; -n-C4H8-C (OH, C7H15) -n-C4H8-; p = p = ZiFi = ZjGj = OH),
- 51ass (A = B = D-glucose; R = -n-C4H8-; p = p '= 1; Z1F1 = Z lG1 = On
C8H17 or On-C12H25),
-51a &gamma; 2 (A = B = D-glucose; R = -CH2-; p = p '= 1; Z1F1 = Z1G1 = O-n-lauroyl),
-51ass2 (A = B = D-glucose; R = n-C4H8-; p = p '= 1; Z1F1 = Z1'G1 = On
Iauroyle)
the solubility in water, at 25 ° C., is of the order of 50 to 200 mol, but these compounds introduced at a rate of 1 to 6% by weight in water-oil media of composition 70: 30 (w / w) at 30: 70 (w / w), generate stable emulsions, gels or creams.

When the total number of free OH groups p + p 'is between 5 and 8, as for example for the compounds:
-31b-gamma or -beta or -3b (A = B = D-glucose; R = -N-C8H16-; -N-C10H20-; -N-C4H8-C8OH, C7H15) -N-C4H8-; p = p ' = 4; ZiFi = ZjGj = OH),
- 32by or 32b # or 3 "2b (A = B = D-galactose; R = -n-C8H16-; -n
C10H20 -; - n-C4H8-C (OH, C7H15) n-C4H8-; 0 = 0 '= 4; ZiFi = ZjGj = OH),
51bss (A = B = D-glucose, R = -N-C4H8-, p = p '= 3, Z1F1 = Z1G1 = O-n-Lauroyl or On-dodecyl),
- 51: 2bss (A = D-glucose, B = D-galactose, R = -N-C4Hg-, p = 3, p '= 4;
Z1F1 = On-dodecyl; Z'1G1 = OH)
the solubility in water, at 250C, varies from 0.10g to 5g / l and these compounds introduced at a rate of 1 to 5% by weight in water-oil media of composition 90: 10 (w / w) at 30.degree. : 70 (w / w), generate stable emulsions, microemulsions, gels or creams.

The compounds having, according to the general formula I according to the present invention, all the OH groups released in step d1b and replaced by the O-acetyl groups in step f4 of the present process according to the invention (p = p '= O ZiFi = ZjGj = O-acetyl), are characterized by:
a catalytic effect which improves the performance of whitening agents when they are introduced into the detergent formulation,
a surfactant effect which improves the distribution of the ink, when they are introduced into the formulation of the inks.

These properties are particularly apparent for the products described in Example 2 according to the present invention:
- 5'4ba (A = B = D-xylitol, R = -CH2-, p = p '= O, ZiFi = Z'jGj = O-acetyl),
- 5'5ba (A = B = glycerol, R = -CH2-, p = p '= O, ZiFi = Z'jGj = O-acetyl).

Example 5: Biological Properties
Example of calcium antagonist properties
The compounds, according to the general formula I according to the present invention, having a group Z1F1 and / or a group Z'lGl in which Z1 and / or Z'1 are oxygen or sulfur atoms and in which F1 and G1 have a hydrocarbon chain with 7 to 9 carbon atoms, and having a number of free OH groups p + p 'of between 1 and 3, exhibit calcium antagonistic properties on the L channels and
P muscular fibers. These properties are manifested in particular by myorelaxant (anticontracturing) effects.

For example, the compound 51ass1 (A = B = D-glucose; R = -C4H8-; p = p '= 1; ZiFi = Z'LG1 = On-octyl) described in Example 1 according to the present invention, causes at concentrations ranging from 10-6 M to 2 × 10 -5 M, a reversible inhibition of muscle contraction on a tissue preparation of rat duodenum. The effect-dose determined on the preparation shows that the contracture is 50% inhibited (ICso) with a solution 6.10-6
M and 100% (igloo) with a solution of 2.10-5 M product 51ass1 in water.

Example of antitumor properties of compounds bearing groups ZiFi =
The compounds according to the general formula I obtained in steps f2 or f3 and / or g of the process according to the present invention, and having groups ZiFi = ZjGj = On-butanoyl whose number varies from 1 to 4 and having a number of free OH groups of between 2 and 6, for example for the compounds described in Example 1 according to the present invention:
- 51aa3 and 51ass3 (A = B = D-glucose, R = -CH2- or -C4H8-; p = p '= I; ZiFi = Z'lGl = On-butanoyl), have the biological properties including, antitumor of butyrates saline (sodium or arginine):
differentiation of the transformed cells (for example MSV cells incubated with this ester at concentrations ranging from 10 -3 M to 5 × 10 -3 M);
inhibition of the proliferation of tumor cells (for example 180 murine TG-U 937 and human MCF-7);
- Increased interferon sensitivity of the transformed cells (for example with NCF4.10.4 cells).

 In addition, these compounds have serum half-lives much greater than those of saline butyrates (12 to 36 hours against 5 minutes) allowing in vivo, prolonged therapeutic effects (delay effect) with low doses.

Claims (19)

CLAIMS:  1- Compounds corresponding to the general formula

 Wherein A and B are hexose, pentose, pentitol or glycerol or an acetalized or etherified derivative of these polyhydroxylated molecules; the ether junctions connecting A, R and B being of glyco sidic type or not.  In which p and p 'represent the number of free OH groups borne respectively by A and B; p and p 'being between 0 and 4.  Wherein n and n 'respectively represent a number of groups (ZiFi) carried by A and (ZjGj) carried by B; n and n 'being between 0 and 4; the groups Fi may be identical or different, i ranging from 0 to n; the groups Gj may be identical or different, j varying from 0 years.  In which the sum n + p of the groups ZiFi and free OH groups carried by the unit A is between 2 and 4. The sum n '+ p' of the groups ZjGj and free OH groups carried by the unit B is between 2 and 4. Fi and Gj represent derivatives of or acetalized or not acetalised or not, functionalized or not, chosen for example from derivatives of hexoses, pentoses, pentitols and glycerol, or principles biologically active, or hydrophobic carbon chains or a protective group.The carbon chain as a hydrophobic pole can be chosen for example from: a saturated or unsaturated chain, cyclic or not, branched or unbranched having at least seven carbon atoms; the protecting group may be chosen, for example, from benzyl or allyl; the biologically active principles ZiFi and / or ZjGj may or may not be released in vivo from the disaccharide substrates.  Wherein the groups F 1 and G 1 are grafted at sites selected in advance through respective atoms or groups of atoms Z 1 and Z 1; the atoms or groups of atoms Zi may be identical or different, as are the atoms or groups of atoms Zj, i and j varying respectively from 0 to n and from 0 to n '. Z 1 and Z 1 are chosen, for example, from an oxygen atom, a sulfur atom or a carboxyl group.  In which R can be an alkylene group whose carbon number is between 1 and 20, or alternatively a bivalent saturated or unsaturated radical, branched or unbranched, cyclic or otherwise, bearing or without functional groups, or heteroatoms.  2-3,3'-O-n-decylene bis (monoacetoneglucose).  3-heptyl bis (o-butyl 3-O-monoacetoneglucose) carbinol.  4- 3,3'-O-n-butylene bis (6-O-octyl monoacetoneglucose).  3,3'-O-n-butylene bis (6-O-dodecyl monoacetoneglucose).  6- 3,3'-O-metylene bis (6-O-lauroyl monoacetoneglucose).  7- 3,3'-O-n-butylene bis (6-O-lauroyl monoacetoneglucose).  8- 3,3'-O-n-decylene bis (D-glucose).  9-heptylbis (> butyl 3-O-D-glucose) carbinol.  10-6,6'-O-n-decylene bis (D-galactose).  11- 3-O - [(ea-butyl) 6'-O-D-galactose] 6-O-dodecyl D-glucose.  12-1, 1'-O-metylene bis (2,3,4,5-tetra-O-acetyl D-xylitol).  13-1, 1'-O-metylene bis (2,3-di-O-acetyl glycerol).  14- 3,3'-O-metylene bis (6-O-butanoyl monoacetoneglucose).  15- 3,3'-O-n-butylene bis (6-O-butanoyl monoacetoneglucose).  16- Process for synthesizing the compounds of general formula I

 by combining two derivatives of oses or itols or glycerol A and B, the junction between the two derivatives A and B being in the form of diethers between sites of A and B chosen in advance and a carbon group R bivalent. characterized in that the following steps are performed Step a of protecting units A and B leading in one or more steps to type 1 compounds having a single free OH group. Step b of etherification of the compound of type 1, derived from unit A, with a bifunctional derivative X-R1-X, to give compounds of type 2 in which unit A bears the group O-R1-X. Step c, etherification of the type 2 compound with the free OH group of the unit B in alcoholate form, to give the disaccharide derivative of type a symmetrical for A = B or asymmetric for A # B, with R = R1 . Step c2 removal of HX on the compound of type 2 in the presence of a base, to yield the compound of type 3 '. Stages c3 and c'3 of formation, by the transformation of the compound of type a into an organometallic compound (step c8) followed by the condensation of this derivative on an ester R'COOR "or on an acyl halide R'COX 'in an anhydrous aprotic solvent (step c'3), symmetrical disaccharide compound of type 3 ". with R = R1-C (OH, R ') - R1 and A = B. Steps d1a, d1b, d2a, d2b, deprotection of compounds of type 3 and 3 "leading respectively to type 4 or 3k and type 4 or  Partial deprotection of hydroxylated sites of units A and / or B according to steps dia and d2a respectively leads to products of type 4 and  The total deprotection of the hydroxylated sites of the units A and B according to the steps d1b and d2b respectively leads to the products of type 3b and Steps e1 and e2 for activation of compounds of type 3a and 4 for subsequent functionalization by regiospecific introduction of a leaving group X chosen for example from chloride, bromide or iodide, or else chosen for example from mesylate, tosylate, nosylate or triflate, or by formation of an anhydro derivative type 4 or a sulfite derivative or sulfato type 4 '.  According to step e, the anhydro derivative of type A is obtained from compounds of type a and 4 activated by the leaving group X as defined previously and having a free OH, by trans-elimination in the presence of a base. The base may be selected from, for example, LiOH, NaOH> KOH or an alcoholate.  According to step e2, the sulfite and sulfato derivatives of type 4 'are obtained respectively by the action of thionyl chloride and sulphuryl chloride on compounds of type 4 and Q "having two free OHs, in a solvent in the presence of The solvent may be a saturated or aromatic hydrocarbon or any other non-hydroxylated solvent The base may be selected from pyridine or any other tertiary amine such as triethylamine for example. Stage F1 of regiospecific grafting of groups F1Z1 and / or G1Z'1 as previously defined on intermediate 4, to lead to the products of type  The previously defined F1Z1 and G1Z'1 groups can be grafted onto the type 4 derivatives in the form of an alcoholate by adding a hydroxyl compound in the presence of a base in an aprotic solvent. The hydroxylated compound may be an alcohol having a number of carbon atoms of between 1 and 20 or a monosaccharide, itol or glycerol derivative carrying a single free OH. The base and the solvent may be chosen from those defined in step b according to the present process.  The previously defined groups F1Z1 and G1Z'1 may be grafted onto the derivatives 4, in thiol form in an apolar solvent which may be a saturated or aromatic hydrocarbon. Grafting in the thiol form may be favored for a Lewis acid such as, for example, lithium ion in the form of, for example, lithium chloride.  The same grafting can be carried out under the above conditions, starting from the compounds of type Q "after the activation defined in The step el of the present process.  Step fi may be followed in all cases of grafting, on the sites carrying a free OH group, of groups F2Z2 and / or G2Z'2 as previously defined. These graftings may be carried out in the form of an ether under the conditions of stage b of the present process according to the invention or in the form of an ester under the conditions of stage f 2 of the present process according to the invention, or still in the form of thioether, after activation of the free OH group. Stage f2 of regioselective grafting of F1Z1 and / or G1Z'1 groups on the products of type 4, to lead to type 4 products.  The groups F1Z1 and / or G1Z'1 can be grafted directly in the form of O-acyl groups by action of an acid chloride on the OH primary site or sites of the compounds of type 4. The step f2 can be followed in all the cases of the introduction on the carrier sites of a free OH group, of groups F2Z2 and / or G2Z'2 in ester form identical or different from F1Z1 and / or G1Z'1.  The same grafting can be carried out under the conditions above from the type 4 compounds. Stage f3 of regiospecific grafting of F1Z1 and / or G1Z'1 groups on the o type intermediate, to lead to XL type products.  The previously defined F1Z1 and / or G1Z'1 groups may be grafted as an O-acyl group by addition of a carboxylic acid salt to the o-type intermediate.  The same grafts can be made from the compounds of type 4 after activation according to step e2 in the form of derivatives analogous to compounds of type 4 '.  Step f3 can be followed in all cases of grafting, on sites carrying a free OH group, F2Z2 and / or G2Z'2 groups as previously defined. These graftings can be carried out in the form of an ether under the conditions of stage b of the present process according to the invention or in the form of an ester under the conditions of stage f 2 of the present process according to the invention, or still in the form of thioether, after activation of the free OH group. Step f4 of peracetylation of the compounds of type 2 to lead to the products of type  Peracetylation can also be performed on compounds of type 3 "b. Step g total deprotection followed or not new grafting.  The total deprotection of the compounds of type 4, carrying F1Z1 and / or G1Z'1 groups as well as the deprotection of their homologues described in steps f1, f2 and f3, carrying groups F2Z2 and / or G2Z'2 can be carried out under the conditions defined in steps dlb and d2b of the present process according to the invention. The products of type k and 3 "b are thus obtained, as well as their homologues carrying group F2Z2 and / or G'2Z'2.  The total deprotection can be followed in all the cases of the grafting, on the sites carrying a free OH group, of groups F3Z3 and F4Z4 and / or G3Z'3 and G4Z'4, as previously defined, under the same conditions as those used for grafting F1Z1 and G1Z'1 or F2Z2 and G2Z'2  17- Medicaments with calcium antagonistic properties according to claims I to 16.  18. Antitumor effect drugs according to claims 1 to 16.  19. Compounds with surfactant properties according to claims 1 to 16.  20- Bleaching agent catalyst compounds according to claims 1 to 16.