Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2000-10-13
2003-10-14
Jones, Dwayne C. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S107000, C536S108000, C536S115000, C536S116000, C536S123100, C514S035000, C514S053000
Reexamination Certificate
active
06632940
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a novel method of chemical preparation of &bgr;-D-glucopyranosyl-(1→3)-D-glucopyranose of formula (I), commonly called laminaribiose.
BACKGROUND OF THE INVENTION
Laminaribiose is a disaccharide which is used notably in the agricultural field and as an antiseptic.
This disaccharide is in general obtained by hydrolysis or by acetolysis of natural polysaccharides of plant origin (see Villa, Phaff, Notario,
Carbohydr. Res.,
1979, 74, 369; Kusama, Kusakabe, Zama, Murakami, Yasui,
Agric. Biol. Chem.,
1984, 48, 1433; Wang, Sakairi, Kuzuhara,
Carbohydr. Res.,
1991, 219, 133; Moreau, Viladot, Samain, Planas, Driguez,
Bioorg. Med. Chem.,
1996, 4, 1849).
Laminaribiose can also be prepared chemically, notably by methods derived from the Koenigs-Knorr method of O-glycosylation (see Koenigs, Knorr,
Ber. Dtsch. Chem. Ges.,
1901, 34, 957) which makes use of glycosyl halides as glycosyl donors.
A first method has thus been proposed by Freudenberg and von Oertzen in 1951 (see Freudenberg, von Oertzen,
Justus Liebigs Ann. Chem.,
1951, 574, 37), and a second method has been described by Bächli and Percival in 1952 (see Bäichli, Percival,
J. Chem. Soc.,
1952, 1243).
The major drawbacks of these two methods reside in a purification which is difficult to carry out and in an overall yield which is lower that 10%.
A third method has been proposed by Takeo in 1979 (see Takeo,
Carbohydr. Res.,
1979, 77, 245), but it necessitates several steps of selective protection and deprotection of the hydroxyls of the acceptor used which is in glucopyranose form.
It has also been proposed to form laminaribiose from ortho-esters (see Kochetkov, Bochtov, Sokolovskaya, Snyatkova,
Carbohydr. Res.,
1971, 16, 17). This method does however prove to be difficult to carry out and enables laminaribiose to be obtained only with an overall yield neighbouring 10%.
Under these circumstances, the aim of the present invention is to provide a novel method of chemical preparation of laminaribiose which has a limited number of steps which are easy to carry out and which enables the product sought after to be obtained in pure form with a high overall yield.
SUMMARY OF THE INVENTION
The solution in accordance with the present invention to solve this technical problem consists of a method of preparing laminaribiose comprising a step of glycosidic coupling between a glycosyl donor and a glycosyl acceptor, characterised in that:
the glycosyl donor is in pyranose form and is of formula (II):
in which:
R
1
represents:
an alkyl or haloalkyl radical having 1 to 6 carbon atoms
an aryl radical which is non-substituted or substituted with one or more groups selected from a halogen atom, an alkoxy radical having 1 to 6 carbon atoms or a nitro group;
X represents an electrophilic leaving group selected from:
a group of formula S(O)
n
R′ in which R′ represents an alkyl radical having 1 to 6 carbon atoms, an aryl radical which is non-substituted or substituted with an alkoxy group having 1 to 6 carbon atoms, a nitro or acetamide group, and n is an integer equal to 0 or 1; or
a trichloroacetimidate group;
the glycosyl acceptor is in furanose form and is of formula (III)
in which:
R
2
and R
3
together form a methylidyl, ethylidyl, trichloroethylidyl, isopropylidyl, hexafluoroisopropylidyl, cyclopentylidyl, cyclohexylidyl, cycloheptylidyl, butylidyl, 1-tert-butylethylidyl, 1-phenylethylidyl, benzylidyl, methoxybenzylidyl, or 1-phenylbenzylidyl radical ; and
R
4
and R
5
together form a methylidyl, ethylidyl, trichloroethylidyl, isopropylidyl, hexafluoroisopropylidyl, cyclopentylidyl, cyclohexylidyl, cycloheptylidyl, butylidyl, 1-tert-butylethylidyl, 1-phenylethylidyl, benzylidyl, methoxybenzylidyl, or 1-phenylbenzylidyl radical, or independently represent a benzyl, acetyl, benzoyl, chlorobenzoyl, methoxybenzoyl, nitrobenzoyl, allyl, chlorobenzyl, methoxybenzyl or nitrobenzyl radical;
said coupling step is carried out in solution in an anhydrous organic solvent, at a temperature between −80° C. and 40° C., for a period of 1 minute to 8 hours, in the presence of a suitable promoter selected from:
a source of halonium ions, combined or not with a Lewis acid or a salt of a strong acid, in the case in which X represents an S(O)
n
R′ group as defined above in which n is equal to 0;
a Lewis acid combined with an amine, in the case in which X represents an S(O)
n
R′ group as defined above in which n is equal to 1; or
a Bronsted acid or a Lewis acid, in the case in which X represents a trichloroacetimidate group ; and
the reaction product thus obtained, neutralised and purified, being subjected to a deprotection treatment to give, after purification, laminaribiose.
DETAILED DESCRIPTION OF THE INVENTION
It has been discovered, and this constitutes the basis of the present invention, that it was possible to chemically prepare laminaribiose with a limited number of steps which enable a relatively high overall yield to be obtained, by a judicial choice of the glycosyl donor and of the glycosyl acceptor, as well as of the promoter used during the coupling reaction.
In the description and claims:
<<alkyl radical having 1 to 6 carbon atoms>> is understood as meaning any linear or branched hydrocarbon chain, such as a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, hexyl, or isohexyl radical, for example;
<<haloalkyl radical having 1 to 6 carbon atoms>> is understood as meaning any alkyl radical 1 to 7 hydrogen atoms of which are substituted by 1 to 7 halogen atoms, such as a chloromethyl radical, a bromomethyl radical, a trifluoromethyl radical, a 2,2,2-trifluoroethyl radical, a pentafluoroethyl radical, or a heptafluoropropyl radical, for example;
<<aryl radical>> is understood as meaning an aromatic ring having 5 or 6 carbon atoms or heteroatoms, such as a phenyl, pyridyl, thienyl, furanyl, or pyrimidyl radical, for example.
The glycosyl donor of formula (II) mentioned above as well as the glycosyl acceptor of formula (III) mentioned above can be obtained relatively easily, in one or two steps, from D-glucose.
Advantageously, the glycosyl donor will in general be selected from the compounds of formula (II) mentioned above in which:
R
1
represents a radical selected from the group consisting of methyl, chloromethyl, trifluoromethyl, tert-butyl, phenyl, chlorophenyl, methoxyphenyl and nitrophenyl radicals;
X represents a radical selected from the group consisting of thiomethyl, thioethyl, thiopropyl, thiophenyl, thionitrophenyl, and thiopyridyl radicals.
In general, the promoter used during the coupling step mentioned above will be selected from:
N-bromosuccinimide or N-iodosuccinimide, combined or not with a Lewis acid selected from ferric chloride, copper ditriflate, tin ditriflate, boron trifluoride dietherate, tin or zirconium tetrachloride, methyl triflate, trimethyl- (or triethyl-) silyl triflate, silver triflate, cadmium ditriflate, cobalt ditriflate, nickel ditriflate, zinc ditriflate, bismuth tritriflate, iron tritriflate, gallium tritriflate, or with a salt of a strong acid such as tetrabutylammonium triflate, in the case in which X represents an S(O)
n
R′ group as defined above in which n is equal to O,
a Lewis acid selected from triflic anhydride, ferric chloride, copper ditriflate, tin ditriflate, boron trifluoride dietherate, tin or zirconium tetrachloride, methyl triflate, trimethyl- (or triethyl-) silyl triflate, silver triflate, cadmium ditriflate, cobalt ditriflate, nickel ditriflate, zinc ditriflate, bismuth tritriflate, iron tritriflate, gallium tritriflate, combined with an amine particularly such as di-tert-butylmethylpyridine, in the case in which X represents an S(O)
n
R′ group as defined above in which n is equal to 1, and
a Bronsted acid particularly such as triflic acid or para-toluenesulphonic acid or a Lewis acid selected from triflic anhydride, ferric chloride, copper ditriflate, tin ditriflate, boron trifluoride dietherate, tin o
Ferrieres Vincent
Jamois Frank
Plusquellec Daniel
Yvin Jean-Claude
Jones Dwayne C.
Laboratoires Goemar
Merchant & Gould P.C.
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