Method for synthesizing C-glycosides of ulosonic acids

Details Method for synthesizing C-glycosides of ulosonic acids Method for synthesizing C-glycosides of ulosonic acids

2001-05-17

2003-07-08

Solola, Taofiq (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S428000, C549S453000, C549S455000

Reexamination Certificate

active

06590110

ABSTRACT:

TECHNICAL FIELD
The present invention relates to a method for synthesizing C-glycosides of ulosonic acids, as well as intermediates thereof and particular C-glycosides prepared by the method.
BACKGROUND ART
Ulosonic acids are a diverse family of complex monosaccharides that serve important biological functions. The most common ulosonic acids are N-acetylneuraminic acid (NANA), 3-deoxy-
D
-glycero-
D
-galactonulosonic acid (KDN) and 3-deoxy-
D
-manno-2-octulosonic acid (KDO), important constituents of many glycoconjugates, often occupying the non-reducing ends of oligosaccharide chains. Glycoproteins containing NANA, for example, are involved in a number of biological processes including cell interactions with other cells, microorganisms, toxins and antibodies.
1
The biologic functions of ulosonic acids are derived from their size, negative charge and their natural position as the terminal residue on cell surface glycoconjugates. C-glycosides of ulosonic acids are of particular interest for their potential pharmaceutical applications. These are expected to have both improved enzymatic hydrolytic stability and exoanomeric conformation similarity to the corresponding O-glycosides.
2
The synthesis of C-glycosides is a well established area of carbohydrate chemistry.
3
The utility of glycosyl chlorides in the formation of C-glycosides has been appreciated for some time. Until recently the aglycone portion of this radical pathway was limited to allylsilane, 1,3-dimethoxy benzene.
3a
Sinaÿ
4
and Wong
5
examined the possibility of coupling chloride and ketone (or aldehyde) under SmI
2
mediated radical reactions. In the presence of a protecting group at C-2, glycal was produced, in place of the desired C-glycoside. NANA-C-glycoside was reported by Bednarski
6
through NANA-glycosyl chloride with (nBu)
3
SnCH
2
CH═CH
2
and catalytic amount of [(nBu)
3
Sn]
2
, affording 1:1 mixture of NANA-C-glycoside. By using glycosyl aryl sulfones, Beau and co-workers prepared the corresponding 1,2-trans-C-glycosides under Barbier conditions.
7
A similar approach was used in the first examples of the NANA
8
and KDN
9
C-disaccharide synthesis in our laboratory, using pyridyl and phenyl sulfones as nucleophiles. There are two disadvantages of using sulfones as nucleophiles: 1) additional steps are required for their preparation and 2) they often produce a very unpleasant odor.
DISCLOSURE OF THE INVENTION
Accordingly, an object of the present invention is to provide a method for synthesizing C-glycosides of ulosonic acids such as Neu5Ac, by which diastereocontrolled synthesis of &agr;-C-glycosides of ulosonic acids is attained, which is simpler than the known method and free from the unpleasant odor caused by the use of a sulfone derivative.
The present inventors intensively studied to discover that the above-mentioned object may be attained by reacting a halogenated ulosonic acid with an aldehyde or ketone compound in the presence of a lanthanide metal halide, thereby completing the present invention.
That is, the present invention provides a method for synthesizing C-glycosides of ulosonic acids comprising the step of reacting a halogenated ulosonic acid with an aldehyde or ketone compound in the presence of a lanthanide metal halide, such as samarium iodide.
By the present invention, a method for synthesizing C-glycosides of ulosonic acids, by which diastereocontrolled synthesis of &agr;-C-glycosides of ulosonic acids is attained, which is simpler than the known method and free from the unpleasant odor caused by the use of a sulfone derivative, was provided.


REFERENCES:
Pouilly et al., Organic Synthesis, pp. 1391-94 (1991).*
Zjawiony et al., No. 213, Abstract of Papers, 216th ACS Nat. Meeting. 0-8412-3627-5, (Boston, MA) Aug. 1998.*
Mazeas et al., Angew. Chem. Int. Ed. Engl., vol. 34, No. 8 (1995), pp. 909-912.*
Vlaho et al., J. Am. Chem. Soc. vol. 119, No. 6 (1997), pp. 1481.*
Hung et al., Angew. Chem. Int. Ed. Engl. vol. 35, No. 22 (1996), pp. 2671-2674.*
Jarreton et al., Chem. Commun. Jul. 1996, pp. 1661-1662.*
Nagy et al. Tetrahedron Lett, vol. 32(B2) (1991) pp. 3953-3956.*
Luthman et al., J. Org. Chem., vol. 52, No. 17, pp. 3777-3784 (1987).
Tomiyama et al., Society National Meeting, Part 2, Abstract No. MEDI-214 (1998).

Affiliated with

Also associated with

Rating

Method for synthesizing C-glycosides of ulosonic acids does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method for synthesizing C-glycosides of ulosonic acids, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for synthesizing C-glycosides of ulosonic acids will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3037849