D-pentofuranose derivatives and process for preparing the same

Details D-pentofuranose derivatives and process for preparing the same D-pentofuranose derivatives and process for preparing the same

1998-01-06

1999-03-09

Trinh, Ba K.

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549438, 549478, C07D30712, C07D30720, C07D31744

Patent

active

058802940

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP97/01427 dated Apr. 24, 1997.


TECHNICAL FIELD

The present invention relates to novel D-pentofuranose derivatives which are useful as industrial synthesis intermediates of 3'-C-substituted ribonucleoside derivatives, and to a process for preparing the same.


BACKGROUND ART

3'-C-Substituted ribonucleoside derivatives represented by the following formula (6): ##STR2## (wherein B represents a nucleic acid base which may have a substituent and Z represents an ethynyl group which may be substituted by a trialkylsilyl group) exhibit excellent antitumor activities, and thus these compounds are useful as antitumor agents (International Patent Application No. PCT/JP95/02554).
Conventionally, 3'-C-substituted ribonucleoside derivatives have been synthesized through nucleophilic addition to 3'-ketonucleoside (Chem. Pharm. Bull., 35, 2605 (1987), Tetrahedron, 47, 1727 (1991)). However, when 3'-ketonucleoside having a protected hydroxyl group at the 5'-position is subjected to nucleophilic addition, nucleosides of the xylose type are mainly formed, and the target ribose type nucleosides can hardly be obtained. Also, Tetrahedron Letters, 36, 10331-1034 (1995) describes that the compound of interest, i.e., 3'-C-substituted ribonucleoside, can be synthesized through nucleophilic addition to 3'-KETONUCLEOSIDE having unprotected hydroxy at the 5'-position. However, since 5'-O-unsubstituted-3'-ketonucleoside is a very unstable compound, it is not suitable for use as an industrial synthesis intermediate.
Independently, it has been reported that the compound of interest, i.e., a 3'-C-substituted ribonucleoside derivative, can be synthesized through reaction between a 3-C-substituted ribofuranose derivative and a silylated nucleic acid base in an aprotic solvent in the presence of a Lewis acid (International Patent Application No. PCT/JP95/02554). However, this process is not suitable for industrial synthesis of the compound, for it requires a purification procedure by column chromatography because respective intermediates cannot be obtained as crystals. According to this invention, the hydroxyl group at the 3-position of xylofuranose is oxidized to obtain an intermediate 3-ketofuranose, wherein the oxidation step generally includes use of dimethylsulfoxide or chromic acid. In the case of dimethylsulfoxide, dimethylsulfide having foul is generated. Chromic acid is harmful heavy metal that may have adverse effects on the environment. Therefore, neither case is preferred.
Accordingly, the object of the present invention is to provide a stable intermediate for preparing 3'-C-substituted ribonucleoside derivatives industrially and economically, with simplicity and efficiency, without use of a harmful reagent, as well as to provide a process for preparing the intermediate.


DISCLOSURE OF THE INVENTION

Under the above circumstances, the present inventors have conducted careful studies, and have found that D-pentofuranose derivatives represented by the following formulas (1), (2), (3), and (4) are useful intermediates for synthesizing 3'-C-substituted ribonucleoside derivatives, thus leading to completion of the invention.
Accordingly, the present invention is directed to a D-pentofuranose derivative represented by the following formula (1): ##STR3## (wherein each of X and Y represents a lower alkyl group and the sugar moiety represents xylose); a D-pentofuranose derivative represented by the following formula (2): ##STR4## (wherein each of X and Y represents a lower alkyl group); a D-pentofuranose derivative represented by the following formula (3): ##STR5## (wherein each of X and Y represents a lower alkyl group, Z represents an ethynyl group which may be substituted by a trialkylsilyl group, and the sugar moiety represents ribose); and to a D-pentofuranose derivative represented by the following formula (4): ##STR6## (wherein R.sup.1 represents a hydrogen atom, an aliphatic lower acyl group, a substituted or unsubstituted benzoyl group, or a lower alkyloxycarbonyl group, Z represents an ethy

REFERENCES:
Rosenthal. A, et al. "Branched-Chain Sugar Nucleosides. Synthesis of 3'-C-Ethyl (And 3'-C-Butyl)Uridine", Carbohydrate Research (1980), vol. 79, pp. 235-242.

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