5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ

Details 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ

1996-01-20

1998-09-22

Wilson, James O.

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

Organic compounds

Carbohydrates or derivatives

536 41, 536 221, 536 281, 536 2853, 536 2854, 536 2855, 536 2913, 536 292, C07H 1906

Patent

active

058115404

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

1. Technical Field
The present invention relates to a novel 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and a production method and a use thereof. More particularly, the present invention is concerned with a 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative useful as an intermediate for synthesizing a .beta.-2',3'-dideoxynucleoside derivative which is known to exhibit an antiviral activity, a method for producing the same, and a method for stereos electively producing a .beta.-2',3'-dideoxynucleoside derivative from the 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative. By the method of the present invention, a .beta.-2',3'-dideoxynucleoside derivative can be easily produced in high yield without producing an .alpha.-anomer corresponding thereto. The .beta.-2',3'-dideoxynucleoside derivative obtained by the method of the present invention is useful as a precursor of various antiviral agents, such as 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine (DDC), and 3'-fluoro-3'-deoxythymidine (FLT), which are capable of suppressing the multiplication of human immunodeficiency virus (HIV). AZT and DDC have been widely used as a therapeutic reagent for AIDS.
2. Background Art
Conventional methods for synthesizing a .beta.-2',3'-dideoxynucleoside derivative can be classified into two groups. In the method of the first group, a .beta.-2',3'-dideoxynucleoside derivative is obtained by deoxidizing the hydroxyl group at each of the 2'- and 3'-positions of a natural or synthesized .beta.-ribonucleoside (C. K. Chu et al., J. Org. Chem., vol. 54, p. 2217, 1989). In the method of the second group, a .beta.-2',3'-dideoxynucleoside derivative is obtained by coupling a 2,3-dideoxysugar derivative with a nucleic acid base. With respect to examples of such a coupling method, reference can be made to a method in which a leaving group at the anomeric carbon atom position of a 2,3-dideoxysugar is eliminated using an activating agent (e.g., a Lewis acid) and then, a nucleic acid base is bonded to the anomeric carbon atom position (C. K. Chu et al., J. Med. Chem., vol. 33, p. 1553, 1990); a method in which a 1-chloro-2, 3-dideoxysugar is reacted with a sodium salt or potassium salt of a nucleic acid base (F. Seela et al., Heterocycles, vol. 29, p. 2193, 1989); and a method in which an addition reaction of a nucleic acid base to a glycal is effected (C. U. Kim et al., Tetrahedron lett., vol. 33, p. 5733, 1992).
However, in the above-mentioned method of the first group, the starting material is expensive, and the deoxidization reaction requires a complicated procedure having a number of synthesizing steps involved therein. On the other hand, in the above-mentioned method of the second group, an undesirable .alpha.-anomer is formed simultaneously with the formation of the desired .beta.-anomer, leading to a lowering in yield of the desired .beta.-anomer. Further, in this method, the .alpha.-anomer and the .beta.-anomer are usually formed in mixture thereof. It is difficult to separate the .beta.-anomer from the .alpha.-anomer by conventional purification processes and, therefore, for obtaining the desired .beta.-anomer in pure form, it is necessary to repeat the separation procedure many times, which is very cumbersome. In the method in which a 1-chloro-2,3-dideoxysugar is used in the coupling reaction, this starting sugar itself is unstable, so that the use of such a starting material is disadvantageous in preparation and handling thereof. The method in which the addition reaction of a base to a glycal is effected is also disadvantageous in that the substituent at the 2'-position of the resultant nucleoside, which substituent is formed by the addition reaction, must be finally removed. Thus, any of the conventional methods for synthesizing a .beta.-2',3'-dideoxynucleoside derivative is not satisfactory for practice on a commercial scale.


DISCLOSURE OF THE INVENTION

With a view toward developing a method for the efficient synthesis of a 2',3'-dideoxynucleoside derivative with a h

REFERENCES:
General Syntheses of 2',3'-Dideoxynucleosides and 2',3'-Didehydro-2',3'-dideoxynucleosides--C.K. Chu et al,--J. Org. Chem. 1989, 54, pp. 2217-2225.
Synthesis and Structure-Activity Relationship of 6-Substituted 2',3'-Dideoxypurine Nucleosides as Potential Anti-Human Immunodeficiency Virus Agents--Chung K. Chu et al,--J. Med. Chem. 1990, 33, pp. 1553-1561. 2',3'-Dideoxyribonucleosides Via Nucleobase Anion Glycosylation with 2,3-Dideoxy-D-Glycero-Pentofuranosyl Chloride--Heterocycles, vol. 29, No. 11, 1989.
Facile, Highly Stereoselective Synthesis of 2',3'-Dideoxy- and 2',3'-dideoxy Nucleosides via a Furanoid Glycal Intermediate--Choung Un Un Kim et al,--Tetrahedron Letters, vol. 33, No. 39, pp. 5733-5737, 1992.
Stereocontrolled Synthesis of .beta.-D-2'-Deoxyribonucleosides by Intramolecular Glycosylation--Keiko Sujino et al,--Chemistry Letters, 1993, pp. 1187-1190.
The Journal of Organic Chemistry--vol. 58, No. 4, Feb. 12, 1993.

Affiliated with

Also associated with

Rating

5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5-O-pyrimidyl-2,3-dideoxy-1-thiofuranoside derivative, and produ will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1622786