Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1988-12-23
1992-09-01
Rollins, John W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C07H 1916, A61K 4726
Patent
active
051440180
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel intermediates useful for synthesizing various dideoxynucleoside derivatives, synthetic processes thereof, and novel dideoxynucleoside derivatives which may be synthesized from these intermediates and may be used as effective antiviral agent.
PRIOR ART
Dideoxynucleosides have now been paid attention as an effective antiviral agent for AIDS virus (HTLV III) which is a kind of retrovirus. Effectiveness of azidothymidine, dideoxycytidine, dideoxyadenosine, etc. has hitherto been confirmed, and researches on other dideoxynucleoside derivatives are also proceeded with (Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides; and Hiroaki Mitsuya and Samuel Broder, Proc. Natl. Acad. Sci., USA vol. 83, pp. 1911-1915, March 1986, Medical Sciences).
2',3'-Dideoxyadenosine, 2',3'-dideoxyinosine, 2',3'-dideoxyguanosine and 2',3'-dideoxycytidine are sold by BIOCHEMICAL CO. in USA. These compounds are prepared using a conventional method for preparing 2',3'-dideoxycytidine (Horwitz et al., J. Org. Chem., 32(3), 817-818 (1967)) or a conventional method for preparing 2',3'-dideoxyguanosine (Prisbe et al., Synth. Commun. 1985, 15(5), 401-409).
European Patent Publication No. 206497A discloses the use of 2',3'-dideoxyinosine as an antiviral agent.
Further, the aforementioned article of Hiroaki Mitsuya et al., and Japanese Patent Unexamined Published Application No. 61-280500 disclose the use of various 2',3'-dideoxynucleosides and their derivatives as an antiviral agent, particularly against AIDS virus.
As for a synthetic method of nucleoside intermediates useful for synthesizing various dideoxynucleoside derivatives, there are prior researches by M. J. Robins, Nyilas, Chattopadhyaya, Reese, Sasaki and others. However, these synthetic methods are not fully satisfactory for industrial synthesis of dideoxynucleoside derivatives from the reason that steps required for the synthesis are long, complicated steps including an oxidation reaction follow, reagents not suitable for a large scale preparation are used, etc. Literatures with respect to these synthetic methods are enumerated below.
1) M. J. Robins et al., J. Org. Chem. 39, 2564 (1974).
2) F. Hansske and M. J. Robins, Tetrahedron Lett., 26, 4295 (1985).
3) F. Hansske, D. Madej, and M. J. Robins, Tetrahedron, 40, 125 (1984).
4) F. Hansske and M. J. Robins, J. A. Chem. Soc., 105, 6736 (1983).
5) A. Nyilas and J. Chattopadhyaya, Synthesis., 1986, 196.
6) H. Bazin and J. Chattopadhyaya, Synthesis, 1985, 1108.
7) D. G. Norman and C. B. Reese, Synthesis, 1983, 304.
8) T. Sasaki, K. Minamoto and S. Tanizawa, J. Org. Chem. 38, 2896 (1973).
Among dideoxynucleoside derivatives, one of which is now practically used as a AIDS therapeutic agent is azidothymidine. However, azidothymidine brings about strong side effects and has only an inadequate AIDS virus growth-inhibiting effect. Therefore, researches on various dideoxynucleoside derivatives must successively be proceeded with.
OBJECTS OF THE INVENTION
An object of the present invention is to provide novel dideoxynucleoside derivatives which are effective as antiviral agents.
Another object of the present invention is to provide novel nucleoside derivatives which are usable as intermediates useful for synthesis of various dideoxynucleoside derivatives.
Further object of the present invention is to provide simple synthetic methods suitable for a large scale synthesis of the above intermediates.
DESCRIPTION OF THE INVENTION The present invention relates to nucleoside
derivatives represented by the following general formula I : ##STR1## wherein B is a purine base residue optionally having a protective group, a pyrimidine base residue optionally having a protective group or a imidazolyl group optionally having a protective group; R.sup.1 and R.sup.3 are a PivO- group, a TsO- group, a DMTrO- group or a benzoyl group; R.sup.2 is a MsO- group, a TflO-g
REFERENCES:
patent: 3658787 (1972-04-01), Russell et al.
patent: 4788181 (1988-11-01), Driscoll et al.
patent: 4921950 (1990-05-01), Wilson
Tetrahedron, vol. 40. No. 1, 1984, pp. 125-135, Pergamon Press, Oxford, GB; F. Hansske et al.: "2' and 3'-ketonucleosides and their Arabino and Xylo reduction products"* Abstract; p. 126; compounds 4-9*.
Tetrahedron Letters, vol. 28, No. 35, 1987, pp. 4075-4078, Pergamon Journals Ltd., Oxford, GB; M. Kawana et al.: "The facile synthesis of 2'-azido-2',3' dideoxyadenosine. Preparative applications of the deoxygenative [1,2]-hydride shift and beta-elimination rections of sulfonates with Mg(OMe)2-NaBH4".
Journal of American Chemical Society, vol. 105, No. 22, Nov. 2, 1983, pp. 6736-6737, Am. Chemical Society; F. Hansske et al.: "A deoxygenative [1,2]-hydride shift rearrangement converting cyclic cis-diol monotosylates to inverted secondary alcohols".
Antiviral Research, vol. 6, No. 17, 1986, pp. 103-112, Elsevier Science Publishers B.V. (Biomedical Div); A. Widell et al.: "Influence of twenty potentially antiviral substances on invitro multiplication of hepatitis A virus".
Chemical Abstracts, vol. 108, No. 1, Jan. 4, 1988, p. 14, abstract No. 119v, Columbus, Ohio, US; V. E. Marquez et al.: "2'3'-Dideoxy-2'-fluoro-ara-A. An acid stable purine nucleoside active against human immunodeficiency virus (HIV)":, & Biochem. Pharmacol, 1987, 36(17), 2719-2722.
Chemical Abstract, vol. 105, No. 17, Oct. 27, 1986, p. 72, abstract No. 146227n, Columbus, Ohio, US; & JP-A-61 103 831 (Yamasa Shoyu Co., Ltd) May 22, 1986.
Chemical Abstracts, vol. 89, No. 1, 1978, p. 560, Abstract No. 6487y, Columbus, Ohio, US; H. Guglielmi et al.; "Imidazole nucleosides. III. Nucleosides of 4(5)-aminoimidazole-5(4)-carboxamide", & Hoppe-Seyler's Z. Physiol Chem. 1977, 358(11), 1463-68 Abstract.
Chemical Abstracts Formula Index, 10th Collective Index, P 3842F, C9H12N406, 1H-imidazole-5-carboxamide, 1H-imidazole-5-carboxamide, 1-(3-deoxy-beta-D-erythro-pentofuranosyl)-4-nitro-, p. 3929f, C9H14N404, 1H-imidazole-5-carboxamide, 4-amino-1-(3-deoxy-beta-D-erythro-pentofuranosyl).
Chemical Abstract. Feb. 5, 1973, Kelvin Ogilvie et al., "Anhydronucleosides VI. Synthesis of 8, 3'-Thioanhydroguanosine", 30127Z.
Barton et al., J. Chem. Soc. Perkin Transacations. I, pp. 1574-1585 (1975).
Chemical Abstracts 107:176403a. Herdewijn et al. J. Med. Chem. 30(11):2131-2137, 1987.
Kawana Masajiro
Kuzuhara Hiroyoshi
Nishikawa Masahiro
Yamasaki Noritsugu
Kunz Gary L.
Rikagaku Kenkyusho
Rollins John W.
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