Glycosylation of Pyrazino[2,3‐c]‐1,2,6‐thiadiazine 2,2‐Dioxides to Sulfur Dioxide Analogs of Pteridine Nucleosides
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Cited by 8 publications
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This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.
This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.
Imidazol4,5-cl[ 1,2,6]thiadiazine ribosides have been prepared from furazanol3,4-cll1,2,6]thiadiazine 5,5-dioxides in a reaction sequence which involves introduction of the glycosidic rest, reductive cleavage of the furazan ring and cyclization. The ribosides were screened against HeLa cell cultures but showed no significant activity. Doridosine (1 -methylisoguanosine)') is a natural nucleoside which exhibits a wide range of pharmacological activitles2). In connection with our work on the chemistry and biological evaluation of analogues of naturally occurring nucleosides3), we wish to report our results on the SO,-analogue of doridosine 6 and related structures.Since our first attempts to prepare this nucleoside by methylation of the corresponding SO,-analogue of isoguanosine had failed4', we decided to use the synthetic strategy developed by Taylor for the preparation of 9-substituted adenines5,? This approach depicted in Scheme 1, had given good resu1ts')in the case of the dimethyl derivative shown. The first step involves introduction of the glycosidic rest at the exocyclic amino group. Attempts to achieve displacement of the 7-amino group of the furazanothiadiazine 18) with glucopyranosylamines failed, but finally 4 and 5 were obtained by direct glycosylation using the "silyl pro~edure"~). Thus, the furazanothiadiazine 1 was silylated with HMDS*)and then treated with suitable sugar derivatives to give the corresponding 7-(2,3,5-tri-O-acetyl-P-~-ribofura- The positions of the sugar moiety were unequivocally assigned by 'H-NMR-spectroscopy since the anorneric protons of 4 and 5 appeared respectively as a quartet and a triplet which collapsed to doublets after addition of D,O ( Table 1). The anorneric configuration of 5 was established as
A factorial design has been used to study the effect of three factors on the reaction between 4-amino-8Y-pyrazino[2,3-~]-1,2,6-thiadiazine 2,2-dioxide and 1,2,3,5-tetra-Q-acetyyl-p-D-ribofuranose. Reaction conditions have been found in which the usually less abundant N-8 isomer is selectively obtained. INTRODUCTIONIn a previous paper' we had described glycosylation of pyrazino[2,3-~]-1,2,6-thiadiazine derivatives in which the N-1 nucleosides were the major products (Scheme 1). Because, for biological reasons, we wanted to prepare larger amounts of the N-8 nucleoside we decided to methodologically study the operating conditions.
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