Synthesis Of Nucleosides

Abstract

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.

1,3-Dipolar cycloadditions of 2-thio-3-chloroacrylamides with diazoalkanes

“…Thus, the pyrazoline cycloadducts are initially formed, but these are unstable and spontaneous elimination of R 1 S(O)Cl gives the pyrazoline intermediate, which on 1,5-trimethylsilyl shift affords the N-trimethylsilyl pyrazole. Hydrolytic cleavage of the N-Si bond [36][37][38][39][40] (presumably when the crude product is purified by chromatography on silica gel) yields the final pyrazole product (Scheme 10).…”

Synthesis of 2,6‐Dihalogenated Purine Nucleosides by Thermostable Nucleoside Phosphorylases

“…Two approaches to the synthesis of purine nucleosides have been widely and extensively studied. The first, convergent approach consists in the condensation of a purine base with a suitable pentofuranose derivative and subsequent deprotection (see, e.g., [5,6,9] and the reviews [10] ). The second comprises the chemical transformation of the purine base or/and the pentofuranose fragment of the natural commercially available ribo-or 2'-deoxyribo-nucleoside in the desired compound.…”

Production, Characterization and Synthetic Application of a Purine Nucleoside Phosphorylase from Aeromonas hydrophila

“…To obtain the b-oriented glycoside bond their use appears to be a convenient alternative to chemical methods which suffer from low stereoselectivity, multi-step procedures and modest total yields. [3] Several procedures based on the "transglycosylation" reaction (Scheme 1) have been employed (using both isolated enzymes and whole cells) to prepare a wide variety of nucleosides. [4][5][6][7][8][9][10][11] Structural analysis revealed that there are two distinct families of NPs: NPI and NPII.…”