Publisher Summary Acetal groups are largely used as protecting groups in synthesis and as model compounds for studying various chemical reactions. With the advent and general accessibility of new physical-chemical methods of analysis, particularly, nuclear magnetic resonance (n.m.r.) spectroscopy and mass spectrometry (m.s.), considerable progress has been made in knowledge of the stereochemistry of these fused-ring systems and of aspects such as diastereoisomerism. Cyclic acetal moieties occur widely in bacterial polysaccharides. The formation of cyclic acetals occurs by condensation of a diol with an aldehyde or ketone, the carbonyl compound often serving as the solvent. The oxonium ion reacts rapidly with the nearest hydroxyl group to give the first product, which can subsequently rearrange to give the thermodynamically most stable product. The reaction can be largely divided into a kinetic and a thermodynamic phase and the product of each of these can differ considerably from each other. Whether or not the products isolated are true equilibrium products depends on the stage at which the reaction is terminated, and on factors such as the solubility and the temperature.

Cyclic Acetals of The Aldoses and Aldosides Highlights of the Literature Since 1964, and A Supplement to the Tables

This compendium focuses on functionalised sugar amino acids (SAAs) and their 3- to 6-membered nitrogen heterocyclic and carbocyclic analogues. The main benefit of using SAAs and their related nitrogen and carbon congeners in the production of peptidomimetics and glycomimetics is that their properties can be readily altered via modification of their ring size, chemical manipulation of their numerous functional groups and fine-tuning of the stereochemical arrangement of their ring substituents. These building blocks provide access to hydrophilic and hydrophobic peptide isosteres whose physical properties allow entry to a region of chemotherapeutic space which is still under-explored by medicinal chemists. These building blocks are also important in providing amino acids whose inherent conformational bias leads to predisposition to secondary structure upon oligomerisation in relatively short sequences. These foldamers, particularly those containing ω-amino acids, provide an additional opportunity to expand access to the control of structures by artificial peptides. The synthesis and biological evaluation of these building blocks in glycomimetics and peptidomimetics systems keep expanding the reach of the glycosciences to the medical sciences, provide a greater outlook onto the wide range of cellular functions of saccharides and their derivatives involved and greater insight into the nature of oligosaccharide and protein folding.

https://link.springer.com/content/pdf/10.1007%2Fs00726-013-1521-1.pdf

A compendium of cyclic sugar amino acids and their carbocyclic and heterocyclic nitrogen analogues

Publisher Summary This chapter discusses the C-nucleoside literature. With respect to the naturally occurring C-nucleosides, most work published since 1970 has been discussed. In reviewing work relevant to the synthesis of C-nucleosides, the various synthetic strategies that have been developed have been discussed. Numerous new compounds for biological testing have been achieved by modification of natural C-nucleosides. synthetic approaches to C-nucleosides have utilized preformed carbohydrates as starting material. Successful syntheses have involved: (a) direct linkage of preformed base and carbohydrate precursors; and/or (b) stepwise construction of a heterocyclic base onto a preformed carbohydrate derivative. The chapter discusses c-nucleosides in biology and medicine. The elegant biological experiments using formycin have made great contributions by calling attention to the subtle and critical roles conformation and conformational flexibility of biomolecules play in their normal functioning. Numerous, perhaps a majority, of the synthetic C-nucleosides are becoming available for study in biological systems.

The chemistry and biochemistry of C-nucleosides.

A microtest has been devised for the rapid preliminary assay in vitro of the effect of over 100 drugs and inhibitors on African trypanosomes (Trypanosoma brucei and T. rhodesiense). Parasite motility and infectivity for mice are indexes, respectively, of respiration and glycolysis and of cell division; trypanocidal titers based on these indexes can show primary metabolic areas of drug attack. Various specific inhibitors have also been tested to detect metabolic sites which might be therapeutically vulnerable. RNA synthesis inhibitors are highly active (adenine nucleosides, daunorubicin, doxorubicin, chromomycin, actinomycin D, mitomycin C); the activity of the nucleoside cordycepin was increased in vitro and in vivo by an adenosine deaminase inhibitor. In view of the polyanionic nature of the trypanocide suramin, a series of polyanions was tested; several showed activity but only poly-d-glutamic acid was active in vivo. Among various miscellaneous inhibitors, quercetin, disulfiram, and the Ca-complexing agents arsenazo I and III showed marked activity, the latter exclusively on the arsenical-resistant T. brucei. The implications of these results for combination chemotherapy and depot prophylaxis (with polyanions) are indicated.

Trypanocidal activity of antitumor antibiotics and other metabolic inhibitors.

Synthesis and oxidative activation of an oxabicyclo[7.2.1]enediyne

3-deoxy-2,5-DI-O-p-nitrobenzoyl-α-D-threo-pentofuranosyl bromide, a starting material for the synthesis of nucleosides☆

3-Deoxy-2,5-di-O-p-nitrobenzoyl-alpha-D-threo-entofuranosyl bromide (1) reacted with mercuric cyanide to give 2,5-anhydro-4-deoxy-D-lyxo-hexononitrile (2) which upon acid hydrolysis of the CN group gave acid 3. Saponification of the protecting groups gave 2,5-anhydro-4-deoxy-D-lyxo-hexonic acid (4) which reacted with 4,5,6-triaminopyrimidine forming an amide (5) that was pyrolized to give 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine (6). Reaction of bromide 1 with 6-(benzamido) chloromercuriopurine followed by saponification yielded 9-(3'-deoxy-alpha-D-threo-pentofuranosyl)adenine(8). 8-(beta-D-Ribofuranosyl)adenine, 8-(beta-D-arabinofuranosyl)adenine, and 8-(3'-deoxy-beta-D-erythro-pentofuranosyl)adenine, as well as compound 6, showed no antimalarial activity.

Synthesis of 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine and 9-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine.

Preparation of a substituted 3-acetamido-3-deoxy-D-ribofuranosyl bromide suitable for the synthesis of puromycin analogs

Synthesis of 8-(3′-deoxy-alpha-d-threo-pentofuranosyl)adenine and 9-(3′-deoxy-alpha-d-threo-pentafuranosyl)adenine

Methyl-D-ribofuranoside is p-nitrobenzoylated to yield crystalline methyl 2,3,5-tri-O-(p-nitrobenzoyl)-β-D-ribofuranoside which can be used to prepare a stable, crystalline 2,3,5-tri-O-(p-nitrobenzoyl)-β-D-ribofuranosyl bromide which in turn is useful as a precursor of natural or synthetic purine and pyrimidine nucleosides, as well as of glycosides. This bromide can also be cyanated to yield crystalline 2,5-anhydro-3,4,6-tri-O-(p-nitrobenzoyl)-D-allononitrile which in turn can be hydrolyzed and subsequently reacted with polyamino pyrimidines to yield nucleoside analogs such as 8-β-D-ribofuranosyl adenine. This bromide also can by hydrolyzed to yield crystalline 2,3,5-tri-O-(p-nitrobenzoyl)-D-ribofuranose which in turn can be p-nitrobenzolated to yield crystalline 1,2,3,5-tetra-O-(p-nitrobenzoyl)-β-D-ribofuranose. This latter compound can be brominated to produce an alphabromide derivative which is useful as a precursor of nucleosides.

Thakur D. Audichya

Papers

3-deoxy-2,5-DI-O-p-nitrobenzoyl-α-D-threo-pentofuranosyl bromide, a starting material for the synthesis of nucleosides☆

Synthesis of 8-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine and 9-(3'-deoxy-alpha-D-threo-pentofuranosyl) adenine.

Preparation of a substituted 3-acetamido-3-deoxy-D-ribofuranosyl bromide suitable for the synthesis of puromycin analogs

Synthesis of 8-(3′-deoxy-alpha-d-threo-pentofuranosyl)adenine and 9-(3′-deoxy-alpha-d-threo-pentafuranosyl)adenine

Crystalline ribofuranosyl halides and other derivatives and methods for producing same