The synthetic methods of acyclonucleosides having antiviral activity are described from the standpoint of two methodologies : i, direct fusion of sugar side chain and aglycone moieties and ii, construction of aglycone moiety starting from sugar side chain bearing amino group and further the other groups.
New dienophiles, dimethyl acetoxymethylenemalonate, and its analogues such as methyl E- 3- acetoxy2-cyanoacrylate, 2, 4-dioxo-1, 3-oxazine-5-carboxylates, 1, 3-dithiethan-, and 1, 3-dithiolan-2-ylidenemalonate oxides, have been synthesized. These dienophiles readily reacted with cyclopentadiene to give Diels-Alder adducts, whose acetonide derivatives were transformed to carbocyclic C- nucleoside precursors via RRA (reductive retrograde aldol) reaction as a key step. The high pressure mediated Diels-Alder reaction of furan with the same dienophiles also gave the cycloadducts, which on RRA reaction afforded the corresponding Cnucleoside precursors. Essentially the same methodology has also been applied successfully to the synthesis of carbocyclic nucleosides. Use of chiral dienophiles, such as di-l-menthyl acetoxymethylenemalonate, for the above reaction has opened a new route to the enantioselective synthesis of C-nucleosides. The mechanism of asymmetric Diels-Alder reaction is also discussed on the basis of possible conformations of the dienophiles in the presence of suitable catalysts or under high pressure.
Syntheses of thioaminyls, a new class of persistent nitrogen-centered free radicals are described. Some aromatic thioaminyls have been isolated as the pure radical crystals or hydrazine-like dimers whose structures have been analysed by X-ray crystallographic method. The ΔH° and ΔS° values for dimers ↔ radicals equilibria have been determined. The relatively low ΔH° values are interpreted in terms of the resonance stabilization by -N-S-↔-N-S+-conjugation. Aliphatic thioaminyl radicals (RNSR') have also been studied by ESR spectroscopy. When R =R'=t-Bu, the corresponding radical was very persistent. Ab initio molecular orbital calculations for a model radical, H-N-S-H, predict that the most stable conformation is a trans planar structure. To examine the reactivity of thioaminyls reactions of the radicals with phenols, heterocycles, and alkenes have been carried out. The results are briefly described.
Novel synthetic methods from ketones and aldehydes through α, β-epoxy sulfoxides are described. The products obtained by this methods are dialkyl ketones, aldehydes, α-substituted carbonyl compounds, vinyl- and divinyl ketones, 1-acylbutadienes, cyclic ethers, α, β-unsaturated carbonyl compounds, epoxides, and allylic alcohols.
New enzymes screened for specific conversions have been purified and characterized from various microorganisms, and successfully applied to organic synthesis. These include : 1) nitrile hydratase from Arthrobacter sp. and Pseudomonas chlororaphis, useful in the hydration of nitriles to produce amides, 2) NAD+-dependent phenylalanine dehydrogenase from Sporosarcina ureae and Bacillus sphaericus, useful in the reductive amination of phenylpyruvate to give L-phenylalanine, 3) D-aminpeptidase from Achromobacter sp. applicable to the kinetic resolution of amino acid amides to give D-amino acid, and the D-stereospecific aminolysis reaction in organic solvents of amino acid esters or amides to yield D-amino acid N-alkylamides.