Rich B. Meyer

Synthesis and Properties of Purine Nucleosides and Nucleotides

Inosinic acid was the first nucleotide obtained from nature and was reported by von Liebig in 1847. This was followed by the isolation of the first nucleoside, guanosine, by E. Schulze and E. Brosshard in 1885. Subsequently, other naturally occurring purine nucleosides and nucleotides were isolated and characterized as the degradation products of ribonucleic acids (RNAs) and deoxyribonucleic acids (DNAs). The biochemical significance of nucleosides and nucleotides became more apparent in the early 1950s when the era of modern molecular biology was introduced by the classical work of J. D. Watson and F. H. C. Crick on the structure of DNA in 1953 and by the great discovery of the “second messenger” of hormone action, adenosine cyclic 3′,5′-(hydrogen)phosphate (cyclic AMP or cAMP) by Earl W. Sutherland in 1957. The synthesis of nucleosides and nucleotides then became instrumental in identifying the naturally occurring nucleosides and their metabolites and in an understanding of the biochemical and enzymatic reactions and pathways. Discoveries made in the field of purine nucleoside and nucleotide chemistry have contributed substantially to a better understanding of biology at the molecular level, which reached a pinnacle with the decoding of the genetic code and ultimate synthesis of the chemical gene by H. G. Khorana.

Quantitative high-pressure liquid chromatographic procedure for the determination of plasma and tissue levels of 2,4-diamino-5-(3,4-dichlorophenyl)-6-methylpyrimidine (metoprine) and its application to the measurement of brain capillary permeability coefficients.

A high-pressure liquid chromatographic assay for metoprine levels in aqueous media, serum, and tissue extracts has been developed that can measure concentrations of the drug in the 25-100 ng range with accuracy, reproducibility, and ease. The half-time for metoprine disappearance from rat plasma and capillary permeability coefficients for metroprine in rate brain tissue determined with this method are in excellent agreement with values determined for related drugs using labeled compounds.

Photochemically induced reaction of 1, N4-dimethylcytosinewith isopropanol

Photoexcited 1, N4-dimethylcytosine (I) adds isopropanol to form 5,6-dihydro-1, N4-dimethyl-6-(2-hydroxy-2-propyl)cytosine (II) as the major product; a small amount of 5,6-dihydro-1-methyluracil (III) is formed as well.