Adenosine 5-tosyl ester

The flask contained 700.0 mg hydroxocobalamin in 20 ml of water, one funnel 200.0 mg sodium borohydride in 10 ml of water, and another the crude isopropylidine adenosine tosyl ester made from 500 mg isopropylidine adenosine dissolved in 10 ml of 50% aqueous methanol. On adding the borohydride to the vitamin, the color changed instantly from red to brown, then slowly to a greenish black. After 15 min the isopropylidine adenosine tosyl ester was added, and the colour slowly changed to a red-brown. After 45 min at room temperature air was admitted and the mixture was shaken to reoxidise any remaining reduced vitamin B12. The alkaline solution was neutralized with dilute hydrochloric acid and extracted with phenol carbon tetrachloride 3 1 in small portions till the aqueous layer was nearly colorless. The combined extracts were washed with water, mixed with about ten parts of carbon tetrachloride-acetone 10 1 and shaken with small portions of water till all red color was removed. 

Tipson devoted most of his years in Levene s laboratory accomplishing seminal work on the components of nucleic acids. To determine the ring forms of the ribose component of the ribonucleosides he applied Haworth s methylation technique and established the furanoid structure for the sugar in adenosine, guanosine, uridine, and thymidine. He showed that formation of a monotrityl ether is not a reliable proof for the presence of a primary alcohol group in a nucleoside, whereas a tosyl ester that is readily displaced by iodide affords clear evidence that the ester is at the 5-position of the pentofuranose. Acetonation of ribonucleosides was shown to give the 2, 3 -C -isopropyl-idene derivatives, which were to become extensively used in nucleoside and nucleotide chemistry, and were utilized by Tipson in the first chemical preparation of a ribonucleotide, inosinic acid. 

Isopropylidine adenosine was converted to the p-toluene sulphonyl (tosyl) ester by reaction with tosyl chlorine solution, following the method of Clark et al. (1951) [J. Chem. Soc. 2952]. Because of its tendency to cyclization, the reagent was used directly it was ready. A reaction flask with separating funnels was set up in such a way that the whole system could be evacuated and filled with pure nitrogen two or three times, to eliminate all oxygen, and reagents could then be added when desired, in the closed system. 

McKenna reported the efiicient synthesis of the alpha, P-difluoromethylene deoxynucleoside 5 -triphosphate of adenosine and cytosine (89a,b), obtained enzymatically from catalytic ATP, phosphoenol pyruvate, nucleoside diphosphate kinase and pyruvate kinase using the nucleoside difluor-omethylene bisphosphonates as substrate for the kinase. The bispho-sphonate was prepared by nucleophilic displacement of the 5 -0-tosyl nucleoside precursor with tris(tetrabutylammonium) difluoromethylenebi-sphosphonate. Finally Mackman synthesised the diphosphate esters of two cyclopentyl based nucleoside phosphonates (90a,b). While (90b) was unstable following reduction of (90a) and therefore unsuitable for biological evaluation, (90a) exhibited potent inhibition against HIV reverse transcriptase. ... 

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