Syntheses of puromycin from adenosine and 7-deazapuromycin from tubercidin, and biological comparisons of the 7-aza/deaza pair. |
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Authors: | M J Robins R W Miles M C Samano R L Kaspar |
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Institution: | Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700, USA. morris_robins@byu.edu |
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Abstract: | Protection (O5') of 2',3'-anhydroadenosine with tert-butyldiphenylsilyl chloride and epoxide opening with dimethylboron bromide gave the 3'-bromo-3'-deoxy xylo isomer which was treated with benzylisocyanate to give the 2'-O-(N-benzylcarbamoyl) derivative. Ring closure gave the oxazolidinone, and successive deprotection concluded an efficient route to 3'-amino-3'-deoxyadenosine. Analogous treatment of the antibiotic tubercidin 7-deazaadenosine; 4-amino-7-(beta-D-ribofuranosyl)pyrrolo2,3-d]pyrimidine] gave 3'-amino-3'-deoxytubercidin. Trifluoroacetylation of the 3'-amino function, elaboration of the heterocyclic amino group into a (1,2,4-triazol-4-yl) ring with N,N'-bis(dimethylamino)methylene]hydrazine, and nucleophilic aromatic substitution with dimethylamine gave puromycin aminonucleoside 9-(3-amino-3-deoxy-beta-D-ribofuranosyl)-6-(dimethylamino)purine] and its 7-deaza analogue. Aminoacylation BOC-(4-methoxy-L-phenylalanine)] and deprotection gave puromycin and 7-deazapuromycin. Most reactions gave high yields at or below ambient temperature. Equivalent inhibition of protein biosynthesis in a rabbit reticulocyte system and parallel growth inhibition of several bacteria were observed with the 7-aza/deaza pair. Replacement of N7 in the purine ring of puromycin by "CH" has no apparent effect on biological activity. |
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