Synthesis of N1-(4-hydroxy-1,2-butadien-1-yl)thymine, an Analogue of 3'-Deoxythymidine

Article abstract of DOI:10.1021/jo00276a032

Attempted isomerization of N¹-(4-hydroxy-2-butyn-1-yl)thymine (3d) with 0.1 M NaOH at 100 deg C led to acetonylthymine (8) instead of thymallene (1d).In 1 M NaOH compound 3d afforded oxacyclopentene 9d, whereas reaction with 1,5-diazabicyclo<4.3.0>non-5-ene (DBN) in dimethylformamide (DMF) gave cyclic imino ether 11.Hydrolysis of 11, effected by 0.1 M NaOH, furnished β-hydroxy ketone 12.At 100 deg C both 11 and 12 yielded 8.The results are explained in terms of ionization of thymine base relative to that of alcoholic hydroxy group of 3d or putative intermediate 1d.Acetoxybutynol 16 was transformed with potassium tert-butoxide (tBuOK) in DMF to butenyne 17.Protection of 16 with <2-(trimethylsilyl)ethoxy>methyl (SEM) group led to compound 19.Ammonolysis of 19 gave SEM derivative 20, which was isomerized with tetrabutylammonium fluoride in tetrahydrofuran to protected thymallene 21.The latter was deblocked with SnCl4 in CH2Cl2 to give thymallene (1d).Attempted isomerization of 19 or 20 with tBuOK in DMF led only to elimination of SEM-substituted thymine.