Synthesis of 4‐β‐D‐arabinofuranosyl‐5,6‐dihydro‐2H‐1,2,4‐thiadiazin‐3‐one 1,1‐dioxide and x‐ray diffraction analysis of its 2′,3‐anhydro precursor

Abstract

Reaction of 2-amino-3',5'-bis(0-tert-butyldimethylsilyl)-~-D-arabinofuran[l',2':4,5]-2-oxazoline with 2-chloroethylsulfonyl chloride in the presence of sodium bicarbonate followed by removal of the protecting groups gave 2',3-anhydro-4-~-D-arabinofuranosyl-5,6-dihydro-2H-1,2,4-thiadiazin-3-one 1,l-dioxide (5), which by treatment with ammonia was converted to 4-~-D-arabinofuranosyl-5,6-dihydro-2H-1,2,4-thiadiazin-%one 1,l-dioxide (6). The structure of compound 5 was unequivocally established by means of an x-ray diffraction analysis. The compound crystallized in the space group P2,2,2, with unit cell dimensions a = 5.883(3), b = 9.352(2), c = 18.769(7) A , Z = 4. Its structure was established by direct multisolution techniques and refined by the full matrix least squares method to a final R value of 0.058 for the 1515 reflections observed.

Synthesis and in vitro cytostatic activity of new β - d -arabino furan[1′,2′:4,5]oxazolo- and arabino-pyrimidinone derivatives

“…The readily available 2-amino-b-D-arabinofuran[1 0 ,2 0 :4,5]-2oxazolines 1-2, either unprotected (compound 1, Schemes 1 and 2) or silylated (compound 2, Scheme 1) were prepared according to previously described procedures [10][11][12][13][14], and used as the starting material for the synthesis of b-D-arabino furan[1 0 ,2 0 :4,5]oxazoloand arabino-pyrimidinone derivatives.…”

“…The oxazoline ring opening was then conducted in dilute aqueous ammonia [11,12] to afford the surprising arabinofuranopyrimidinedione 5 bearing an enamine function. The N,N 0 -dimethyl-N 0 -alkylformamide 3 was engaged in an alkylation with diketene acetone adduct, followed by spontaneous elimination of dimethylamine, to give the fused b-D-arabinofuran[1 0 ,2 0 :4,5]oxazolopyrimidin-6-one 4.…”