Face selective 6,1 '-(1-oxo)ethano bridge formation of uracil nucleosides under hypoiodite reaction conditions

Synthesis of novel spiro uracil nucleosides with an anomeric orthoester str ucture in a stereoselective manner under the hypoiodite reaction conditions of Heusler-Kalvoda and Suarez is fully described. While 2'-deoxy-6-(hydrox ymethyl)uridine 2 and 2'-deoxy-6-[(1-hydroxy-1-methyl)ethyl]uridine 4 gave beta- and alpha-spiro nucleosides in 43-68% yields with low beta/alpha sele ctivity (1/1.3 similar to 3/1), the second ary alcohols 3a and 3b showed 68 -79% chemical yields with significantly better beta/alpha selectivity (6.5/ 1 similar to 1/46). The beta/alpha orientation of the 6-(hydroxyalkyl)uridi ne counterparts 6-8, 16-17, and 19 seemed to be controlled not only by the 2'-substituent but also by the chirality at the CS-stereocenter of the CG-s ide chain like in the 2'-deoxyuridine series. The transition state geometri es of the reaction were postulated based on the X-ray crystallographic stru ctures of cyclized products 20 alpha and 24 beta. (C) 1999 Elsevier Science Ltd. All rights reserved.