Highly Stereoselective Total Synthesis of 2,5-Anhydro-3-deoxy- and -4-deoxy-D-hexonic Acids and of the Related Deoxyadenosines-C

Article abstract of DOI:10.1021/jo00295a039

(1R,2S,4R)-2-Cyano-7-oxabicyclo<2.2.1>hept-5-en-2-yl (1S')-camphanate (5) has been converted into 2,5-anhydro-3-deoxy-D-ribo-hexonic acid (8, eight steps, 38percent) and 2,5-anhydro-3-deoxy-D-xylo-hexonic acid (9, seven steps, 40percent).Similarly, (1S,4S)-7-oxabicyclo<2.2.1>hept-5-en-3-one ((-)-6, derived from (1S,2R,4S)-2-cyano-7-oxabicyclo<2.2.1>hept-5-en-2-yl (1R')-camphanate (7) was converted into 2,5-anhydro-4-deoxy-D-ribo-hexonic acid (10, nine steps, 29percent) and 2,5-anhydro-4-deoxy-D-xylo-hexonic acid (11, eight steps, 31percent).The methods exploit the high regioselectivity of the electrophilic additions of the C=C double bonds in 7-oxabicyclo<2.2.1>hept-5-en-2-yl derivatives 5 and 7 ("naked sugars") and the high exo-face preference for the hydride reduction of 5- and 6-chloro-7-oxabicyclo<2.2.1>hept-5-en-2-ones (21,35). 2'-Deoxyadenosine-C (12) and cordycepin-C (14) were derived from 8 and 10, respectively.Similarly, the corresponding 2'- and 3'-epimers 13 and 15 (C-nucleosides deriving from 2-deoxy- and 3-deoxy-β-D-threo-pentofuranose, respectively) were obtained in few steps and with high stereoselectivity from 9 and 11, respectively.