Sulfurization of dinucleoside phosphite triesters with chiral disulfides

Sixteen chiral analogues of phenylacetyl disulfide (PADS) and 5-methyl-3H-1,2,4-dithiazol-3-one (MEDITH) were used to sulfurize five dithymidine phosphite triesters, each incorporating a β-cyanoethoxy or siloxy group. Each mixture of S(P):R(P) phosphite triester diastereomers was combined with approximately one fourth of an equivalent of each of the sulfurizing reagents, and the R(PS):S(PS) diastereomer ratios of the resulting phosphite sulfides or phosphorothioates were determined by reverse-phase HPLC. Diastereoselectivities and corresponding diastereomeric excess (de) values were calculated by correcting for the starting triester diastereomer ratios. The highest de values for R(PS) and S(PS) phosphorothioates were 14.7% and 7.9%, respectively, both using MEDITH analogues.