Scalable synthesis of substituted 2,7-dimethyl-9-phenylxanthen-9-ol (DMPx-OH): useful for the preparation of crystalline 5′-O-DMPx-protected nucleosides

A convenient single-step synthesis of several 2,7-dimethyl-9-phenylxanthen-9-ol (DMPx-OH) analogs has been accomplished using a Friedel–Crafts reaction. Treatment of various DMPx-OH with unprotected 2′-O-methoxyethyl-ribonucleosides (MOE) in the presence of B(C6F5)3, as a Lewis Acid catalyst, furnished 5′-O-protected derivatives of 2′-MOE-ribonucleosides in good yields. The deprotection of the DMPx groups was accomplished by acid hydrolysis under very mild conditions. Among the five DMPx analogs synthesized, the 2,7-dimethyl-9-(4-nitrophenyl)xanthene-9-yl group furnished crystalline products enabling non-chromatographic isolation of 5′-O-protetced nucleosides.