One-Pot Synthesis of TBMPS (bis [tert-Butyl)-1 Pyrenylmethyl-Silyl) Chloride as a Novel Fluorescent Silicon-Based Protecting Group for Protection of 5′-OH Nucleosides and Its Use as Purification Handle in Oligonucleotide Synthesis

Abstract

An efficient and novel synthesis of bis(tert-butyl)-1-pyrenylmethyl-silyl group (TBMPS) has been reported having fluorescent properties conferred by the pyrenyl group. This silyl group being base labile is efficiently used for one-pot protection of the 5′-OH of the nucleosides. While incorporated terminally at the 5′-OH of long sequences viz. AA TGG AGC CAG T and GC TAT GTC AGT TCC CCT TGG TTC TC, this group is also helpful in subsequent purification by HPLC as well as PAGE. Besides these, a labeled dimer (T*T) and a labeled tetramer (T*TTT) were also synthesized to compare the fluorescence properties of short and long labeled sequences. Fluorescence properties of these sequences were studied in detail to find the suitability of the approach.

Thanks are due to RSIC, CDRI, Lucknow, India, for mass and NMR spectra. Financial support from Isis Pharmaceuticals, Calsbad, CA, is gratefully acknowledged. We thank Dylan Harris for critical review of the manuscript.