Synthesis of (R)- and (S)-Fmoc-Protected Diethylene Glycol Gamma PNA Monomers with High Optical Purity

TY - JOUR

T1 - Synthesis of (R)- and (S)-Fmoc-Protected Diethylene Glycol Gamma PNA Monomers with High Optical Purity

AU - Hsieh, Wei-Che

AU - Shaikh, Ashif Yasin

AU - Perera, J Dinithi R

AU - Thadke, Shivaji Ashokrao

AU - Ly, Danith H

PY - 2019/2/1

Y1 - 2019/2/1

N2 - A robust synthetic route has been developed for preparing optically pure, Fmoc-protected diethylene glycol-containing (R)- and (S)-γPNA monomers. The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of epimerization in the O-alkylation and reductive amination steps. The optical purities of the final monomers were determined to be greater than 99.5% ee, as assessed by 19 F-NMR and HPLC. The new synthetic methodology is well-suited for large-scale monomer production, with most synthetic steps providing excellent chemical yields without the need for chromatographic purification other than a simple workup and precipitation.

AB - A robust synthetic route has been developed for preparing optically pure, Fmoc-protected diethylene glycol-containing (R)- and (S)-γPNA monomers. The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of epimerization in the O-alkylation and reductive amination steps. The optical purities of the final monomers were determined to be greater than 99.5% ee, as assessed by 19 F-NMR and HPLC. The new synthetic methodology is well-suited for large-scale monomer production, with most synthetic steps providing excellent chemical yields without the need for chromatographic purification other than a simple workup and precipitation.

U2 - 10.1021/acs.joc.8b02714

DO - 10.1021/acs.joc.8b02714

M3 - Journal article

C2 - 30608165

SN - 0022-3263

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

ER -