We describe the development of new triphenylsulfonium photoacid generators (TPS PAGs) with semifluorinated sulfonate anions containing glucose or other natural product groups, and their successful application to patterning sub-100 nm features using 254 nm and e-beam lithography. The TPS PAGs with functionalized octafluoro-3-oxapentanesulfonate were synthesized efficiently in high purity and high yield by utilizing simple and unique chemistries on 5-iodooctafluoro-3-oxapentanesulfonyl fluoride. The PAGs has been fully evaluated in terms of chemical properties, lithographic performance, environmental friendliness or toxicological impact. The PAGs are non-toxic and it is susceptible to chemical degradation and to microbial attack under aerobic/anaerobic conditions. These new PAGs are very attractive materials for high resolution photoresist applications and they are particularly useful in addressing the environmental concerns caused by PFOS and other perfluoroalkyl surfactants.