(9<i>H</i>‐Fluoren‐9‐yl)methanesulfonyl (Fms): An Amino Protecting Group Complementary to Fmoc

Abstract

Abstract A sulfonamide‐based protecting group (PG), (9 H ‐fluoren‐9‐yl)methanesulfonyl (Fms), which can be used in a similar way to the well‐established Fmoc PG, was developed. The advantages of this new PG were demonstrated in the successful formation of a phosphonamide between an N ‐Fms‐protected α‐phosphonoalanine monoester and secondary alkylamines, including ( R )‐2‐phenylethylamine, ( S )‐phenylalanine tert ‐butyl ester (H‐Phe‐O t Bu), H‐Pro‐Gly‐O t Bu, and H‐Phe‐Phe‐O t Bu, without formation of oxazaphospholine, which is a serious problem associated with the Fmoc PG. The success should pave the way to the solid‐phase synthesis of unnatural peptides substituted with α‐amino phosphonic acid (AP) at essentially any arbitrary position without significant modification of the Fmoc‐based chemistry that has been accumulated since Carpino's report in 1970. The N ‐Fms‐AP monomer would attract much attention in the field of peptide mimetics.