(9H-Fluoren-9-yl)methanesulfonyl (Fms): An Amino Protecting Group Complementary to Fmoc

• Published in: European Journal of Organic Chemistry Vol. 2010; no. 22; pp. 4201 - 4204
• Main Authors: Ishibashi, Yoshitaka, Miyata, Kengo, Kitamura, Masato
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.08.2010; WILEY‐VCH Verlag; Wiley; Wiley-VCH
• Subjects: Chemistry; Chemistry, Organic; Condensed benzenic and aromatic compounds; Exact sciences and technology; Organic chemistry; Peptides; Phosphorus; Physical Sciences; Preparations and properties; Protecting groups; Science & Technology; Sulfon­amides; REAGENT; Peptides; Sulfonamides; Protecting groups; Phosphorus; PHASE PEPTIDE-SYNTHESIS; ANHYDRIDES; ACID CHLORIDES; SECONDARY-AMINES; SALTS; AMIDE-ASSISTED HYDROLYSIS; Protecting group; Sulfonamide; Phenylalanine; Sulfone; Peptidomimetic compound; Alkylamine; Phosphorus Organic compounds; Ester; α-Aminoacid; Amine; Aminoacid; Aromatic compound; Solid phase; Phosphonic acid derivatives; Chemical synthesis; Fluorene derivatives; Protection
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201000682

A sulfonamide‐based protecting group (PG), (9H‐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‐OtBu), H‐Pro‐Gly‐OtBu, and H‐Phe‐Phe‐OtBu, 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. A new Fmoc‐type protecting group, (9H‐fluoren‐9‐yl)methanesulfonyl (Fms), has been developed. Use of Fms led to successful condensation of Fms‐AlaP(OCH3)‐OH with the N‐terminus of peptides, avoiding aserious problem associated with Fmoc, and thereby paving a new way to the synthesis of α‐amino phosphonic acid containing peptide mimetics without losing the well‐established Fmoc chemistry.