Phospholyl(borane) Amino Acids and Peptides: Stereoselective Synthesis and Fluorescent Properties with Large Stokes Shift

Abstract

The synthesis of phospholyl(borane) amino acids was stereoselectively achieved by reaction of phospholide anion with iodo α-amino ester derived from l-aspartic acid or l-serine, followed by in situ complexation with borane. Phospholyl(borane) amino acids are easy to store and can be subjected to direct transformation into the corresponding free phospholyl, gold complex, oxide or sulfur derivatives as well as phospholinium salts, thus offering a variety of side chains. After selective deprotection of carboxylic function or amine, C- or N- peptide coupling with an alanine moiety proved the possible incorporation into peptides. Such phospholyl amino acid and peptide derivatives exhibit fluorescent properties with a large Stokes shift (160 nm) and fluorescence up to 535 nm, depending on the phosphole aromaticity and the chemical environment. These phospholyl(borane) amino acids constitute a new class of unnatural amino acids useful for structure-activities relationship studies and appear to be promising fluorophores for the development of labeled peptides.

Phosphorus-containing amino acids with a P–C bond in the side chain or a P–O, P–S or P–N bond: from synthesis to applications

“…For our part, we recently reported the rst synthesis of phospholyl(borane) a-amino acids, as a new class of uorescent amino acids, via the nucleophilic substitution of bor giodoamino esters with phospholide anions. 67 The phospholide anion 193 0 was generated via the deprotonation of dibenzophosphole or via the cleavage of the P-phenyl bond starting from the phenylphosphole in the presence of potassium. Aer the removal of the excess metal, the anion was added to a solution of g-iodoamino ester 170 and the resulting tertiary phospholyl amino ester was complexed in situ with BH 3 .DMS (Scheme 48).…”

“…Aer the removal of the excess metal, the anion was added to a solution of g-iodoamino ester 170 and the resulting tertiary phospholyl amino ester was complexed in situ with BH 3 .DMS (Scheme 48). 67 Under these conditions, the phospholyl(borane) (L)-a-amino ester derivatives 194-197 were isolated as stable compounds, which were easy to store and handle for further use.…”

“…The phospholyl(borane) a-amino ester 194 was successfully transformed via decomplexation, oxidation, sulfuration, complexation with gold and quaternization, respectively, to provide the derivatives 198-202 with tunable uorescence emission. 67 Via a tandem reaction involving decomplexation and sulfuration, the binaphtyl sulfur amino ester 7 was obtained with 64% yield. It exhibits remarkable uorescence emission in the green range at 535 nm, with a large Stokes shi of 160 nm.…”

[​4+2] versus [​2+2] Homodimerization in P(V) Derivatives of 2,4-Disubstituted Phospholes

“…Phospholes have found widespread interest in many areas, including catalysis, material sciences, and biological applications, due to the ready modification of their electronic, steric, and physicochemical properties and their different coordination modes to metals [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Among the various possibilities, changing the substituents or the substitution pattern on the phosphole ring or on the phosphorus atom can modify the stability and the aromaticity of these heterocycles [15][16][17].…”

“…A major change is often induced by oxidation of the weakly aromatic P(III) compounds to non-or anti-aromatic P(V) derivatives employing oxygen/peroxides, sulphur, or selenium [18]. In material sciences and biological applications, the P(V) phospholes are mainly employed [8][9][10][11][12][13][14], whereas for catalysis and coordination chemistry purposes the P(III) heterocycles act as phosphine ligands or cyclopentadienyl analogues, or a combination of both [4][5][6][7].…”