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

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.

Conformational flexibility in amidophosphoesters: a CSD analysis completed with two new crystal structures of (C6H5O)2P(O)X [X = NHC7H13 and N(CH2C6H5)2].

The crystal structures of diphenyl (cycloheptylamido)phosphate, C19H24NO3P or (C6H5O)2P(O)(NHC7H13), (I), and diphenyl (dibenzylamido)phosphate, C26H24NO3P or (C6H5O)2P(O)[N(CH2C6H5)2], (II), are reported. The NHC7H13 group in (I) provides two significant hydrogen-donor sites in N-H...O and C-H...O hydrogen bonds, needed for a one-dimensional hydrogen-bond pattern along [100] in the crystal, while (II), with a (C6H5CH2)2N moiety, lacks these hydrogen bonds, but its three-dimensional supramolecular structure is mediated by C-H...π interactions. The conformational behaviour of the phenyl rings in (I), (II) and analogous structures from the Cambridge Structural Database (CSD) were studied in terms of flexibility, volume of the other group attached to phosphorus and packing forces. From this study, synclinal (±sc), anticlinal (±ac) and antiperiplanar (±ap) conformations were found to occur. In the structure of (II), there is an intramolecular Cortho-H...O interaction that imposes a +sc conformation for the phenyl ring involved. For the structures from the CSD, the +sc and ±ap conformations appear to be mainly imposed by similar Cortho-H...O intramolecular interactions. The large contribution of the C...H/H...C contacts (32.3%) in the two-dimensional fingerprint plots of (II) is a result of the C-H...π interactions. The differential scanning calorimetry (DSC) analyses exhibit peak temperatures (Tm) at 109 and 81 °C for (I) and (II), respectively, which agree with the strengths of the intermolecular contacts and the melting points.

Diastereoselective Palladium-Catalyzed (3 + 2)-Cycloadditions from Cyclic Imines and Vinyl Aziridines.

The synthesis of cyclic imidazolidines via two N-C bond-forming sequences has been developed. The transformation goes through a (3 + 2)-cycloaddition reaction in the presence of catalytic amounts of palladium by combining several vinyl aziridines and cyclic N-sulfonyl imines. Interestingly, the use of LiCl as additive allowed the improvement of diastereoselectivities when less encumbered substrates were used. The imidazolidine derivatives that bear aminal cores are isolated in high yields (15 examples, up to 96% yield) and diastereoselectivities (up to >20:1).