Stereocontrolled Synthesis of Phosphoproline Analogues Containing a trans-Fused Octahydroindole Bicyclic System.

Herein we report for the first time the diastereoselective synthesis of (2R,3aR,7aS)- and (2S,3aS,7aR)-octahydroindole-2-phosphonic acid (OicP trans-fused stereoisomers) from diethyl (R)- and (S)-phosphopyroglutamate derivative. The key steps of this procedure are the ruthenium tetroxide oxidation of enantiomerically pure diethyl (R)- and (S)-phosphoprolinate obtained through Katritzky's benzotriazole-oxazolidine methodology, a highly diastereoselective successive double 4,5-diallylation of diethyl (R)- and (S)-phosphopyroglutamate with allyl bromide and allyltrimethylsilane with a trans-addition mode, and a ring-closing metathesis with Grubbs' first-generation ruthenium catalyst.

Experimental and theoretical study of novel aminobenzamide-aminonaphthalimide fluorescent dyads with a FRET mechanism.

In this work, both experimental and theoretical methods were used to study the photophysical and metal ion binding properties of a series of new aminobenzamide-aminonaphthalimide (2ABZ-ANAPIM) fluorescent dyads. The 2-aminobenzamide (2ABZ) and 6-aminonaphthalimide (ANAPIM) fluorophores were linked through alkyl chains (C2 to C6) to obtain four fluorescent dyads. These dyads present a highly efficient (0.61 to 0.98) Förster Resonant Energy Transfer (FRET) from the 2ABZ to the ANAPIM due to the 2ABZ emission and ANAPIM excitation band overlap and the configurational stacking of both aromatic systems which allows the energy transfer. These dyads interact with Cu2+ and Hg2+ metal ions in solution inhibiting the FRET mechanism by the cooperative coordination of both 2ABZ and ANAPIM moieties. Both experimental and theoretical results are consistent and describe clearly the photophysical and coordination properties of these new dyads.

Synthesis and anion recognition studies of new oligomethylene bis(nitrophenylureylbenzamide) receptors.

A new series of oligomethylene bis(nitrophenylureylbenzamide) receptors were synthesized varying the relative position of the urea and amide groups (ortho4 and meta8) and the length of the oligomethylene chain (C2 to C8). An anion recognition study was performed with TBAX salts (X = AcO-, BzO-, F-, H2PO4 -, and HP2O7 3-) by UV-vis and 1H NMR. The flexibility of these receptors allows a cooperative effect of both ureylbenzamide units in the receptors. Noteworthy, the ortho position favored the 1 : 1 stoichiometry in the complexes with the carboxylates. The formation of 2 : 1 receptor-anion complexes with both types of receptors 4 and 8 and with hydrogen pyrophosphate and high log K values obtained were very significant in this work. The NMR studies evidenced the formation of supramolecular complexes, even in a competitive solvent, such as DMSO.

A novel and highly regioselective synthesis of new carbamoylcarboxylic acids from dianhydrides.

A regioselective synthesis has been developed for the preparation of a series of N,N'-disubstituted 4,4'-carbonylbis(carbamoylbenzoic) acids and N,N'-disubstituted bis(carbamoyl) terephthalic acids by treatment of 3,3',4,4'-benzophenonetetracarboxylic dianhydride (1) and 1,2,4,5-benzenetetracarboxylic dianhydride (2) with arylalkyl primary amines (A-N). The carbamoylcarboxylic acid derivatives were synthesized with good yield and high purity. The specific reaction conditions were established to obtain carbamoyl and carboxylic acid functionalities over the thermodynamically most favored imide group. Products derived from both anhydrides 1 and 2 were isolated as pure regioisomeric compounds under innovative experimental conditions. The chemo- and regioselectivity of products derived from dianhydrides were determined by NMR spectroscopy and confirmed by density functional theory (DFT). All products were characterized by NMR, FTIR, and MS.

Study of the fragmentation pathway of α-aminophosphonates by chemical ionization and fast atom bombardment mass spectrometry.

The diastereoisomers of α-aminophosphonates are key intermediates in the synthesis of enantiomerically pure α-aminophosphonic acids, which are analogs of α-amino acids. Although several methods have been reported for the diastereoselective synthesis of α-aminophosphonates, their mass spectrometry (MS) fragmentation patterns have not yet been fully investigated. The work described here involved a detailed study of the fragmentation of enriched α-aminophosphonate diastereoisomers by chemical ionization (CI-MS) and fast atom bombardment (FAB)-MS. The complete characterization of the different conventional MS fragmentation pathways is represented and this intriguing exercise required the use of tandem mass spectrometry (MS/MS) experiments and high-resolution accurate mass measurements. All α-aminophosphonates gave prominent pseudomolecular ions, protonated molecules [MH](+) , and their fragmentations mainly showed a loss of dimethyl phosphite to give the corresponding iminium ions as base peaks for α-aminophosphonates bearing methylbenzyl and 2,2-dimethylbutyl fragments. The loss of the chiral fragment from the iminium ions bearing the (S)-1-(1-naphthyl)ethyl group gave rise to a base peak due to aryl cations. The nature of all fragment ions were confirmed by high-resolution mass spectrometry (HRMS).

Synthesis of syn-gamma-amino-beta-hydroxyphosphonates by reduction of beta-ketophosphonates derived from L-proline and L-serine.

The reduction of gamma-N-benzylamino-beta-ketophosphonates 6 and 10, readily available from L-proline and L-serine, respectively, can be carried out in high diastereoselectivity with catecholborane (CB) in THF at -78 degrees C to produce the syn-gamma-N-benzylamino-beta-hydroxyphosphonates 11 and 13 as a single detectable diastereoisomer, under non-chelation or Felkin-Anh model control.