δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated ß-Turn-Inducing Properties.

Enantiopure (R) and (S) cyclic α,α-disubstituted amino acid derivatives displaying a δ-valerolactam side chain were prepared from a common isoxazolidine precursor. The (R)-configured δ-valerolactam 11 was converted into diastereoisomeric pseudopeptides to investigate its ability to induce secondary structures in peptidomimetics. Conformational studies of these pseudopeptides were carried out in the solid state (X-ray diffraction), in solution (NMR analyses), and in silico (computer-aided conformational analysis), which demonstrated that such quaternary amino acids induce ß-turn conformations stable enough to be retained in polar media (DMSO). Incorporation of this new type of α,α-disubstituted amino acid into a representative pseudopeptidic sequence by N- then C-elongation and N-debenzylation is also described herein and could serve for the synthesis of various structured peptidomimetics.

Yttrium-Mediated Ring-Opening Copolymerization of Oppositely Configurated 4-Alkoxymethylene-ß-Propiolactones: Effective Access to Highly Alternated Isotactic Functional PHAs.

The ring-opening copolymerization (ROCOP) of functional 4-alkoxymethylene-ß-propiolactones (BPLOR s) by yttrium-bisphenolate complexes was investigated. The ROCOP of equimolar mixtures of BPLOR s of opposite configurations, namely (R)-BPLOR1 /(S)-BPLOR2 [R1 , R2 =OMe, OAllyl, OCH2 Ph (=OBn), OSiMe2 tBu (=OTBDMS)], by the syndioselective Y{ONOOcum }/iPrOH catalyst/initiator system affords P(HBOR1 -alt-HBOR2 ) copolymers with high alternation degrees (altern.=89-94 %), as determined by comprehensive kinetic, 13 C{1 H} NMR spectroscopy, MALDI-ToF MS and ESI MS/MS fragmentation studies. The ROCOP of the (R)-BPLOMe /(S)-BPLOTBDMS combination, featuring a large difference in the substituents' bulkiness, constitutes the only observed exception to this trend (altern.=64 %). On the other hand, the isoselectivity of the Y{ONNOCl }/iPrOH catalyst/initiator system has been exploited to generate, in a one-pot/one-step procedure, original mixtures of isotactic poly(hydroxyalkanoate)s (PHAs). This system efficiently transforms equimolar mixtures of (R)-BPLOAll /(S)-BPLOMe into a 1:1 mixture of the corresponding isotactic iso-(R)-PHBOAll and iso-(S)-PHBOMe homopolymers; almost no copolymerization defects are observed. This new approach has been extended successfully to the ROCOP of equimolar mixtures of racemic monomers, rac-BPLOAll /rac-BPLOMe .

Steric vs. electronic stereocontrol in syndio- or iso-selective ROP of functional chiral ß-lactones mediated by achiral yttrium-bisphenolate complexes.

Origins of stereoselectivity in ROP of racemic chiral cyclic esters promoted by achiral yttrium complexes, resulting in the formation of highly heterotactic polylactide, and highly syndiotactic or, more uniquely, highly isotactic poly(3-hydroxybutyrate)s, are discussed. A close interplay between the nature of the cyclic ester, most particularly of the exocyclic functional chain installed on the chiral center of ß-lactones, and the ortho-substituents installed on the phenolate rings of the ligand, results in various determining secondary interactions of steric and also electronic nature.

Evaluation of Band-Selective HSQC and HMBC: Methodological Validation on the Cyclosporin Cyclic Peptide and Application for Poly(3-hydroxyalkanoate)s Stereoregularity Determination.

Band-selective (bs) HSQC, improving spectral resolution by restriction of the heteronuclear dimension without inducing spectral folding, has been recently used for polymer tacticity determination. Herein is reported an evaluation of various bs-HSQC and bs-HMBC sequences, first from a methodological point of view (selectivity, dependence to INEPT interpulse delay or relaxation delay), using the cyclic peptide cyclosporin selected as a model compound, and then from an applicative approach, comparing tacticity determined from bs-HSQC and bs-HMBC experiments to the one obtained from 1D 13C{¹H} on poly(3-hydroxyalkanoate)s samples. For HSQC sequences, the 13C selectivity scheme consisting in substituting a 13C broadband refocalization by a selective one revealed itself problematic, with unwanted aliased signals, whereas the insertion of double pulsed field gradients spin-echo (DPFGSE) or the use of opposite sign gradients bracketing a selective refocalization gave satisfactory results. Determination of the probability of syndiotactic enchainments, Ps, by bs-HSQC is fully consistent and no precision loss was observed when decreasing acquisition time (37 min vs. 106 min for 1D 13C{¹H}). Bs-HMBC, although not straightforwardly applicable for tacticity determination, could provide (after a calibration step) an alternative for compounds of which only 13C carbonyl signals are resolved enough for discriminating between syndiotactic and isotactic configurations.

One-step synthesis of conjugated enynenitriles from bromocyanoacetylene.

The chemical reactivity of bromocyanoacetylene has been evaluated for the first time by making it react with terminal alkynes and secondary amines in the presence of bis(triphenylphosphine)palladium dichloride and copper iodide as co-catalysts. This reaction provides new conjugated enynenitriles stereoselectively in one step in variable yields.

Highly Syndiotactic or Isotactic Polyhydroxyalkanoates by Ligand-Controlled Yttrium-Catalyzed Stereoselective Ring-Opening Polymerization of Functional Racemic ß-Lactones.

Reported herein is the first stereoselective controlled ROP of a specific family of racemic functional ß-lactones, namely 4-alkoxymethylene-ß-propiolactones (BPLOR s). This process is catalyzed by an yttrium complex stabilized by a nonchiral tetradentate amino alkoxy bisphenolate ligand {ONOOR'2 }2- , which features both a good activity and a high degree of control over the molar masses of the resulting functional poly(3-hydroxyalkanoate)s. A simple modification of the R' substituents in ortho and para position on the ligand platform allows for a complete reversal from virtually pure syndioselectivity (Ps up to 0.91 with R'=cumyl) to very high isoselectivity (Pi up to 0.93 with R'=Cl), as supported by DFT insights. This is the first example of a highly isoselective ROP of a racemic chiral ß-lactone.