Designed asymmetric coordination helicates with bis-β-diketonate ligands.

A new bis-(β-diketone) ligand featuring built-up structural asymmetry yields non-symmetric Fe(iii) and Ga(iii) dinuclear, triple-stranded helicates by design. Their structural properties have been studied, both in solid state and in solution, and compared with their corresponding symmetric analogues. The robustness observed shows the potential of this synthetic strategy to develop non-symmetric helicoidal motifs with specific functional groups.

A Magneto-optical Molecular Device: Interplay of Spin Crossover, Luminescence, Photomagnetism, and Photochromism.

A bis(pyrazolylpyridyl) ligand, L, containing a central photochromic dithienylethene spacer predictably forms a ferrous [Fe L ] helicate exhibiting spin crossover (SCO). In solution, the compound [Fe L ](ClO ) (1) preserves the magnetic properties and is fluorescent. The structure of 1 is photo-switchable following the reversible ring closure/opening of the central dithienylethene via irradiation with UV/visible light.

Molecules Designed to Contain Two Weakly Coupled Spins with a Photoswitchable Spacer.

Controlling the charges and spins of molecules lies at the heart of spintronics. A photoswitchable molecule consisting of two independent spins separated by a photoswitchable moiety was designed in the form of new ligand H L, which features a dithienylethene photochromic unit and two lateral coordinating moieties, and yields molecules with [MM⋅⋅⋅MM] topology. Compounds [M L (py) ] (M=Cu, 1; Co, 2; Ni, 3; Zn, 4) were prepared and studied by single-crystal X-ray diffraction (SCXRD).

A Useful Allene for the Stereoselective Synthesis of Protected Quaternary 2-Amino-2-vinyl-1,3-diols.

Treatment of readily available allene 1 with CyBH followed by addition of an aldehyde led to quaternary protected 2-amino-2-vinyl-1,3-diols in high yield and excellent stereochemical purity. The choice of benzoyl as N-protecting group is critical since the observed N- to O-Bz transfer during the process prevents later undesired isomerizations in the adducts and keeps all heteroatoms protected.

Total synthesis of (-)-isoavenaciolide.

An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1-undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2-thiophenecarboxaldehyde.

Use of the SPhos ligand to suppress racemization in arylpinacolboronate ester Suzuki couplings involving alpha-amino acids. Synthesis of biaryl derivatives of 4-hydroxyphenylglycine, tyrosine, and tryptophan.

Alpha-amino acid derivatives, particularly those of phenylglycine, can suffer significant racemization in Suzuki couplings. When arylpinacolboronate esters are used as coupling partners this unwanted side reaction can be suppressed by the use of Pd(OAc)(2) as Pd(0) source, in the presence of Buchwald's SPhos ligand. The syntheses of biaryl amino acids of tyrosine, phenylglycine, and tryptophan, including Phg-Trp units similar to those found in the chloropeptin family of natural products, are reported.

Racemization in suzuki couplings: a quantitative study using 4-hydroxyphenylglycine and tyrosine derivatives as probe molecules.

Reaction conditions considered to be typical in Suzuki couplings can cause significant (up to 34% of the unwanted enantiomer) loss of optical purity in sensitive substrates such as hydroxyphenylglycine 1. This may be remedied using sodium succinate instead of sodium carbonate as base, but chemical yields are somewhat lower. Optically pure biaryl amino acids related to those found in the chloropeptins and vancomycin were synthesized by Suzuki coupling of 1 with indolylboronic acids 6-8 and with cyclic boronic acid 9.

Synthesis, conformational analysis, and cytotoxicity of conformationally constrained aplidine and tamandarin A analogues incorporating a spirolactam beta-turn mimetic.

With the aim of studying the contribution of the beta II turn conformation at the side chain of didemnins to the bioactive conformation responsible for their antitumoral activity, conformationally restricted analogues of aplidine and tamandarin A, where the side chain dipeptide Pro8-N-Me-d-Leu7 is replaced with the spirolactam beta II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues, where the aplidine (pyruvyl9) or tamandarin A [(S)-Lac9] acyl groups are replaced with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared.

Arylboronic acids and arylpinacolboronate esters in Suzuki coupling reactions involving indoles. Partner role swapping and heterocycle protection.

Yields of Suzuki couplings involving indoles depended upon (i) whether arylboronic acids or arylpinacolboronate esters were used, (ii) whether the heterocycle was the aryl halide or the arylboron coupling partner, and (iii) whether the heterocycle was protected or not. Highest yields, which were unaffected by incorporating Boc or Tos protection at the heterocyclic nitrogen, were obtained when indole bromides were reacted with phenylboronic acids. When indolylboronic acids were reacted with phenyl bromides, yields were somewhat lower and depended on the nitrogen substituent, being highest in the absence of protection, lower in the presence of the Boc group, and lowest of all with the Tos group.

Analysis of conformational equilibria in aplidine using selective excitation 2D NMR spectroscopy and molecular mechanics/dynamics calculations.

Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity currently in multicenter phase II clinical trials, exists in DMSO as a mixture of four slowly interconverting conformations in a ratio of 47:33:13:7. NMR spectroscopy shows that these arise as a consequence of cis/trans isomerization about the NMe-Leu(7)-Pro(8) and Pro(8)-Pyr amide bonds of the molecule's side chain. Two major conformations account for 47% and 33% of the total population, a ratio of 60:40 between the two.

Total Synthesis of Dehydrodidemnin B. Use of Uronium and Phosphonium Salt Coupling Reagents in Peptide Synthesis in Solution.

New total syntheses of didemnin A and of dehydrodidemnin B are described. The latter didemnin has the highest antiproliferative activity of all members of this family of macrocyclic depsipeptides. It was produced on coupling the side chain Pyr-Pro-OH to didemnin A, which was itself synthesized by two novel routes.