Phosphoramidite approach for the synthesis of cardiolipin

A phosphoramidite approach was utilized for the first time to synthesize cardiolipin. Optically active 1,2-di-O-acyl-sn-glycerol was coupled with 2-O-protected glycerols utilizing mono- and bifunctional phosphitylating agents to yield, after final removal of protecting groups, the title compound.     

Novel biferrocene-based phosphoramidite ligands: The combination of a rather unexplored chiral backbone and a privileged ligand scaffold

A small library of novel chiral monodentate phosphoramidite ligands, characterized by a dihydroazepine-biferrocene backbone was prepared. In order to obtain this biferrocene substructure, a mild and efficient homocoupling was developed. This allowed to synthesize the dihydroazepine ligand precursor and the phosphoramidite ligands with good overall yields and high enantiomeric excess. These ligands were successfully tested in a rhodium(I)-catalyzed hydrogenation of activated olefins.     

Phosphoramidites and solid supports based on N-substituted 2,4-dihydroxybutyramides: universal reagents for synthesis of modified oligonucleotides

A general and convenient method for synthesis of modified oligonucleotides by use of new non-nucleoside phosphoramidites is reported. A chiral 1,3-diol backbone of the modifying reagents is generated either from (R)-(+)-α-hydroxy-γ-butyrolactone or (R)-(−)-pantolactone. Aliphatic amines were acylated with the lactones to give the corresponding N-substituted 2,4-dihydroxybutyramides. After protection of a side chain, if necessary, the diols were converted into phosphoramidites or solid supports suitable for use in oligonucleotide synthesis. The reagents allow single, multiple or combined introduction of various functions (e.g., alkylamine, imidazole and pyrene residues) into synthetic oligonucleotides. The structures of the conjugates were confirmed by MALDI-TOF mass spectrometry.     

Building‐Block Approach for the Straightforward Incorporation of a New FRET (Fluorescence‐Resonance‐Energy Transfer) System into Synthetic DNA

The synthesis of the two new phosphoramidites 5 and 8 bearing a carbostyril (=quinolin‐2(1H)‐one) chromophore used as donor entity in our recently developed new FRET (fluorescence‐resonance‐energy transfer) system is described (Schemes 1 and 2) The high stability of the chromophore to basic conditions enables the incorporation of the phosphoramidites directly into DNA during solid‐phase synthesis (Schemes 3 and 4). Since this is also possible for the (bathophenanthroline)ruthenium(II) complex used as acceptor (Scheme 4, Steps d and e), the whole labelling procedure to insert the FRET system into synthetic DNA is straightforward and represents a major improvement to our previous strategy.     

Synthesis of cyclic bis(3′-5′)diguanylic acid (c-di-GMP) analogs

This paper reports the synthesis of cyclic bis(3′-5′)diguanylic acid (c-di-GMP) analogs, including the monophosphorothioic acid of c-di-GMP (c-GpGps), cyclic bis(3′-5′)guanylic/adenylic acid (c-GpAp), and cyclic bis(3′-5′)guanylic/inosinic acid (c-GpIp). These compounds are expected to be important, both in elucidating the mechanism of bioactive c-di-GMP and in designing and creating new bioactive c-di-GMP-related artificial derivatives.     

The coordination chemistry and reactivity of amino-dithiaphospholanes with rhodium, iridium, and ruthenium

Novel amino-dithiaphospholane complexes of ruthenium, iridium, and rhodium were synthesized, and their properties were studied. Reaction of the new amino-dithiaphospholane (RS)₂ (R = binaphthyl, R′ = CH₂Ph, (rac)-4) with [RuCl₂(p-cymene)]₂ afforded [RuCl₂(p-cymene)((rac)-4)] in 67% isolated yield. Similarly, the new amino-dithiaphospholanes (RS)₂ (R = cyclohexyl, (rac)-7) and (RS)₂ (R = phenyl, 9) gave upon reaction with [RhCl(CO)₂]₂ and [IrCp^∗Cl₂]₂ the novel complexes [RhCl(CO)(L)₂] and [IrCp^∗Cl₂(L)] (L = (rac)-7, 9) in 61-96% yields. The ruthenium complex is catalytically active for the etherification of propargylic alcohols with methanol and ethanol (8-48 h, 90 °C, 40-85% isolated yields).     

Large-scale synthesis of high purity “Phos reagent” useful for oligonucleotide therapeutics

A large-scale, cost-effective, and environmentally clean synthesis of high purity 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (Phos reagent) has been accomplished on a commercial scale. Treatment of PCl₃ with diisopropylamine followed by 3-hydroxylpropionitrile furnished the Phos reagent in excellent yield. The ³¹P NMR of the Phos reagent prepared at large-scale show consistent purities >99% when several key factors are controlled. These controlling factors include sourcing high purity key raw materials, identification and elimination of critical impurities, stability and storage of Phos reagent.     

Rh-catalysed asymmetric hydrogenations with a dynamic library of chiral tropos phosphorus-ligands

A library of 16 chiral tropos phosphorus-ligands, based on a chiral P-bound alcohol or secondary amine and a flexible (tropos) P-bound biphenol unit, was synthesised. This ligand library allowed the screening of 16 homocombinations and 115 heterocombinations for the rhodium catalysed asymmetric hydrogenation of methyl N-acetamido acrylate. The screening resulted in the identification of a phosphite/phosphoramidite heterocombination, which proved to be extremely effective and enantioselective (100% yield, 94% ee).     

Phosphoramidites based on phenyl-substituted 1,2-diols as ligands in palladium-catalyzed asymmetric allylations: the contribution of steric demand and chiral centers to the enantioselectivity

A small family of readily available phosphoramidite ligands, including compounds with P^∗-stereocenters, has been prepared from phenyl-substituted 1,2-diols as simple and cheap starting materials. Using these ligands, up to 84% ee was achieved in Pd-catalyzed asymmetric allylic substitution. The influence of structural modules such as asymmetric atoms and steric demand on the enantioselectivity is discussed.     

Copper-catalyzed enantioselective conjugate addition of Grignard reagents to acyclic enones using monodentate phosphoramidite ligands

Herein, we report efficient catalysts based on phosphoramidites for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to acyclic α,β-unsaturated ketones. A variety of Grignard reagents can be added to aliphatic and aromatic acyclic enones with good yields and moderate to good enantioselectivities.