Transformation of a [4+6] Salicylbisimine Cage to Chemically Robust Amide Cages.

In recent years, interest in shape-persistent organic cage compounds has steadily increased, not least because dynamic covalent bond formation enables such structures to be made in high to excellent yields. One often used type of dynamic bond formation is the generation of an imine bond from an aldehyde and an amine. Although the reversibility of the imine bond formation is advantageous for high yields, it is disadvantageous for the chemical stability of the compounds. Amide bonds are, in contrast to imine bonds much more robust. Shape-persistent amide cages have so far been made by irreversible amide bond formations in multiple steps, very often accompanied by low yields. Here, we present an approach to shape-persistent amide cages by exploiting a high-yielding reversible cage formation in the first step, and a Pinnick oxidation as a key step to access the amide cages in just three steps. These chemically robust amide cages can be further transformed by bromination or nitration to allow post-functionalization in high yields. The impact of the substituents on the gas sorption behavior was also investigated.

Synthetic Access to Noncanonical Strigolactones: Syntheses of Carlactonic Acid and Methyl Carlactonoate.

Strigolactones are plant hormones regulating essential stages of a plant's development. Their low natural abundance combined with a low chemical stability significantly hampered the detailed investigation of their biological activity. Noncanonical strigolactones lack the fused tricyclic ABC-ring system commonly present in canonical-type strigolactones but feature an open-chain unit linking structurally diverse A-ring moieties to the butenolide D-ring. We herein present an efficient synthetic access to enantiomerically pure noncanonical strigolactones by a Stille cross-coupling approach to forge the central diene moiety and demonstrate this strategy by syntheses of natural products methyl carlactonoate and carlactonic acid. Furthermore, a synthetic access to deuterium-labeled analogues of these natural products has been developed.

Cooperative Effects between Chiral Cpx -Iridium(III) Catalysts and Chiral Carboxylic Acids in Enantioselective C-H Amidations of Phosphine Oxides.

An enantioselective C-H amidation of phosphine oxides by using an iridium(III) catalyst bearing an atropchiral cyclopentadienyl (Cpx ) ligand is reported. A very strong cooperative effect between the chiral Cpx ligand and a phthaloyl tert-leucine enabled the transformation. Matched-mismatched cases of the different acid enantiomers are shown. The amidated P-chiral arylphosphine oxides are formed in yields of up to 95 % and with excellent enantioselectivities of up to 99:1 er. Enantiospecific reduction provides access to valuable P-chiral phosphorus(III) compounds.

Chiral cyclopentadienyl iridium(III) complexes promote enantioselective cycloisomerizations giving fused cyclopropanes.

The cyclopentadienyl (Cp) group is a very important ligand for many transition-metal complexes which have been applied in catalysis. The availability of chiral cyclopentadienyl ligands (Cp(x) ) lags behind other ligand classes, thus hampering the investigation of enantioselective processes. We report a library of chiral Cp(x) Ir(III) complexes equipped with an atropchiral Cp scaffold. A robust complexation procedure reliably provides Cp(x) Ir(III) complexes with tunable counterions. In a proof-of-concept application, the iodide-bearing members are shown to be highly selective for enyne cycloisomerization reactions. The dehydropiperidine-fused cyclopropane products are formed in good yields and enantioselectivities.

Modular total synthesis of rhizopodin: a highly potent G-actin dimerizing macrolide.

A highly convergent total synthesis of the potent polyketide macrolide rhizopodin has been achieved in 29 steps by employing a concise strategy that exploits the molecule's C2 symmetry. Notable features of this convergent approach include a rapid assembly of the macrocycle through a site-directed sequential cross-coupling strategy and the bidirectional attachment of the side chains by means of Horner-Wadsworth-Emmons (HWE) coupling reactions. During the course of this endeavor, scalable routes for synthesis of three main building blocks of similar complexity were developed that allowed for their stereocontrolled construction. This modular route will be amenable to the development of syntheses of other analogues of rhizopodin.

Concise synthesis of the macrocyclic core of rhizopodin by a Heck macrocyclization strategy.

A highly convergent synthesis of the central dimeric core of the potent antibiotic macrolide rhizopodin is reported. Notable features of the highly concise route include an effective preparation of the key C8-C22 building block based on an iridium-catalyzed Krische allylation and a chemoselective cross-coupling approach toward the macrocycle involving a highly advantageous Heck reaction for macrocyclization.

Stereoselective total synthesis of etnangien and etnangien methyl ester.

A highly stereoselective joint total synthesis of the potent polyketide macrolide antibiotics etnangien and etnangien methyl ester was accomplished by a convergent strategy and proceeds in 23 steps (longest linear sequence). Notable synthetic features include a sequence of highly stereoselective substrate-controlled aldol reactions to set the characteristic assembly of methyl- and hydroxyl-bearing stereogenic centers of the propionate portions, an efficient diastereoselective Heck macrocyclization of a deliberately conformationally biased precursor, and a late-stage introduction of the labile side chain by means of a high-yielding Stille coupling of protective-group-free precursors. Along the way, an improved, reliable protocol for a Z-selective Stork-Zhao-Wittig olefination of aldehydes was developed, and an effective protocol for a 1,3-syn reduction of sterically particularly hindered beta-hydroxy ketones was devised. Within the synthetic campaign, a more detailed understanding of the intrinsic isomerization pathways of these labile natural products was elaborated. The expedient and flexible strategy of the etnangiens should be amenable to designed analogues of these RNA-polymerase inhibitors, thus enabling further exploration of the promising biological potential of these macrolide antibiotics.

Total synthesis of etnangien.

The first total synthesis of the potent RNA-polymerase inhibitor etnangien is described, which establishes unequivocally the relative and absolute configuration of this sensitive macrolide antibiotic. Key features of the expedient and modular synthesis include stereoselective substrate-controlled boron- and tin-mediated aldol couplings to set the characteristic sequences of methyl and hydroxyl bearing stereogenic centers with high degrees of stereoselectivity and yield, an efficient Heck macrocyclization of a conformationally restricted substrate, and a late-stage introduction of the labile side chain. The convergent approach should be amenable to designed analogues.

Stereoselective synthesis of 1,3-anti diols by an Ipc-mediated domino aldol-coupling/reduction sequence.

A novel domino process for 1,3-anti diol synthesis by the union of a methyl ketone with an aldehyde is described. The operationally simple procedure is based on an Ipc-boron-aldol coupling and subsequent Ipc-mediated reduction of the intermediate ß-hydroxy-ketone. The sequence proceeds with excellent anti-selectivities and enables the rapid construction of complex polyketide fragments.

Occurrence of hemotrophic mycoplasmas in horses with correlation to hematological findings.

Hemotrophic mycoplasmas (HM) are small, cell wall-less bacteria and infections are known for a wide range of animals. One possible indication of equine HM infection was given in 1978, when a 'haemobartonellosis' outbreak was diagnosed in Nigerian horses by microscopy. However the first molecular proof of HM in horses was not reported until 2010, when a fragment of about 900 bp of the 16S rRNA of the equine HM was obtained. This sequence was used for the development of a SYBR green I real-time PCR assay specific for equine HM. The lower detection limit of the PCR was ten 16S rDNA copy numbers per ml of blood. The newly designed assay was successfully applied for the detection and quantification of HM in horses in Germany. A high sample prevalence of 26.5% (95% CI: 18.8-35.5%) was found (31 out of 117 horses). The mean bacterial load was 1.10×10(6) 16S rDNA copy number/ml blood (range: minimum 1.05×10(3), maximum 1.27×10(7)). Equine HM were also detected by microscopy (Giemsa and acridine orange stained blood smears), but results do not correlate very well with PCR results, as microscopy proved rather unspecific and not sensitive. In horses younger than one year, a significant correlation between PCR positive status and anemia was found. No correlation was found in PCR-positive animals older than one year. Therefore we assume that HM infection has a higher clinical relevance in young animals.

Haemotrophic Mycoplasma infection in horses.

Haemotrophic mycoplasmas (HM) are parasites on the surface of red blood cells and known to infect a wide range of animals. However, there are no previous evidences of HM infections in horses. In this study HM were detected for the first time in the blood of two horses suffering from poor performance, apathy, weight loss, and anaemia. Using a HM specific PCR assay and subsequent sequencing the infective agents isolated from the blood of said horses were confirmed as closely related to the HM species Mycoplasma haemofelis and 'Candidatus Mycoplasma haemobos'.