High yield synthesis and reactivity of a phosphinidene bridged dimolybdenum complex

Protonation of [Mo2Cp2(mu-H)(mu-PHR*)(CO)4] (Cp = eta5-C5H5, R* = 2,4,6-C6H2tBu3) with HBF4.OEt2 gives the hydridophosphinidene complex [Mo2Cp2(mu-H)(mu-PR*)(CO)4]BF4, which is easily deprotonated with H2O to give the known phosphinidene complex [Mo2Cp2(mu-PR*)(CO)4] in 95% yield. Reaction of the latter with I2 gives the unsaturated phosphinidene complex [Mo2Cp2I2(mu-PR*)(CO)2], which exhibits an intermetallic distance of 2.960(2) A. Irradiation of solutions of [Mo2Cp2(mu-PR*)(CO)4] with UV light gives a mixture of the triply bonded [Mo2Cp2(mu-PR*)(mu-CO)2] and the hydridophosphido derivative [Mo2Cp2(mu-H){mu-P(CH2CMe2)C6H2tBu2}(CO)4] as major species. The latter complex results from an intramolecular C-H bond cleavage from a tBu group and has been characterized by spectroscopy and an X-ray study. Irradiation in the presence of HCC(p-tol) results in the insertion of the alkyne into the Mo-P bond to give [Mo2Cp2{mu-eta1:eta2,kappa-C(p-tol)CHPR*}(CO)4] structurally characterized through an X-ray study.     

Stereoselective functionalization of pyrrolidinone moiety towards the synthesis of salinosporamide A

An important feature of the synthesis of salinosporamide A, a potent proteasome inhibitor, is the establishment of the quaternary stereocenter at C3. A new route has been developed based on the methylation of a functionalized pyrrolidinone. Direct methylation reaction led to the unwanted diastereomer; however, by means of a Corey–Chaykovsky reaction followed by LiAlH₄ epoxide opening, the desired alcohol was obtained. The pyrrolidinone was elaborated through a key allylation reaction between a tertiary allyltitanium reagent and an aldehyde bearing a spiroketal moiety in α-position.     

Mechanism and kinetics of protein transport in chromatographic media studied by confocal laser scanning microscopy. Part I. The interplay of sorbent structure and fluid phase conditions

An experimental study on the interplay of sorbent structure and fluid phase conditions (pH) has been carried out examining adsorption and transport of bovine serum albumin (BSA) and a monoclonal antibody (IgG 2a) on SP Sepharose Fast Flow and SP Sepharose XL. SP Sepharose Fast Flow is characterised by a relatively open pore network, while SP Sepharose XL is a composite structure with ligand-carrying dextran chains filling the pore space. Both adsorbents have similar ionic capacity. Protein transport and adsorption profiles were evaluated using confocal laser scanning microscopy. Under all investigated conditions, BSA uptake could be adequately explained by a pore diffusion mechanism. The adsorption profiles obtained for IgG 2a, however, indicated that changes in fluid phase conditions as well as a change in the solid phase structure could result in a more complex uptake mechanism as compared to pore diffusion alone. This mechanism results in a fast transport of proteins into the adsorbent, followed by an overshoot of protein in the center of the sorbent and a setback towards a homogeneous adsorption profile.     

Gemischte Sandwichkomplexe der 4 f‐Elemente: Enantiomerenreine Cyclooctatetraenyl‐Cyclopentadienyl‐Komplexe des Samariums und Lutetiums mit donorfunktionalisierten Cyclopentadienylliganden

Organometallic Compounds of the Lanthanides. 139 Mixed Sandwich Complexes of the 4 f Elements: Enantiomerically Pure Cyclooctatetraenyl Cyclopentadienyl Complexes of Samarium and Lutetium with Donor‐Functionalized Cyclopentadienyl Ligands The reactions of [K{(S)‐C₅H₄CH₂CH(Me)OMe}], [K{(S)‐C₅H₄CH₂CH(Me)NMe₂}] and [K{(S)‐C₅H₄CH(Ph)CH₂NMe₂}] with the cyclooctatetraenyl lanthanide chlorides [(η⁸‐C₈H₈)Ln(μ‐Cl)(THF)]₂ (Ln = Sm, Lu) yield the mixed cyclooctatetraenyl cyclopentadienyl lanthanide complexes [(η⁸‐C₈H₈)Sm{(S)‐η⁵ : η¹‐C₅H₄CH₂CH(Me)OMe}] ( 1 a ), [(η⁸‐C₈H₈)Ln{(S)‐η⁵ : η¹‐C₅H₄CH₂CH(Me)NMe₂}] (Ln = Sm ( 2 a ), Lu ( 2 b )) and [(η⁸‐C₈H₈)Ln{(S)‐η⁵ : η¹‐C₅H₄CH(Ph)CH₂NMe₂}] (Ln = Sm ( 3 a ), Lu ( 3 b )). For comparison, the achiral compounds [(η⁸‐C₈H₈)Ln{η⁵ : η¹‐C₅H₄CH₂CH₂NMe₂}] (Ln = Sm ( 4 a ), Lu ( 4 b )) are synthesized in an analogous manner. ¹H‐, ¹³C‐NMR‐, and mass spectra of all new compounds as well as the X‐ray crystal structures of 3 b and 4 b are discussed.     

Molecular Recognition of Nucleotides in Water by Scorpiand‐Type Receptors Based on Nucleobase Discrimination

The detection of nucleotides is of crucial importance because they are the basic building blocks of nucleic acids. Scorpiand‐based polyamine receptors functionalized with pyridine or anthracene units are able to form stable complexes with nucleotides in water, based on coulombic, π–π stacking, and hydrogen‐bonding interactions. This behavior has been rationalized by means of an exploration with NMR spectroscopy and DFT calculations. Binding constants were determined by potentiometry. Fluorescence spectroscopy studies have revealed the potential of these receptors as sensors to effectively and selectively distinguish guanosine‐5′‐triphosphate (GTP) from adenosine‐5′‐triphosphate (ATP).     

Peptoid‐Ligated Pentadecanuclear Yttrium and Dysprosium Hydroxy Clusters

A new family of pentadecanuclear coordination cluster compounds (from now on simply referred to as clusters) [{Ln₁₅(OH)₂₀(PepCO₂)₁₀(DBM)₁₀Cl}Cl₄] (PepCO₂=2‐[{3‐(((tert‐butoxycarbonyl)amino)methyl)benzyl}amino]acetate, DBM=dibenzoylmethanide) with Ln=Y and Dy was obtained by using the cell‐penetrating peptoid (CPPo) monomer PepCO₂H and dibenzoylmethane (DBMH) as supporting ligands. The combination of an inorganic cluster core with an organic cell‐penetrating peptoid in the coordination sphere resulted in a core component {Ln₁₅(μ₃‐OH)₂₀Cl}²⁴⁺ (Ln=Y, Dy), which consists of five vertex‐sharing heterocubane {Ln₄(μ₃‐OH)₄}⁸⁺ units that assemble to give a pentagonal cyclic structure with one Cl atom located in the middle of the pentagon. The solid‐state structures of both clusters were established by single‐crystal X‐ray crystallography. MS (ESI) experiments suggest that the cluster core is robust and maintained in solution. Pulsed gradient spin echo (PGSE) NMR diffusion measurements were carried out on the diamagnetic yttrium compound and confirmed the stability of the cluster in its dicationic form [{Y₁₅(μ₃‐OH)₂₀(PepCO₂)₁₀(DBM)₁₀Cl}Cl₂]²⁺. The investigation of both static (dc) and dynamic (ac) magnetic properties in the dysprosium cluster revealed a slow relaxation of magnetization, indicative of single‐molecule magnet (SMM) behavior below 8 K. Furthermore, the χT product as a function of temperature for the dysprosium cluster gave evidence that this is a ferromagnetically coupled compound below 11 K.     

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti‐Cancer Properties

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti‐fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF‐1α) as the primary target for this compound class. Nannocystin A ( 1 ) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti‐cancer compound didemnin B on EF‐1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.