Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents and cleaning solutions well in soil remediation, electroplating, waste treatment, so on. For instance, iron-chelation therapy, which is used treat iron-overload disorders, involves removing excess iron from the blood through use particular molecules, like deferoxamine, that have ability chelate metal. The creation bioinspired...

Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds evaluated their vitro inhibitory activity against 11 human HDACs isoforms. After identification of "hit" molecule, programmed variation at cap group and linker was carried out order increase inhibition and/or paralogue selectivity. Some derivatives showed increased number isoforms, even if overall range...

Abstract A broad biophysical analysis was performed to investigate the molecular basis of neuroprotective action Curcuma longa extracts in Alzheimer’s disease. By combining circular dichroism and electron paramagnetic resonance experiments with modeling calculations, minor components extracts, such as demethoxycurcumin ( 2 , DMC), bisdemethoxycurcumin 3 BDMC) cyclocurcumin 4 CYC), were analyzed a membrane environment mimicking phospholipid bilayer. Our study provides first evidence on...

Abstract The introduction of a cyclic amino acid in peptide is one the best methods to rigidify strand. A general approach towards new class seven‐membered ring acids described starting from ( S )‐tribenzyl glutamic γ‐aldehyde, which reacts with β‐keto phosphonates generate Horner–Wadsworth–Emmons product. In presence H 2 and Pd catalyst, four‐step process occurs involving double‐bond hydrogenation, hydrogenolysis three benzyl protecting groups, imine formation, reductive amination produce...

Secondary amines are obtained with low environmental impact a minimal amount of surfactants and organic solvents (biomass derived) employed only for product separation.

An alternative route: The fungal metabolite FR235222, a potent inhibitor of mammalian histone deacetylase (HDAC), has been synthesized. Key steps are the preparation unusual amino acids Ahoda and (2R,4S)-MePro. A 3D model for cyclopeptide interaction with HDAC active site (see picture) highlights differences between binding mode small-molecule inhibitors. Supporting information this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z501995_s.pdf or from author....

Galactose oxidase (GOase) was shown to oxidise several C2/C3 fluorinated galactose analogues. Interestingly, the enzyme able distinguish between 2,3-tetrafluorinated and its epimeric glucose analogue, this represents first reported biotransformation of a heavily sugar.

Abstract Starting from 2‐aminobenzyl alcohols and 1,2‐amino alcohols, 2,3,4,5‐tetrahydro‐1 H ‐1,4‐benzodiazepines (TH‐BDZ) can be prepared through a one‐pot ruthenium‐catalyzed reaction encompassing two consecutive borrowing hydrogen cycles. First, benzyl alcohol oxidation, condensation with the amino alcohol, imine reduction occurs. This is followed by oxidation of other functionality reductive cyclocondensation to give TH‐BDZ derivatives. A single catalyst does entire job, molecules water...

Microwave-assisted organic synthesis (MAOS) provides a novel and efficient means of achieving heat reactions. Nevertheless, the potential arcing phenomena via microwave (MW) interaction with solid metal catalysts has limited its use by chemists. As are now better understood, new applications Pd/C-catalyzed reactions under MW dielectric heating possible. In this review, state art, benefits, challenges coupling heterogeneous Pd/C catalysis discussed to inform chemists about their one most...

Abstract Reductive amination can be carried in i ‐PrOH/H 2 O as hydrogen sources using commercially available iron carbonyl complexes. Within an aqueous alkaline environment, a hydridocarboferrate is formed and its reducing potential exploited for hydrogenation of the imine (or iminium ion) obtained situ from aldehydes or ketones, primary secondary amines almost equimolar ratio. This completely sustainable hydrogen‐free process proceeds at 100 °C Fe 3 (CO) 12 catalyst precursor under...

A new weapon is added to the ADC arsenal, a thiol based HDAC inhibitor. Low toxic, hits target and stops tumor growth in many mouse models.

Gallic acid, a key component of red wine tannins, has been transformed into linker that releases Doxorubicine or Combretastatin A4 at pH 5.5 in cancer cells.

Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of hystone deacetylase (HDAC), have been prepared using a convergent approach. The configuration position 2 was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochemistry substituent 9 lactic acid glyceraldehyde derivatives. Starting allylglycine, (S)-Aodas, protected at nitrogen as Boc Fmoc, were obtained four steps about 30% overall yield. These products...

Abstract Various structurally modified analogues of FR235222 ( 1 ), a natural tetrapeptide inhibitor mammalian histone deacetylases, were prepared in convergent approach. The design the compounds was aimed to investigate effect structural modifications core involved enzyme binding order overcome some synthetic difficulties connected with product . introduced could also help identify key features mechanism action these compounds. molecules subjected vitro pharmacological tests, and their...

Tamed by chelation: The MgBr2 chelation of prochiral malonaldehydes allows diastereoselective monoaddition reactions with allyl stannane nucleophiles (see scheme; PG=protecting group, TBDMS=tert-butyldiphenylmethylsilyl, Tr=trityl). In the same pot, addition a second nucleophile proceeds in high diastereoselectivity to generate nonsymmetric products up five contiguous stereogenic centers, including chiral all-carbon quaternary center. Detailed facts importance specialist readers are...

Abstract A ruthenium‐catalysed dehydrogenative cross‐coupling of primary alcohols and imines in the presence TFA provided a library differently substituted quinolines. Imines can be prepared situ from various anilines several benzyl using hydrogen‐transfer procedure. Without changing catalyst, quinolines obtained moderate to good yields by adding (30 mol%) via “telescopic” protocol. The use alcohols, absence strong oxidants diversity potential starting materials make this modern version...

Mono alkylation of 1,3-dicarbonyls is now possible with alcohols and catalytic amount Hantzsch ester under Ru catalysis.

Abstract The novel rhodium complex [Rh( S )‐Phanephos(cod)]‐catalyzed hydrogenation of disubstituted ( E )‐enol acetate carboxylic acids is reported. catalytic cycle works under 30 bar hydrogen conventional heating giving different 3‐acetoxy‐2,3‐disubstituted with ee ≥90%. Hydrogenation occurred also microwave dielectric without eroding the enantioselectivity but improving overall efficiency process. With microwaves, pressure and reaction time required for complete dropped to 5 min,...

A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which carbon acts as a nucleophile amino group is introduced by Curtius rearrangement, follows simultaneous stereocontrolled generation C4 stereogenic centers asymmetric hydrogenation. Operational simplicity, step economy, good overall yield makes this amenable to manufacture scale.

Targeted therapy using monoclonal antibodies conjugated to toxins is gaining space in the treatment of cancer. Here, we report anti-tumor effect a new antibody drug conjugate (ADC) delivering HDAC inhibitor ErbB2+ solid tumors. Trastuzumab was partially reduced with tris [2-carboxyethyl] phosphine (TCEP) and ST7464AA1, active form prodrug ST7612AA1, through maleimide-thiol linker obtain Antibody Drug Conjugate ST8176AA1. The average drug/antibody ratio (DAR) 4.5 as measured by hydrophobic...

In the last 25 years, influence of microwave (MW) irradiation in chemical synthesis has intrigued chemists for exceptional results obtained shortening reaction times. Inspired by recent papers that demonstrate existence a non‐thermal effect some MW assisted reactions, we examine herein series reactions catalysed homogeneous and heterogeneous metals occurring under irradiation. The review contains examples hydroformylation, hydrogenation (including enantioselective versions with 98 % ee),...

The tumor microenvironment is characterized by a poor circulation which results in the selection of neoplastic cells that can grow or survive under hypoxic conditions. relationship between hypoxia and histone deacetylase (HDAC) inhibitors has been previously established. In this work we evaluated effects novel HDAC (the natural peptide FR235222 three tetrapeptide analogs) human breast cancer cell line MDAMB231, cultured (2% O2 ≉ 14 mmHg) normoxia (20% 140 mmHg). First, found reduced...