Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile.

(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.

Aqueous phosphoric acid as a mild reagent for deprotection of tert-butyl carbamates, esters, and ethers.

Aqueous phosphoric acid (85 wt %) is an effective, environmentally benign reagent for the deprotection of tert-butyl carbamates, tert-butyl esters, and tert-butyl ethers. The reaction conditions are mild and offer good selectivity in the presence of other acid-sensitive groups, including CBZ carbamates, azetidine, benzyl and methyl esters, TBDMS, and methyl phenyl ethers. The mildness of the reaction is further demonstrated in the synthesis of clarithromycin derivative, in which a tert-butyl ester is removed in the presence of cyclic carbamate, lactone, ketal, acetate ester, and epimerizable methyl ketone functionalities.

Highly selective asymmetric hydrogenation using a three hindered quadrant bisphosphine rhodium catalyst.

A concise synthesis of both enantiomers of ligand 2 and rhodium complex 5 is presented. The crux of the synthesis is a chiral HPLC separation of the enantiomers of 4. Rhodium complex 5 possesses three hindered quadrants in the steric environment within which a substrate binds.

[The drama of hyperextension trauma--chronic whiplash syndrome with its neuropsychological and psychiatric findings. An analysis of 80 cases from expert assessment].

The problem "whiplash associated disorder" was studied in a multidisciplinary analysis of 80 patients who all had a "simple whiplash-accident", this means a whiplash-accident without concomitant head trauma apart from contact with the car seat and without unconsciousness. The opinions of a rheumatologist and of a psychiatrist were considered in each case, and in 47 patients, a neuropsychological expertise was present. 43% of the patients who had been neuropsychologically tested revealed specific cognitive deficits as they are described after mild traumatic brain injuries and after whiplash accidents.

[Fibromyalgia (generalized tendomyopathy) in expert assessment. Analysis of 158 cases].

MEDAS-agencies are medical institutions within the Swiss Disability Insurance, which specialize in assessing the working capacity of candidates who apply for a disability pension. Degenerative and other chronic pain disorders of the musculoskeletal system form the majority of cases that we investigate. Fibromyalgia is one of our most frequent diagnoses (8.

Restriction analysis of lambda EMBL3 background recombinants: occurrence of lambda phages carrying a head to tail oriented left arm DNA sequence.

Eight representative recombinant background clones of lambda EMBL3 were analysed using KpnI, BamHI, SalI, EcoRI and HindIII digestion. We found that lambda EMBL3 carries its own left arm in the BamHI cloning site. In the way, recombinant molecules were found to be generated which can grow on Escherichia coli strain NM539.

Antibodies targeted against hypervariable and constant regions of cytochromes P450IIB1 and P450IIB2.

Fusion proteins constructed between beta-galactosidase and six different segments of either cytochrome P450IIB1 or cytochrome P450IIB2 (ranging from 18 to 33 amino acids in length) were expressed in Escherichia coli. Rabbit antibodies raised against these fusion proteins were first adsorbed through a beta-galactosidase column and then immunopurified on a second column containing the corresponding fusion protein. With the exception of the antibodies directed against the hydrophobic amino-terminal segment of cytochrome P450IIB1, all the antipeptide antibodies recognized the major phenobarbital-inducible cytochromes P450IIB1 and -IIB2 on immunoblots of liver microsomal proteins.

Perfluorodecanoic acid decreases the enzyme activity and the amount of glutathione S-transferases proteins and mRNAs in vivo.

The effects of the anti-wetting agent perfluoro-n-decanoic acid (PFDA) on various glutathione S-transferase (GST) enzyme activities were studied in vitro and in vivo. In addition the effects of PFDA treatment on the amount of some glutathione S-transferase subunits and their corresponding translatable mRNA were studied in vivo. PFDA like some other peroxisome proliferators was a non-competitive inhibitor of several GST enzyme activities in vitro.