The Novartis Foundation Series is a popular collection of the proceedings from Novartis Foundation Symposia , in which groups of leading scientists from a range of topics across biology, chemistry and medicine assembled to present papers and discuss results. The Novartis Foundation, originally known as the Ciba Foundation, is well known to The Novartis Foundation Series is a popular collection of the proceedings from Novartis Classical studies of steroid hormones are concerned with their regulation of protein synthesis via the modulation of genomic transcription. But many of the actions of these hormones occur too rapidly to be explained in this manner, particularly their effects on the central nervous system.
This text deals with recent discoveries showing that Classical studies of steroid hormones are concerned with their regulation of protein synthesis via Contains the presentations and discussions that took place during a symposium at the CIBA Foundation on October , on the subject of catalytic antibodies. The recognition that monoclonal antibodies can possess catalytic activity is a recent advance with profound ramifications for chemistry.
In addition to their potential commercial Contains the presentations and discussions that took place during a symposium at the CIBA Foundation A panel of internationally renowned experts present papers on cell signalling--an area in which there has been recent important advances. Coverage includes the inositol 1, 4, 5-triphosphate receptor, signal-induced phospholipid degradation cascade and protein kinase C activation, cyclic AMP interactions in sustained cellular response, the A panel of internationally renowned experts present papers on cell signalling--an area in which The past decade has seen mounting global concern regarding viral outbreaks such as SARS, avian influenza and West Nile virus.
In and , reports of bird-to-human, and possible human-to-human, transmissions of the H5N1 influenza viruses raised fears that these viruses could cause a pandemic on the scale of the Spanish flu pandemic of The past decade has seen mounting global concern regarding viral outbreaks such as SARS, avian Prestigious contributors summarize current knowledge regarding the biosynthesis of tetrapyrrole pigments--chlorophyll, haem, vitamin B Authors contributing to RSC publications journal articles, books or book chapters do not need to formally request permission to reproduce material contained in this article provided that the correct acknowledgement is given with the reproduced material.
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The ice-water bath was removed and the reaction was stirred for 2 to 4 h at room temperature. To a solution of N-Boc dipeptide 0. To a solution of alkylated N-Betsyl amino acid 0. A solution of the dipeptide TFA salt 0. The reaction mixture was then stirred for 10 min at the same temperature. To a solution of the TFA salt of alkylated tripeptide 0. The reaction mixture was stirred for 1 to 3 h at room temperature Thin Layer Chromatography monitoring of the reaction. Brine 50 mL and 1. The crude can be purified by flash column chromatography if necessary.
Potassium trimethylsilanolate 0. N-Bts-cyclotripeptide 0. The resulting mixture was stirred for 1 h and evaporated to dryness. Polystyrene-thiophenol Resin 0. The solution was removed by filtration. The resulting mixture was stirred for 1 h. The filtrate was concentrated to give the crude product in quantitive yield. The free amine macrocycle see example 2 was added to a mixture of formic acid 0. To the Kaiser resin 2. After shaking for 5 min, diisopropylcarbodiimide 1.
The unreacted hydroxy group on the resin was then capped by reacting with acetic anhydride 5 mL and diisopropyl-ethylamine 1 mL in dichloromethane 20 mL at room temperature for 2 h. The resin was washed and dried by the same procedure mentioned above. The substitution level was 0.
Diisopropylethylamine 2. The mixture was agitated for 2 h and the resin was washed and dried by the same procedure mentioned above. The N-alkylated linear tripeptide 0. Toluene 2 mL , acetic anhydride 1 mL and diisopropyl-ethylamine 1 mL were added to the above resin and agitated for 2 h. An aliquot of the filtrate was analysized by LC-MS. The filtrate was concentrated and then diluted with ethyl acetate 15 mL. The solution was washed with 1N hydrochloric acid 2 mL , saturated sodium bicarbonate 2 mL , brine 3 mL , dried and evaporated to give the crude product.
Dowex 50WX ion-exchange resin 53 g was added to a suspension of 2-butyne-1,4-diol The resulting mixture was stirred for 60 min and quenched with triethylamine 10 mL.
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The resin was removed by filtration. To a solution of monoprotected 2-butyne-1,4-diol Diisopropyl azodi-carboxylate Triphenylphosphine After stirring for 1 h, brine mL and dichloromethane mL were added. Potassium carbonate The combined organic extract was washed with brine 50 mL , dried over magnesium sulfate, filtered and evaporated under reduced pressure. A solution of di-tert-butyl dicarbonate The reaction mixture was stirred for an additional 40 min and water 1 Lg was added.
Dimethyl sulfoxide mL, 4. Sulfur trioxide pyridine complex To a solution of the above crude aldehyde 1.
The reaction was quenched with water 50 mL. The acetonitrile solvent was removed by evaporation under reduced pressure. Diisobutylaluminium hydride 1. The resulting mixture was stirred for an additional 1 h and then poured slowly into a 1M tartaric acid aqueous solution 1. The combined organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure.
A solution of 2,4-dimethylpentanol The mixture was stirred for an additional 30 min at the same temperature. A solution of Doc-Cl Water mL and hexane mL were added to the reaction mixture. N-Betsyl protected amino acids Bts-AA1 were synthesized by the reaction of amino acids with Betsyl chloride benzothiazolesulfonylchloride which was obtained from mercaptobenzothiazole and chlorine. A solution of mercaptobenzothiazole 0. The solid was then washed with cold diethyl ether mL , cold acetonitrile mL , filtered and pumped to give betsyl chloride benzothiazolesulfonylchloride.
To a solution of amino acid 0. The resulting mixture was stirred vigorously for 18 h. The pH of the reaction was adjusted between 9. These building blocks correspond to building blocks of type C which have been alkylated using Mitsunobu reaction conditions with the building blocks of type D.
To be able to carry out this alkylation, the acid functional group of C must be protected. The protecting group used is finally removed to get the desired compounds. Dihydrofuran 90 mmol and pyridinium p-toluenesulfonate 1. The reaction mixture was diluted with diethyl ether mL , washed with saturated aqueous sodium bicarbonate 20 mL , brine 20 mL , dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the tetrahydrofuranyl ester of amino acid.
A mixture of this ester 30 mmol , an alcohol type D building block i,e, 4- tert-butoxycarbonylamino -cisbutenol, or 4- tert-butoxycarbonylamino butynol, or 5- tert-butoxycarbonylamino -transpentenol The residue was dissolved in tetrahydrofuran 40 mL. Diisopropyl azodicarboxylate Effective date : A library of macrocyclic compounds of the formula I. What is claimed is: 1. R 10 and R 11 are independently —H or —CH 3 ; and.
A compound having one of the following structures:. Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery. USB1 en. EPB1 en.
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Macrocyclic antagonists of the motilin receptor for treatment of gastrointestinal dysmotility disorders. BRPIA2 en. AUA1 en. Macrocyclic ghrelin receptor antagonists and inverse agonists and methods of using the same. Libraries of diverse macrocyclic compounds and methods of making and using the same. USA en.
Isolation of syn 2-aminothiazolyl - methoxyimino acetamidoacetoxymethylcephemcarboxylic acid. Conformationally restricted mimetics of beta turns and beta bulges and peptides containing the same. WOA1 en. Peptido-mimetic compounds containing RGD sequence useful as integrin inhibitors.