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Upstream product

• 6306-52-1 L-valine methylester hydrochloride 
• 103-80-0 phenylacetyl chloride 
• 103-82-2 phenylacetic acid 
• 67-56-1 methanol 
• 68858-20-8 Fmoc-Val-OH 

Relevant academic research and scientific papers

Lipophilic Permeability Efficiency Reconciles the Opposing Roles of Lipophilicity in Membrane Permeability and Aqueous Solubility

As drug discovery moves increasingly toward previously "undruggable" targets such as protein-protein interactions, lead compounds are becoming larger and more lipophilic. Although increasing lipophilicity can improve membrane permeability, it can also incur serious liabilities, including poor water solubility, increased toxicity, and faster metabolic clearance. Here we introduce a new efficiency metric, especially relevant to "beyond rule of 5" molecules, that captures, in a simple, unitless value, these opposing effects of lipophilicity on molecular properties. Lipophilic permeability efficiency (LPE) is defined as log D7.4dec/w - mlipocLogP + bscaffold, where log D7.4dec/w is the experimental decadiene-water distribution coefficient (pH 7.4), cLogP is the calculated octanol-water partition coefficient, and mlipo and bscaffold are scaling factors to standardize LPE values across different cLogP metrics and scaffolds. Using a variety of peptidic and nonpeptidic macrocycle drugs, we show that LPE provides a functional assessment of the efficiency with which a compound achieves passive membrane permeability at a given lipophilicity.

Direct amidation of amino acid derivatives catalyzed by arylboronic acids: Applications in dipeptide synthesis

The direct amidation of amino acid derivatives catalyzed by arylboronic acids has been examined. The reaction was generally slow relative to simple amine-carboxylic acid combinations though proceeded at 65-68 °C generally avoiding racemization. 3,4,5-Trifluorophenylboronic and o-nitrophenylboronic acids were found to be the best catalysts, though for slower dipeptide formations, high catalyst loadings were required and an interesting synergistic catalytic effect between two arylboronic acids was discovered. Arylboronic acids can be used to catalyze the direct amide formation of protected amino acid derivatives. For less reactive amino acids, cooperative catalysis can be used involving two arylboronic acids, one electron-rich and one electron-deficient, at high catalyst loadings to give good conversions at moderate temperatures. Copyright

Direct amide formation from unactivated carboxylic acids and amines

The direct coupling of unactivated carboxylic acids with amines can be performed in toluene 110 °C in the absence of catalyst. The use of simple zirconium catalysts at 5 mol% loading gave amide formation in as little as 4 h.

Oxidative C-H homodimerization of phenylacetamides

A range of secondary and tertiary phenylacetamides undergo oxidative homodimerization to afford biaryls. The reaction proceeds under palladium catalysis in the presence of a copper cocatalyst and oxygen and is most effective for electron-rich substrates.