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Intrinsically safe and shelf stable diazo transfer reagent for fast synthesis of diazo compounds

At the Scientific Update OPRD conference in Milan earlier this month, Xiaohu Deng from Kura Oncology discussed a pyrimidine-derived diazo intermediate that exists predominantly in the tautomeric ‘tetrazole’ form at equilibrium in solution.[1] The compound was shown as a putative retrosynthetic building block for synthesis of a J&J P2X7 antagonist (Figure 1).[2] I’d not come

A concise total synthesis of Quinine and analogues via C-H activation

                    The naturally occurring cinchona alkaloids, and Quinine in particular, have been of interest to synthetic chemistry practitioners for many years, due ostensibly to its antimalarial activity, particularly against resistant strains of the disease. The original synthesis, by Woodward and Doering in 1944 was heralded as

The Chichibabin amination reaction

         2-Aminopyrides are useful synthetic intermediates and pharmacophores in a number of drugs.[1] The Chichibabin reaction, developed in the 1900’s gives a direct method for the amination of pyridine and pyridine derivatives (azines and azoles) using sodium or potassium amides. Intramolecular amination reactions are also known. The reaction can be run either

Cyanomethylene trimethylphosphorane (CMMP)- a safer reagent for Mitsunobu couplings

The Mitsunobu reaction is a powerful coupling method for alkylation of various nucleophiles (H-A) with alcohols (R-OH).[1] The classical conditions use a redox system comprising of an azodicarboxylate (such as diethylaziodicarboxylate, DEAD) and a phosphine (normally triphenylphosphine, TPP). The alcohol is essentially activated in situ and coupling occurs with the generation of the phosphine oxide

Bio-Transforming: Stereodivergent cyclopropanation of non-activated alkenes  

One of the challenges associated with biocatalysis is the resulting stereochemistry is not always easy to predict and more often than not gives the unwanted isomer. The problem is compounded if the substrate has limited steric or electronic components to aid stereocontrol. A way around this problem is to engineer the wildtype protein. A resect

Protecting group free radical C-H trifluoromethylation of peptides  

The resurgence of peptide and protein-based therapeutics and the demand for chemical probes to elucidate complex biological pathways has driven the development of synthetic chemistry compatible with post translational modification and/or bioconjugation. The use of fluorine-modified biomolecules has enabled the 19F nucleus to be used in NMR experiments to study protein structure, dynamics and protein-ligand

Biocatalytic oxidation and synthesis of Esomeprazole

Esomeprazole is a proton pump inhibitor developed by Astra Zeneca in 2001 and marked under the trade name Nexium. Esomeprazole is the S-enantiomer of omeprazole (the racemate) and is an example of the controversial so-called “chiral switch” in with single isomers are developed and marked as having improved pharmacodynamic or phmacokinetic properties over the originally

Synthesis of biaryls without using heavy metals- the photosplicing approach

Medicinal chemists love introducing aromatic rings into their pharmacophores. These flat rings make important lipophilic and pi-stacking interactions with proteins and are good synthetic handles for attaching functionality to reach and bind to all the nooks and crannies of an active site. With the advent of cross-coupling chemistry and the simplicity and efficiency of transition

Syntactic fantastic: A practical, ortho- selective mono-halogenation and phenylselenation of phenols by direct C-H halogenation.

The direct halogenation of phenols using electrophilic halogenating reagents such as NBS are frequently used to prepare halogenated phenols. The problem with this method is that selectivity can often be low- the ortho– isomer is usually the minor component in a statistical mixture due to steric and electronic effects, and over reaction to give polyhalogenated