A practical microwave method for the synthesis of fluoromethy 4-methylbenzenesulfonate in tert-amyl alcohol.

Fluorine substitution is an established tool in medicinal chemistry to favourably alter the molecular properties of a lead compound of interest. However, gaps still exist in the library of synthetic methods for accessing certain fluorine-substituted motifs. One such area is the fluoromethyl group, particularly when required in a fluoroalkylating capacity. The cold fluorination of methylene ditosylate is under evaluated in the literature, often proceeding with low yields or harsh conditions. This report describes a novel microwave method for the rapid nucleophilic fluorination of methylene ditosylate using inexpensive reagents in good isolated yield (65%).

An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement.

Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12-14).

Smart bandages--a colourful approach to early stage infection detection & control in wound care.

With the recent increase in bacterial resistance to conventional antibiotics, the early-stage detection and control of infection has become imperative in the fight against opportunistic pathogens in healthcare. The traditional ß-lactam wonder-drugs (e.g. penicillin and cephalosporins), are rendered inactive due to enzymatic hydrolysis by bacterial ß-lactamase enzymes as a bacterial defence mechanism. However, this deactivation mechanism produces different responses in the two aforementioned drugs - with the cephalosporins showing a molecular rearrangement mechanism which could be utilised for prodrug delivery. This unique mechanism could mean that inactive forms of cephalosporin antibiotics, once used as chemotherapeutics in oncology, could once again be used in the fight against disease as sensors to detect and treat bacterial colonisation. Therefore, we hypothesize that cephalosporin-dye bandages might provide an effective method to visually detect, and subsequently control, the early stages of an infection using photoantimicrobial chemotherapy (PACT).