Daniel Bellus

A new electrophilic 2-pyrone bearing a CF3-group, its preparation and its [4+2] cycloaddition reactions

Abstract An efficient method for the synthesis of 4-methoxycarbonyl-6-trifluoromethyl-2H-pyran-2-one (4) starting from the 1:1-adduct of the CuCl-catalysed addition of 1,1,1-trichloro-2,2,2-trifluoroethane to dimethyl itaconate is presented. The new electrophilic 2-pyrone 4 affords [4+2] cycloadducts with a number of olefins and acetylenes. Their formation follows the reactivity patterns of a typical Diels-Alder reaction with inverse electron demand. The overall sequence represents a new methodology for the transfer of the CF3- group from a simple freon into more complex organic compounds.

Stereoselective ketene-claisen rearrangement of chiral allylthioethers

Abstract A new method for the preparation of chiral β-branched, γ,δ-unsaturated thioesters and derivatives is presented, which involves the ketene-Claisen rearrangement of chiral allylthioethers. A novel synthesis of the starting chiral allylthioethers is also described.

PHOTOPOLYMERS AS A POWERFUL TOOL IN MODERN TECHNOLOGY

Light does not only provide the ultimate energy for natures biological processes, it is also serving modern technology. Eficient and accurate photo-imaging spanning from submicron photolithography to three-dimensional stereolithography requires specially tuned photopolymers as functional materials. Classical photopolymers, combination approaches and tailor-made solutions to technological problems will be described.

Synthesis of novel cyclobutylphosphonic acids as inhibitors of imidazole glycerol phosphate dehydratase

Abstract Diethyl 3-oxocyclobutylphosphonate (5) has been synthesised via a novel one-pot cyclisation reaction of the α-phenylsulphonyl-γ,δ-epoxyphosphonate 8. Addition of 5-lithio-1-trityl-1,2,4-triazole to ketone 5 and deprotection then afforded cis-3-hydroxy-3-(1,2,4-triazol-3-yl)cyclobutylphosphonic acid (cis-4) which showed modest in vitro inhibition of the enzyme imidazole glycerol phosphate dehydratase. In an attempt to obtain the corresponding trans isomer (trans-4), whose inhibitory activity was anticipated to be higher, an efficient three-step synthesis was developed employing base-mediated cyclisation of the γ,δ-epoxy-γ-(1,2,4-triazol-5-yl)phosphonate 35. Although this latter route stereoselectively afforded cis-36, an efficient epimerisation reaction could be subsequently used to obtain the desired trans stereochemistry. However, all attempts at deprotection of trans-36 proceeded with simultaneous re-epimerisation to give the previously prepared cis-4. High level ab initio calculations have been used to rationalise the relative thermodynamic stability of cis-4 and trans-4.

How do specialty polymers modify the chemical and pharmaceutical industries

Abstract Specialty polymers play an increasingly important role in all stages of the enormously complex development process of new biologically active products. They widen and facilitate the discovery stage. For example, the use of solid polymer supports for automated peptide and oligo-nucleotide synthesis (the application of “Affymax” technology) enables the light-directed parallel chemical synthesis of a highly diverse set of oligopeptides. The chiral DNA and RNA backbones of antisense oligonucleotides can be replaced by synthetic archiral ones. In the testing stages the rapid chromatographic separation of racemates on chiral polymer supports has been established as an invaluable tool. The search for better application methods has led to the development of smart polymer patches that often provide excellent transdermal delivery of pharmaceutical drugs; water-soluble bags and microencapsulation technology have greatly improved the environmental safety of agrochemicals. Finally, the diverse synthetic activ...

Moniliformin and Related Cyclobutenediones

Five different routes to l-hydroxy-1-cyclobuten-3,4-dione, the free acid of the mycotoxine Moniliformin (= alkali salt), which possesses plant growth regulating activity, are described. A common feature of all pathways is the synthesis of cyclobutanes having the oxidation level 6, which are easily transformed to moniliformin by acid hydrolysis. These include 2+2-cycloadducts of ketene with tetraalkoxyolefins (this is the most facile route with 57% overall yield), polyf1uorinated cyclobutenes, the brominated 2+2-cycloadduct of ethyl vinyl ether and dichloroketene, 2+2-photocycloadducts of dichlorovinylenecarbonate with dichloroethylenes, and the dimer of chloroketene. In addition, very convenient general syntheses of 2-substituted moniliformins and squaric acid are described, which involve the 2+2-cycloadditions of substituted ketenes to readily available tetraalkoxyethylenes as the cyclobutane-forming step. Esters of squaric acid show contact herbicidal activity.