Sustainable Syntheses of Paracetamol and Ibuprofen from Biorenewable ß-pinene.

Scalable processes have been developed to convert ß-pinene into 4-isopropenylcyclohexanone, which is then used as a feedstock for the divergent synthesis of sustainable versions of the common painkillers, paracetamol and ibuprofen. Both synthetic routes use Pd0 catalysed reactions to aromatize the cyclohexenyl rings of key intermediates to produce the benzenoid ring systems of both drugs. The potential of using bioderived 4-hydroxyacetophenone as a drop-in feedstock replacement to produce sustainable aromatic products is also discussed within a terpene biorefinery context.

Selective Catalytic Synthesis of 1,2- and 8,9-Cyclic Limonene Carbonates as Versatile Building Blocks for Novel Hydroxyurethanes.

The selective catalytic synthesis of limonene-derived monofunctional cyclic carbonates and their subsequent functionalisation via thiol-ene addition and amine ring-opening is reported. A phosphotungstate polyoxometalate catalyst used for limonene epoxidation in the 1,2-position is shown to also be active in cyclic carbonate synthesis, allowing a two-step, one-pot synthesis without intermittent epoxide isolation. When used in conjunction with a classical halide catalyst, the polyoxometalate increased the rate of carbonation in a synergistic double-activation of both substrates. The cis isomer is shown to be responsible for incomplete conversion and by-product formation in commercial mixtures of 1,2-limomene oxide. Carbonation of 8,9-limonene epoxide furnished the 8,9-limonene carbonate for the first time. Both cyclic carbonates underwent thiol-ene addition reactions to yield linked di-monocarbonates, which can be used in linear non-isocyanate polyurethanes synthesis, as shown by their facile ring-opening with N-hexylamine. Thus, the selective catalytic route to monofunctional limonene carbonates gives straightforward access to monomers for novel bio-based polymers.

Characterization of the first naturally thermostable terpene synthases and development of strategies to improve thermostability in this family of enzymes.

The terpenoid family of natural products is being targeted for heterologous microbial production as a cheaper and more reliable alternative to extraction from plants. The key enzyme responsible for diversification of terpene structure is the class-I terpene synthase (TS), and these often require engineering to improve properties such as thermostability, robustness and catalytic activity before they are suitable for industrial use. Improving thermostability typically relies on screening a large number of mutants, as there are no naturally thermostable TSs described upon which to base rational design decisions. We have characterized the first examples of natural TSs exhibiting thermostability, which catalyse the formation of the sesquiterpene τ-muurolol at temperatures up to 78 °C. We also report an enzyme with a kcat value of 0.95 s-1 at 65 °C, the highest kcat recorded for a bacterial sesquiterpene synthase. In turn, these thermostable enzymes were used as a model to inform the rational engineering of another TS, with the same specificity but low sequence identity to the model. The newly engineered variant displayed increased thermostability and turnover. Given the high structural homology of the class-I TS domain, this approach could be generally applicable to improving the properties of other enzymes in this class. DATABASE: Model data are available in the PMDB database under the accession number PM0080780.

Switching pathways: room-temperature neutral solvolysis and substitution of amides.

Stick or twist: By introducing steric hindrance at the nitrogen atom, stable linear amides bearing an electron-withdrawing α-substituent (Z = Ar, PhSO(2), P(O)(OR)(2), CN, or CO(2)R) can be induced to undergo solvolysis and substitution reactions through an elimination-addition mechanism (see picture). Key to this process is a low barrier to rotation around the amide bond and the α-substituent Z.

Room-temperature palladium-catalyzed C-H activation: ortho-carbonylation of aniline derivatives.

Pd and CO--ureally got me! The title reaction proceeds efficiently at 18 degrees C under CO (1 atm) with 5 % [Pd(OTs)(2)(MeCN)(2)] as precatalyst. Depending on the solvents used, either anthranilates or cyclic imides can be obtained in high yields (see picture, BQ = benzoquinone, Ts = 4-toluenesulfonyl).