Brominated compounds such as 7-bromo-l-tryptophan (7-Br-Trp) occur in Nature. Many synthetic and natural brominated compounds have applications in the agriculture, food, and pharmaceutical industries, for example, the 20S-proteasome inhibitor TMC-95A that may be derived from 7-Br-Trp. Mild halogenation by cross-linked enzyme aggregates containing FAD-dependent halogenase, NADH-dependent flavin reductase, and alcohol dehydrogenase as well as by fermentation with recombinant Corynebacterium glutamicum expressing the genes for the FAD-dependent halogenase RebH and the NADH-dependent flavin reductase RebF from Lechevalieria aerocolonigenes have recently been developed as green alternatives to more hazardous chemical routes. In this study, the fermentative production of 7-Br-Trp was established. The fermentative process employs an l-tryptophan producing C. glutamicum strain expressing rebH and rebF from L. aerocolonigenes for halogenation and is based on glucose, ammonium and sodium bromide. C. glutamicum tolerated high sodium bromide concentrations, but its growth rate was reduced to half-maximal at 0.09 g L−1 7-bromo-l-tryptophan. This may be, at least in part, due to inhibition of anthranilate phosphoribosyltransferase by 7-Br-Trp since anthranilate phosphoribosyltransferase activity in crude extracts was half-maximal at about 0.03 g L−1 7-Br-Trp. Fermentative production of 7-Br-Trp by recombinant C. glutamicum was scaled up to a working volume of 2 L and operated in batch and fed-batch mode. The titers were increased from batch fermentation in CGXII minimal medium with 0.3 g L−1 7-Br-Trp to fed-batch fermentation in HSG complex medium, where up to 1.2 g L−1 7-Br-Trp were obtained. The product isolated from the culture broth was characterized by NMR and LC-MS and shown to be 7-Br-Trp.

Mild reactionc onditions are highly desirable for bio-orthogonal side chain derivatizations of amino acids, peptides or proteins due to the sensitivity of these substrates. Transition metal catalysed cross-couplingss uch as Suzuki-Miyaura reactions are highly versatile, but usually require unfavourable reaction conditions, in particular,w hen applied with aryl bromides. Ligand-free solvent-stabilised Pd-nanoparticles represent an efficient and sustainable alternative to conventional phosphine-based catalysts,b ecause the cross-coupling can be performed at considerably lower temperature. We report on the applicationo fs uch ah ighly reactive heterogeneousc atalystf or the Suzuki-Miyaura cross-coupling of brominated tryptophan derivatives. The solvent-stabilised Pd-nanoparticles are even more efficient than the literature-known ADHP-Pd precatalyst. Interestingly, the latter also leads to the formation of quasi-homogeneous Pd-nanoparticles as the catalytic species. One advantage of our approach is the compatibilityw ith aqueousa nd aerobic conditions at near-ambient temperatures and short reaction times of only 2h.T he influence of different N a-protecting groups,b oronic acids as well as the impact of different amino acid side chainsi nb romotryptophan-containing peptides has been studied.N otably,asurprising acceleration of the catalysis was observed when palladium-coordinating side chainsw ere presenti np roximal positions.

Dimethylbenzofulvene adds Piers' borane [HB(C6F5)2] at the indene double bond to give a mixture of regioisomeric boranes 8a,b. Subsequent isomerization under equilibrium conditions gives the isopropyl substituted 1H and 3H borylindenes 10a,b. Their treatment with the bulky LiTMP base under frustrated Lewis pair conditions resulted in a clean deprotonation reaction to give the borata-alkene 14. Its X-ray crystal structure analysis indicated a pronounced B[double bond, length as m-dash]C double bond character and thus a borata-benzofulvene description. The borata-alkene underwent (probably stepwise) [4 + 2] cycloaddition reactions with chalcone derivatives and a formal [6 + 2] cycloaddition with phenylmethylketene. Many products and derivatives were characterized by X-ray diffraction.

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