Photoredox C(2)-Arylation of Indole- and Tryptophan-Containing Biomolecules.

We introduce a novel and straightforward methodology for photoredox arylation of an indole scaffold using aryldiazonium salts under mild and metal-free conditions. Our approach enables the regioselective and chemoselective introduction of several aryl groups to the C(2) position of indoles and tryptophan, even in competition with other amino acids. This approach extends to the late-stage functionalization of peptides and lysozyme, heralding the unprecedented arylation of tryptophan residues in wild-type proteins and offering broad utility in chemical biology.

Developing Amphetamine Certified Reference Materials: From Batch and Continuous-Flow Synthesis to Certification Protocol.

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds.

Continuous-flow synthesis of dimethyl fumarate: a powerful small molecule for the treatment of psoriasis and multiple sclerosis.

Dimethyl fumarate (DMF) is a methyl ester of fumaric acid and has recently gained attention due to its use as a pro-drug in different pharmaceutical preparations, besides the low price of the final molecule and no active patents being available for the synthesis of DMF, the prices of multiple sclerosis treatment are still high. In our continuous effort for the development of process intensification strategies towards the synthesis of active pharmaceutical ingredients, here we present our work on a cascade methodology for dimethyl fumarate synthesis in short reaction times and quantitative yields.

Expanding the toolbox of asymmetric organocatalysis by continuous-flow process.

Despite all the organic chemistry reaction methodologies already developed for the continuous-flow process, asymmetric synthesis is one that has gained less attention. Since the pioneering work of Barbas and MacMillan, organocatalysis has emerged as the third pillar of asymmetric catalysis. In this review, we present a survey of literature regarding the use of organocatalysis under continuous-flow conditions.

Enantioselective intramolecular aldehyde α-alkylation with simple olefins: direct access to homo-ene products.

A highly selective method for the synthesis of asymmetrically substituted carbocycles and heterocycles from unactivated aldehyde-olefin precursors has been achieved via enantioselective SOMO-catalysis. Addition of a catalytically generated enamine radical cation across a pendent olefin serves to establish a general asymmetric strategy toward the production of a wide range of formyl-substituted rings with alkene transposition. Conceptually, this novel mechanism allows direct access to "homo-ene"-type products.

(±)-(4aR,5R,8S,8aR)-8-(tert-Butyl-dimethyl-sil-yloxy)-2,5,8a-trimethyl-4a,5,8,8a-tetra-hydro-naphthalene-1,4-dione.

In the title compound, C19H30O3Si, both rings adopt a half-boat conformation. Overall, the mol-ecule approximates a U-shape as the cyclo-2-ene-1,4-dione and butyl-dimethyl-sil-yloxy substituents lie to the same side of the central cyclo-hexene ring; the methyl substituent lies to the other side of the mol-ecule. In the crystal, linear supra-molecular chains along the b axis are sustained by C-H⋯O inter-actions.