Helvetica Chimica Acta

Biswas, Animesh; Greiner, Luca C.; Bonowski, Jana; Pahl, Axel; Sievers, Sonja; Schmidt, Annika; Strohmann, Carsten; Ziegler, Slava; Grigalunas, Michael; Waldmann, Herbert

doi: 10.1002/hlca.202500155pmid: N/A

In pseudo‐natural product (PNP) design, natural product fragments are combined in arrangements not found in nature to afford novel biologically relevant NP‐related compound classes. A pseudo‐natural product compound collection inspired by aspidospermidine‐, strychnos‐, and koumine monoterpene alkaloids was designed and rapidly synthesized to afford a collection of 78 compounds representing eight structurally different PNP classes. Evaluation of the collection for biological relevance by means of the cell painting assay, including a recently reported subprofile analysis, revealed that one of the structural classes is enriched in and defines a new chemotype of de novo pyrimidine biosynthesis inhibitors. Our results exemplify the combination of pseudo‐natural product design and unbiased morphological screening technologies as an efficient means to rapidly access and identify novel biologically relevant chemotypes.

Nedelcu, Georgian; Yakunin, Sergii; Yanchak, Artem; Driess, Matthias; Grützmacher, Hansjörg; Dirin, Dmitry N.; Kovalenko, Maksym V.

doi: 10.1002/hlca.202500162pmid: N/A

Colloidal III–V arsenide quantum dots (QDs) are promising low‐toxicity, solution‐processable materials for near‐infrared optoelectronics, yet their development has been constrained by the scarcity of suitable precursors and proneness to oxidation. Existing routes either rely on highly reactive but toxic, pyrophoric group‐14‐substituted arsines, or on safer aminoarsines that require in situ reduction and cause staggered rather than a single burst nucleation. We introduce aluminum tris[bis(mesitoyl)arsenide] as a nonpyrophoric and air‐stable precursor that, upon nucleophilic attack, directly delivers the formally As3− species. Using this precursor, we synthesized 2.3–4.6 nm large InAs QDs and 2–5.5 nm large Cd3As2 QDs with photoluminescence tunable in the 800–2250 nm range. These results establish aluminum tris[bis(mesitoyl)arsenide] as a versatile precursor, enabling safe and controlled syntheses of various arsenide QDs.

Vantourout, Julien

doi: 10.1002/hlca.202500173pmid: N/A

Pedada, Abhilash; Wahl, Johannes M.

doi: 10.1002/hlca.202500169pmid: N/A

Ortho‐alkoxy trifluoroacetophenones undergo efficient cyclization to benzofuranols under UV light irradiation (370 nm). Key to success is a 1,6‐hydrogen atom transfer (1,6‐HAT), which is enabled by the unique properties of the trifluoroacetophenone unit and strategic positioning of the methoxy group. The reaction proceeds best under dilute conditions, in polar aprotic solvents, and with high‐intensity irradiation. Although triplet quenching and intermolecular HAT limit certain aromatic substitution patterns, the reaction still accommodates a diverse set of substrates, providing access to tertiary benzofuranols, including spirocyclic compounds (12 examples, up to 92% yield, up to 90:10 diastereomeric ratios [dr]). Subsequent dehydration provides trifluoromethyl‐substituted benzofurans, offering a convenient route to these heterocycles.

Cognet, Michael; Renno, Giacomo; Rose, Nicholas; Zhang, Yuheng; Josso, Pierre; Moreno, Julia; Ren, Xudong; Bouffard, Jules; Saidjalolov, Saidbakhrom; Sakai, Naomi; Matile, Stefan

doi: 10.1002/hlca.202500129pmid: N/A

To appreciate 10 years of cell‐penetrating poly(disulfide)s (CPDs), this review comprehensively covers the structures realized by now. CPDs have been introduced as dynamic covalent polymers that i) are obtained from cyclic disulfide monomers by ring‐opening polymerization (ROP) and ii) enter cells by thiol‐mediated uptake. They were discovered in 2014 and have been used since then for diverse delivery applications in vitro and in vivo. The introduction briefly sketches their mode of action, as far as it is known. The main part lists the CPDs realized so far, organized by their structures, with selected examples for biological applications. The final chapters cover the few cyclic monomers other than lipoic acid derivatives that have been explored and links to related topics such as templated ROP of cyclic disulfides in lipoplexes and liposomes and related delivery motifs. We hope this review offers a solid and productive basis for future progress with CPD research and its use in science and society.

Wenzel, Jonas O.; Breher, Frank

doi: 10.1002/hlca.202500138pmid: N/A

Bis(pyridylimino) isoindolides (BPIs) are important redox non‐innocent ligands in coordination chemistry and homogeneous catalysis. BPIs can be doubly reduced allowing a change between the mono‐, di‐ and trianionic state. In this article, the first isolation of a monomeric compound with radical dianionic BPI ligand is reported, realized as potassium complex with supporting crown ether ligands. Single‐crystal X‐ray diffraction (SC‐XRD) revealed an η5‐coordination of the five‐membered isoindolide ring, which is so far unprecedented in BPI chemistry. The radical was investigated by electron paramagnetic resonance (EPR) spectroscopy. Structures of the pincer‐type rotamers of BPI in the mono‐, di‐ and trianionic state were calculated by density functional theory (DFT) methods to benchmark the BPI bond lengths theoretically upon varied redox states. Bond lengths within the herein described BPI radical deviate significantly from the free BPI dianion, depicting how careful structure‐redox‐state correlations must be drawn in the coordination chemistry of redox‐active BPIs.

Millward, Francis; Zysman‐Colman, Eli

doi: 10.1002/hlca.202500161pmid: N/A

Mechanochemistry can mediate reactions containing components that are poorly soluble in organic solvents, thereby facilitating access to new chemical space. These reagents may also be safer to handle and less costly than analogs used in solution‐state reactions, providing secondary tangible benefits. In this study, we report the use of sodium ascorbate as a sacrificial reductant in net reductive pinacol couplings of aromatic aldehydes and ketones driven by mechanophotocatalysis. Sodium ascorbate replaces the sacrificial reductants typically used to deliver these 1,2‐diol products (such as DIPEA and the Hantzsch ester). The solvent‐minimized protocol returned more consistent results than the solution‐state reference reaction, highlighting mechanophotocatalysis as a valuable tool for mediating heterogeneous photochemical reactions. An initial positive result for a reductive amination protocol using ascorbate is also disclosed.

Davey, P. N.; Tse, C.‐L.; Ellwood, S.; Lovchik, M.; Navarria, M.; Toth, F.; Lorincz, K.; Ondi, L.; Goeke, A.

doi: 10.1002/hlca.202500113pmid: N/A

This study describes the applications of molybdenum‐catalyzed homogeneous cross‐metathesis approaches, which led to the production of the unique macrocyclic musk lactone Ambrettolide under essentially solvent free conditions. Renewable octenyl decenoate 16 was pretreated to remove traces of water, oxygen, and peroxides and polymerized at low catalyst loadings to control the rate of ethylene evolution. In a subsequent intramolecular transesterification‐based depolymerization step, a new quality of Ambrettolide was obtained with an E/Z ratio of 85/15 and desired organoleptic properties, now available as AmbreXolide™.