Supramolecular Capsule Catalysis Enables the Exploration of Terpenoid Chemical Space Untapped by NatureNémethová, Ivana; Schmid, Dario; Tiefenbacher, Konrad
doi: 10.1002/anie.202218625pmid: 36727480
Terpenes represent the largest and the most diverse class of natural compounds. This is remarkable as the whole variety is accessed from just a handful of highly conserved linear precursors. Modification of the cyclization precursors would enable a dramatic expansion of the accessible chemical space. However, natural enzymes do not enable us to tap into this potential, as they do not tolerate larger deviations from the prototypical substrate structure. Herein we report that supramolecular capsule catalysis enables facile access to diverse and novel terpenoid skeletons that formally can be traced back to C3‐phenyl, benzyl, and homoprenyl derivatives of farnesol. Novel skeletons related to the presilphiperfolane core structure, as well as novel neoclovene derivatives were accessed efficiently in only four synthetic steps. Importantly, the products obtained carry functional groups that may be readily derivatized further.
Converting Non‐strained γ‐Valerolactone and Derivatives into Sustainable Polythioesters via Isomerization‐driven Cationic Ring‐Opening Polymerization of Thionolactone IntermediateXia, Yongliang; Yuan, Pengjun; Zhang, Yanping; Sun, Yangyang; Hong, Miao
doi: 10.1002/anie.202217812pmid: 36757807
This contribution reports the efficient conversion of γ‐valerolactone and its derivatives, abundant but unexplored renewable feedstocks, into sustainable and degradable polythioesters via the establishment of the first isomerization‐driven ring‐opening polymerizations (IROPs) of corresponding thionolactone intermediates. The key to this success relies on the development of a new simple and robust [Et3O]+[B(C6F5)4]− cationic initiator which possesses high activity, exclusive selectivity, living nature, and broad scope of thionolactones. A complete inversion of configuration during IROP of enantiopure γ‐thionovalerolactone is also disclosed, affording isotactic semicrystalline polythioesters (Tm=87.0 °C) with mechanical property compared well to the representative commodity polyolefins. The formation of a highly crystalline supramolecular stereocomplex with enhanced thermal property (Tm=117.6 °C) has also been revealed.
Hydroxylation with Unusual Stereoinversion Catalyzed by an FeII/2‐OG Dependent Oxidase and 3,6‐Diene‐2,5‐diketopiperazine Formation in the Biosynthesis of Brevianamide KXu, Zhuo‐Zheng; Zhuang, Zheng; Cai, Runlin; Lin, Guo‐Qiang; She, Zhigang; Zhao, Qunfei; He, Qing‐Li
doi: 10.1002/anie.202216989pmid: 36750406
Natural products with the 3,6‐diene‐2,5‐diketopiperazine core are widely distributed in nature; however, the biosynthetic mechanism of 3,6‐diene‐2,5‐diketopiperazine in fungi remains to be further elucidated. Through heterologous expression and biochemical investigation of an FeII/2‐oxoglutarate‐dependent oxidase (AspE) and a heme‐dependent P450 enzyme (AspF), we report that AspE, AspF and subsequent dehydration account for the formation of the 3,6‐diene‐2,5‐diketopiperazine substructure of brevianamide K from Aspergillus sp. SK‐28, a symbiotic fungus of mangrove plant Kandelia candel. More interestingly, in‐depth investigation of the enzymatic mechanism showed that AspE promotes hydroxylation of brevianamide Q with unprecedented stereoinversion through hydrogen atom abstraction and water nucleophilic attack from the opposite face of the resultant iminium cation intermediate.
Tailorable and Biocompatible Supramolecular‐Based Hydrogels Featuring two Dynamic Covalent ChemistriesMarić, Ivana; Yang, Liangliang; Li, Xiufeng; Santiago, Guillermo Monreal; Pappas, Charalampos G.; Qiu, Xinkai; Dijksman, Joshua A.; Mikhailov, Kirill; Rijn, Patrick; Otto, Sijbren
doi: 10.1002/anie.202216475pmid: 36744522
Dynamic covalent chemistry (DCC) has proven to be a valuable tool in creating fascinating molecules, structures, and emergent properties in fully synthetic systems. Here we report a system that uses two dynamic covalent bonds in tandem, namely disulfides and hydrazones, for the formation of hydrogels containing biologically relevant ligands. The reversibility of disulfide bonds allows fiber formation upon oxidation of dithiol‐peptide building block, while the reaction between NH−NH2 functionalized C‐terminus and aldehyde cross‐linkers results in a gel. The same bond‐forming reaction was exploited for the “decoration” of the supramolecular assemblies by cell‐adhesion‐promoting sequences (RGD and LDV). Fast triggered gelation, cytocompatibility and ability to “on‐demand” chemically customize fibrillar scaffold offer potential for applying these systems as a bioactive platform for cell culture and tissue engineering.
Carboxylic Acid Salts as Dual‐Function Reagents for Carboxylation and Carbon Isotope LabelingWang, Shuo; Larrosa, Igor; Yorimitsu, Hideki; Perry, Gregory J. P.
doi: 10.1002/anie.202218371pmid: 36746757
The potassium salts of carboxylic acids are developed as efficient carboxylating agents through CO2 exchange. We describe these carboxylates as dual‐function reagents because they function as a combined source of CO2 and base/metalating agent. By using the salt of a commercially available carboxylic acid, this protocol overcomes difficulties when using CO2 gas or organometallic reagents, such as pressurized containers or strictly inert conditions. The reaction proceeds under mild conditions, does not require transition metals or other additives, and shows broad substrate scope. Through the preparation of several biologically important molecules, we show how this strategy provides an opportunity for isotope labeling with low equivalents of labeled CO2.
Enantioselective Intramolecular α‐Arylation of Benzylamine Derivatives: Synthesis of a Precursor to LevocetirizineSaunthwal, Rakesh K.; Schwarz, Maria; Mallick, Rajendra K.; Terry‐Wright, William; Clayden, Jonathan
doi: 10.1002/anie.202216758pmid: 36698284
A practical, transition metal‐free method allows the enantioselective synthesis of α,α‐diarylmethylamines by asymmetric α‐arylation of benzylamines. Enantioselective lithiation of N′‐aryl‐N‐benzyl‐N‐isopropyl ureas using a chiral lithium amide base generates a benzyllithium that undergoes an unactivated stereospecific intramolecular nucleophilic aromatic substitution to generate an α,α‐diarylmethylamine in the form of its urea derivative, in up to >99 % ee. Treatment with acid induces an “azatropic shift” with retention of configuration, the product of which may be hydrolysed to the target amine.