LongLarf

Abstract

Selective reduction of esters to alcohols was accomplished through Mn(I)‐mediated hydrosilylation reaction. The manganese tricarbonyl complex [Mn(bis‐NHC)(CO)₃Br] resulted an active pre‐catalyst for the reduction of a variety of esters using phenylsilane and the cheap and readily available polymethylhydrosiloxane. An in situ examination of the catalytic reaction using ⁵⁵Mn NMR spectroscopy allowed us to detect the formation of Mn(I) intermediate active species.

Catch and release : A new cleavable linker based on secondary amino alcohols is reported for application in peptide discovery. The linker is easily incorporated into peptides during on‐resin synthesis and is shown to be rapidly cleaved in the presence of NaIO₄. Peptide‐library and cell‐based experiments demonstrate that this linker enables the recovery of hit sequences after affinity capture.

Abstract

Capture and release of peptides is often a critical operation in the pathway to discovering materials with novel functions. However, the best methods for efficient capture impede facile release. To overcome this challenge, we report linkers based on secondary amino alcohols for the release of peptides after capture. These amino alcohols are based on serine (seramox) or isoserine (isoseramox) and can be incorporated into peptides during solid‐phase peptide synthesis through reductive amination. Both linkers are quantitatively cleaved within minutes under NaIO₄ treatment. Cleavage of isoseramox produced a native peptide N‐terminus. This linker also showed broad substrate compatibility; incorporation into a synthetic peptide library resulted in the identification of all sequences by nanoLC‐MS/MS. The linkers are cell compatible; a cell‐penetrating peptide that contained this linker was efficiently captured and identified after uptake into cells. These findings suggest that such secondary amino alcohol based linkers might be suitable tools for peptide‐discovery platforms.

Nature, Published online: 30 March 2020; doi:10.1038/d41586-020-00971-z

An ortho ‐selective C−H perfluoroalkylation including trifluoromethylations of anilines and indoles is reported without the need of protecting groups using R_fI and R_fBr as commercially available reagents (see scheme). The availability and price of the starting materials and the inherent selectivity make this methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks.

Abstract

Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report an ortho ‐selective C−H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using R_fI and R_fBr as commercially available reagents. The availability and price of the starting materials and the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, for example, for bioactive compounds and materials.

Transfer hydrogenation : An efficient Ir(III)‐catalyzed transfer hydrogenation of ketones into corresponding alcohol using methanol as liquid organic hydrogen carrier is demonstrated.

Abstract

Herein, we demonstrate an efficient protocol for transfer hydrogenation of ketones using methanol as practical and useful liquid organic hydrogen carrier (LOHC) under Ir(III) catalysis. Various ketones, including electron‐rich/electron‐poor aromatic ketones, heteroaromatic and aliphatic ketones, have been efficiently reduced into their corresponding alcohols. Chemoselective reduction of ketones was established in the presence of various other reducible functional groups under mild conditions.

Nature Catalysis, Published online: 23 March 2020; doi:10.1038/s41929-020-0434-0

Synlett
DOI: 10.1055/s-0040-1708009

A new family of dienone musks was discovered by alkylation of different aldehydes with but-3-en-1-yn-1-yllithium and subsequent domino reaction of a Saucy–Marbet transfer vinylation–Claisen rearrangement with an intramolecular Diels–Alder reaction, and concluding Lewis acid catalyzed double-bond isomerization. The newly synthesized dienone structures possess pleasant musk odors displaying fatty, slightly fruity and green facets. Although the dienone musks were predicted in silico to bind to the OR5AN1 receptor based on QM/MM calculations, they were found to be inactive in the in vitro assay. The latter results suggest that the OR5AN1 receptor is not the prime musk receptor but primarily responsible for the animalic character of certain macrocyclic ketones and nitro musks.
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© Georg Thieme Verlag Stuttgart · New York

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In rerum natura: Wild‐type cytochrome P450_BM3 catalyzes the oxidation of hydrosilanes to silanols both in vivo and in vitro. Directed evolution was used to generate an efficient and selective biocatalyst that delivers a broad range of aryl‐ and alkyl‐substituted silanols. Computational studies revealed a sequence of H atom abstraction and OH rebound as the mechanism, in analogy to the native C−H hydroxylation activity.

Abstract

Compared to the biological world's rich chemistry for functionalizing carbon, enzymatic transformations of the heavier homologue silicon are rare. We report that a wild‐type cytochrome P450 monooxygenase (P450_BM3 from Bacillus megaterium, CYP102A1) has promiscuous activity for oxidation of hydrosilanes to give silanols. Directed evolution was applied to enhance this non‐native activity and create a highly efficient catalyst for selective silane oxidation under mild conditions with oxygen as the terminal oxidant. The evolved enzyme leaves C−H bonds present in the silane substrates untouched, and this biotransformation does not lead to disiloxane formation, a common problem in silanol syntheses. Computational studies reveal that catalysis proceeds through hydrogen atom abstraction followed by radical rebound, as observed in the native C−H hydroxylation mechanism of the P450 enzyme. This enzymatic silane oxidation extends nature's impressive catalytic repertoire.

Synlett
DOI: 10.1055/s-0039-1690849

The isocyano group is the structurally most compact bioorthogonal group known. It reacts with tetrazines under physiological conditions and has great potential for widespread use in the biosciences. In this account, we highlight the unique properties of the isocyano group as a bioorthogonal functionality. Protecting group chemistry based on the reaction of isonitriles and tetrazines that allows releasing payloads is a particular focus of the article. We further discuss the atypical steric attractions that take place in the transition state of the reaction between isonitriles and tetrazines, which result in an increase in the rate of the reaction with steric bulk of the tetrazine substituents. These findings will open up new possibilities in bioorthogonal chemistry where reactivity and stability are simultaneously desired.1 Introduction2 The Isocyano Group: A Structurally Compact Group for Bioorthogonal Chemistry3 Bioorthogonal Protecting Group Chemistry4 Steric Attractions in the Transition State Accelerate the Cycloaddition of Isonitriles and Tetrazines5 Reactions of Tetrazines and Isonitriles are Compatible with Biomolecules and Living Organisms6 Conclusions
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© Georg Thieme Verlag Stuttgart · New York

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Publication date: 11 June 2020

Source: Chem, Volume 6, Issue 6

Author(s): Frederik Sandfort, Felix Strieth-Kalthoff, Marius Kühnemund, Christian Beecks, Frank Glorius