Synlett

Synlett 2024; 35: V-DOI: 10.1055/s-0043-1774867Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

Synlett 2024; 35: A87-A102DOI: 10.1055/s-0043-1763985Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

The development of complex molecular scaffolds with defined folding properties represents a central challenge in chemical research. Proteins are natural scaffolds defined by a hierarchy of structural complexity and have evolved to manifest unique functional characteristics; for example, molecular recognition capabilities that facilitate the binding of target molecules with high affinity and selectivity. Utilizing these features, proteins have been used as a starting point for the design of synthetic foldamers and enhanced biocatalysts, as well as bioactive reagents in drug discovery. In this account, we describe the strategies used in our group to stabilize protein folds, ranging from the constraint of bioactive peptide conformations to chemical protein engineering. We discuss the evolution of peptides into peptidomimetics to inhibit protein–protein and protein–nucleic acid interactions, and the selective chemical modification of proteins to enhance their properties for biotechnological applications. The reported peptide- and proteomimetic structures cover a broad range of molecular sizes and they highlight the importance of structure stabilization for the design of functional biomimetics.1 Introduction2 Constraining the Conformation of Peptides3 Peptide-Based Covalent Protein Modifiers4 Chemical Protein Engineering5 Conclusions

N-(Difluoropropenyl)amides/amines are an important class of fluorinated compounds. Here, we report an efficient method for synthesizing these compounds without the use of transition metals. Under simple base-promoted conditions, 3-bromo-3,3-difluoroprop-1-ene reacts with N-methylanilines or N-arylacrylamides, with the elimination of one molecule of HBr, to give the target compound. Another efficient method for synthesizing difluoroalkenes is the reaction of 2-bromo-3,3,3-trifluoroprop-1-ene with indole or its analogues.

The catalytic intermolecular cyclization of thiophenols with allylic alcohols in the presence of bismuth triflate afforded the corresponding thiochromane derivatives in a one-pot reaction. The Bi(OTf)3-catalyzed reaction was also applied to the intermolecular cyclization of diaryl disulfides with 3-methylbut-2-en-1-ol to produce the corresponding thiochromanes.

A convergent approach to the forskolin skeleton is described. Assembly of a simplified tricyclic framework is achieved in a single step via the dihydropyrone Diels–Alder reaction. Selective manipulation of the resulting cycloadduct, in conjunction with an unusual equilibration of the C8 stereocenter, provides access to scaffolds that differ in relative stereochemistry at both the A/B and B/C ring junctions.

Hydrazine and its derivatives have served as a conventional bipropellant fuel for several decades. However, their extremely acute toxicity and carcinogenicity, high volatility, and environmental impact have attracted significant attention. In order to synthesize green bipropellant fuels with high density, high specific impulse, and good thermal stability, three novel N-alkyl-1,2,4-triazole–borane complexes were successfully synthesized by reacting alkylated 1,2,4-triazole coordinated with sodium borohydride in the presence of ammonium sulfate. During the droplet test with white fuming nitric acid, there was a relatively short ignition delay time of 98 ms. Additionally, these hypergolic fuels possessed a high density exceeding 1.10 g cm–3, and the specific impulse is ranging from 187 to 199 s, and the highest decomposition temperature reaches 153.4 °C. These results demonstrate their great potential as hypergolic fuels or hypergolic ionic liquid additives in the field of hypergolic materials.

A new and simple method to prepare 3-cinnamoyl-3-hydroxyphthalide derivatives from 2-hydroxy-3-methyl-1,4-naphthoquinone and substituted benzaldehydes was unexpectedly uncovered. The reaction was conveniently performed in DMSO at 100 °C with K3PO4 as a base and AlCl3 as a catalyst. We propose that the reaction proceeds by a cascade process involving nucleophilic addition followed by demethylation and rearrangement. The products were typically obtained in moderate to good yields. The highest yield (95%) was obtained when the reaction of 2-bromobenzaldehyde was performed for 24 hours. X-ray crystallography of the product derived from 2-fluorobenzaldehyde unequivocally confirmed the structure of the hydroxyphthalide derivatives.

A new type of functionalized BODIPY dyes is described. Utilizing an established procedure for Buchwald–Hartwig reactions, we have been able to convert α-chloro BODIPYs to α-azo-BODIPYs using phenylhydrazines. Optimization of the reaction conditions and variation of the BODIPY core and the phenylhydrazine were conducted. Absorption and emission spectra were recorded.

A palladium-catalyzed β-C(sp3)–H arylation of aliphatic ketones by using acetohydrazide as a transient directing group has been developed. The reaction proceeds through a less-favored [5,5]-bicyclic palladacycle intermediate and is promoted by a pyridine ligand.