Organic & Biomolecular Chemistry最新文献

C-2 Fluorinated castanospermines have been synthesized from a well-protected aldehyde precursor and evaluated as glycosidase inhibitors in comparison with castanospermine, 1-epi-castanospermine and C-1 fluorinated castanospermines. While C-1 fluorinated castanospermines lose nearly all the glycosidase inhibition shown by castanospermine and 1-epi-castanospermine, C-2 fluorinated derivatives of castanospermine were found to be potent and highly specific α-glucosidase inhibitors; however, the C-2 fluorinated 1-epi-castanospermines showed a sharp decrease in inhibition towards all tested enzymes. Docking calculations attributed the sharp decrease of glycosidase inhibition of C-1 fluorinated castanospermines to the disappearance of hydrogen bonds between the original C-1 hydroxyls and residues Arg-526 and Asp-327. The retained potent and specific α-glucosidase inhibition of C-2 fluorinated castanospermines was achieved by the fluorine-induced reestablishment of the docking mode in the active site; and the sharply decreased inhibition of C-2 fluorinated 1-epi-castanospermines can be attributed to obvious binding distorsion and disappearance of the hydrogen bonding with residues His-600 and Arg-526. Reliability of the docking results was evaluated by Molecular Dynamics (MD) simulation, which provided necessary calibrations to the calculation results. The interaction modes of fluorine reported herein are different from the "mimic effect" of fluorine for hydrogen, offering insights and extending our previous work on fluorinated casuarines. These results would be important for the development of castanospermine-related drug candidates for the treatment of diabetes, viral infections and Pompe disease.

A Cu(I)-Pybox-diPh catalyzed enantioselective [3 + 2] cycloaddition reaction of CF₃-substituted tertiary propargylic esters as C2-bis-electrophiles with cyclic 1,3-dicarbonyl compounds as C,O-bis-nucleophiles has been reported. The methodology furnishes a variety of optically active oxygen heterocycles containing a CF₃-substituted quaternary stereocenter in good yields and enantioselectivities. Moreover, the scalability of the reaction and transformations of chiral compounds into their derivatives demonstrated the synthetic and practical relevance of the approach.

Two compact far-red cationic benzoquinone diimine dyes were synthesized, having molecular weights lower than 400 or 300 Da and featuring light absorption properties centered around 700 nm. Their redox and optical properties were investigated experimentally, alongside theoretical studies of their structural and excited-state characteristics.

Polyene cyclization has emerged as a powerful tool for increasing molecular complexity. In recent years, gold-catalyzed polyene cyclization reactions have made significant progress, particularly in the total synthesis of complex polycyclic natural products with biological activity. Simultaneously constructing multiple stereogenic centers and core polycyclic ring structures, especially through the catalytic asymmetric reactions, greatly improves the efficiency of natural product synthesis. The alkynyl functional group can initiate polyene cyclization reactions, and the resulting vinyl moiety can facilitate subsequent functional group transformations, making it highly versatile. This review mainly summarizes the synthetic methodology of polyene cyclization reactions based on the underlying mechanisms and their applications in the total synthesis of polycyclic natural products.

A scalable and diastereoselective synthesis of four icafolin-methyl plant metabolites bearing a 4-hydroxy-2-isoxazoline scaffold is described. The key to success was a practical cyclocondensation of 3,5-difluoronitromethane with α-formylbutyrolactone and a multigram-scale Grieco dehydration protocol, performed in continuous flow.

A NRPKS gene cluster cic in Aspergillus nidulans was activated by overexpression of the pathway-specific transcriptional factor CicD. Large-scale fermentation and chemical investigation of the engineered strain A. nidulans A1145/cicD led to the discovery of two new isoindolone-amino acid adducts, isoleucylcichorine (1) and leucylcichorine (2), along with three known derivatives. The structures of the new compounds were clearly determined by nuclear magnetic resonance (NMR) analysis, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. This study revealed that the overexpression of the pathway-specific transcriptional factor represents a promising approach for the discovery of new natural products in fungi.

We have developed a visible-light-mediated three-component tandem reaction of aromatic aldehydes with acrylates using a Hantzsch ester as the hydrogen atom transfer reagent, generating diethyl pentanedioate products in a one-pot synthesis. The reaction facilitates direct formation of acyl groups from the corresponding aldehydes, which are subsequently coupled successively to two molecules of acrylate in a Giese addition.

A palladium(II)/Lewis acid-catalyzed C-H olefination of 2-benzamidopyridine 1-oxide with acrylates followed by intramolecular aza-Michael addition for the synthesis of isoindolinones has been developed. The use of a heterobimetallic Pd(II)/Cu(II) catalyst enhances the efficiency of the reaction, enabling the synthesis of a potential anti-sedative agent.

A selective temperature and steric hindrance-regulated method for nucleophilic substitution or Favorskii rearrangement reactions of 2-aryl-2-bromo-cycloketones with aliphatic amines has been developed to prepare ketamine derivatives and 2-aryl-cycloketone-1-carboxamides. In the presence of secondary amines or ortho-substituted 2-aryl-2-bromocycloketones, steric hindrance directs the Favorskii rearrangement to occur. Conversely, with primary amines, the product ratio of nucleophilic substitution to Favorskii rearrangement is temperature-dependent, with higher temperatures favoring the Favorskii rearrangement. At lower temperatures (-25 °C or below), nucleophilic substitution predominates, yielding ketamine derivatives in yields of 60% to 85%. This method effectively utilizes temperature and steric hindrance to control the reaction pathway and optimize product formation.

A cascade reaction utilizing benzylamines and two equivalents of isatylidene malononitriles in alcohols effectively produces dispiro[indoline-cyclopentapyrimidine-indoline] structures with high chemical yields, reaching up to 93%, and remarkable diastereoselectivity (dr ≥ 19 : 1). This one-pot synthesis, facilitated by nucleophilic solvent participation, provides a practical method for obtaining multicyclic dispiro-cyclopentene-linked bisoxindoles, generating four chiral centers in a diastereoselective fashion. The practical applicability of this approach was further illustrated through a gram-scale experiment, and the final product's structure was confirmed via single-crystal X-ray analysis, affirming the successful synthesis of the target compounds.