Organic & Biomolecular Chemistry最新文献

A practical, (E)-stereoselective synthesis of enamides and N-alkenyl heterocycles via cobalt-catalyzed positional isomerization is reported. The catalytic system consists of commercially available and bench-stable reagents. This method represents the first cobalt-catalyzed positional isomerization of N-allyl imides, sulfonamides, and nitrogen heterocycles (indoles, carbazoles and pyrroles). Mechanistic studies suggest a cobalt-hydride-type pathway.

We disclose a concise asymmetric synthesis of a naturally occurring RAL, neocosmosin A, from an appropriately substituted isocoumarin framework. The isocoumarin was constructed through Ag(I)-mediated 6-endo-dig cyclization of appropriately substituted 2-alkynylated benzoates. The same isocoumarin compound was synthetically manipulated to naturally occurring fusariumin in a diverted way. The total synthesis of another naturally occurring isocoumarin, penicipyran D, was also accomplished for the first time through Ag(I)-catalysed 6-endo-dig cyclization of penta-substituted 2-alkynylated benzoates. An improved synthesis of neocosmosin A was also established through a late-stage RCM reaction from an isocoumarin-derived advanced intermediate.

We present an effective Mn(III)-mediated approach for the C(sp³)-H functionalisation of N-aryl cyclic amines and their intramolecular coupling with a malonate partner. This methodology facilitates the efficient synthesis of six- to nine-membered benzo-fused tetrahydroquinoline and benzo[b]azepine dicarboxylates under mild conditions. The methodology avoids the use of harsh oxidants, with Mn(III) playing a key role in the oxidative annulation of N-aryl cyclic amines with malonates. It demonstrates high functional-group tolerance and operational simplicity. Overall, this approach provides a sustainable and practical alternative to traditional hydride-shift-based methods for accessing diverse benzo-fused aza-heterocycles.

This review article presents recent advances relating to the use of nanostructured catalysts in the construction of drug-like small hybrid molecules with structural diversity and molecular complexity incorporating medicinally privileged heterocyclic substructures. The nanocatalyzed synthetic methods and reaction mechanisms involving the facilitation of reactions with the interaction of reacting molecules with nanostructured catalysts have also been included. The nanocatalyzed reactions will play a significant role in the design and synthesis of potential pharmaceutical products of structural complexity with desired activity, with fused privileged heterocyclic substructures in their structures. Moreover, the nanocatalyzed synthetic methods are environmentally sustainable and will provide access to a diverse range of natural product mimetic scaffolds through combinatorial chemistry under environmentally sustainable reaction conditions. The present review article will contribute substantially, not only to organic synthesis, catalysis and materials science but also to pharmaceutical and medicinal chemistry, including drug discovery research, in exploring future opportunities in medicinal chemistry.

Direct α-C(sp³)-H arylation of 4-aminopyrazolones involving arynes, enabled by dual phase-transfer catalysis and ultraviolet irradiation, has been developed. The dual phase-transfer catalytic pathway powered by triaminocyclopropenium salts gave rise to the generation of structurally diverse 4-amino-4-arylpyrazolones in moderate to excellent yields, while the photochemical protocol furnished the products in moderate yields. Notably, these products are tentatively proposed as candidates for carbamate pesticides based on the preliminary structural analysis. The synthetic potentials of the methods were shown by gram-scale reactions, and the possibilities for greater structural diversity of the product were highlighted by derivatizations. The results of control experiments indicated that the timely capture of the transient arynes by the activated 4-aminopyrazolone nucleophiles is the key to the success of the reactions.

Through a very efficient, step-economical (only 4 steps) and diastereoselective-chemoselective procedure, bio-based levoglucosenone has been converted into a versatile azide, which may be regarded as a synthetic equivalent of a 6-amino-6-deoxysugar. This procedure involves: (a) reduction of the ketone of LGO; (b) opening of the 1,6-anhydro moiety with acetic anhydride and a protic acid to give a triacetate; (c) biocatalytic deacetylation of the primary alcohol; (d) substitution of the alcohol with the azide. The overall yield from LGO is 59%. This azide has been employed in two diversity-generating protocols: Huisgen-Sharpless 1,3-dipolar cycloaddition with alkynes (also derived from bio-based phenols), and the Ugi multicomponent reaction. Furthermore, the double bond has been dihydroxylated with nearly complete diastereoselection both at the azide level or on the triazoles derived from Huisgen cycloadditions, furnishing compounds with the rare D-altro configuration. The chemistry described in this work may help in devising synthetic applications of levoglucosenone, a densely functionalised product of pyrolysis of lignocellulosic matter.

The biocatalytic sulfoxidation of heterobiaryl indole- and pyrrole-based sulfides was investigated using unspecific peroxygenases (UPOs) and Baeyer-Villiger monooxygenases (BVMOs) as complementary oxidative biocatalysts. Among the UPOs tested, only the UPO from Marasmius rotula showed outstanding catalytic efficiency, reaching up to 99% conversion at substrate concentrations as high as 60 mM, with excellent chemoselectivity toward sulfoxides (>90%), albeit with moderate enantioselectivities (17-64% ee). In contrast, screening of a panel of BVMOs revealed superior stereochemical control: TmCHMO enabled the sulfoxidation of indole-based sulfides with enantioselectivities up to 94% ee, while OTEMO proved particularly effective for pyrrole-based substrates, affording sulfoxides in up to 90% ee. Reaction parameters such as temperature, pH, cosolvent and substrate loading have been optimized, allowing reaction rates of up to 22.4 mmol L^-1 h^-1 at 50 mM substrate concentration without enantioselectivity loss. Overall, pyrrole-based sulfides displayed higher optical purities than indole analogues under BVMO catalysis, whereas UPOs excelled in terms of productivity and operational simplicity. Selected BVMO- and UPO-catalyzed reactions were successfully scaled up, demonstrating the practical applicability of these biocatalytic systems. These results highlight the complementary strengths of UPOs and BVMOs for the efficient and selective synthesis of chiral heterobiaryl sulfoxides.

We disclose a gold-catalyzed conversion of unactivated β-ketopropargyl amines to polysubstituted pyrroles under mild, operationally simple conditions. A broad substituent survey reveals clear structure-reactivity trends. With application of the revealed protocol, leveraging the propargyl tolerance, combining AuCI₃ with TBACN telescopes the sequence to a bicyclic indolizine ring.

The migration and invasion of tumor cells are major contributors to mortality in malignant tumors. Studies have shown that matrix metalloproteinase 14 (MMP14) plays a crucial role in promoting tumor cell metastasis. Its activity can be suppressed by tissue inhibitor of metalloproteinases 2 (TIMP2), which acts as a natural inhibitor. However, the development of MMP14 inhibitors for clinical use has been unsuccessful, partly due to the unclear mechanism of the interaction between TIMP2 and MMP14. In this work, we successfully obtained the N-terminal domain of TIMP2 (N-TIMP2) protein through a four-segment-three-ligation total chemical synthesis strategy and confirmed its correct refolding, thus providing a novel tool for elucidating the specific interaction mechanisms between N-TIMP2 and MMP14.

This review focuses on the effective application of ¹³C NMR characteristics of ¹³C-labeled heterocyclic compounds [chemical shifts of ¹³C-labeled carbon, analysis of direct and long-range ¹³C-¹³C coupling constants (J_CC)] for structural elucidation, and for determining mechanisms and transformation pathways in various azoles, azines and N-heterocyclic carbenes. Moreover, this review outlines methods for incorporating ¹³C isotopes into structures of different heterocyclic compounds.