A Pd-catalyzed novel and efficient protocol has been developed for the direct functionalization of 2-phenyl-4H-benzo[d][1,3]oxazin-4-ones with α-oxo carboxylic acids resulting in 5H-benzo[4,5][1,3]oxazino [2,3-a]isoindole-5,11(6aH)-diones using (NH 4 ) 2 S 2 O 8 as effective oxidant and AgNO 3 as co-oxidant. All the explored substrates were found to be compatible for this transformation and delivered the corresponding desired products in moderate to excellent yields.

A highly efficient, single‐step, metal‐free synthetic approach to the synthesis of coumarin‐3‐carboxamides has been developed. The protocol employs tert‐butyl peroxybenzoate as a radical initiator to achieve the regioselective carboxamidation of coumarins at C‐3 in good‐to‐moderate yields. The established reaction protocol offers a wide substrate scope as it allows the use of both formamides as well as aldehydes as coupling partners with excellent regioselectivity. Furthermore, mechanistic investigations illustrate that the reaction proceeds by a free‐radical pathway.

Toluenes, aldehydes, and benzyl alcohols have been utilized in the radical‐induced direct functionalization of 4H‐benzo[d][1,3]oxazin‐4‐one derivatives by using a palladium‐catalyzed C–H activation strategy. The stability, low toxicity, and ease of access to toluenes, aldehydes, and benzyl alcohols have made them suitable candidates for this transformation. The reaction proceeded smoothly with high functional group compatibility and afforded the desired products in moderate to good yields. Mechanistic investigations illustrate the radical pathway and highlight the importance of both catalyst and oxidant.

Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogues. AntiAspergillus activity was observed for an optically enriched derivative, (Ϫ)-S-2-(2=,4=-difluorophenyl)-1-hexyl-amino-3-(1ٞ,2ٞ,4ٞ)triazol-1ٞ-yl-propan-2-ol, which exhibits MIC values of 15.6 g/ml and 7.8 g/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 g/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against Aspergillus fumigatus (MIC, 1.63 g/ml).These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting antiAspergillus activity may have reduced toxicity. KEYWORDS chemoenzymatic synthesis, fluconazole, antifungal agents, AspergillusA spergillosis remains a significant threat to public health, and in spite of continuous efforts to improve timely diagnosis and clinical therapies, mortality caused by this disease remains unacceptably high (1, 2). Current therapeutic options for treating Aspergillus-induced disorders include antifungal agents such as polyenes, azoles, and echinocandins (3, 4). Thus, the discovery of new antifungal compounds remains important given the need to address the development of drug resistance in pathogenic fungi (5-7). One approach to accomplishing this goal is to prepare new derivatives of existing drugs with broad-spectrum activity and enhanced pharmacokinetic properties. As part of our ongoing efforts to use lipases (8-12), which catalyze reactions with high degrees of chemo-, regio-, and stereoselectivity in organic synthesis, we became interested in preparing new antifungals using biocatalysis.Fluconazole, introduced in 1990, is a bis-triazole antifungal drug which possesses

We are reporting a palladium catalyzed microwave assisted halogenation of 3-phenyl-2H-benzo[b][1,4]oxazine-2-ones.