Gold(I)-Catalyzed Tandem Synthesis of Polycyclic Dihydroquinazolinones

A gold-catalyzed cascade process for the synthesis of dihydroquinazolinone scaffolds was developed. A series of gold catalysts were screened for this tandem transformation, and the (PPh3)AuCl/AgOTf catalyst combination was found to be the best catalyst system. This method is characterized by good yields, high regioselectivity, and broad substrate scope. This method is also applicable to the synthesis of tetracyclic dihydroquinazolinones and seven-membered ring-fused dihydroquinazolinones.

New pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one hybrids linked to arene units: synthesis of potential MRSA, VRE, and COX-2 inhibitors

In the current study, we reported the tandem synthesis of two series of arene-linked pyrimidinone hybrids with related fused thieno[2,3-b]pyridine moiety. The target hybrids were prepared, in moderate to excellent yields, by the reaction of a ternary mixture of the appropriate of 3-aminothieno[2,3-b]pyridine-2-carboxylate, DMF-DMA, and a series of aryl amines in dioxane at 110 °C for 8 h. The antibacterial activity of the new hybrids was estimated against six susceptible ATCC strains. Hybrids 5g and 7g, linked to a sulfonamide unit, showed the best efficacy against S. aureus and E. faecalis strains with minimum inhibitory concentration (MIC) values of 1.7–1.8 μM, which exceed ciprofloxacin. Furthermore, some of new hybrids were examined as potential inhibitors of four different MRSA and VRE strains. Hybrids 5g and 7g demonstrated more potent efficacy than linezolid against MRSA strains with MIC values of 3.6/3.4 and 1.8/1.7 μM against ATCC:33591 and ATCC:43300 strains, respectively. The prior hybrids displayed a comparable efficacy with linezolid against VRE strains with MIC values of 7.3/6.9 and 3.6/3.4 μM against ATCC:51299 and ATCC:51575 strains, respectively. Additionally, some of the new hybrids were examined as potential COX-2 inhibitors using the reference celecoxib (IC50 of 0.117 µM). Hybrid 7g revealed more potent inhibitory efficacy than celecoxib with IC50 of 0.112 µM, whereas hybrid 5g showed almost inhibitory activity equivalent to celecoxib with IC50 of 0.121 µM. Molecular docking was performed to predict the possible binding interactions between hybrids 5g and 7g with the target COX-2 enzyme.

New cleavable spacers for tandem synthesis of multiple oligonucleotides

In solid-phase oligonucleotide synthesis, a single oligonucleotide is generally acquired from a column loaded with a specific solid support. Herein, we have developed new cleavable spacer (CS) derivatives for tandem synthesis of multiple oligonucleotides on a single column. Four CS analogs were designed, synthesized, and inserted between two oligonucleotide sequences using an automated oligonucleotide synthesizer. The CS derivatives bearing a cyclic cis-1,2-diol exhibited efficient release of the two oligonucleotides under commonly employed basic conditions of aqueous ammonia. Among the CS analogues, it was found that CS with a robust structure can potentially be applied as a spacer molecule in the tandem synthesis of multiple oligonucleotides in a single sequence.