Study of methylation reactions of 2-phenylquinazoline-4-tion with “soft” and “hard” methylation agents and determination of its biological activity

Alkylation reactions of 2-phenylquinazoline-4-thion with methylation agents “soft” (methyl iodide) and “hard” (dimethyl sulfate, methyltozylate) were studied. It was found that the reaction proceeds with the formation of alkyl products at the N3 - and S4 - reaction centers, depending on the methylation agent, solvent and temperature. This indicated the ambivalent nature of the 2-phenylquinazoline-4-tion anion. Prolongation of the reaction time leaded to the formation of a second isomeric product (VII). A slight increase in phenyl N3-product (VII) yield was noted when dimethyl sulfate and methylfolate were used as methylation agents. In non-polar proton-free solvent DMF and dipolar proton-free solvent acetonitrile, only N-methyl product (VII) was formed because of the reaction. An increase in the polarity of the solvent and the “hardness” of the methylation agent leads to an increase in the yield of N3 products.

‘Atypical Ugi’ tetrazoles

We surprisingly found that combining the substrates of Ugi tetrazole reaction gives two different constitutional isomeric Ugi products A and B. A is the expected classical Ugi products whereas B is an isomeric product (‘atypical Ugi’).

Pyridoxal-5′-phosphate as an oxygenase cofactor: Discovery of a carboxamide-forming, α-amino acid monooxygenase-decarboxylase

Capuramycins are antimycobacterial antibiotics that consist of a modified nucleoside named uridine-5′-carboxamide (CarU). Previous biochemical studies have revealed that CarU is derived from UMP, which is first converted to uridine-5′-aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5′-C-glycyluridine (GlyU), an unusual β–hydroxy-α-amino acid, in a reaction catalyzed by the pyridoxal-5′-phosphate (PLP)-dependent transaldolase CapH. The remaining steps that are necessary to furnish CarU include decarboxylation, O atom insertion, and oxidation. We demonstrate that Cap15, which has sequence similarity to proteins annotated as bacterial, PLP-dependent l-seryl-tRNA(Sec) selenium transferases, is the sole catalyst responsible for complete conversion of GlyU to CarU. Using a complementary panel of in vitro assays, Cap15 is shown to be dependent upon substrates O2 and (5′S,6′R)-GlyU, the latter of which was unexpected given that (5′S,6′S)-GlyU is the isomeric product of the transaldolase CapH. The two products of Cap15 are identified as the carboxamide-containing CarU and CO2. While known enzymes that catalyze this type of chemistry, namely α-amino acid 2-monooxygenase, utilize flavin adenine dinucleotide as the redox cofactor, Cap15 remarkably requires only PLP. Furthermore, Cap15 does not produce hydrogen peroxide and is shown to directly incorporate a single O atom from O2 into the product CarU and thus is an authentic PLP-dependent monooxygenase. In addition to these unusual discoveries, Cap15 activity is revealed to be dependent upon the inclusion of phosphate. The biochemical characteristics along with initiatory mechanistic studies of Cap15 are reported, which has allowed us to assign Cap15 as a PLP-dependent (5′S,6′R)-GlyU:O2 monooxygenase-decarboxylase.

Development of a novel chiral palladacycle and its application in asymmetric hydrophosphination reaction

A novel chiral palladacycle promoted the asymmetric hydrophosphination reaction between diphenylphosphine and dimethyl acetylenedicarboxylate, affording only one stereo-isomeric product.

Synthetic approaches towards 5H-[1]benzopyrano[3,4-c]pyridin-5-ones

The construction of 5H-[1]benzopyrano[3,4-c]pyridin-5-ones 2 was achieved through the reaction of 1-aryl-3-(2-hydroxyphenyl)-2-propen-1-ones 1 with malononitrile in alcoholic KOH solution affording the compound 2 along with 2-alkoxy-4-amino-6-aryl-3,5-pyridinedicarbonitriles 3. Single crystal X-ray diffraction of 3e confirmed the established structure and excluded the formation of the isomeric product 4.