Regioselective synthesis of 2,3-disubstituted 1-alkyl pyrrolo[2,3-b] quinoxalines through palladium-catalyzed Heck reaction of chalcones and evaluation of their anti-bacterial activities

The regioselective synthesis of 1-alkyl-2-aryl-3-acyl pyrrolo[2,3-b]quinoxalines through palladium-catalyzed Heck coupling reaction/heteroannulation was reported. The reaction of N-alkyl/benzyl-3-chloroquinoxaline-2-amines with chalcones catalyzed by Pd(OAc)₂ in the presence of KO^tBu, as the base, in DMSO afforded the desired products in good-to-high yields. The MIC and MBC determinations revealed that these compounds could be used in the future research works for the development of antibiotics.     

Diastereoselective addition of α-substituted α-amino-H-phosphinates to imines using Yb(OTf)3 as an efficient Lewis acid catalyst

Diastereoselective addition of α-substituted α-amino-H-phosphinates to imines is described. Among Lewis acids, Yb(OTf)₃ was found to be the best catalyst. α,α′-Diaminophosphinic derivatives were obtained with de's ranging from 10 to 95% in the presence of Yb(OTf)₃ as an efficient Lewis acid catalyst. The reaction proceeded with retention of configuration at the phosphorus atom.     

Catalyst-free Petasis-type reaction: Three-component decarboxylative coupling of boronic acids with proline and salicylaldehyde for the synthesis of alkylaminophenols

A simple method is reported for the synthesis of alkylaminophenols in moderate to good yields via a three-component, catalyst-free decarboxylative coupling of proline with salicylaldehyde and boronic acids.     

Synthesis of acyclic nucleotide analogues possessing a difluoromethylene phosphonyl group at the side chain

A synthetic approach to a new type of acyclic nucleotide analogues 8 and 9 was examined. The design was based on acyclic modification of MRS 2179, a P2Y₁-antagonist, and replacement of one of two phosphate groups characterized by MRS 2179 with an isosteric difluoromethylenephosphonyl group. The nucleotide analogues 8 and 9 were enantio-divergently prepared as their ester-protecting derivatives from a highly differentiated 1,5-pentanediol derivative possessing a difluoromethylenephosphonyl group at the 3-position.     

Molecular organogel-forming porphyrin derivative with hydrophobic l-glutamide

An l-glutamide-functionalized tetraphenylporphyrin derivative has been newly synthesized. This can dissolve in various organic solvents to form nanofibrillar aggregates with both right-handed and left-handed chiral stacking structures among the porphyrin rings. It is also discussed on thermotropic and lyotropic phase transitions between gel and sol states.     

Odd-even effect of repeating aminoethylene units in the side chain of N-substituted polyaspartamides on gene transfection profiles

A series of the N-substituted polyaspartamides possessing repeating aminoethylene units in the side chain was prepared in this study to identify polyplexes with effective endosomal escape and low cytotoxicity. All cationic N-substituted polyaspartamides showed appreciably lower cytotoxicity than that of commercial transfection reagents. Interestingly, a distinctive odd-even effect of the repeating aminoethylene units in the polymer side chain on the efficiencies of endosomal escape and transfection to several cell lines was observed. The polyplexes from the polymers with an even number of repeating aminoethylene units (PA-Es) achieved an order of magnitude higher transfection efficiency, without marked cytotoxicity, than those of the polymers with an odd number of repeating aminoethylene units (PA-Os). This odd-even effect agreed well with the buffering capacity of these polymers as well as their capability to disrupt membrane integrity selectively at endosomal pH, leading to highly effective endosomal escape of the PA-E polyplexes. Furthermore, the formation of a polyvalent charged array with precise spacing between protonated amino groups in the polymer side chain was shown to be essential for effective disruption of the endosomal membrane, thus facilitating transport of the polyplex into the cytoplasm. These data provide useful knowledge for designing polycations to construct safe and efficient nonviral gene carriers.