No abstract

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure–antibacterial activity relationship of these cationic polymers was investigated against E. coli and S. aureus, including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB35/T57) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB33/T56). Furthermore, mPB35/T57 with appropriate mole fraction of alkyl side chains (f alkyl = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both E. coli (MIC = 8 μg/mL, selectivity > 250) and S. aureus (MIC = 4 μg/mL, selectivity > 500). More importantly, mPB35/T57 could effectively eradicate E. coli biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB35/T57 provided valuable information for improving the antibacterial activity of cationic polymers.

A bifunctional squaramide-catalyzed reaction of pyrazolin-5-ones with o-quinone methides in situ generated from 2-(1-tosylalkyl)phenols has been successfully developed, providing a facile access to chiral pyrazolones with high enantioselectivities. In addition, the chiral spiropyrazolones with adjacent tertiary and quaternary stereogenic centers can also be obtained through cascade chlorination/cyclization of the chiral pyrazolones.

The direct regio- and enantioselective C6 functionalization of 2,3-disubstituted indoles with azadienes has been developed using chiral phosphoric acid as catalyst, providing a convenient approach to synthesize the optically active heterotriarylmethanes with excellent yields, broad substrate scope, and up to 98% ee. Mechanistic studies revealed that N-alkylation of 2,3-disubstituted indoles with azadienes would be reversible, and enantioselective C6 functionalization could be enabled.

The extension of racemization strategies of dynamic kinetic resolution in organic synthesis is a longstanding challenge, especially racemizing two or more stereogenic centers simultaneously. Through the combination of a palladium-catalyzed asymmetric allylic alkylation and a base-promoted retro-oxa-Michael addition, a dynamic kinetic resolution of 2,3-disubstituted flavonoids was achieved with up to 99% enantioselectivities, and two contiguous stereocenters (including a quaternary stereogenic center) were constructed simultaneously on the nucleophile flavonoids. The key feature of the reaction was a base-promoted retro-oxa-Michael addition for fast racemization of two stereogenic centers on the nucleophiles, which can pave the way to developing asymmetric reactions of flavonoids through dynamic kinetic resolution.

Penicisteckins A–D (1–4), two pairs of atropodiastereomeric biaryl-type hetero- and homodimeric bis-isochromans with 7,5′- and 7,7′-linkages and a pair of atropodiastereomeric 2-(isochroman-5-yl)-1,4-benzoquinone derivatives [penicisteckins E (5) and F (6)], were isolated from the Penicillium steckii HNNU-5B18. Their structures including the absolute configuration were determined by extensive spectroscopic and single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Both the bis-isochromans and the isochroman/1,4-benzoquinone conjugates represent novel biaryl scaffolds containing both central and axial chirality elements. The monomer anserinone B (8) exhibited potent antibacterial activities against Staphylococcus aureus ATCC 29213 and methicillin-resistant Staphylococcus aureus with minimal inhibition concentration values ranging from 2 to 8 μg mL–1. Plausible biosynthetic pathways of 1–6 are proposed, which suggest how the absolute configurations of the isolates were established during the biosynthetic scheme.

Compared with the well-established asymmetric Pictet−Spengler reactions on the pyrrole ring of indoles, the catalytic asymmetric Pictet−Spengler reaction on the benzene ring of indoles has been rarely studied. Herein the C6-selective Pictet− Spengler reactions of indoles have been realized by employing 2-(1H-indol-7-yl)anilines and isatins in the presence of chiral phosphoric acid, affording novel polycyclic indole derivatives bearing spiro quaternary stereocenters in excellent yields with excellent enantioselectivities. This reaction could be conducted on the gram scale without any loss of activity or enantioselectivity.

Improving siRNA delivery efficiency often encounters a dilemma with poor or decreased biocompatibility for polycationic micelles.