Studies toward the total synthesis of dihydrolycolucine. Preparation of AB and CEF ring fragments.

A strategy for the synthesis of the lycopodium alkaloid dihydrolycolucine (1) has been investigated. Synthetic routes were developed based on N-acylpyridinium salt chemistry to prepare target fragments 3 and 4 that could ultimately converge to the natural product. Key reactions include IMDA cycloadditions and retro-Mannich ring-openings to form both the AB and the EF ring fragments. The ring C precursor was prepared using pyridine substitution and directed lithiation chemistry. A Suzuki cross-coupling of rings C and EF led to the CEF ring fragment. Initial attempts at closure of the seven-membered D ring were unsuccessful.

A fluorogenic 1,3-dipolar cycloaddition reaction of 3-azidocoumarins and acetylenes.

Copper(I)-catalyzed 1,3-dipolar cycloaddition reaction of nonfluorescent 3-azidocoumarins and terminal alkynes afforded intense fluorescent 1,2,3-triazole products. The mild condition of this reaction allowed us to construct a large library of pure fluorescent coumarin dyes. Since both azide and alkyne are quite inert to biological systems, this reaction has potential in bioconjugation and bioimaging applications. [reaction: see text]

Functionalised nanoparticles complexed with antibiotic efficiently kill MRSA and other bacteria.

Antibiotic-resistant bacterial infections are a vexing global health problem and have rendered ineffective many previously-used antibiotics. Here we demonstrate that antibiotic-linkage to surface-functionalized silica nanoparticles (sNP) significantly enhances their effectiveness against Escherichia coli, and Staphylococcus aureus, and even methicillin-resistant S. aureus (MRSA) strains that are resistant to most antibiotics. The commonly-used antibiotic penicillin-G (PenG) was complexed to dye-labeled sNPs (15 nm diameter) containing carboxyl groups located as either surface-functional groups, or on polymer-chains extending from surfaces. Both sNPs configurations efficiently killed bacteria, including MRSA strains. This suggests that activities of currently-ineffective antibiotics can be restored by nanoparticle-complexation and used to avert certain forms of antibiotic-resistance.