Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products.

The formal syntheses of N-methylwelwitindolinone C isothiocyanate (4) and several other welwitindolinones 5-8 were achieved by the independent synthesis of 79. The synthesis featured a Lewis acid-mediated coupling between a heteroaryl carbinol and bis-TMS enol ether, an intramolecular enolate arylation, and an unprecedented intramolecular allylic alkylation of a γ-acyloxyenone.

Expedient Synthesis of SMAMPs via Click Chemistry.

A novel series of synthetic mimics of antimicrobial peptides (SMAMPs) containing triazole linkers were assembled using click chemistry. While only moderately active in buffer alone, an increase in antimicrobial activity against Staphylococcus aureus and Escherichia coli was observed when these SMAMPs were administered in the presence of mouse serum. One compound had minimum inhibitory concentrations (MICs) of 0.39 µg/mL and 6.25 µg/mL, respectively, and an HC50 of 693 µg/mL. These values compared favorably to peptide-based antimicrobials. A correlation between the net positive charge and SMAMP antimicrobial activity was observed. The triazole linker, an amide surrogate, was found to provide better antimicrobial activity against both S. aureus and E. coli when compared to other analogues.

Formal syntheses of naturally occurring welwitindolinones.

The formal syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone C isonitrile, N-methylwelwitindolinone D isonitrile, 3-hydroxy-N-methylwelwitindolinone C isothiocyanate, and 3-hydroxy-N-methylwelwitindolinone C isonitrile are reported. The synthesis features several novel processes, including a Lewis acid mediated coupling between a benzylic-type heteroaromatic alcohol and a highly functionalized silyl ketene acetal, an intramolecular enolate arylation, and a regioselective, Pd(0)-catalyzed π-allylic cyclization of a γ-benzoyloxy enone moiety that is revealed by unmasking a furan ring.

Synthesis of ß-Heteroaryl Propionates via Trapping of Carbocations with π-Nucleophiles.

A variety of heterocyclic alcohols and acetates were coupled with silyl ketene acetals and other π-nucleophiles in the presence of trimethylsilyl trifluoromethanesulfonate to provide an array of substituted ß-heteroaryl propionates, including those with contiguous quaternary centers, as well as vinylogs thereof. This reaction also proceeds with high diastereoselectivity when the π-nucleophile bears a chiral auxiliary.