Synthesis of bicyclic carbamates as precursors of Sedum alkaloid derivatives

Synthesis of a N-Boc-protected piperidin-2-yl phosphine oxide starting from piperidine in three steps, followed by olefination using a variety of α,β-unsaturated aldehydes resulted in tert-butyl 2-(2′-alkenylidene)piperidine-1-carboxylates in high yields. A novel type of intramolecular cyclization of these enamides furnished a new family of 3-alkyl-4,6,7,8-tetrahydro-3H-pyrido[1,2-c][1,3]oxazin-1-ones as useful substrates for further elaboration. Subsequent reduction of these unsaturated bicyclic carbamates using NaCNBH₃ or NaBH₄ afforded the corresponding 3-alkylhexahydropyrido[1,2-c][1,3]oxazin-1-ones in a highly stereoselective way. Reductive ring opening of two representatives furnished the corresponding Sedum alkaloid derivatives in good yields.     

Alaninyl variants of the marine natural product halocyamine A and their antibacterial properties

In an effort to explore the antibacterial potential of the marine natural product halocyamine A, a series of analogues including desbromo and alanine-substituted variants were synthesised and evaluated for biological activity against a panel of Gram-positive and –negative bacteria. The analogues were synthesised by a combination of solid-phase peptide synthesis and ruthenium complex/ytterbium triflate catalysed hydroamidation chemistry. Single alanine substitutions ([Ala¹]-halocyamine A and [Ala²]-halocyamine A) gave only modest increases in activity towards Gram-positive bacteria, while di-alaninyl variants exhibited more potent activity with MIC values of 12.5–50?μM towards the Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis. A lipophilic trityl-protected intermediate of [Ala²]-halocyamine was the most active against the Gram-negative bacterium Escherichia coli.     

AgOTf-catalyzed reaction of sulfonyl hydrazones with ynamides led to stereoselective synthesis of α-amino alkenyl-substituted hydrazone derivatives

A novel method for the synthesis of α-amino alkenyl-substituted hydrazone derivatives was disclosed through silver-catalyzed reaction of sulfonyl hydrazones with ynamides. The present method features mild conditions, high stereoselectivity and good yields. The proposed mechanism involves silver-mediated generation of a keteniminium ion intermediate to facilitate the stereoselective addition of hydrazones in the presence of K₂CO₃, while pyrazole ring could not be constructed under the current conditions.