Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• addition; keramaphidin B; nitro-Mannich lactamisation cascade; Introduction Keramaphidin B (1) is a marine alkaloid first isolated by Kobayashi in 1994 from the Okinawan marine sponge Amphimedon sp and has been shown to be cytotoxic against KB human epidermoid carcinoma cells (IC50 0.28 μg/mL) and P388

• turn be synthesised by an aminolysis/oxidation/olefination sequence of the terminal alcohol 6, following traceless nitro group removal. 5-Nitropiperidin-2-one 6 in turn could be accessed by a nitro-Mannich lactamisation cascade reaction between Michael adduct 7, formaldehyde and a suitable primary

• favoured attack at the more reactive δ-lactone carbonyl instead of that of the methyl ester. Pleasingly, this was indeed realised at the next stage; performing a nitro-Mannich lactamisation cascade on 13 with formaldehyde and butylamine in methanol afforded lactam 15 in 63% yield, possessing the

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• /bjoc.8.64 Abstract A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot

• reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of

• ]. Arguably the most general route employs cycloadditions and subsequent manipulation of the partially unsaturated ring system [49][50][51][52][53]. We believed a powerful entry to piperidine rings and related heterocyclic structures could employ a nitro-Mannich/lactamisation cascade of γ-nitro ester starting