ß-Aryl-α-nitro-α,ß-enals as heterodienes and dienophiles.

As demonstrated with the ß-(2-furyl)-substituted analogue 1b, ß-aryl-α-nitro-α,ß-enals (1) behave as heterodienes against enamines and enol ethers using their enal unit (e.g., 1b → 12). α-Nitro-α,ß-enals can act as well as highly reactive dienophiles to render adducts endowed with nitrogenated quaternary centers (e.g., 1b → 15a). A hetero-Diels-Alder (HDA)/Diels-Alder (DA) sequence from 1b also proved feasible on serial treatment with ethyl vinyl ether and Danishefsky's diene (1b → 14).

A convergent approach to the dioxaadamantane core of (±)-tetrodotoxin.

A fully stereocontrolled 1,3-diol orthoesterification and a water-promoted intramolecular Henry addition, combined with the previously reported formal (3 + 3) annulation of α-nitro-α,ß-enals and 2,2-dimethyl-1,3-dioxan-5-one, provided for a short convergent pathway to the dioxaadamantane core of (±)-tetrodotoxin.

Enantioselective synthesis of protected nitrocyclohexitols with five stereocenters. Total synthesis of (+)-pancratistatin.

2-Methoxymethylpyrrolidine best performed, among several other proline derivatives, to control the enantioselective [3+3] annulation of ß-(hetero)aryl-α-nitro-α,ß-enals with commercial 2,2-dimethyl-1,3-dioxan-5-one, a procedure that renders highly oxygenated nitrocyclohexanes endowed with five new stereocenters. Use of this reaction allowed the development of a total synthesis of the antitumoral natural product (+)-pancratistatin; it also converted our previous racemic route to tetrodotoxin into an enantioselective one.

A formal [3+3]-annulation-based approach to pancratistatins: total synthesis of (±)-7-deoxy-pancratistatin and its 2-epi and 2,4-diepi analogues.

A full account is given for the total synthesis and the cytotoxic activity against the human lung tumoral cell line NCI-H460 of (±)-7-deoxy-pancratistatin and its 2-epi- and 2,4-diepi- unnatural analogues.