mardi 17 avril 2007

Synthesis of the camptothecin core

The post of today deals with the synthesis of the camptothecin core.

This synthesis described by Fortunak in 1996, has an intramolecular Diels-Alder [4+2] cycloaddition as key step between an unactivated alkyne and a imidate generated
in situ by action of Me3OBF4 on a N-arylamide.

This synthesis has been recently improved by Yao et al. using a mixture of Ph
3PO and Tf2O (2:1) instead of Me3OBF4, by this methodology a wide range of tetracyclic "camptothecin-like" molecules has been synthesized.

Organic Letters, ASAP, April 14, 2007

samedi 14 avril 2007

Synthesis of methyl 5-methylpicolinate or methyl 5-methylpyridine-2-carboxylate

The post of today concerns a very beautiful synthesis of the pyridine ring, and more precisely of methyl pyridine-2-carboxylate. This synthesis has been described by Danheiser et al. and with a "imination" of the Meldrum's acid with sodium nitrite (NaNO2) followed by tosylation (TosCl). The tosylimine obtained has been engaged in aluminium catalyzed (Et2AlCl) Diels-Alder reaction with isoprene as diene (of course other dienes can be used, see reference), the bicyclic spiro compound has been treated by sodium methylate, N-chlorosuccinimide in a THF/MeOH mixture to give the desired methyl 5-methylpyridinecarboxylate.

Ref: Organic Syntheses, Vol. 80, p.133 (2003).