Organocatalyzed synthesis of biologically active compounds
The cross-aldol addition is one of the most important carbon-carbon bond forming reaction, both as synthetic and as biosynthetic reaction. Among the approaches to control the regio- and stereochemistry of the adducts, organocatalysis is a very promising feature, as it avoids the use of any metal. The regio- and stereochemistry of this reaction has been extensively studied, and very interesting results have been obtained when more then one stereogenic centre is formed. The best results were obtained with 10 mol% of H-D-Pro-L-β3-hPhg-OBn as catalyst. Following this approach, the first total synthesis of (R)-Convolutamydine A has been achieved by the organocatalytic addition of acetone to 4,6-dibromoisatin and the metal free cross-aldol addition of hydroxyacetone (HA) to p-nitro and m-nitrobenzaldehyde catalysed by three di- or tripeptides, all containing D-Pro in the N-terminal position has been studied.
Furthermore the synthesis of imidazolidin-2-one-4-carboxylate and of (tetrahydro)pyrimidin-2-one-5-carboxylate via an efficient modification of the Hofmann rearrangement has been achieved. In our approach, imidazolidin-2-ones-4-carboxylates and (tetrahydro)pyrimidin-2-one-5-carboxylates were obtained in a short time and under very mild conditions by reaction. PhI(OAc)2 was the source of iodine (III); this method proved to be quite general because it can be applied to both amino acids in the presence of several protecting groups.
- Gianluigi Luppi, Magda Monari, Rodrigo J. Corrêa, Flavio de A. Violante, Angelo C. Pinto, Bernard Kaptein, Quirinus B. Broxterman, Simon J. Garden, Claudia Tomasini – “The First Total Synthesis of (R)-Convolutamydine A”, Tetrahedron, 2006, 62, 12017–12024
- .Gaetano Angelici, Simone Contaldi, Sarah Lynn Green, Claudia Tomasini – “Synthesis of imidazolidin-2-one-4-carboxylate and of (tetrahydro)pyrimidin-2-one-5-carboxylate via an efficient modification of the Hofmann rearrangement”, Org. & Biomol. Chem., 2008, 6, 1849-1852