Chemistry Unprotected

The ideal total synthesis of a natural product would proceed in one step and in 100% yield from commercially available starting material- this dream is increasingly driving natural product synthesis as a science.

Dr. Phil Baran and colleagues at Scripps Institute, La Jolla, California, promises to generate natural products in much larger amounts than conventional methods, making biological testing much easier for drug discovery scientists. Most total syntheses make liberal use of protecting groups. Adding and removing protecting groups can add many steps to a synthesis, cutting overall yields drastically.

Baran's team have now made a collection of marine natural products without using a single protecting group. Instead, they take advantage of the intrinsic reactivity of the molecule's different functional groups.

Fig(-)-fisherindole to (+)- welwitindolinone.

The reactions were enatioselective and they made only the preferred mirror-image form, or enantiomer, of the molecule, instead of a racemic mixture containing equal amounts of both enantiomers. This methodology takes advantage of the intrinsic reactivity of the molecule's different functional groups.

Novel Reactions: Are anymore waiting to be Discovered?

Inspired by Barton's landmark total synthesis of Usnic acid, a method was devised by Baran for the direct oxidative coupling of indoles and pyrroles to a range of carbonyl compounds (Baran et al., J. Am. Chem. Soc. 2007, 129, 12857-69).

When one examines the piece of work to which such a description has been applied, it often contains only a minor improvement on a well-known reaction or a new application of an old technique.