Claisen rearrangement over the past nine decades.

Stereocontrol in the synthesis of acyclic systems: applications to natural product synthesis

Natural products have been a rich source of agents of value in medicine. They have also inspired, at various levels, the fashioning of nonnatural agents of pharmaceutical import. Hitherto, these nonnatural derivatives have been primarily synthesized by manipulating the natural product. As a consequence of major innovations in the subscience of synthetic methodology, the capacity of synthesis to deal with molecules of considerable complexity has increased dramatically. In this paper, we show by example some total syntheses which draw from strategy-enabling advances in methodology. Moreover, we show how these capabilities can be used to discover and develop new agents of potential pharmaceutical value without recourse to the natural product itself.

Small molecule natural products in the discovery of therapeutic agents: the synthesis connection.

The synthesis of insect sex phermones

Stereo- and regiochemistry of the Claisen rearrangement: applications to natural products synthesis

Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene

Olefinic ketal Claisen reaction. Facile route to juvenile hormone

A short, highly stereoselective (over 97%) synthesis of all-trans squalene is described Starting with succinaldehyde, a tetraenedichlorodione having the complete squalene skeleton with the four internal trans olefinic bonds has been developed in four steps involving a sequence of two double Claisen rearrangements Three simple operations convert this intermediate into squalene

Application of the Chloro Ketal Claisen Reaction to the Total Synthesis of Squalene

A very short synthesis of the racemic cecropia hormone has been realized, utilizing a Claisen reaction. Methyl 6-hydroxy-3-methyl-7-methylene-2-trans-nonenoate, on treatment with the dimethyl ketal of 3-chloro-3-methyl-2-pentanone and a catalytic amount of 2,4-dinitrophenol, is transformed directly into methyl 11-chloro-3,11-dimethyl-7-ethyl-10-oxo-2-trans, 6-trans-tridecadienoate. Selective reduction gives a mixture of diastereoisomeric chlorohydrins separable by chromatography. The predominant threo-chlorohydrin is transformed into the juvenile hormone.

A Short Stereoselective Synthesis of Cecropia Juvenile Hormone

The experimental details are reported for a previously described synthesis of squalene.

Lucius Werthemann

Papers

Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene

Olefinic ketal Claisen reaction. Facile route to juvenile hormone

Application of the Chloro Ketal Claisen Reaction to the Total Synthesis of Squalene

A Short Stereoselective Synthesis of Cecropia Juvenile Hormone

Application of the Chloro Ketal Claisen Reaction to the Total Synthesis of Squalene. Experimental Details