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Jhonson Polyene Cyclization
This reaction is a paradigm in the bioinspired pathways synthesis, and its main utility is the formation of polycyclic compoundsfrom polyene systems. Its name is due to Professor William S. Jhonson from Stanford University who published in 1967 the paper Non Enzymic Biogenetic- like Olefinic Cyclizations This idea arose from the biosyntesis of Lanosterol, a tetracyclic triterpenoid steroid precursor of cholesterol, that is synthesized from acetyl conezime A. The precursor of Lanosterol is squalene 2,3-epoxide. The enzyme squalene-2,3-epoxide cyclase catalyzed the transformation. .

As can be seen in the scheme a polycyclic compound is generated from a polyene system. During the biosynthesis also some carbons shift occur but this is out of the discussion. .

It is remarkable that squalene-2,3-epoxide does not have any chiral center, and the Lanosterol has seven. This means that 128 different stereoisomers are possible, but only one stereoisomer is produced. In here the double bonds acts as nucleophiles

Jhonson polyene cyclazation makes possible that systems like this may be synthetized out of the enzyme environment. To do this, it is necessary to form a carbenium near to a double bond. This is done by the addition of the proper acid (sulfuric acid, triifluoroacetic acid, hydrofluoric acid, tin tetrachlorine, etc) to a therminal π bond. There are several factors that are involved to achieve this in high yields and in a clean way without the generation of byproducts, mainly polymeric material.


 * The formation of the carbenium in the proximity of a double bond. This pathaway is a carbenium rearrangement


 * A proper orientation of the molecule previous to the reaction. It is necessary that the orientation of the double bonds adopt a steroideal conformation with all-trans alkenes, in order to produce the more stable trans-fused ring..


 * The cyclization process should be stopped. It is important to terminate the cationic generation to minimize the side reactions.

Some examples are provided bellow

Using a Bronsted acid

Using a lewis acid

Jhonson, W.S. Acc. Chem. Res. 1968,1, 1 William S. Johnson, Daniel Berner, Donald J. Dumas, Pieter J. R. Nederlof, John Welch J. Am. Chem. Soc., 1982, 104 (12), pp 3508–3510 DOI: 10.1021/ja00376a046 Voet D, Voet JG. 1990. Biochemistry. New York: J Wiley. 1223 p Gilbert Stork, A. W. Burgstahler J. Am. Chem. Soc., 1955, 77 (19), pp 5068–5077