Johnson-Polyene Cyclization

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The Johnson-polyene cyclization , even biomimetic polyene cyclization called, is a named reaction of bioorganic chemistry . William Summer Johnson first reported this reaction in 1968 . In general, this is a cationic process for ring formation from alkenes . This reaction enables steroids such as testosterone or cholesterol to be synthesized.

Overview reaction

Johnson-polyene cyclization is a cationic ring formation process. Suitable initiators for the reaction are, for example, acetals , allyl alcohols or epoxides , since they can easily be converted into carbenium ions by protonation . This protonation then enables spontaneous ring formation. The following is an example of the reaction of an epoxide:

Overview reaction of the Johnson-polyene cyclization

When forming a ring, six rings are preferred. With only short reaction times, however, five-membered rings are also formed . In addition, ( E ) compounds are preferentially formed. For the reaction to be successful, it is important to stabilize the carbocation. In addition, a stable final state is important.

mechanism

The reaction mechanism is shown here only in a simplified manner in order to explain the general processes. A detailed mechanism can be found under Application.

simplified mechanism of Johnson-polyene cycling

First, the epoxy group is protonated. To do this, one electron from the oxygen lone pairs of electrons attacks the hydrogen atom 1 . The oxygen now has one electron too few, which is why a positive partial charge is formed. Due to the high instability of the positively partially charged oxygen, one of the electron pair bonds to the neighboring carbon atom folds by 2 . This creates a carbenium ion (3) . Since carbenium ions are not particularly stable either, the reactive double bond flips over. A six-membered ring molecule with a positive partial charge 4 forms . Because of this charge, a proton splits off and a double bond is formed. This is then rearranged in the ring, as this is the most stable connection 5 . This is a Wagner-Meerwein rearrangement .

application

With the help of this reaction, steroids can be synthesized. It is a biomimetic reaction, which means that the reaction is modeled on an enzymatic reaction in the body.

Representation of cholesterol by Johnson polyene cycling

The best-known example is the synthesis of cholesterol (3) from squalene-2,3-epoxide (1) , shown above, via the stable intermediate product lanosterol (2) . The first steps are analogous to the reaction mechanism shown in simplified form above. The last two steps lead to the products via several Wagner-Meerwein rearrangements. In nature , the last two steps are carried out by enzymes . Here the reaction is called squalene folding .

Individual evidence

  1. ↑ William Summer Johnson: Nonenzymic biogenetic-like Olefinic cyclizations . In: Accounts of Chemical Research . tape 1 , no. 1 , 1968, p. 1-8 , doi : 10.1021 / ar50001a001 .
  2. ↑ a b c d B. P. Mundy, MG Ellerd, FG Favaloro Jr .: Name Reactions & Reagents in Organic Synthesis . John Wiley & Sons, New Jersey 2005, ISBN 978-0-471-22854-7 , pp. 348-449 .
  3. ^ A b William S. Johnson: Biomimetic Polyene Cyclizations . In: Angewandte Chemie International Edition in English . tape 15 , no. 1 , 1976, p. 9-17 , doi : 10.1002 / anie.197600091 .
  4. ↑ a b Reinhard Brückner: reaction mechanisms . Elsevier Spektrum Verlag, Munich 2004, ISBN 3-8274-1579-9 , pp. 599-602 .