Biomimetic polyene cyclizations: A review

Abstract

It has been shown that certain polyenic substances, having trans olefinic bonds in the 1,5 relationship, can be induced to undergo stereospecific, nonenzymic, cationic cyclization to give polycyclic products with the all trans (“natural”) configuration. These transformations appear to mimic in principle the biogenetic conversion of squalene into polycyclic triterpenoids, e.g., lanosterol. Acetal as well as allylic alcohol functions have proved to be effective initiators for such cyclizations, many of which proceed to a remarkable degree of completion giving mainly totally cyclized products. Thus, it has been possible to convert, in a single step, an open chain tetraenic acetal having no chiral centers, into a tetracyclic product having seven such centers. The process is highly stereoselective giving only two of 64 possible racemates. Methylacetylenic and also styryl end groups are particularly useful cyclization terminators as they provide a means of realizing five-membered ring formation. Systems with these terminators have been developed for effecting the total synthesis of the steroid nucleus in a single step starting from a substrate containing only one ring. The mechanism of these biomimetic as well as of the enzymic cyclizations is open to question, but the balance of the evidence is somewhat in favor of a synchronous process.