Reviewing the Polyolefin Cyclization Reaction of the C-35 Polyprene Catalyzed by Squalene-Hopene Cyclase

摘要

Squalene-hopene cyclase (SHC) catalyzes the polycyclization of squalene (C-30) to the pentacyclic hopene With regio- and stereochemical specificity. In this study, we reviewed the polycyclization reaction of the C-35 polyprenoid catalyzed by SHC. Surprisingly, our results completely disagreed with a previous publication in which it was reported that a hexacyclic skeleton was constructed as the single product in 10% yield (I. Abe. H. Tanaka, H. Noguchi, J. Am. Chem. Soc. 2002, 124, 14514-14515). Our experimental results showed that many tri- and tetracyclic products, up to 12. including novel carbocyclic cores, were generated in a high conversion ratio (97%), but no detectable amounts of the penta- and hexacycle were produced. The mechanisms for the formation of the C-31 Polyprene products isolated by us are discussed in this paper. The following four conformations were generated during the polycyclization cascade: chair-chair-boat, chair-chair-chair, chairchair-chair-boat, and chair-chair-chair-chair. Larger amounts of the false intermediates with 13 alpha-H (tricycle) and 17 alpha-H (tetracycle) were produced compared with the true intermediates (13 beta-H and 17 beta-H), which indicates that the C-35 polyprene cannot fold correctly in the enzyme cavity due to the extra C-5 unit appended to squalene. This Would have promoted the formation of the aborted cyclization products With tri- and tetracycles. In addition, the fact that no penta- or hexacyclic products were formed further indicates that SHC does not have sufficient space to accommodate the entire carbon framework of C-31.