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Reviewing the Polyolefin Cyclization Reaction of the C 35 Polyprene Catalyzed by Squalene‐Hopene Cyclase
Author(s) -
Hoshino Tsutomu,
Kumai Yuko,
Sato Tsutomu
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200802142
Subject(s) - cyclase , squalene , chemistry , stereochemistry , catalysis , cyclohexane conformation , enzyme , molecule , organic chemistry , hydrogen bond
A review of the polycyclization reaction of the C 35 polyprenoid by squalene‐hopene cyclase: Surprisingly, our results completely disagree with a previous publication in which it was reported that a hexacyclic skeleton was constructed as the single product. In our work many tri‐ and tetracyclic scaffolds were isolated, but no penta‐ or hexacycles. The reasons for the different results and the mechanism of the polycyclization reaction are discussed (see figure).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 35 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, chair‐chair‐chair‐boat, and chair‐chair‐chair‐chair. Larger amounts of the false intermediates with 13α‐H (tricycle) and 17α‐H (tetracycle) were produced compared with the true intermediates (13β‐H and 17β‐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 35 .