Enzymatic Syntheses of novel carbocyclic scaffolds with a 6,5+5,5 ring system by squalene-hopene cyclase
Squalene-hopene cyclase (SHC) converts acyclic squalene 1 into the 6,6,6,6,5-fused pentacyclic triterpenes hopene and hopanol. Previously, we reported the polycyclization products of 27-norsqualene (13a) and 28-norsqualene (13b) by SHC, and suggested the importance of Me-27 of 1 for the normal polycyclization pathway. To further ensure the theory, (3R, S)-27-noroxidosqualenes (18 and 19) were incubated, and the structures of products 20─25 thus obtained prompted us to reinvestigate the SHC reaction of 13a (13b).One new product 29, composed of a 6,5+5,5 ring system with 13α-H and 17α-H, was obtained from 13a in addition to the previously isolated products 14 and 15 with the novel ring systems. We propose the name “nor-allodammarane” for this novel tetracyclic 6,5+5,5 ring system and the name “nor-allogammacerane” for the pentacyclic 6,5+5,5+6 ring system. The stereochemistry of 29 indicated that 13a folded in the following chair-boat-boat-boat conformation: 10α-H, 11β-H; 14α-H, 15β-Me; 18α-H and 19β-Me, which further allowed us to predict the configuration of 20R for 14 and that of 20S for 15. Substrates 18 and 19 were also cyclized only into allodammarane scaffolds 20─25, and all the structures of 20─25 further indicated that 18 and 19 also folded in the same conformation as 13a, providing further evidence that Me-27 groups of 1 and oxidosqualene are essential for the normal polycyclization pathway by SHC.