53837-34-6Relevant articles and documents
Synthesis and inhibition studies of sulfur-substituted squalene oxide analogues as mechanism-based inhibitors of 2,3-oxidosqualene-lanosterol cyclase
Stach, Dirk,Zheng, Yi Feng,Perez, Alice L.,Oehlschlager, Allan C.,Abe, Ikuro,Prestwich, Glenn D.,Hartman, Peter G.
, p. 201 - 209 (1997)
The synthesis and biological evaluation of three new sulfur-substituted oxidosqualene (OS) analogues (1-3) are presented. In these analogues, C-11, C-15, or C-18 in the OS skeleton was replaced by sulfur. The sulfur position in the OS skeleton was chosen to disrupt one or more key processes involved in cyclization: (a) the folding of the B-ring into a boat conformation, (b) the anti-Markovnikov cyclization leading to the C-ring, or (c) the formation of the D-ring during the lanosterol biosynthesis. Enzyme inhibition kinetics using homogeneous mammalian oxidosqualene cyclases (OSC) were also examined for the previously reported S-19 analogue 4. The four analogues were potent inhibitors of mammalian OSCs (IC50 = 0.05-2.3 μM for pig and rat liver OSC) and fungal cell-free Candida albicans OSC (submicromolar IC50 values). In particular, the S-18 analogue 3 showed the most potent inhibition toward the rat liver enzyme (IC50 = 50 nM) and showed potent, selective inhibition against the fungal enzyme (IC50 = 0.22 nM, 10-fold more potent than the S- 19 analogue 4). Thus, 3 is the most potent OSC inhibitor known to date. The K(i) values ranged from 0.5 to 4.5 μM for pig OSC, with 3 and 4 showing about 10-fold higher potency for rat liver OSC. Interestingly, the S-18 analogue 3 showed time-dependent irreversible inhibition with homogeneous pig liver OSC (k(inact) = 0.06 min-1) but not with rat OSC.
Asymmetric Cation-Olefin Monocyclization by Engineered Squalene–Hopene Cyclases
Aeberli, Natalie,Berweger, Raphael,Bornscheuer, Uwe T.,Buller, Rebecca,Dossenbach, Sandro,Eichenberger, Michael,Eichhorn, Eric,Flachsmann, Felix,Hüppi, Sean,Hortencio, Lucas,Patsch, David,Voirol, Francis,Vollenweider, Sabine
supporting information, p. 26080 - 26086 (2021/09/20)
Squalene–hopene cyclases (SHCs) have great potential for the industrial synthesis of enantiopure cyclic terpenoids. A limitation of SHC catalysis has been the enzymes’ strict (S)-enantioselectivity at the stereocenter formed after the first cyclization step. To gain enantio-complementary access to valuable monocyclic terpenoids, an SHC-wild-type library including 18 novel homologs was set up. A previously not described SHC (AciSHC) was found to synthesize small amounts of monocyclic (R)-γ-dihydroionone from (E/Z)-geranylacetone. Using enzyme and process optimization, the conversion to the desired product was increased to 79 %. Notably, analyzed AciSHC variants could finely differentiate between the geometric geranylacetone isomers: While the (Z)-isomer yielded the desired monocyclic (R)-γ-dihydroionone (>99 % ee), the (E)-isomer was converted to the (S,S)-bicyclic ether (>95 % ee). Applying the knowledge gained from the observed stereodivergent and enantioselective transformations to an additional SHC-substrate pair, access to the complementary (S)-γ-dihydroionone (>99.9 % ee) could be obtained.
Capturing the Monomeric (L)CuH in NHC-Capped Cyclodextrin: Cavity-Controlled Chemoselective Hydrosilylation of α,β-Unsaturated Ketones
Bistri-Aslanoff, Olivia,Derat, Etienne,Leloux, Sébastien,Leyssens, Tom,Ménand, Micka?l,Meijide Suárez, Jorge,Riant, Olivier,Roland, Sylvain,Sollogoub, Matthieu,Xu, Guangcan,Zhang, Pinglu,Zhang, Yongmin
, p. 7591 - 7597 (2020/03/23)
The encapsulation of copper inside a cyclodextrin capped with an N-heterocyclic carbene (ICyD) allowed both to catch the elusive monomeric (L)CuH and a cavity-controlled chemoselective copper-catalyzed hydrosilylation of α,β-unsaturated ketones. Remarkably, (α-ICyD)CuCl promoted the 1,2-addition exclusively, while (β-ICyD)CuCl produced the fully reduced product. The chemoselectivity is controlled by the size of the cavity and weak interactions between the substrate and internal C?H bonds of the cyclodextrin.
