13720-13-3Relevant academic research and scientific papers
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.
Studies on the synthesis of acanthodoral and nanaimoal: Evaluation of cationic cyclization routes
Engler,Ali,Takusagawa
, p. 8456 - 8463 (2007/10/03)
Intramolecular Lewis acid-promoted reactions of α,β-unsaturated ketone 6 and aldehydes 7 and 8 were examined as potential routes to acanthodoral (1), a structurally interesting natural product. Ketone 6 afforded ene product 22 exclusively, and both 7 and 8 gave mixtures of bicyclic aldehydes 3 and 26 and tricyclic aldehyde 25. The latter most likely results from 7 by intramolecular cyclization of the alkene onto the Lewis acid-activated carbonyl moiety affording carbocation 31 followed by a 1,2-hydride shift and ring closure. Starting from 8, tricyclic aldehyde 25 apparently forms by cyclization to cation 35 and ring closure to cyclobutane 36, followed by ring opening to 31, the same cation as formed in reactions of 7. Nanaimoal (3) results from loss of H+ from 31, and bicyclic aldehyde 26 may be formed in a similar manner or by a concerted ene reaction. The configuration of 25 establishes that the stereochemistry of the initial cyclization to 31 precludes the possible use of this strategy for the synthesis of acanthodoral. However, acid-promoted cyclization of allylic alcohol 23 efficiently gives diene 29 which undergoes selective hydroboration/oxidation to afford nanaimoal.
Synthesis of trans-γ-Monocyclofarnesol
Vig, O. P.,Sharma, M. L.,Trehan, Navneet,Verma, N. K.
, p. 450 - 452 (2007/10/02)
The starting material, 2-formyl-6,6,dimethylcyclohexanone (II) in the synthesis of the title compound, is converted into the corresponding 2-isobutoxymethylene-6,6-dimethylcylohexanone (III).Reduction of (III) with LAH followed by treatment with 50percent sulphuric acid gives the α,β-unsaturated aldehyde (IV).LAH reduction of IV yields 1-hydroxymethyl-3,3-dimethylcylohex-1-ene (V) which on mercuric acetate catalysed transetherification with ethyl vinyl ether affords the vinyl ether (VI).Claisen rearragement of VI under an inert atmosphere furnishes 2-(6',6'-dimethyl-2'-methylenecylohexyl)ethanal (VII).Aldehyd VII on Wittig reaction with methoxymethylenetriphenylphosphorane provides the ether (VIII) which is readily converted into the ketal (IX) on treatment with ethylene glycol in the presence of catalytic amount of PTS in dry benzene.Deketalisation of IX with PTS in aq. acetone gives the aldehyde (X) which on Grignard reaction with methylmagnesium iodide furnishes 4-(6',6'-dimethyl-2'-methylenecylohexyl)butan-2-ol (XI).Oxidation of XI with pyridinium chlorochromate in anhydrous methylene chloride yields the ketone (XII) which when subjected to Grignard reaction with vinylmagnesium bromide in dry THF provides the vinylic alcohol (XIII).Treatment of XIII with acetic anhydride and glacical acetic acid in the presence of PTS furnishes the allylic acetate (XIV) which on refluxing with methanolic potassium hydroxide in the presence of a little water gives trans-γ-monocyclofarnesol (I).
