60686-82-0Relevant academic research and scientific papers
On the bi-enzymatic behaviour of Saccharomyces cerevisiae-mediated stereoselective biotransformation of 2,6,6-trimethylcyclohex-2-ene-1,4-dione
Uzir, Mohamad Hekarl,Najimudin, Nazalan
, p. 56 - 64 (2018/02/13)
Baker's yeast has been well-known to have the ability to reduce a variety of substrates into many optically active compounds. One of the important chemicals is (4R,6R)-4-hydroxy-2,2,6-trimethylcyclohexanone or in short, (4R,6R)-actinol, a product formed f
An engineered old yellow enzyme that enables efficient synthesis of (4R,6R)-actinol in a one-pot reduction system
Horita, Shoichiro,Kataoka, Michihiko,Kitamura, Nahoko,Nakagawa, Takuya,Miyakawa, Takuya,Ohtsuka, Jun,Nagata, Koji,Shimizu, Sakayu,Tanokura, Masaru
, p. 440 - 445 (2015/03/05)
(4R,6R)-Actinol can be stereo-selectively synthesized from ketoisophorone by a two-step conversion using a mixture of two enzymes: Candida macedoniensis old yellow enzyme (CmOYE) and Corynebacterium aquaticum (6R)-levodione reductase. However, (4S)-phorenol, an intermediate, accumulates because of the limited substrate range of CmOYE. To address this issue, we solved crystal structures of CmOYE in the presence and absence of a substrate analogue p-HBA, and introduced point mutations into the substrate-recognition loop. The most effective mutant (P295G) showed two- and 12-fold higher catalytic activities toward ketoisophorone and (4S)-phorenol, respectively, than the wild-type, and improved the yield of the two-step conversion from 67.2 to 90.1%. Our results demonstrate that the substrate range of an enzyme can be changed by introducing mutation(s) into a substrate-recognition loop. This method can be applied to the development of other favorable OYEs with different substrate preferences.
Synthesis of biotinylated retinoids for cross-linking and isolation of retinol binding proteins
Nesnas, Nasri,Rando, Robert R,Nakanishi, Koji
, p. 6577 - 6584 (2007/10/03)
The synthesis of (3R)-3-[Boc-Lys(biotinyl)-O]-11-cis-retinol bromoacetate and 3-[Boc-Lys(biotinyl)-O]-all trans-retinol chloroacetate is described. These biotinylated retinoids are instrumental in labeling the retinol binding proteins (RBPs) via a nucleophilic displacement of the haloacetate by a residue in the binding site of the protein. The covalently linked biotin will allow for a facile isolation and purification of the protein on a streptavidin column thus rendering the protein ready for a tryptic digest followed by mass spectrometric analysis. The 11-cis retinoid was synthesized via metal reduction of an alkyne intermediate generated from a Horner-Wadsworth-Emmons (HWE) reaction whereas the all-trans was synthesized via two consecutive HWE couplings.
Reduction of aliphatic and aromatic cyclic ketones to sec-alcohols by aqueous titanium trichloride/ammonia system. Steric course and mechanistic implications
Clerici, Angelo,Pastori, Nadia,Porta, Ombretta
, p. 2235 - 2243 (2007/10/03)
In contrast to the dissolved metal and metal hydride reductions, the reduction of cyclic ketones by the aqueous TiCl3/NH3 system favours the formation of the less thermodynamically stable axial alcohol. The ammonium ion formed in situ is essential for the reduction to proceed because it behaves as a mild Br?nsted acid in basic medium and favours the protonation of the intermediate ketyl. The corresponding α-hydroxy radical is then rapidly reduced under conditions where the first electron transfer to the substrate takes place. We suggest that the stereoselectivity is determined by the second reduction step, which occurs through the less hindered transition state, regardless of whether the radical to be reduced is thermodynamically favoured or not.
Cloning, sequence analysis, and expression in Escherichia coli of the gene encoding monovalent cation-activated levodione reductase from Corynebacterium aquaticum M-13.
Yoshisumi,Wada,Takagi,Shimizu,Nakamori
, p. 830 - 836 (2007/10/03)
The gene encoding (6R)-2,2,6-trimethyl-1,4-cyclohexanedione (levodione) reductase was cloned from the genomic DNA of the soil isolate bacterium Corynebacterium aquaticum M-13. The gene contained an open reading frame consisting of 801 nucleotides correspo
Experimental and Computational Studies of Nucleophilic Additions of Metal Hydrides and Organometallics to Hindered Cyclohexanones
Ando, Kaori,Houk,Busch, Joachim,Menasse, Alexander,Sequin, Urs
, p. 1761 - 1766 (2007/10/03)
The stereochemistries of nucleophilic additions of several hydride, methyl, and acetylenic Grignard and lithium reagents to hindered cyclohexanones were investigated experimentally. Acetylenic ' reagents attack hindered cyclohexanones from the axial direction, in contrast to the result with other reagents. Ab initio calculations and a modified MM2 transition-state force field were used to study the origins of stereoselectivity.
Total synthesis and biological activities of (+)- and (-)-boscialin and their 1'-epimers
Busch, Joachim,Grether, Yvonne,Ochs, Dietmar,Sequin, Urs
, p. 591 - 597 (2007/10/03)
Natural (-)-boscialin [(-)-1] has recently been described as one of the constituents of various medicinal plants. To obtain more material for investigations of its biological activities, we carried out the synthesis of (-)-1 and its isomers. Starting from the chiral building block 2, the key steps of the synthesis involved a regioselective reduction and a nucleophilic addition. The enantiomer of the natural product, (+)-boscialin [(+)-1], could be obtained via acid-catalyzed epimerization of hydroxyketone 4 to (+)-3. Starting the synthesis with (-)-3 led to (-)-boscialin [(-)-1] with the natural absolute configuration. In addition to (+)- and (-)-boscialin, the corresponding 1'-epimers (+)- and (-)-epiboscialin were also obtained. In vitro assays with (-)-boscialin [(-)-1] and its three stereoisomers were carried out to test for activity against microbes, parasites, and human fibroblasts. The investigations revealed activity against various microbes and against Trypanosoma brucei rhodesiense and also revealed cytotoxicity against human cancer cells.
Total synthesis of (±)-phaseic acid
Abrams, Garth D.,Abrams, Suzanne R.,Nelson, Lloyd A. K.,Gusta, Lawrence V.
, p. 5543 - 5554 (2007/10/02)
A highly stereoselective synthesis of (±)-phaseic acid is described. Photochemical reaction of the nitrite derived from trans-4-hydroxy-2,2,6-trimethylcyclohexanone functionalizes the methyl group of the geminal pair cis to the hydroxyl group of the start
Synthesis of optically active cyclohexanone analogs of the plant hormone abscisic acid
Lamb, Nancy,Abrams, Suzanne R.
, p. 1151 - 1162 (2007/10/02)
The abscisic acid analogs (-)-(4R,5R)-, (+)-(4S,5S)-, and (-)-(4S,5R)-4(1E,3Z)-4-(4-carboxy-3-methyl-1,3-butadienyl)-4-hydroxy-3,3,5-trimethylcyclohexanones (dihydroabscisic acids), and (-)-(4S,5R)-, (+)-(4R,5S)-, and (-)-(4R,5R)-4(Z)-4-hydroxy-4-(5-hydroxy-3-methylpent-3-en-1-ynyl)-3,3,5-trimethylcyclohexanones were synthesized from a common precursor, (-)-(6R)-2,2,6-trimethylcyclohexan-1,4-dione, which was readily prepared by the fermentation of oxoisophorone with bakers' yeast.
