- Substrate-dependent stereospecificity of Tyl-KR1: An isolated polyketide synthase ketoreductase domain from Streptomyces fradiae
-
The stereospecificity of an enzymatic reaction depends on the way in which a substrate and its enantiomer bind to the active site. These binding modes cannot be easily predicted. We have studied the stereospecificity and stereoselectivity of the ketoreductase domain Tyl-KR1 of the tylactone polyketide synthase from Streptomyces fradiae by analysing the stereochemical outcome of the reduction of five different keto ester substrates. The absolute configuration of the Tyl-KR1 reduction products was determined by using vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations. The conversion of only one of the tested substrates, 2-methyl-3-oxovaleric acid N-acetylcysteamine thioester, afforded the expected anti-(2R,3R) configuration of the α-methyl-β-hydroxyl ester product, representing the stereochemistry observed for the physiological polyketide product tylactone. For all other substrates, which were modified with respect to the type of ester and/or the chain length (C4 instead of C 5), the opposite configuration (anti-(2S,3S)) was obtained with significant enantio- and diastereoselectivity. Inversion of both stereocentres suggests completely different binding modes invoked by only minor modifications of the substrate structure. Substrate dependence: The stereospecificity of an enzymatic reduction depends on the way a substrate binds to the active site. By using vibrational circular dichroism, it was shown that the stereospecificity and stereoselectivity of the ketoreductase Tyl-KR1 from a polyketide synthase complex in Streptomyces fradiae are inverted for different surrogates of polyketide-like substrates (see figure). Copyright
- H?ckh, Matthias,Müller, Michael,Lüdeke, Steffen
-
-
Read Online
- A study on the cataluminescence of propylene oxide on FeNi layered double hydroxides/graphene oxide
-
In this work, FeNi layered double hydroxides/graphene oxide (FeNi LDH/GO) was prepared, which exhibits excellent selective cataluminescent performance towards propylene oxide. The selectivity and sensitivity of the cataluminescence (CTL) reaction were investigated in detail. Moreover, the catalytic reaction mechanism, including the intermediate products and the conversion of reactants to products, was discussed based on both the experimental and computational results. Furthermore, the proposed FeNi LDH/GO based CTL sensor was successfully applied for the determination of propylene oxide residue in fumigated raisins, which indicates extensive application potential for rapid food safety evaluation.
- Li, Ming,Hu, Yufei,Li, Gongke
-
p. 11823 - 11830
(2021/07/11)
-
- Asymmetric cross- and self-aldol reactions of aldehydes in water with a polystyrene-supported triazolylproline organocatalyst
-
A polystyrene (PS) immobilized triazolylproline has been prepared by a bottom-up approach involving co-polymerization with full regiocontrol. The resulting PS resin swells in water and has been applied to the enantioselective cross-aldol reaction and to the self-aldol reaction of aldehydes under essentially neat conditions, excellent yields and stereoselectivities being recorded.
- Llanes, Patricia,Sayalero, Sonia,Rodríguez-Escrich, Carles,Pericàs, Miquel A.
-
supporting information
p. 3507 - 3512
(2016/07/06)
-
- Synthesis of (4R,6S,7R)-7-hydroxy-4,6-dimethyl-3-nonanone and (3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-octanone
-
The synthesis of (4R,6S,7R)-7-hydroxy-4,6-dimethyl-3-nonanone and (3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-octanone is described as their acetates using a desymmetrization strategy as well as an Evans syn aldol strategy.
- Sabitha, Gowravaram,Srinivas, Chitti,Maruthi, Chittapragada,Yadav, Jhillu Singh
-
experimental part
p. 2071 - 2079
(2012/03/27)
-
- The asymmetric total synthesis of (+)-cytotrienin A, an ansamycin-type anticancer drug
-
(Chemical Equation Presented) A star-studded lineup: (+)-Cytotrienin A was the target of an asymmetric total synthesis featuring an enantioselective aldol reaction, α-aminoxylation, deoxygenation, and a ring-closing metathesis to form the 21-membered macrolactam. This first total synthesis confirms the relative and absolute confguration of the molecule.
- Hayashi, Yujiro,Shoji, Mitsuru,Ishikawa, Hayato,Yamaguchi, Junichiro,Tamura, Tomohiro,Imai, Hiroki,Nishigaya, Yosuke,Takabe, Kenichi,Kakeya, Hideaki,Osada, Hiroyuki
-
supporting information; experimental part
p. 6657 - 6660
(2009/03/12)
-
- Small organic molecule in enantioselective, direct aldol reaction "in water"
-
A small organic molecule, Pro-NH2, catalyzing the enantioselective aldol reaction "in water" not merely "in the presence of water" with good enantioselectivity has been discovered for the first time. The Royal Society of Chemistry.
- Aratake, Seiji,Itoh, Takahiko,Okano, Tsubasa,Usui, Takahiro,Shoji, Mitsuru,Hayashi, Yujiro
-
p. 2524 - 2526
(2008/02/11)
-
- Combined proline-surfactant organocatalyst for the highly diastereo- and enantioselective aqueous direct cross-aldol reaction of aldehydes
-
(Chemical Equation Presented) Why not combine the two? The asymmetric direct aldol reaction of two different aldehydes was catalyzed by a combined proline-surfactant organic catalyst in the presence of water. A stable emulsion was formed in the reaction mixture, and the aldols were obtained with excellent diastereo- and enantioselectivities (see scheme).
- Hayashi, Yujiro,Aratake, Seiji,Okano, Tsubasa,Takahashi, Junichi,Sumiya, Tatsunobu,Shoji, Mitsuru
-
p. 5527 - 5529
(2007/10/03)
-
- The direct, enantioselective, one-pot, three-component, cross-Mannich reaction of aldehydes: The reason for the higher reactivity of aldimine versus aldehyde in proline-mediated Mannich and aldol reactions
-
In the proline-mediated Mannich and aldol reactions of propanal as a nucleophile, the aldimine prepared from benzaldehyde and p-anisidine is about 7 times more reactive than the corresponding aldehyde, benzaldehyde, as an electrophile. This higher reactivity of aldimine over aldehyde is attributed to the carboxylic acid of proline protonating the basic nitrogen atom of the aldimine more effectively than the oxygen atom of the aldehyde, an explanation which has been both experimentally and theoretically verified.
- Hayashi, Yujiro,Urushima, Tatsuya,Shoji, Mitsuru,Uchimaru, Tadafumi,Shiina, Isamu
-
p. 1595 - 1604
(2007/10/03)
-
- 24-and 25-substituted avermectin and milbemycin derivatives
-
Novel avermectin and milbemycin derivatives are disclosed, where the C-24 and C-25 carbon atoms are substituted by hydrogen, alkyl, alkenyl, substituted alkyl or substituted alkenyl groups. These compounds can be further substituted at the 4"-, 5-, 13-, and 23-positions. The new C-24 and C-25 substituted avermect prepared by cleavage of known and suitably protected avermectin and milbemycin compounds. The new compounds are potent anti-parasitic agents, in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.
- -
-
-
- Attainment of syn-selectivity for boron-mediated asymmetric aldol reactions of carboxylic esters
-
A new chiral reagent for syn-selective aldol reactions has been developed based on the recent finding that the stereochemistry of the boron-mediated aldol reaction of a carboxylic ester is controlled by the bulkiness of the alcohol moiety of the ester, by the proper choice of reagents, and by the enolization conditions. This readily available, inexpensive reagent has been utilized in studies directed towards the synthesis of the macrolide tedanolide.
- Liu, Ji-Feng,Abiko, Atsushi,Pei, Zhonghua,Buske, Dana C.,Masamune, Satoru
-
p. 1873 - 1876
(2007/10/03)
-
- A practical enantioselective synthesis of the cigarette beetle sex pheromone serricornin
-
(4RS,6S,7S)-7-hydroxy-4,6-dimethyl-3-nonanone (serricornin and its C4- epimer) may be prepared from oxazolidinone 5 in 8 steps with an overall yield of 33%.
- Chan, Philip C.-M.,Chong, J. Michael,Kousha, Karim
-
p. 2703 - 2714
(2007/10/02)
-
- A short formal synthesis of (-)-serricornine
-
A short and efficient formal synthesis of serricornine (1), the sex pheromone of Lasioderma serricorne F., is described. The homochiral aldol 5 is straightforwardly converted to tosylate 9 to give homochiral lactone 2a (6 steps. 22% overall yield from oxazolidinone 4), a known precursor of (-)-1.
- Pilli,De Andrade
-
p. 233 - 241
(2007/10/02)
-
- 4"-and 4'-alkylthio avermectin derivatives
-
Avermectin derivatives are disclosed wherein the 4"-hydroxy group is replaced by a substituted alkylthio or acylthio group or an iodo group. These avermectin derivatives can be further derivatized at the 5- and 23-positions as ketoximes or O-substituted ketoximes. The 4"-substituted avermectin derivatives are prepared from the 4"- and 4'-trifluoromethanesulfonyl avermectin derivatives with halo- or sulfur-containing nucleophiles. The 4"- and 4'-α- and β-trifluoromethane sulfonates are prepared selectively and converted into 4"- or 4'-alkyl- or acylsulfides, or iodides using the appropriate sulfur-containing or iodine nucleophile. Substituted sulfoxy and sulfonyl substituents at the 4"- and 4'-positions are prepared from oxidation of the corresponding substituted sulfides. The new compounds are potent anti-parasitic agents; in particular, the compounds are anthelmintic, insecticidal and acaricidal agents.
- -
-
-
- The Synthesis of Glycols by Mercury-Photosensitized Alcohol Dehydrodimerization
-
A variety of alcohols can be dehydrodimerized to give 1,2-diols on a multigram scale at 1 atm pressure and reflux temperature on photolysis (254 nm) in the presence of a trace of Hg vapor.Initial C-H bond breaking is followed by recombination of the resulting α-centered radicals, which normally leads to C-C bond formation α to oxygen.The reaction rate and selectivity can be increased by operating at lower temperatures under H2, in which case H atoms replace Hg* as the principal abstracting reagent and H atom abstraction from the α-CH bond leads directly to the α-C-centered radical.Under H atom conditions, unsaturated alcohols also react, in which case diols other than the 1,2-isomer can be formed selectively.The product can be rationalized on the basis of H atom addition to the C=C double bond to give the most stable radical which then dimerizes.For the special case of t-BuOH, H atom abstraction from the t-BuOH β-CH group under H atom conditions leads to the β-centered radical, which dimerizes to the 1,4-diol.Radical disproportionation accounts for some of the byproducts observed.The following previously unknown C-H bond strengths (kcal/mol) were determined from the results, assuming the literature BDE for the α-C-H of 2-propanol (91.0 +/-1.0); n-butanol, 92.8 +/- 1.0( α), 95.2 +/- 1.0 (β), and 94.3 +/- 1.0 (γ); n-propanol, 93.1 +/- 1.0 (α), and 95.0 +/- 1.0 (β), respectively.
- Lee, Jesse C.,Boojamra, Constantine G.,Crabtree, Robert H.
-
p. 3895 - 3900
(2007/10/02)
-
- NEW STEREOCONTROLLED APPROACH TO THE INSECT SEX PHEROMONE SERRICORNIN
-
The (Z)-allylic alcohol 1 was subjected to Sharpless asymmetric epoxidation to give the key intermediate 2.Ring opening of the epoxide 2 afforded the diol 3, which was then converted to serricornin 4, the sex pheromone of the cigarette beetle (Lasioderma serricorne F.) by routine transformations.
- Szurdoki, F.,Novak, L.,Baitz-Gacs, Eszter,Szantay, Cs.
-
p. 303 - 309
(2007/10/02)
-
- Triisobutylaluminum-Assisted Reductive Rearrangement of Alkyl 1-Alkenyl Acetals: An Easy Synthesis of β-Alkoxy Alcohols
-
Alkyl 1-alkenyl acetals react with Al-i-Bu3 to give very good yields of β-alkoxy alcohols through a reductive rearrangement.The reaction is totally regioselective, but no stereocontrol occurs.
- Menicagli, R.,Malanga, C.,Dell'Innocenti, M.,Lardicci, L.
-
p. 5700 - 5704
(2007/10/02)
-
- CHIRALITY TRANSFER IN THE ESTER ENOLATE CLAISEN REARRANGEMENT OF (R)-1-METHYL-(E)-2-BUTENYL HYDROXYACETATE AND ITS APPLICATION TO THE STEREOCONTROLLED PHEROMONE SYNTHESIS
-
The ester enolate Claisen rearrangement of (R)-1-methyl-(E)-2- butenyl hydroxaacetate provides complete asymmetric transfer along with 98percent erythroselectivity to give (2R,3S)-2-hydroxy-3-methyl-(E)-4-hexenoic acid.Its synthetic utility is demonstrated by the stereocontrolled synthesis of optically active pheromones.
- Fujisawa, Tamotsu,Tajima, Kazuhisa,Sato, Toshio
-
p. 1669 - 1672
(2007/10/02)
-
- SYNTHESIS AND ABSOLUTE STEREOCHEMISTRY OF SERRICORNIN
-
The absolute stereochemistry of serricornin (4,6-dimethyl-7-hydroxy-3-nonanone) was established as 4S, 6S, 7S by synthesizing both (4S, 6S, 7S)-isomer and its antipode.Only the natural enantiomer was bioactive.by
- Mori, Kenji,Nomi, Hiroko,Chuman, Tatsuji,Kohno, Masahiro,Kato, Kunio,Noguchi, Masao
-
p. 3705 - 3712
(2007/10/02)
-