- Enzymatic kinetic resolution and chemoenzymatic dynamic kinetic resolution of δ-hydroxy esters. An efficient route to chiral δ-lactones
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A successful kinetic resolution of a racemic mixture of δ-hydroxy esters 1 was obtained via lipase-catalyzed transesterification (E value up to 360). The combination of the enzymatic kinetic resolution with a ruthenium-catalyzed alcohol racemization led t
- Pamies, Oscar,Baeckvall, Jan-E.
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- Biocatalyst-Mediated Efficient Preparation of Highly Enantiomerically Enriched (R)-5-Hexanolide
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Biocatalyst-mediated efficient preparation of highly enantiomerically enriched (R)-5-hexanolide (1) is described. The enantioselective reduction of 5-oxohexanoic acid with Yamadazyma farinosa IFO 10896 and the subseqent lipase-catalyzed kinetic resolution gave (R)-1 in 62% yield with 99.7% e.e.
- Sugai, Takeshi,Hamada, Keiji,Akeboshi, Tomohiro,Ikeda, Hajime,Ohta, Hiromichi
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- TFA-catalyzed trimerization of R-(+)-6-methyl-tetrahydro-pyran-2-one
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The enantiomerically pure (≥98% ee) title compound R-(+)-6-methyl-tetrahydro-pyran-2-one (R)-1 in the presence of traces of trifluoroacetic acid (TFA) converts into an equilibrium mixture with its trimer 4 [(R)-1:4=20:80] corresponding to a ΔG?-0.8 kcal mol-1. The transformation can be followed by 1H and 13C NMR spectroscopy. The structure of 4 was established by chemical correlation with (R)-1 and its molecular weight determined via its colligative properties.
- Fazio, Fabio,Schneider, Manfred P.
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- Synthesis method of gamma-or delta-substituted alkyl chiral lactone
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The invention discloses a synthesis method of gamma-or delta-substituted alkyl chiral lactone, the synthesis method comprises the following steps: mixing nickel salt, a chiral bidentate organic phosphorus ligand, aliphatic gamma-or delta-ketonic acid and a solvent, and carrying out asymmetric reduction reaction under the action of a reducing agent to obtain the gamma-or delta-substituted alkyl chiral lactone. According to the invention, asymmetric hydrogenation of aliphatic gamma-and delta-ketonic acids is realized through a cheap, green and efficient homogeneous chiral nickel-phosphorus complex catalytic system, and gamma-or delta-substituted alkyl chiral lactone is obtained with excellent yield and high enantioselectivity.
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Paragraph 0011; 0036-0040
(2022/03/17)
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- Iridium-Catalyzed Asymmetric Hydrogenation of ?- A nd ?-Ketoacids for Enantioselective Synthesis of ?- A nd ?-Lactones
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A highly efficient asymmetric hydrogenation of ?- A nd ?-ketoacids was developed by using a chiral spiro iridium catalyst (S)-1a, affording the optically active ?- A nd ?-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.
- Hua, Yun-Yu,Bin, Huai-Yu,Wei, Tao,Cheng, Hou-An,Lin, Zu-Peng,Fu, Xing-Feng,Li, Yuan-Qiang,Xie, Jian-Hua,Yan, Pu-Cha,Zhou, Qi-Lin
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supporting information
p. 818 - 822
(2020/02/15)
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- Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans
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Flavin-containing mono-oxygenases are known as potent drug-metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
- Fiorentini, Filippo,Geier, Martina,Binda, Claudia,Winkler, Margit,Faber, Kurt,Hall, Mélanie,Mattevi, Andrea
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p. 1039 - 1048
(2016/05/19)
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- Stereodivergent preparation of valuable γ- Or δ-hydroxy esters and lactones through one-pot cascade or tandem chemoenzymatic protocols
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A series of enantiopure hydroxy esters and lactones has been synthesized in a chemodivergent manner via alcohol dehydrogenase (ADH) reduction of the corresponding keto esters by means of cascade or tandem protocols. Thus, ADH from Rhodococcus ruber (ADH-A) or Lactobacillus brevis (LBADH) afforded both antipodes in a very selective way when dealing with small derivatives. With bulkier substrates, ADH from Ralstonia sp. (RasADH) was successfully employed to achieve the synthesis of enantioenriched γ- or δ-hydroxy esters. To isolate the corresponding lactones, two different approaches were followed: a cascade reaction by spontaneous cyclization of the hydroxy ester intermediate, or a one-pot two-step tandem protocol. Moreover, a chemoenzymatic route was designed to obtain a chiral brominated lactone, which enabled further modifications in a sequential fashion by Pd-catalyzed reactions, affording relevant functionalized lactones.
- Diaz-Rodriguez, Alba,Borzeicka, Wioleta,Lavandera, Ivan,Gotor, Vicente
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p. 386 - 393
(2014/03/21)
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- Optical resolution of medium-size lactones by inclusion crystallization with optically active host compounds: remarkable odd-even effects on the chiral recognition
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Molecular recognition of medium-size lactones by inclusion complexation with optically active hosts derived from tartaric acid is described. Odd-even effects on the chiral recognition were observed in the enantioselective inclusion with the optically active host compounds in the solid state.
- Tanaka, Koichi,Kuchiki, Daisuke,Caira, Mino R.
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p. 1678 - 1683
(2007/10/03)
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- Optical resolution of 5-alkyl-δ-valerolactones and synthesis of optically active 5-fluoroalkanols
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Optical resolutions of 5-alkyl-δ-valerolactones were carried out by derivatization to the diastereomeric amides, in which (R)-(+)-1-(1-naphthyl)ethylamine or (S)-(-)-1-phenylethylamine were used as resolving agents. Optically active 5-fluoroalkanols, useful intermediates for fluorinated ferroelectric liquid crystals, were derived from the resolved lactones in four steps without racemization.
- Riswoko, Asep,Aoki, Yoshio,Hirose, Takuji,Nohira, Hiroyuki
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- Chemoenzymatic synthesis of (2R)-2-hydroxyundecan-6-one
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Optimisation of kinetic resolution of racemic 5-hydroxyhexanenitrile (2) was performed; acetylation with vinyl acetate, catalyzed by Pseudomonas cepacia lipase immobilized on ceramics (PS-C) in n-hexane, afforded (5R)-acetoxy-hexanenitrile [(R)-3] with 94% ee and 94% yield; E = 83. Deacetylation of (R)-3, protection of (R)-2 by tert-butyldimethylsilyl group, Grignard reaction of (R)-4 with n-pentyl magnesium bromide, and final deprotection of (R)-5 afforded the title compound (R)-6 in 32% overall yield from 1 and 94% enantiomeric purity. Absolute configuration of (R)-6 was assigned by chemical correlations to (5R)-methyl-5-pentanolide [(R)-7].
- Ljubovic,Sunjic
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p. 423 - 426
(2007/10/03)
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- Synthesis and biological activity of artificial analogs of mycalamide A
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Artificial analogs of mycalamide A, a potent antitumor and antiviral compound isolated from a New Zealand marine sponge, were synthesized and their biological activities were tested.
- Fukui, Hideto,Tsuchiya, Yoshinori,Fujita, Keiko,Nakagawa, Tadakiyo,Koshino, Hiroyuki,Nakata, Tadashi
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p. 2081 - 2086
(2007/10/03)
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- (2S,6S,8S)-2,8-Dimethyl-1,7-dioxaspiroundecane: A Natural Spiroacetal Lacking Anomeric Stabilisation
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The absolute stereochemistry of the non-anomerically stabilised spiroacetal, (Z,Z)-2,8-dimethyl-1,7-dioxaspiroundecane, 4 which is a significant component of the pheromonal gland secretion of the cucumber fly (Bactrocera cucumis French) is shown to b
- Chen, Junjie,Fletcher, Mary T.,Kitching, William
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p. 967 - 972
(2007/10/03)
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- Total synthesis of the antiparasitic agent avermectin B1a
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The synthesis of avermectin B1a has been completed by a route that assembles the aglycon from three subunits consisting of the hexahydrobenzofuran moiety (A), the spiroketal segment (B), and the acyclic portion (C) comprising C9-C15. Connection is made in a B + C → (B -C) + A sequence, and the synthesis is concluded by attachment to the aglycon of the L-oleandrosyl-L-oleandrose disaccharide via the pyridylthio glycoside.
- White, James D.,Bolton, Gary L.,Dantanarayana, Anura P.,Fox, Christina M. J.,Hiner, Roger N.,Jackson, Randy W.,Sakuma, Kazuhiko,Warrier, Ulhas S.
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p. 1908 - 1939
(2007/10/02)
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- Asymmetric Hydrogenation of Olefins with Aprotic Oxygen Functionalities Catalyzed by BINAP-Ru(II) Complexes
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Cyclic α,β-unsaturated ketones, alkylidene lactones, and alkenyl ethers have been hydrogenated in high enantiomeric excesses by use of BINAP-Ru(II) complexes (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) as catalysts. 2-Alkylidenecyclopentanones were hydrogenated in the presence of Cl, Ru2Cl4(BINAP)2(NEt3), or Ru(OCOCH3)2(BINAP) in up to 98percent ee, while in the case of 2-benzylidene- and 2-(3-phenylpropylidene)cyclopentanones, enantiomeric excesses of the hydrogenation were below 50percent under the same conditions.The sense of asymmetric induction as well as the enantioselectivity (95percent ee) obtained in the hydrogenation of (E)-2-propylidene-γ-butyrolactone were the same as those of the (Z)-isomer.Lactones, 2- and 4-alkylidene-γ-butyrolactones, were converted to the corresponding saturated γ-butyrolactones in 95percent ee.Hydrogenation of diketene with the catalytic system derived from (benzene)>Cl and triethylamine or complex Ru2Cl42(NEt3) established a new synthetic route to (R)-4-methyl-2-oxetanone, a promising monomer of biodegradable polymers, in up to 97percent selectivity and 92percent ee.Alkenyl ethers, 2-methylenetetrahydrofuran, and 2-methyl-3,4-dihydrofuran have also been hydrogenated to give 2-methyltetrahydrofuran in 91 and 87percent ee, respectively.
- Ohta, Tetsuo,Miyake, Tsutomu,Seido, Nobuo,Kumobayashi, Hidenori,Takaya, Hidemasa
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p. 357 - 363
(2007/10/02)
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- Asymmetric Hydrogenation of 3,5-Dioxoesters Catalyzed by Ru-binap Complex: A Short Step Asymmetric Synthesis of 6-Substituted 5,6-dihydro-2-pyrones
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Asymmetric hydrogenation of 3,5-dioxoesters 1a-c using Ru2Cl4((R) or (S)-binap)2(NEt3) as the catalyst gave dominantly anti 3,5-dihydroxyesters 2, which were then converted into unsaturated lactones 5a-b (ca. 80percent e.e.).The pathway of the hydrogenation reaction was also investigated by asymmetric hydrogenation of (R)- or (S)-5-hydroxy-3-oxoesters 8a-c.It was revealed that the Ru-binap catalyzed hydrogenation of 1a-b proceed dominantly via the β-diketone mode.A convenient asymmetric synthesis of hydroxylactone 3c and unsaturated lactone 5c was presented.Key words: 3,5-dioxoester; Ru-binap catalyst; asymmetric hydrogenation; asymmetric synthesis; lactone
- Shao, Liming,Kawano, Hiroyuki,Saburi, Masahiko,Uchida, Yasuzo
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p. 1997 - 2010
(2007/10/02)
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- Enantioselective syntheses of (R)-(+)-δ-methyl-δ-valerolactone and (R)-(+)-6-methyl-ω-lactone
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Enantioselective syntheses of (R)-(+)-δ-methyl-δ-valerolactone (1) and (R)-(+)-6-methyl-ω-lactone (2) are reported using (R)-(-)-2-amino-n-dibutyl ether (3) as an enamine complexing agent in the chiral synthesis.
- Gadkari,Kapadi
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p. 407 - 408
(2007/10/02)
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- Enzymatic Resolution of Medium-Ring Lactones. Synthesis of (S)-(+)-Phoracantholide I
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The horse liver and pig liver esterase hydrolysis of racemic medium ring lactones gives with excellent enantiomeric excess the S- (or R) lactones and the corresponding R- (or S) hydroxy acids.This is the first general method to obtain optically pure medium ring lactones.Application to the preparation of (S)-(+)-Phoracantholide I is reported.
- Fouque, Elie,Rousseau, Gerard
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p. 661 - 666
(2007/10/02)
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- EPOXY-SILANES IN ORGANIC SYNTHESIS
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Stereoselective reactions involving functionalised β,γ-epoxysilanes and epoxide-allylsilanes provide a range of synthetically useful transformations.
- Procter, Garry,Russell, Andrew T.,Murphy, Patrick J.,Tan, T.S.,Mather, Andrew N.
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p. 3953 - 3974
(2007/10/02)
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- Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsaeurederivate, (R)- und (S)-Methyl- sowie (R)-Trifluormethyl-γ-butyrolactone und δ-valerolactone
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The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1,4- and 1,5-distance of the functional groups.The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1-6), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid, see 7) are decarboxylatively dimerized or "codimerized" with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate.The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9, 10), of (R)- and (S)-5-hydroxyhexanoic acid (see 11) and its trifluoro analogue (see 12, 13), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20), of (S)-2-hydroxy-4-methylpentanoic acid ("OH-leucine", see 21), and of (S)-2-hydroxy-6-aminohexanoic acid ("OH-lysine", see 22).Some of these products are further converted to CH3- or CF3-substituted γ- and δ- lactones of (R)- or (S)-confuguration (14, 16-19), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24).Possible uses of these new chiral building blocks for the synthesis of natural products and their CF3 analogues (brefeldin, sulcatol, zearalenone) are discussed.The olfactory properties of (R)- and (S)-δ-caprolactone (18) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone (19).
- Seebach, Dieter,Renaud, Philippe
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p. 2342 - 2349
(2007/10/02)
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- SYNTHESIS OF THE ENANTIOMERS OF CIS-2-METHYL-5-HEXANOLIDE, THE MAJOR COMPONENT OF THE SEX PHEROMONE OF THE CARPENTER BEE
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(2R,5S)-2-Methyl-5-hexanolide and its antipode were synthesized in highly optically pure state (98-99percent e.e.) starting from ethyl (S)-lactate and the enantiomers of methyl β-hydroxyisobutyrate.The specific rotations of our samples were D +/- 91.0 -93.5 deg (CHCl3), while the reported values of the samples prepared by resolution or asymmetric synthesis were +/- 64.5-65.6 deg.
- Mori, Kenji,Senda, Shuji
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p. 541 - 546
(2007/10/02)
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