22791-77-1Relevant academic research and scientific papers
Highly Enantioselective Intermolecular Cu(I)-Catalyzed Cyclopropanation of Cyclic Enol Ethers. Asymmetric Total Synthesis of (+)-Quebrachamine
Temme, Oliver,Taj, Shabbir-Ali,Andersson, Pher G.
, p. 6007 - 6015 (2007/10/03)
A set of cyclic enol ethers derived from 2,3-dihydrofuran 35 and 3,4-dihydropyran 8 with a varying substitution pattern at the olefinic system were synthesized. Evans's ligand 5 with Cu(I)OTf was found to be an effective catalyst in the cyclopropanation reaction between cyclic enol ethers 14, 19, 28-31, and 33 and ethyl diazoacetate 6 to give diastereoselectivities up to exo/endo = 95:5 and enantioselectivities higher than 95% in nearly all cases. Because of the selective building of a quarternary carbon center and good yields in the formation of bicyclic structures 34c-h, the reaction was used as a key step in the asymmetric synthesis of (+)-quebrachamine 7, an indole alkaloid of the Aspidosperma family. After acid-induced ring opening of bicyclic compound 34f to lactone 40 followed by LiAlH4 reduction to the masked aldehyde 41, a reaction with tryptamine gave intermediate 42. This alcohol was efficiently converted into the indole alkaloid (+)-quebrachamine 7 in an overall yield of 37% starting from the chiral synthon 34f. Moreover it revealed the absolute configuration of the quarternary center of the cyclopropanation product 34f to be S.
New strategies in carbonylation chemistry: The synthesis of δ-lactones from saturated alcohols and CO
Tsunoi, Shinji,Ryu, Ilhyong,Okuda, Tohru,Tanaka, Minoru,Komatsu, Mitsuo,Sonoda, Noboru
, p. 8692 - 8701 (2007/10/03)
This paper describes the δ-carbonylation of saturated alcohols which uses a 1,5-hydrogen-transfer reaction of alkoxyl radicals and subsequent carbonylation at the δ-carbon atoms as the key. The carbonylation reactions of five classes of saturated alcohols, namely, primary alcohols having primary δ-carbons, primary alcohols having secondary δ-carbons, primary alcohols having tertiary δ-carbons, secondary alcohols having primary δ- carbons, secondary alcohols having secondary δ-carbons, were carded out, in which lead tetraacetate (LTA) was used as a one-electron oxidant to generate the alkoxyl radicals. Carbonylation of these saturated alcohols, except for primary alcohols having tertiary δ-carbons, took place to afford δ-lactones in moderate to good yields. The mechanism of the remote carbonylation likely involves (1) alkoxyl radical generation via LTA oxidation of a saturated alcohol, (2) conversion of this alkoxyl radical to a δ-hydroxyalkyl radical by a 1,5-hydrogen-transfer reaction, (3) CO trapping of the δ-hydroxyalkyl radical yielding an acyl radical, and (4) oxidation and cyclization of the acyl radical to give a δ-lactone. A metal salt-free system was also tested for a substrate derived from a tertiary alcohol having a secondary δ- carbon; the photolysis of an alkyl 4-nitrobenzenesulfenate under CO pressures gave a δ-lactone in moderate yield.
Catalytic iron-mediated ene carbocyclizations: Formal [4+4]-ene reactions of triene esters
Takacs, James M.,Newsome, Peter W.,Kuehn, Cynthia,Takusagawa, Fusao
, p. 5507 - 5522 (2007/10/02)
2-Substituted-2,7,9-decatrienoates undergo an iron-catalyzed carbocyclization to yield trans-disubstituted cyclopentanes in moderate-to-good chemical yields. The cyclization products are formally the result of a [4+4]-ene reaction in which cis-propenyl and 2-acroyl functionalities are introduced as appendages to the newly formed cyclopentane ring by the cyclization. Triene ester substrates bearing an alkyl substituent at the 4- or 6-positions cyclize with high 1,2-stereoinduction to yield trisubstituted cyclopentanes in which the relative stereochemistry between three contiguous stereocenters is controlled.
Asymmetric Synthesis of 2-Substituted Butyrolactones and Valerolactones
Meyers, A. I.,Yamamoto, Yukio,Mihelich, Edward D.,Bell, Richard A.
, p. 2792 - 2796 (2007/10/02)
The use of chiral oxazolines 1, 2, 5, and 8 under asymmetrically induced alkylation conditions gave α-substituted oxazolines 3, 6, 9, and 13 which were hydrolyzed to α-substituted butyro- and valerolactones 4 and 11.Either enantiomer of the lactones could be prepared in predictable absolute configuration by reversing the order of alkyl group introduction.The lactones were prepared in 60-86 percent enantiomeric excess which was determined by either chemical correlation or high-pressure liquid chromatography of the diastereomers 10.
Metabolite pattern of valproic acid. I. Gaschromatographic determination of the valproic acid metabolite artifacts, heptanone-3, 4- and 5-hydroxyvalproic acid lactone
Schaefer,Luehrs
, p. 657 - 662,658,660 (2007/10/05)
Metabolites arising from enzymatic oxidation of valproic acid (VPA, Orfiril) are determined after incubating body fluids at 37°C with an equal volume of diluted mineral acid, such as 85% w/w H3PO4/1 N HCl (1 : 1, v/v) for 3 h. 3-Ketovalproic acid (3-keto-VPA, 2-propyl-3-ketovaleric acid), which appears as the main metabolite, is hereby converted into heptanone-3 by ketonic hydrolysis. 4-Hydroxyvalproic acid (4-hydroxy-VPA, 2-propyl-4-hydroxyvaleric acid) and 5-hydroxyvalproic acid (5-hydroxy-VPA, 2-propyl-5-hydroxyvaleric acid) are converted into their corresponding lactones (4-HVL, 5-HVL). The kinetics of these reactions was studied using synthesized reference substances. Ketonic hydrolysis and lactone formation under the conditions for extraction procedures were reproducible and almost quantitative. An accurate and rapid determination of these metabolites as well as VPA from body fluids, if necessary after treating with glucuronidase, is thus made possible. A preliminary study of the metabolite patterns of patients on VPA therapy is presented. 3-Keto-VPA, 4-hydroxy-VPA and 5-hydroxy-VPA are excreted predominantly as the non-conjugates. 4-Hydroxy-VPA is also occasionally detected in the serum in quantities of 1-2 μg/ml.
