4111-54-0Relevant articles and documents
229. Bestimmung des Aggregationsgrads lithiumorganischer Verbindungen durch Kryoskopie in Tetrahydrofuran
Bauer, Walter,Seebach, Dieter
, p. 1972 - 1988 (1984)
The association behaviour of alkyl-, aryl- and alkinyl-lithium compounds as well as of lithium enolates and chiral lithium azaenolates is determined from-freezing point depression values in dilute tetrahydrofuran solutions at -108 grad C.Compared to X-ray-crystallographic data (lithiated methyldithiane, phenyllithium, lithio derivatives of a ketone, carboxylic amide and -ester, and a diketopiperazine-bislactim-ether), desaggregation is found under these conditions.The structutres determined by 13C-NMR spectroscopy for BuLi, lithiophenylacetylene and (t-butyl)lithioacetylene are confirmed.The dilithio salt of a carboxylic acid is polymeric, a chiral lithio-hydrazone and a chiral lithio-oxazolidine are monomeric and dimeric, respectively.Lithium diisopropylamide is a monomer-dimer equilibrium mixture.The apparatus described permits both synthesis and measurement of the reactive species under inert atmosphere conditions in the same vessel.
Newcomb,Ford
, p. 2968,2970 (1974)
Synthesis of C-5a-substituted derivatives of 4-epi-isofagomine: Notable β-galactosidase inhibitors and activity promotors of GM1-gangliosidosis related human lysosomal β-galactosidase mutant R201C
Thonhofer, Martin,Weber, Patrick,Gonzalez Santana, Andres,Tysoe, Christina,Fischer, Roland,Pabst, Bettina M.,Paschke, Eduard,Schalli, Michael,Stütz, Arnold E.,Tschernutter, Marion,Windischhofer, Werner,Withers, Stephen G.
, p. 71 - 80 (2016)
From an easily available partially protected analog of 1-deoxy-L-gulo-nojirimycin, by chain-branching at C-4 and suitable modification, lipophilic analogs of the powerful β-D-galactosidase inhibitor 4-epi-isofagomine have been prepared. New compounds exhibit considerably improved inhibitory activities when compared with the unsubstituted parent compound and may serve as leads toward new pharmacological chaperones for GM1-gangliosidosis and Morquio B disease.
Synthesis of a potent antimalarial amphilectene
Pronin, Sergey V.,Shenvi, Ryan A.
, p. 19604 - 19606 (2012)
7-Isocyano-11(20),14-epiamphilectadiene, the most potent of antimalarial amphilectenes, is synthesized in seven steps from readily available materials. The synthesis is enabled by a new dendrimeric triene (Danishefsky [3]-dendralene) and a new method for stereo- and chemoselective isocyanation. This chemistry provides a useful entry into an underexplored yet promising family of antimalarial terpenoids.
Total synthesis of marine eicosanoid (-)-hybridalactone
Ota, Koichiro,Sugata, Naoto,Ohshiro, Yoshihiko,Kawashima, Etsuko,Miyaoka, Hiroaki
, p. 13531 - 13537,7 (2012)
(-)-Hybridalactone (1) is a marine eicosanoid isolated from the red alga Laurencia hybrida. This natural product contains cyclopropane, cyclopentane, 13-membered macrolactone and epoxide ring systems incorporating seven stereogenic centers. Moreover, this compound has an acid-labile skipped Z,Z-diene motif. In this paper, we report on the total synthesis of (-)-hybridalactone (1). The unique eicosanoid (-)-hybridalactone (1) was synthesized starting from optically active γ-butyrolactone 2 in a linear sequence comprising 21 steps with an overall yield of 21.9 %. A key step in the synthesis of (-)-hybridalactone (1) is the methyl phenylsulfonylacetate-mediated one-pot synthesis of the cis-cyclopropane-γ-lactone derivative. This reaction provided an efficient and stereoselective access to cis-cyclopropane-γ-lactone 12. Further elaboration of the latter compounds through desulfonylation, epoxidation, oxidation, Wittig olefination and Shiina macrolactonization afforded (-)-hybridalactone.
Synthesis method of 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester
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Paragraph 0017-0018; 0039-0046; 0055-0056; 0065-0066, (2021/03/03)
The invention relates to a synthesis method of 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester. According to the method, by using lithium metal and diisopropylamine as raw materials, reaction isinitiated under the action of styrene to prepare an intermediate product LDA, thereby solving the problem of overlow reaction temperature in the prior art, and the intermediate is directly mixed witha raw material tert-butyl acetate without further treatment to prepare an intermediate tert-butyl lithioacetate in a micro-channel reactor, and then the intermediate tert-butyl lithioacetate and ethyl 4-cyano-3-hydroxybutyrate are used for preparing the target product 3-oxo-5-hydroxy-6-cyanohexanoic acid tert-butyl ester in the micro-channel reactor. The reaction time is greatly shortened, the pollution is small, the pollutant emission is less, the cost is low, and the post-treatment is simple; and the yield reaches 99%, the purity is 99% or above, and the method is especially suitable for industrial large-scale production.
Selective Continuous Flow Iodination Guided by Direct Spectroscopic Observation of Equilibrating Aryl Lithium Regioisomers
Dunn, Anna L.,Leitch, David C.,Journet, Michel,Martin, Michael,Tabet, Elie A.,Curtis, Neil R.,Williams, Glynn,Goss, Charles,Shaw, Tony,O'Hare, Bernie,Wade, Charles,Toczko, Matthew A.,Liu, Peng
supporting information, p. 129 - 137 (2018/10/09)
The iodination of 4-fluoro-2-(trifluoromethyl)benzonitrile via C-H lithiation and subsequent treatment with iodine under continuous flow conditions is described. Screening identified both LDA and PhLi as effective bases, giving the desired 3-iodo regioisomer as the major product. Use of LDA results in varying amounts of the undesired 5-iodo isomer, while PhLi results in more reliable formation of the 3-iodo product. An initial flow process was developed using PhLi that produced 4-fluoro-3-iodo-2-(trifluoromethyl)benzonitrile in 63% yield on a gram scale. Process modifications to enable pilot-scale operation resulted in a yield decrease to 50%, persistent formation of a byproduct resulting from PhLi addition to the nitrile, and formation of solids during longer runs. As a result, the use of LDA was investigated under continuous flow conditions. In situ NMR and IR spectroscopy allowed observation of the 5-[Li] species and its conversion to the thermodynamically preferred 3-[Li] species. These mechanistic insights drove development of a second-generation continuous flow process using LDA that achieves 30:1 regioselectivity and an 84% solution yield of the desired product (67% isolated yield after recrystallization). Furthermore, this process increases throughput by 10-fold, providing a path to manufacturing-scale operation.
