936-13-0Relevant academic research and scientific papers
COMPOUNDS, COMPOSITIONS, AND METHODS
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Paragraph 0354, (2018/01/18)
The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, deuterated analog, prodrug, tautomer, stereoisomer, or mixture of stereoisomers thereof, and methods of making and using thereof.
Substrate-directable electron transfer reactions. Dramatic rate enhancement in the chemoselective reduction of cyclic esters using SmI2-H 2O: Mechanism, scope, and synthetic utility
Szostak, Michal,Spain, Malcolm,Choquette, Kimberly A.,Flowers, Robert A.,Procter, David J.
supporting information, p. 15702 - 15705 (2013/11/06)
Substrate-directable reactions play a pivotal role in organic synthesis, but are uncommon in reactions proceeding via radical mechanisms. Herein, we provide experimental evidence showing dramatic rate acceleration in the Sm(II)-mediated reduction of cyclic esters that is enabled by transient chelation between a directing group and the lanthanide center. This process allows unprecedented chemoselectivity in the reduction of cyclic esters using SmI2-H2O and for the first time proceeds with a broad substrate scope. Initial studies on the origin of selectivity and synthetic application to form carbon-carbon bonds are also disclosed.
Sml2-mediated carbon-carbon bond fragmentation in a-aminomethyl malonates
Xu, Qiongfeng,Cheng, Bin,Ye, Xinshan,Zhai, Hongbin
supporting information; experimental part, p. 4136 - 4138 (2009/12/30)
A new and efficient samarium diiodide-promoted carbon-carbon bond fragmentation reaction of α-aminomethyl malonates, taking place normally at room temperature and generating the corresponding deaminomethylation products In 74-94% yields, is reported. The presence of the amino group Is necessary for the success of the current transformation.
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.
Titanocene-Catalyzed Reduction of Lactones to Lactols
Verdaguer, Xavier,Hansen, Marcus C.,Berk, Scott C.,Buchwald, Stephen L.
, p. 8522 - 8528 (2007/10/03)
A convenient method for the conversion of lactones to lactols is described. The hydrosilylation to lactols is carried out via air-stable titanocene difluoride or a titanocene diphenoxide precatalyst using inexpensive polymethylhydrosiloxane (PMHS) as the stoichiometric reductant. These procedures have been demonstrated with a variety of substrates and proceed in good to excellent yield.
Synthesis and 29-14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-carboxymethyl-5 beta-cholestan-26-oic acid. A bile acid occurring in peroxisomal diseases.
Parmentier,Busson,Janssen,Mannaerts,Eyssen
, p. 351 - 356 (2007/10/02)
The synthesis and 14C-labeling of 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-carboxymethyl-5 beta-cholestan-26-oic acid by two different approaches is described. One of them involves chain elongation of cholic acid via Wittig-Horner condensation of its formylated 24-aldehyde with tetraethyl phosphonoglutarate. The resulting cholestenoate, on deprotection and hydrogenation, affords the unusual C29 bile acid in good yield. An alternative procedure consists in a malonic ester synthesis starting from the formylated 24-alcohol which, after conversion into a mesylate, is reacted with sodium salt of 2-carboethoxy-gamma-butyrolactone. Alkaline hydrolysis, decarboxylation, esterification with diazomethane and selective tosylation of the newly introduced primary hydroxyl function give a C28 precursor, which is easily chain-elongated into a labeled or unlabeled C29 bile acid by reaction with cyanide and hydrolysis. Due to the easy lactonization of some of the C28 intermediates, the latter method provides a better way for introducing a C-29 label than the sequence usually employed for carboxyl labeling of bile acids and consisting in a decarboxylative halogenation of the parent acid followed by substitution of the norhalogenide with [14C]cyanide and hydrolysis. The structure of the synthesized acid or its dimethyl ester is confirmed by 13C nuclear magnetic resonance spectroscopy and mass spectrometry, and is also shown by gas liquid chromatography to be identified with an authentic sample of biosynthetic C29 dioic bile acid extracted from body fluids of Zellweger patients.
Cyclopropane Derivatives, 2. - Self-Acylation of α-Alkyl-γ-lactones To Give Bis(1-alkylcyclopropyl)ketones via Spiroacetals
Boehrer, Gerald,Knorr, Rudolf,Boehrer, Petra
, p. 2161 - 2166 (2007/10/02)
High-yield synthetic ways are recommended for the title lactones 1.The coupling of two 2-alkyl-4-butanolides is possible in an inter-(1b, c) or intramolecular fashion (4c) to give spiroacetals 8 or 9, respectively, in the absence of hindering substituents.Symmetrically substituted bis(1-alkylcyclopropyl)ketones 12 and 13 may be prepared by acidic cleavage of those spiroacetals lacking 2,7-substituents.
ALKYLATION OF MALONIC ESTER WITH β-CHLOROETHYL VINYL ETHER
Krasavtsev, I. I.,Basalkevich, E. D.,Matvienko, L. P.,Lozinskii, M. O.
, p. 1046 - 1048 (2007/10/02)
The conditions for the alkylation of malonic ester with β-chloroethyl vinyl ether were determined.It was shown that during hydrolysis the alkylation product is converted into γ-butyrolactone or 3-ethoxycarbonyl-γ-butyrolactone, depending on the conditions.The bromination of the alkylation product takes place not at the active hydrogen atom but at the double bond.The action of bases on the obtained dibromide leads to intramolecular alkylation, and this leads to cyclic derivatives of acetoacetic ester.
Bis(trimethylsilyl) Sulfate Catalysis in γ-Lactonization of Cyclopropanecarboxylates Activated by Carbonyl Substituents on α-Carbon
Morizawa, Yoshitomi,Hiyama, Tamejiro,Oshima, Koichiro,Nozaki, Hitosi
, p. 1123 - 1127 (2007/10/02)
The title reaction of 1-carbonyl substituted cyclopropanecarboxylates proceeds under C(1)-C(2) bond cleavage to produce γ-lactones.Stereochemically, the reaction takes two pathways: (1) substrates with a cationstabilizing group like vinyl on C(2) give thermodynamically favored γ-lactones having the thermodynamically more stable arrangement of substituents irrespective of the configuration of the cyclopropane substrates, (2) substrates without such a cation-stabilizing group afford γ-lactones under ca. 70percent inversion at C(2) reaction center.
