74892-81-2Relevant articles and documents
A Concise, Enantiospecific Total Synthesis of Chilocorine C Fueled by a Reductive Cyclization/Mannich Reaction Cascade
Lisnyak, Vladislav G.,Snyder, Scott A.
, p. 12027 - 12033 (2020)
Among defensive alkaloids isolated from ladybugs, the heterodimeric member chilocorine C possesses an alluring monomeric unit that combines quinolizidine and indolizidine substructures. Indeed, the overall stereochemical disposition of its ring fusions is distinct from those of related natural products. Herein we show that a carefully orchestrated sequence with several chemoselective transformations, including a designed cascade that accomplishes nine distinct chemical reactions in one-pot, can smoothly forge that domain and ultimately enable a 15-step, 11-pot enantiospecific synthesis of the natural product. Mechanistic studies, density functional theory calculations, and the delineation of several other unsuccessful approaches highlight its unique elements.
Preparation method for argatroban intermediate
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Paragraph 0063; 0064; 0065; 0067, (2018/11/03)
The invention discloses a preparation method for an argatroban intermediate. The preparation method comprises the following steps: subjecting (R)-4-methyldihydrofuran-2(3H)-one to ring opening and then to a reaction with sodium methoxide or potassium methoxide to form R-3-methyl-4-methyl-3-hydroxybutyrate; oxidizing R-3-methyl-4-methyl-3-hydroxybutyrate to form methyl (3R)-3-methyl-4-formylbutyrate; then reacting (3R)-3-methyl-4-formylbutyrate with hydantoin to form (3R)-3-methylene-butyric acid carbomethoxyhydantoin; successively carrying out purification, heating reflux and purification so as to obtain (4S)-4-methyl-2-oxoadipate; reacting (4S)-4-methyl-2-oxoadipate with an amino donor under the action of a catalyst, and carrying out purification so as to obtain (2R,4S)-2-amino-4-methyladipate; reacting (2R,4S)-2-amino-4-methyladipate with methanol, and carrying out purification so as to obtain (2R,4S)-2-amino-6-methoxy-4-methyl-6-oxohexanoic acid; and reacting (2R,4S)-2-amino-6-methoxy-4-methyl-6-oxohexanoic acid with a reducing agent, and carrying out purification so as to obtain the argatroban intermediate. The preparation method of the invention is mild in reaction conditions, low in cost and suitable for industrial production.
Enantioselective synthesis of trans-4-methylpipecolic acid
Alegret, Carlos,Santacana, Ferran,Riera, Antoni
, p. 7688 - 7692 (2008/02/13)
(Chemical Equation Presented) An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).
Asymmetric syntheses of enantiopure 4-substituted pipecolic acid derivatives
Agami, Claude,Bisaro, Fabrice,Comesse, Sebastien,Guesne, Sebastien,Kadouri-Puchot, Catherine,Morgentin, Remy
, p. 2385 - 2389 (2007/10/03)
(2R,4R)-4-Methylpipecolic acid and (2S,4R)-4-hydroxypipecolic acid, two biologically active amino acids, were synthesized using the same strategy. A third amino acid, obtained in a protected form, was also obtained in the same way. The key step of these syntheses involves an intramolecular eneiminium cyclization which occurs with complete stereoselectivity. The resulting exocyclic double bond can react in a diastereoselective way to afford pure lactones, which can then be efficiently converted into the amino acids.
Direct diastereoselective synthesis of (±)-cis- and (±)-trans-4-methylpipecolic acid and derivatives
Cossy, Janine,Belotti, Damien
, p. 2119 - 2120 (2007/10/03)
(±)-cis- or (±)-trans-4-Methylpipecolic acid and ester derivatives can be obtained directly by addition of electrophiles to α-lithiated N-Boc 4-methylpiperidine.
Asymmetric Synthesis of Unsaturated Pipecolic Acid Derivatives
Agami, Claude,Bihan, Dominique,Morgentin, Rémy,Puchot-Kadouri, Cathy
, p. 799 - 800 (2007/10/03)
Two enantiopure pipecolic acid derivatives having an olefinic moiety were synthesized from an intramolecular addition of allyl silanes on an iminium double bond. The iminium moiety was generated via a reaction of chiral β-amino alcohols with glyoxal.
HETEROAROMATIC AMINE THROMBIN INHIBITORS
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, (2008/06/13)
Sulfonamide thrombin inhibitors are provided which have the structure STR1 including all stereoisomers thereof, wherein n is 1, 2 or 3; m is 0, 1 or 2; R 1 and R 2 are independently H, lower alkyl, cycloalkyl, aryl, heteroaryl or heteroaryl-alkyl, or R 1 and R. sup.2 can be taken together with the N atom to which they are attached to form a 4-to 8-membered ring; R 3 is monocyclic heteroaryl; and R 4 is alkyl, cycloalkyl, aryl, heteroaryl, quinolinyl or tetrahydroquinolinyl, and pharmaceutically acceptable salts thereof.
An Improved Synthesis of Homoproline and Derivatives
Shuman, Robert T.,Ornstein, Paul L.,Paschal, Jonathan W.,Gesellchen, Paul D.
, p. 738 - 741 (2007/10/02)
An improved, general synthesis of substituted homoprolines has been developed by using readily available substituted pyridines (1).A key step in this synthetic procedure involves the known conversion of pyridine-N-oxides to 2-cyanopyridines (3) in nearly quantitative yields.The resulting nitriles are hydrolyzed to the corresponding pyridine-2-carboxylic acids (4).Subsequent reduction of the aromatic ring with PtO2/H2 gives the homoprolines (5) in good yields as racemic cis isomers.This procedure also can be utilized for the preparation of 5,6-benzohomoprolines fromthe appropriate quinoline precursors.The N-tert-butyloxycarbonyl (Boc) derivatives of these amino acids (useful intermediates for peptide synthesis) were also prepared in good yields.
