1,721,002 research outputs found
Synthesis and Reactivity of Uhle’s Ketone and Its Derivatives
No full textUhle's ketone and its derivatives are highly versatile intermediates for the synthesis of a variety of 3,4-fused tricyclic indole frameworks, i.e. indole alkaloids of the ergot family, that are found in various bioactive natural products and pharmaceuticals. Therefore, the development of a convenient preparative method for this structural motif as well as its opportune/useful derivatization have been the subject of longstanding interest in the fields of synthetic organic chemistry and medicinal chemistry. Herein, we summarize recent and less recent methods for the preparation of Uhle's ketone and its derivatives as well as its main reactivity towards the synthesis of bioactive substances. Regarding the preparation, it can be roughly classified into two categories: (a) using 4-unfunctionalized and 4-functionalized indole derivatives as starting materials to construct a fused six-member ring, and (b) constructing the indole ring through intramolecular cycloaddition. Principally, the reactivity of the cyclic Uhle's ketone shown here is derived from the classical electrophilicity of the carbonyl carbon or the acidity of the alpha-hydrogen and, though less intensively investigated, chemical reactions that induce ring expansion to form novel ring skeletons
Synthesis of (−)-Epi-Indolactam V by an Intramolecular Buchwald–Hartwig C–N Coupling Cyclization Reaction
Full text linkThe synthetic efforts toward the concise synthesis of (−)-indolactam V from simple and commercially available starting materials using palladium- and copper-catalyzed intramolecular N-arylation strategy for the elaboration of the requisite nine-membered lactam ring as the key step are described. The incorporation of a turn-inducing structural element along the linear precursor was fundamental to achieve the heterocyclization step as well as obtain the correct regio- and chemoselectivity. The stereoselective nature in the C–N coupling cyclization reaction is interpreted in terms of minimization of allylic strain at the transition state for the palladium-amido complex formation. Meanwhile, the synthesis of the (−)-epi-indolactam V and its enantiomer have been accomplished
General Access to Clavine Alkaloids via a Rhodium(I)‐Catalyzed Diastereoselective Hayashi‐Miyaura Reaction
Full text linkWe report the development of the diastereoselective rhodium(I)-catalyzed intramolecular conjugate addition (Hayashi-Miyaura reaction) of robust and easily handled 4-pinacolboronic ester D-tryptophan derivatives tethering an activated alkene as the acceptor. This methodology provides, access to the functionalized chiral tricyclic core of the ergoline skeleton diastereoselectivity and allows further modification for the cyclization of the fused fourth ring present in several clavine alkaloids
C3-Alkylation of indoles and oxindoles by alcohols by means of borrowing hydrogen methodology
No full textTransition metal‐catalyzed C3‐alkylation of indoles and oxindoles with nonderivatized alcohols, by means of borrowing hydrogen (BH) activation of the alcohol substrates, avoids the use of environmentally unfriendly alkylating agents. Only water is formed as the byproduct, thus making the BH process atom‐economical and environmentally benign. Diverse homogeneous and heterogeneous transition‐metal catalysts, indoles and oxindoles, and nonderivatized alcohols can be used for this transformation, hence rendering the BH process promising for replacing those procedures that use traditional alkylating agents. Although some earlier literature is discussed, this review mainly covers the literature published since 2015
Metodo di sintesi di derivati del glutatione [Method for the synthesis of glutathione derivatives]
No full textA synthesis method for the production of N-acyl glutathione, comprising an acylation step, during which, in a water solution with a pH ranging from 8 to 10, glutathione is caused to react with an anhydride with formula (RCO)2O with a formation of S,N-diacyl glutathione, and a subsequent S-acyl group selective alcoholysis step, during which the S,N-diacyl glutathione produced in the previous step is dissolved in an alkoxide/alcohol solution (R'O-/R'OH) and, subsequently, the obtained product is treated with a cation-exchange resin. R is H or a straight or branched hydrocarbon group with a number of carbon atoms ranging from C1 to C24 while R' is a straight or branched radical hydrocarbon group with a number of carbon atoms ranging from C1 to C4
A Short Synthesis of (−)‐6,7‐Secoagroclavine via Metal‐Free Reductive Coupling
Full text linkA concise, convergent, and enantioselective synthesis of (−)-6,7-secoagroclavine, a pivotal intermediate in the synthesis of both clavine and ergot alkaloids, was accomplished from a derivative of the renowned Uhle's ketone. The synthesis is centered on metal-free reductive coupling of the tosylhydrazone derivative of protected 4-amino Uhle's ketone and commercially available 2,2-dimethylethenylboronic acid, which is used as a four-carbon building block. This novel approach directly sets the stereochemistry on the difficult-to-access aryl vinyl methane carbon stereogenic center of (−)-6,7-secoagroclavine
Development of a practical and sustainable strategy for the synthesis of ST1535 by an iron-catalyzed Kumada cross-coupling reaction
No full textA simple, convenient, and environmentally friendly route to ST1535 employing an iron-catalyzed cross-coupling reaction and butylmagnesium chloride is described
Concise and Convergent Enantioselective Total Syntheses of (+)- and (-)-Fumimycin
No full textThe concise and convergent total syntheses of (+)- and (-)-Fumimycin have been achieved by taking advantage of strategies for the asymmetric aza-Friedel-Crafts reaction of a highly substituted hydroquinone and N-fumaryl ketimine generated from the corresponding dehydroalanine. The enantiomerically pure natural product and its enantiomer were prepared in seven steps and 22% overall yield by employing both enantiomers of a BINOL-derived chiral phosphoric acid (CPA) catalyst
Direct, Regioselective, and Chemoselective Preparation of Novel Boronated Tryptophans by Friedel–Crafts Alkylation
Full text linkA facile synthetic approach to the direct preparation of various novel unnatural boronated protected tryptophans using a regio- and chemoselective electrophilic substitution of 4- and 5-boronated indoles with N-protected dehydroalanine is described. The gram-scale synthesis of two free tryptophan boronic acids is also reported
Total Synthesis of (-)-Clavicipitic Acid via γ,γ-Dimethylallyltryptophan (DMAT) and Chemoselective C-H Hydroxylation
Full text linkThe first total synthesis of natural (-)-clavicipitic acid from γ,γ-dimethylallyltryptophan (DMAT), its biosynthetic precursor, is described. This is done by regio- and chemoselective, remote, nondirected C(sp3)-H hydroxylation followed by aminocyclization. This study also features regio- and chemoselective Pd(0)-catalyzed linear prenylation at C4 of l-tryptophan boronic pinacol ester derivate, the latter obtained by a Lewis acid-promoted aziridine amino acid ring opening with 4-boronated indole. In addition, these results support the hypothesis that oxidative cyclization between amino acid nitrogen and the prenyl chain during clavicipitic acid biosynthesis can occur through the transient hydroxylated intermediate
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