- Asymmetric Synthesis of Spiroketals with Aminothiourea Catalysts
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Chiral spiroketal skeletons are found as core structures in a range of bioactive compounds. These natural compounds and their analogues have attracted much attention in the field of drug discovery. However, methods for their enantioselective construction are limited, and easily available optically active spiroketals are rare. We demonstrate a novel catalytic asymmetric synthesis of spiroketal compounds that proceeds through an intramolecular hemiacetalization/oxy-Michael addition cascade mediated by a bifunctional aminothiourea catalyst. This results in spiroketal structures through the relay formation of contiguous oxacycles, in which multipoint recognition by the catalyst through hydrogen bonding imparts high enantioselectivity. This method offers facile access to spiroketal frameworks bearing an alkyl group at the 2-position, which are prevalent in insect pheromones. Optically active (2S,5S)-chalcogran, a pheromone of the six-spined spruce bark beetle, and an azide derivative could be readily synthesized from the bicyclic reaction product. Around and around: A catalytic asymmetric synthesis of spiroketals through an intramolecular hemiacetalization/oxy-Michael addition cascade with a bifunctional aminothiourea catalyst was developed. This method offers facile access to spiroketal frameworks bearing an alkyl group at the 2-position. Optically active (2S,5S)-chalcogran, a pheromone from the six-spined spruce bark beetle, and a derivative were readily synthesized from the bicyclic reaction product.
- Yoneda, Naoki,Fukata, Yukihiro,Asano, Keisuke,Matsubara, Seijiro
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- Preparation of Optically Enriched Secondary Alkyllithium and Alkylcopper Reagents—Synthesis of (?)-Lardolure and Siphonarienal
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Optically enriched secondary alkyl iodides were converted into secondary alkyllithium and secondary alkylcopper compounds with very high retention of configuration. Quenching with various electrophiles, including chiral epoxides, provided a range of chira
- Morozova, Varvara,Skotnitzki, Juri,Moriya, Kohei,Karaghiosoff, Konstantin,Knochel, Paul
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supporting information
p. 5516 - 5519
(2018/04/02)
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- Asymmetric transfer hydrogenation of quinolines using tethered Ru(II) catalysts
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The first report of an asymmetric transfer hydrogenation, in formic acid/triethylamine, of quinolines is described. Using a Ru(II) catalyst containing a 4-carbon tether, products of up to 73% ee were formed, whilst a Rh(III)-tethered catalyst gave products of up to 94% ee.
- Parekh, Vimal,Ramsden, James A.,Wills, Martin
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experimental part
p. 1549 - 1556
(2010/11/02)
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- Structure determination of an endogenous sleep-inducing lipid, cis-9-octadecenamide (oleamide): A synthetic approach to the chemical analysis of trace quantities of a natural product
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The pursuit of endogenous sleep-inducing substances has been the focus of an extensive, complicated body of research. Several compounds, including Δ-sleep-inducing peptide and prostaglandin D2, have been suggested to play a role in sleep induction, and yet, the molecular mechanisms of this physiological process remain largely unknown. In recent efforts, the cerebrospinal fluid of sleep-deprived cats was analyzed in search of compounds that accumulated during sleep deprivation. An agent with the chemical formula C18H35NO was found to cycle with sleep-wake patterns, increasing in concentration with sleep deprivation and decreasing in amount upon recovery sleep. Since the material was generated in minute quantities and only under the special conditions of sleep deprivation, efforts to isolate sufficient material for adequate characterization, structure identification, and subsequent detailed evaluation of its properties proved unrealistic. With the trace amounts of the impure endogenous compound available, extensive MS studies on the agent were completed, revealing key structural features of the molecule including two degrees of unsaturation, a long alkyl chain, and a nitrogen substituent capable of fragmenting as ammonia. Additionally, HPLC traces suggested a weak UV absorbance for the unknown material. With this data in hand and encouraged by the relatively small size of the molecule, MW = 281, a synthetic approach toward the structural identification of the natural compound was initiated. Herein, we report the full details of the synthesis and comparative characterization of candidate structures for this endogenous agent that led to the unambiguous structural correlation with synthetic cis-9-octadecenamide.
- Cravatt, Benjamin F.,Lerner, Richard A.,Boger, Dale L.
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p. 580 - 590
(2007/10/03)
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