78324-15-9Relevant articles and documents
Total Synthesis of Resiniferatoxin Enabled by Radical-Mediated Three-Component Coupling and 7-endo Cyclization
Hashimoto, Satoshi,Katoh, Shun-Ichiro,Kato, Takehiro,Urabe, Daisuke,Inoue, Masayuki
supporting information, p. 16420 - 16429 (2017/11/22)
Resiniferatoxin (1) belongs to a daphnane diterpenoid family and has strong agonistic effects on TRPV1, a transducer of noxious temperature and chemical stimuli. The densely oxygenated trans-fused 5/7/6-tricarbocycle (ABC-ring) of 1 presents a daunting challenge for chemical synthesis. Here we report the development of a novel radical-based strategy for assembling 1 from three components: A-ring 9, allyl stannane 18b, and C-ring 17b. The 6-membered 17b, prepared from d-ribose derivative 19, was designed to possess the caged orthoester structure with α-alkoxy selenide as a radical precursor. Upon treatment of 17b with 18b, 9, and V-40, the potently reactive α-alkoxy bridgehead radical was generated from 17b and then sequentially coupled with 9 and 18b to yield 16b. This first radical reaction formed the hindered C9,10-linkage between the A and C-rings and extended the C4-chain on the A-ring in a stereoselective fashion. After derivatization of 16b into 15, the remaining 7-membered B-ring was cyclized in the presence of n-Bu3SnH and V-40 by utilizing the xanthate on the C-ring as the radical precursor and the allylic dithiocarbonate as the terminator. The second radical reaction thus enabled not only the 7-endo cyclization but also construction of the C8-stereocenter and the C6-exo olefin. Tricycle 14 was elaborated into the targeted 1 by a series of highly optimized chemoselective reactions. The present total synthesis of 1 demonstrates the advantages of radical reactions for linking hindered bonds within carbocycles without damaging preexisting functionalities, thereby offering a new strategic design for multistep target-oriented synthesis.
Reaction discovery by using a sandwich immunoassay
Quinton, Julia,Kolodych, Sergii,Chaumonet, Manon,Bevilacqua, Valentina,Nevers, Marie-Claire,Volland, Herve,Gabillet, Sandra,Thuery, Pierre,Creminon, Christophe,Taran, Frederic
supporting information; experimental part, p. 6144 - 6148 (2012/07/17)
Mmm, a reaction sandwich Using an immunoassay-based technique able to monitor any kind of cross-coupling reaction, a systematic and rapid evaluation of a large panel of random reactions was carried out. This approach led to the discovery of two new copper-promoted reactions: a desulfurization reaction of thioureas leading to isoureas and a cyclization reaction leading to thiazole derivatives from alkynes and N-hydroxy thioureas. Copyright
