Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity.

The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI2)-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy. Finally, the synthetic compounds significantly inhibited lipotoxicity-mediated inflammatory and fibrotic responses in mouse renal proximal tubular cells.

[1]  Fu‐She Han,et al.  Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)-Toxicodenane A. , 2021, Organic letters.

[2]  G. Ferrence,et al.  Efforts toward the total synthesis of (±)-toxicodenane A utilizing an oxidopyrylium-based [5+2] cycloaddition of a silicon-tethered BOC-pyranone , 2020 .

[3]  D. Ramachary,et al.  Organocatalytic Reductive Propargylation: Scope and Applications. , 2019, The Journal of organic chemistry.

[4]  Yizhou Zhao,et al.  Synthesis of Cyclic Enones by Allyl-Palladium-Catalyzed α,β-Dehydrogenation. , 2018, Organic letters.

[5]  H. Abe,et al.  Diastereoselective Total Synthesis of (±)‐Toxicodenane A , 2017 .

[6]  T. Uzu,et al.  1-Methylnicotinamide ameliorates lipotoxicity-induced oxidative stress and cell death in kidney proximal tubular cells. , 2015, Free radical biology & medicine.

[7]  Yong‐Xian Cheng,et al.  Two New Sesquiterpenes from the Resin of Toxicodendron vernicifluum , 2015 .

[8]  Bin Cheng,et al.  Total synthesis of (±)-sculponeatin N. , 2014, Organic letters.

[9]  J. Lessard,et al.  Converting cycloalkanones into N-heterocycles: formal synthesis of (-)-gephyrotoxin 287C. , 2013, The Journal of organic chemistry.

[10]  Yong‐Xian Cheng,et al.  Sesquiterpenoids with new carbon skeletons from the resin of Toxicodendron vernicifluum as new types of extracellular matrix inhibitors. , 2013, Organic letters.

[11]  C. Lindsley,et al.  Enantioselective total synthesis of (+)-amabiline. , 2012, Organic letters.

[12]  Siyu Ye,et al.  Total synthesis of (+)-asteriscanolide: further exploration of the rhodium(I)-catalyzed [(5+2)+1] reaction of ene-vinylcyclopropanes and CO. , 2012, Chemistry, an Asian journal.

[13]  E. Corey,et al.  Highly enantioselective oxazaborolidine-catalyzed reduction of 1,3-dicarbonyl compounds: role of the additive diethylaniline. , 2009, Organic letters.

[14]  S. Castillón,et al.  Synthesis of D- and L-carbocyclic nucleosides via rhodium-catalyzed asymmetric hydroacylation as the key step. , 2008, Organic letters.

[15]  Cory Valente,et al.  Assessing synthetic strategies: total syntheses of (+/-)-neodolabellane-type diterpenoids. , 2008, Chemistry.

[16]  E. Corey,et al.  Conversion of Torgov's synthesis of estrone into a highly enantioselective and efficient process. , 2007, Journal of the American Chemical Society.

[17]  D. Ramachary,et al.  Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland-Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation sequence: scope and applications of organocatalytic biomimetic reductions. , 2007, The Journal of organic chemistry.

[18]  F. Matsuda,et al.  Efficient medium-ring cyclization under non-high-dilution conditions using SmI 2. , 2004, Organic letters.

[19]  M. Schlaf,et al.  Synthesis of allyl and alkyl vinyl ethers using an in situ prepared air-stable palladium catalyst. Efficient transfer vinylation of primary, secondary, and tertiary alcohols. , 2003, The Journal of organic chemistry.

[20]  F. Matsuda,et al.  Stereoselective Cyclization Mediated by Samarium(II) Iodide Using Allyl Sulfides and Sulfones as Ketyl Radical Acceptors , 1994 .

[21]  J. Clayden,et al.  Homoallylic alcohols from samarium diiodide-mediated coupling of allylic sulfones with carbonyl compounds , 1994 .