Asymmetric Total Synthesis of Toxicodenane A

An organic chemistry minilecture on the Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity by Keisuke Nishikawa,* Koki Kikuta, Tomoki Tsuruta, Hitoshi Nakatsukasa, Sho Sugahara, Shinji Kume and Yoshiki Morimoto*. It features an asymmetric reductive Knoevenagel condensation, a samarium mediated radical cyclization and a zinc-promoted α,β-dehydrogenation reaction. SUPPORT THE CHANNEL ON PATREON:   / simplifyingsynthesis   Socials:   / simplifyingsynthesis     / simplifyingsyn1     / simplifyingsynthesis   References: Org. Lett. 2022, 24, 531−535 (This work) Org. Lett. 2013, 15, 3602−3605 (Isolation) Eur. J.Org. Chem. 2017, 2017, 6693−6699 (Previous synthesis) Tetrahedron Lett. 2020, 61, 152324−152326 (Previous synthesis) Org. Lett. 2021, 23, 8570−8574 (Previous synthesis) J. Org. Chem. 2007, 72, 14, 5056–5068 (Knoevenagel condensation) Org. Biomol. Chem., 2006, 4, 1641–1646 (Knoevenagel condensation) J. Org. Chem. 2007, 72, 8298-8307 (Mechanistic studies on the attack of P nucleophiles on disulfides) Nat Protoc. 2007, 2, 2451–2458 (Mosher Analysis) RSC Adv. 2013, 4, 308–321 (Magnetic Anisotropy in π systems) J. Chem. Soc., Chem. Commun., 1994, 2261-2262 (SmI2 coupling) J. Org. Chem. 1994, 59, 5111−5113 (SmI2 coupling) Org. Lett. 2018, 20, 3, 684–687 (α,β-Dehydrogenation) Free Radic. Biol. Med. 2015, 89, 831−841 (Bioassay) 0:00 Introduction 1:15 Retrosynthesis 2:11 Reductive Knoevenagel Condensation 3:13 Deprotection 3:25 Sulfidation 3:54 Corey-Bakshi-Shibata Reduction 4:51 Mosher Analysis 6:11 Riley Allylic Oxidation 8:10 Dess-Martin Periodinane Oxidation 9:22 Conjugate Methylation 10:14 Enantiodivergent Route 10:47 Biological Analysis