Towards the total synthesis of keramaphidin B

Abstract

SummaryThe enantio- and diastereoselective Michael addition of a δ-valerolactone-derived pronucleophile to a substituted furanyl nitroolefin catalysed by a bifunctional cinchonine-derived thiourea has been used as the key stereocontrolling step in a new synthetic strategy to the heavily functionalised piperidine core of keramaphidin B.

Relevant Developments in the Use of Three‐Component Reactions for the Total Synthesis of Natural Products. The last 15 Years

“…[55] Since this pioneering work, several other (formal) total syntheses were reported; Interestingly, however, the group of Dixon developed an approach entailing a 3CR to synthesize the piperidin-2-one ring of the key intermediate 64 (Scheme 9). [56] In this work, the precursor 62 was obtained by a Michael addition of the β-ketoester 60 and the Michael acceptor 61 using KHMDS with 18-crown-6 (65 % yield, dr = 3 : 1), and used to perform a 3CR reaction, which involves a nitro-Mannich/ lactamization [57] cascade with formaldehyde and the amine 63. This transformation resulted in 4-nitro-piperidin-2-one 64 in 88 % yield.…”

The Last Fortress of Tin's Tyranny – Protodenitration of Nitroalkanes

“…[187] *Protodenitration was accompanied by a reduction of a methoxycarbonyl moiety. 2013), [188] Thomson (2013), [189] Zhao (2013), [190] Hayashi (2014), [191] Pascal Jr. (2014), [192] Dixon and Ye (2015), [193] Lu (2015), [194] Gong and Meggers (2015), [195] Enders (2015), [196] Wolf (2016), [197] Dixon (2016), [198] Lu and Xiao (2016), [199] Gu and Tian (2016), [200] You (2017), [201] Hayashi (2017), [202] Ryan and Hyland (2017), [203] Anderson (2018), [204] Liang (2018), [205] Hayashi (2018), [206] Li (2018), [207] Xu and Yuan (2018), [208] Xu and Yuan (2018), [209] Hayashi (2019), [210] Ishikawa (2019) [211] and Ye (2019). [212] *Denitration was accompanied by a reduction of a xanthate ester moiety.…”

The Stereoselective Nitro-Mannich Reaction in the Synthesis of Active Pharmaceutical Ingredients and Other Biologically Active Compounds

“…It is also a member of the manzamine family of alkaloids, and it contains an intricate structure comprising a 6,6,6,11,13 pentacycle possessing 4 stereogenic centers including one quaternary center. Dixon and coworkers reported an approach to the synthesis of this alkaloid in 2016 (Jakubec et al, 2016). The stereochemistry of the molecule was established in an early step, a Michael addition reaction of a δ-valerolactone-derived pronucleophile to a substituted furanyl nitroolefin catalyzed by a bifunctional cinchonine-derived thiourea.…”