Total Synthesis of the Initially Reported and Revised Structures of the Neuroprotective Agent Palmyrolide A

Abstract

The total syntheses of the initially reported and revised structures of the neuroprotective agent palmyrolide A are reported. The key macrocyclization step was achieved using a sequential ring closing metathesis/olefin isomerization reaction. The synthetic work described herein serves to confirm the recent structural revision of this unusual natural product.

Shellfish Toxins Targeting Voltage-Gated Sodium Channels

“…In 2012, Maio and coworkers reported the first total synthesis of (+)-ent-palmyrolide A and the first asymmetric total synthesis, along with the absolute configurations of products they obtained [114,115]. Meanwhile, Brimble and coworkers accomplished a total synthesis of the initially reported and the revised structures [116]. In 2013, Reddy et al disclosed the shortest synthetic route for (+)-palmyrolide A and produced (−)- cis -palmyrolide A for the first time by modifying Maio’s macrocyclization conditions [112].…”

Synthesis of palmyrolide A and its cis-isomer and mechanistic insight into trans–cis isomerisation of the enamide macrocycle

“…A solution of keto compound 6 (20.0 mg, 0. (S)-(3S,5S)-9-Amino-2,2,5-trimethyl-9-oxononan-3-yl 2-methylhex-5-enoate (8) 4 : To a solution of acid 7 6 (100 mg, 0.78 mmol) in benzene (3.0 mL), was added 2,4,6trichlorobenzylchloride (0.17 mL, 1.12 mmol), followed by Hunigs base (0.16 mL, 0.95 mmol), alcohol 4 (120 mg, 0.56 mmol) and DMAP (170 mg, 1.40 mmol). The reaction mixture was stirred at room temperature for 12 h before being diluted with EtOAc (10 mL).…”

Impact of copper-catalyzed cross-coupling reactions in natural product synthesis: the emergence of new retrosynthetic paradigms

“…75 In this synthesis, a rst copper-catalyzed intramolecular arylation of the amine in 96 under ligandless conditions, reported by the same group, 76 was used to form the rst indoline ring system in 67% yield. The formation of the second ring was found to be remarkably efficient when a carbamate (98) was used as the N-nucleophile, provided that a stoichiometric amount of copper(I) iodide was used. As a note, the indole The development and the robustness of these copper-catalyzed cyclization reactions for the installation of small nitrogenheterocycles together with the possibility of using non-classical bond disconnections prompted further studies which culminated in the design of remarkably efficient copper-catalyzed macrocyclization procedures that are excellent alternatives to standard macrolactamization techniques.…”