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

Abstract

Concise and protecting-group free synthesis of ent-palmyrolide A and (-)-cis-palmyrolide A were achieved starting from commercially available (S)-citronellal. The key fragment of palmyrolide A, "(5S,7S)-7-hydroxy-5,8,8-trimethylnonanamide", which makes up the most challenging part of the target molecule, was prepared in just three steps. A plausible mechanism for the trans-cis isomerization of the double bond in the macrocycle has been investigated.

Shellfish Toxins Targeting Voltage-Gated Sodium Channels

“…Palmyrolide A (C 20 H 36 O 3 N, m/z : 338.2690) ( Figure 8 ) is a novel neuroactive macrolide that features a rare N -methyl enamide and t -butyl branch [ 112 ]. In 2010, Gerwick and co-workers reported the isolation, structure determination, and biological activity of palmyrolide A.…”

“…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 ].…”

Total Synthesis of Kanamienamide and Clarification of Biological Activity

“… a CuI, K 3 PO 4 , trans -1,2-diaminocyclohexane, 1,4-dioxane 100–110 °C b CuI, Cs 2 CO 3 , N , N ′-dimethylethylenediamine (DMEDA), DMF, 60 °C. , …”

Total Synthesis and Structural Reassignment of Laingolide A

“…In 2010, Gerwick and co-workers reported the isolation of palmyrolide A ( 5 ), a structurally closely related 15-member macrolide from a cyanobacterial assemblage comprised of Leptolyngbya and Oscillatoria species collected at Palmyra Atoll, south of Hawaii [ 6 ]. One of the absolute configurations present in palmyrolide A was correctly assigned upon its initial isolation [ 15 ], and the absolute configurations of the remaining stereocentres were later established via total syntheses [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. The structurally intriguing laingolides have attracted considerable attention from the synthetic community [ 25 , 26 , 27 ].…”