A Convergent Synthesis of Gonytolide C Using an Intramolecular Oxa‐Michael Addition

Abstract

A full account of the evolution of a convergent total synthesis of gonytolide C is reported. The assembly of the natural product core relies on a Horner-Wadsworth-Emmons (HWE) olefination followed by an intramolecular oxa-Michael addition. Robust and efficient preparations of both HWE coupling part-

Chromanone Lactones: A Neglected Group of Natural Products – Isolation, Structure Elucidation, Bioactivity, and Synthesis

“…[47] The procedure published starts with a palladium-catalyzed asymmetric allylic CÀ H oxidation utilizing the chiral ligand 117, to produce compound 118 in 82 % yield with an ee of 92 % from 116 (Scheme 14). Modifications of the side chain allowed the production of the lactone moiety and ultimately, compound 122, which was used by Li et al to synthesize gonytolide C. [45] The procedure differs from that of Li et al in the preparation of the first stereogenic center, as in the first procedure it comes from a commercial starting material (98). In the second its created using the chiral ligand (117).…”

“…Scheme 12. Synthesis of gonytolide C and (2-epi)-gonytolide C by Li et al [45] Scheme 13. Synthesis of gonytolide C and blennolide C by Adachi et al [46] Scheme 14.…”

“…Modifications of the side chain allowed the production of the lactone moiety and ultimately, compound 122 , which was used by Li et al. to synthesize gonytolide C [45] . The procedure differs from that of Li et al.…”

“…Li et al in 2016, proposed a different methodology for the synthesis of gonytolide C; for this new procedure an intramolecular oxa-Michael addition was used to generate the desired chromanone lactone (Scheme 12). [45] The synthesis starts with the preparation of the chiral lactone 100 from tri-Oacetyl-D-glucal. Horner-Wadsworth-Emmons reaction with phosphonate 101 afforded the precursor for the oxa-Michael addition (102) that is converted into the CL 103 as a mixture of diastereomers.…”

Unprecedented Water Effect as a Key Element in Salicyl-Glycine Schiff Base Synthesis

“…To clarify the above observations, we hypothesized that trace amounts of water present in methanol led to the desired product, whereas an excess of water led to hydrolysis and, in its absence, other, different side reactions occurred. It is probable that under these anhydrous conditions, as the next step of condensation, the resulting ligand reacts with salicylaldehyde in an oxo-Michael reaction to form a chromanone derivative which can further react with compounds present in the mixture (Scheme 4) [28][29][30][31][32]. Additionally, we performed experimental studies on the thermal stability of both forms 1a and 1b in their solid states and the reversibility of their transformation to each other.…”