Isolation, Structure, and Total Synthesis of the Marine Macrolide Mangrolide D

Abstract

The isolation, characterization and total synthesis of the macrocyclic polyene mangrolide D is reported. A 16-step total synthesis relies on robust Suzuki and ring-closing metathesis reactions, and an iron-catalyzed hydroazidation of an exo-methylene substituted tetrahydropyran as a key step for the synthesis of the appended 4-epi-vancosamine sugar. Although mangrolide D did not display antibiotic activity, this work should prove enabling towards the synthesis of the antitubercular tiacumicins which display a virtually identical macrocyclic backbone.

Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β‐Glycosylations

“…Following similar strategies, Gademann also synthesized three congeners of Tcn‐B: tiacumicin A and mangrolides A and D . In 2019, de Brabander also reported a total synthesis of mangrolide D . As to our contribution, we reported two related synthetic pathways leading to the aglycone .…”

“…b) The rhamnosylation was carried out on the macrolide, using an imidate donor (a/b: 1/4, b: 62 %). Following similar strategies, Gademann also synthesized three congeners of Tcn-B: tiacumicin A [12] and mangrolides A [14] and D. [15] In 2019, de Brabander also reported a total synthesis of mangrolide D. [16] As to our contribution, we reported two related synthetic pathways leading to the aglycone. [17] We designed an original strategy for the synthesis of the C12-C15 diene region of this aglycone and this resulted in the discovery that Pd-nanoparticles catalyze the Kumada-Corriu reaction of vinylsulfides, [18] and also led us to study Griggs allene/alkyne cross-coupling and to propose a mechanism based on DFT calculations.…”

Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β‐Glycosylations

“…Following similar strategies, Gademann also synthesized three congeners of Tcn‐B: tiacumicin A and mangrolides A and D . In 2019, de Brabander also reported a total synthesis of mangrolide D . As to our contribution, we reported two related synthetic pathways leading to the aglycone .…”

Chemistry and Biology of the Clinically Used Macrolactone Antibiotic Fidaxomicin

“…In the following section, the different approaches will be presented and compared. Apart from these syntheses, also total syntheses of natural products containing a similar macrocyclic scaffold, mangrolides A and D, have been recently synthetically prepared …”