Total Synthesis and Structural Revision of Mangrolide D

Hattori, Hiromu; Hoff, Lukas; Gademann, Karl

doi:10.1021/acs.orglett.9b01256

“…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.…”

Section: Dedicated To Professor Henri-philippe Hussonmentioning

confidence: 70%

“…b) The rhamnosylation was carried out on the macrolide, using an imidate donor ( α / β : 1/4, β : 62 %). 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 .…”

Section: Methodsmentioning

confidence: 99%

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

Norsikian

¹

,

Tresse

²

,

François-Eude

³

et al. 2020

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A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen‐bond‐mediated aglycone delivery (HAD). This new HAD variant permitted highly β‐selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1–C3 fragment thus obtained was anchored to the C4–C19 aglycone fragment by adapting the Suzuki–Miyaura cross‐coupling used for the aglycone synthesis. Ring‐size‐selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.

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“…b) The rhamnosylation was carried out on the macrolide, using an imidate donor ( α / β : 1/4, β : 62 %). 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 .…”

Section: Methodsmentioning

confidence: 99%

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

Norsikian

¹

,

Tresse

²

,

François-Eude

³

et al. 2020

View full text Add to dashboard Cite

A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen‐bond‐mediated aglycone delivery (HAD). This new HAD variant permitted highly β‐selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1–C3 fragment thus obtained was anchored to the C4–C19 aglycone fragment by adapting the Suzuki–Miyaura cross‐coupling used for the aglycone synthesis. Ring‐size‐selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.

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“…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 …”

Section: Total Synthesesmentioning

confidence: 99%

Chemistry and Biology of the Clinically Used Macrolactone Antibiotic Fidaxomicin

Dorst

¹

,

Gademann

²

2020

Helvetica Chimica Acta

Self Cite

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Fidaxomicin (1, lipiarmycin A3, clostomicin B1, tiacumicin B) constitutes a glycosylated 18-membered macrolactone and is a natural product isolated from various soil bacteria. Since 2011, fidaxomicin is a marketed antibiotic for the treatment of intestine infections caused by C. difficile in the clinic. Its promising in vitro antibacterial properties against resistant S. aureus and M. tuberculosis continue to attract interest. This review article describes the early history of the antibiotic fidaxomicin and highlights recent advances in the field, such as the elucidation of its mode of action and biosynthesis, as well as known derivatives. Furthermore, different synthetic strategies towards the total synthesis of fidaxomicin are summarized.

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Total Synthesis and Structural Revision of Mangrolide D

Cited by 14 publications

References 34 publications

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

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

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

Chemistry and Biology of the Clinically Used Macrolactone Antibiotic Fidaxomicin

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