Total Synthesis of (−)-Fusarisetin A and Reassignment of the Absolute Configuration of Its Natural Counterpart

Deng, Jun; Zhu, Bo; Lu, Zhaoyong; Yu, Hou; Li, Ang

doi:10.1021/ja211444m

Cited by 75 publications

(52 citation statements)

References 27 publications

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“…Synthetic (−)-fusarisetin A was identical in all aspects with naturally occurring fusarisetin A ( 1 H-NMR, 13 C-NMR and HR-MS), except for the optical rotation (synthetic: [α] D 23 = −86.2 (c = 0.065 in MeOH); natural: [α] D 25 = +84.6 (c = 0.2 in MeOH) 13 , reported synthetic (−)- 1 : [α] D 27 = −88.0 (c = 0.15 in MeOH). 14 The structure of ent -C 5 - epi -1 was confirmed by comparison to the literature data. 14,16 …”

Section: Resultssupporting

confidence: 56%

“…37 Reduction of the alkoxylamine bond of ent -14 under Zn/AcOH conditions 38 liberated the C 5 -alcohol that underwent the desired hemiketalization, along with concomitant deprotection of the TBS group, to form a compound that was spectroscopically identified as the C 5 -epimer of (−)-fusarisetin A ( ent -C 5 -( epi -1 ). 14 …”

Section: Resultsmentioning

confidence: 99%

“…To avoid the difficult separation of these diastereomers, ent -19 was directly treated with m -CPBA 39 to oxidatively cleave the N - O bond producing ent -20 in 95% yield. Regio- and stereo-selective reduction of this compound under Luche conditions 40,14 followed by a one-pot Dieckmann condensation/hemiketalization yielded (−)-fusarisetin A ( ent -1 ) together with its C 5 -epimer (dr = ca 4:1, 42% over 2 steps). Synthetic (−)-fusarisetin A was identical in all aspects with naturally occurring fusarisetin A ( 1 H-NMR, 13 C-NMR and HR-MS), except for the optical rotation (synthetic: [α] D 23 = −86.2 (c = 0.065 in MeOH); natural: [α] D 25 = +84.6 (c = 0.2 in MeOH) 13 , reported synthetic (−)- 1 : [α] D 27 = −88.0 (c = 0.15 in MeOH).…”

Section: Resultsmentioning

confidence: 99%

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Fusarisetin A: scalable total synthesis and related studies

Caro‐Diaz

Lacoske

et al. 2012

Chem. Sci.

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Fusarisetin A (1) is a recently isolated natural product that displays an unprecedented chemical motif and remarkable bioactivities as a potent cancer migration inhibitor. We describe here our studies leading to an efficient and scalable total synthesis of 1. Essential to the strategy was the development of a new route for the formation of a trans-decalin moiety of this compound and the application of an oxidative radical cyclization (ORC) reaction that produces fusarisetin A (1) from equisetin (2) via a bio-inspired process. TEMPO-induced and metal/O2-promoted ORC reactions were evaluated. Biological screening in vitro confirms the reported potency of (+)-1. Importantly, ex vivo studies show that this compound is able to inhibit different types of cell migration. Moreover, the C5 epimer of (+)-1 was also identified as a potent cancer migration inhibitor, while (−)-1 and 2 were found to be significantly less potent. The optimized synthesis is applicable on gram scale and provides a solid platform for analogue synthesis and methodical biological study.

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Fusarisetin A: scalable total synthesis and related studies

Caro‐Diaz

Lacoske

et al. 2012

Chem. Sci.

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“…Despite the moderate diastereoselectivity, this onepot radical cyclization/aminolysis reaction cascade 24 offers a concise way to build up the fusarisetin core structure. Subsequently, the C-5 hydroxy group of compound 4 was liberated under Zn/AcOH conditions 25 Treatment of the resulting C-5 alcohol under basic conditions (NaOMe) induced a one-pot Dieckmann condensation/ hemiacetaliza- tion 5,7 (construction of DE rings) ultimately producing fusarisetin A ( 1 ) in 42% overall yield. Importantly, the C 5 - epi - 4 could be also converted to fusarisetin A via a 3-step sequence that included: a) oxidative cleavage of the N-O bond with m CPBA 26 to form ketone 16 ; b) regioselective and stereoselective reduction of the C-5 ketone with NaBH 4 (d.r.= ca.…”

mentioning

confidence: 99%

“…The isolated sample of synthetic 1 was found to be identical in all aspects with naturally occurring fusarisetin A ( 1 H-NMR, 13 C-NMR and HR-MS), except for the optical rotation [synthetic: [α] D 23 = −86.2 (c = 0.065 in MeOH); natural: [α] D 25 = +84.6 (c = 0.2 in MeOH) 1 , reported synthetic (−)- 1 : [α] D 27 = −88.0 (c = 0.15 in MeOH) 7 ]. The chemical synthesis of 1 confirmed that the absolute stereochemistry of natural fusarisetin A is opposite to our synthetic 1 and provides support for its proposed biosynthesis.…”

mentioning

confidence: 99%

Nature-Inspired Total Synthesis of (−)-Fusarisetin A

et al. 2012

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A concise, protecting group-free total synthesis of (−)-fusarisetin A (1) was efficiently achieved in 9 steps from commercially available (S)-(−)-citronellal. The synthetic approach was inspired by our proposed biosynthesis of 1. Key transformations of our strategy include a facile construction of the decalin moiety that sets the stage for a stereoselective IMDA reaction and a one-pot TEMPO induced radical cyclization/aminolysis that forms the C ring of 1. Our route is amenable to analogue synthesis for biological evaluation.

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Wacker Oxidation, The

2014

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Terminal alkene substrates can be converted to methyl ketone products via a palladium‐catalyzed process known as the Wacker oxidation. This process has found widespread application in targeted synthesis, since alkene substrates are easily accessed and unreactive under diverse reaction conditions substrates and the resultant carbonyl products are common precursors for diverse synthetic manipulations. This chapter covers the application of the Wacker oxidation and variations of the Wacker oxidation to various types of alkene substrates. The literature covered spans the inception of the reaction in 1959 through November 2012. A discussion of the current mechanistic understanding is presented, emphasizing considerations that are relevant to synthetic application, including how the nature of the alkene substrate and nucleophiles other than water are proposed to influence the mechanistic pathways and ultimately the product distribution. The “Scope and Limitations” section is separated into discussions relating to functional group tolerance, the influence of heteroatoms proximal to the alkene substrate, and Wacker‐type oxidations that do not result in carbonyl products, such as cyclization reactions and aza‐Wacker reactions. Select applications of the Wacker oxidation in total synthesis are presented, as well as a comparison to other methods and examples of experimental conditions.

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Total Synthesis of (−)-Fusarisetin A and Reassignment of the Absolute Configuration of Its Natural Counterpart

Cited by 75 publications

References 27 publications

Fusarisetin A: scalable total synthesis and related studies

Fusarisetin A: scalable total synthesis and related studies

Nature-Inspired Total Synthesis of (−)-Fusarisetin A

Wacker Oxidation, The

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