Total Synthesis and Conformational Analysis of the Antifungal Agent (−)-PF1163B

Bouazza, Fodil; Renoux, Brigitte; Bachmann, Christian; Gesson, Jean‐Pierre

doi:10.1021/ol035309c

Cited by 24 publications

(15 citation statements)

References 16 publications

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“…Their intriguing bioactivity in combination with their complex chemical structure make cyclodepsipeptides challenging targets for total synthesis, not only for having access to larger quantities and other congeners but also to confirm the structural assignment and absolute configuration of the stereochemical centers. In the next section, four examples of relevant metathesis-based syntheses of cyclodepsipeptides will be discussed, e.g., cryptophycin-24 (arenastatin A) 109 [148]; (À)-spongidepsin (111) [149]; (À)-PF1163B (113) [150], as shown in Scheme 26; and lagunamide A (116a) [151], as shown in Scheme 27. The cryptophycins, a unique class of 16-membered macrolides with antimitotic activity, have been isolated from the cyanobacteria Nostoc sp.…”

Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

“…Another example of an efficient RCM approach to obtain a 13-membered macrocycle deals with the synthesis of (À)-PF1163B (113) [150], a cyclodepsipeptide with antifungal properties. This class of bioactive peptides was isolated from the fermentation broth of Penicillium sp.…”

Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

“…The 13-membered macrocycle incorporates an O-2-hydroxyethyl-N-methyl-Ltyrosine moiety, and a total synthesis starting with L-tyrosine and (R)-citronellol has been described in the literature [165]. This synthesis requires 13 steps, while the synthesis reported by Gesson [150] requires eight steps in which RCM of precursor 114 is the key step (Scheme 26). Ring-closing metathesis was attempted with different amounts of G1 as the catalytic species.…”

Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

“…For this purpose, diene 131 was synthesized by SPPS and treated with an appropriate catalyst. For this purpose, G2 and HG2 (both 15 mol%) in 1,2-dichloroethane (DCE) under microwave irradiation at 150 C for 5 min were evaluated in this conversion, and after cleavage from the resin, complex mixtures of poorly separable compounds (like ring-contracted and double-bond migration products) were obtained, and only a 14-membered analog (with a shifted double bond compared to the peptide backbone) could be isolated in sufficient amounts. The addition of 1,4-dibenzoquinone (15 mol%) and a lower catalyst loading (7 mol% HG2) in combination with microwave heating at 120 or 140 C for 5 min in DCE resulted in the isolation of compound 130 as an E/Z mixture, in which the (E)-diastereoisomer was consistently the predominant 14-membered macrocycle (>60%).…”

Section: Rcm For the Synthesis Of Bioactive Peptides And Peptidomimeticsmentioning

confidence: 99%

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Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Rijkers

2015

Topics in Heterocyclic Chemistry

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This review surveys developments in the field of ring-closing metathesis and cross-metathesis reactions applied to the synthesis of constrained amino acids, peptides, and peptidomimetics. Examples, in which metathesis is used as one of the synthetic tools to arrive at the desired peptide molecules as well as examples that describe in-depth optimized metathesis protocols, will be discussed. Currently, metathesis reactions are well-accepted synthetic tools within the field of peptide chemistry and provide peptides unprecedented properties like conformational, metabolic, and chemical stability and improved bioactivity.

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Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

Section: Rcm Of Depsipeptidesmentioning

confidence: 99%

Section: Rcm For the Synthesis Of Bioactive Peptides And Peptidomimeticsmentioning

confidence: 99%

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Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Rijkers

2015

Topics in Heterocyclic Chemistry

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“…The 13-membered ring lactone and lactam antifungal-antibiotic (−)-PF1163B (178), isolated from Streptomyces, was synthesized using 12 mol% of Ru-[II] (Scheme 5.42) in 60% yield [74]. The natural product was eventually obtained after hydrogenation.…”

Section: Cyclodepsipeptidesmentioning

confidence: 99%

Synthesis of Natural Products Containing Macrocycles by Alkene Ring‐Closing Metathesis

Gradillas¹,

Pérez‐Castells²

2010

Metathesis in Natural Product Synthesis

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IntroductionThe impact of metathesis in modern synthetic chemistry is evidenced by the number of publications and reviews that have appeared in the last decade, some of them covering the specific field of macrocyclization in natural product synthesis [1]. It is therefore difficult not to repeat the reports done by other authors or duplicate their critical views on the chemistry. This chapter is exclusively devoted to the total syntheses of natural bioactive macrocycles involving diene and the diene-ene metathesis, and focuses on the reaction conditions used in the macrocyclization key step and on the stereochemical outcome of the reaction. As we shall see, the choice of the catalyst, solvent, temperature, concentration, and reaction time is crucial in these transformations. In addition, we show how subtle variations on the structure of the substrate lead to modifications in the conformational organization of the molecule, which are critical for the success of ring-closing metathesis (RCM). In particular, the substitution pattern, the steric hindrance of the substituents, the ring size to be formed, and the presence of coordinating heteroatoms are particularly important as they have an important influence on the outcome of the reaction. This chapter has been organized around the various families of natural products in order to compare the reaction conditions for compounds bearing structural similarities. We have deliberately decided to reveal only the information regarding the metathesis step and thus not disclose other details of the syntheses.Synthetic efforts toward macrocycles are often laborious and unpractical. The classical strategies involved are macrolactonizations, macrolactamizations, and macroaldolizations. The macrocyclization approach encounters several problems including the competition between the desired intramolecular reaction and intermolecular processes, which result in the formation of polymers. RCM has the advantage of being compatible with a wide variety of functional groups and forming double bonds that can eventually be converted into other functionalities. The main disadvantages are the control of the stereochemistry of the newly formed double bond and the optimization of the yield. On the other hand, the concomitant loss of ethylene makes this reaction highly atom economical and entropically Metathesis in Natural Product Synthesis: Strategies, Substrates and Catalysts. Edited by

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Organic Synthesis Using Metal‐Mediated Metathesis Reactions

Kissling

Nolan

2005

Encyclopedia of Inorganic Chemistry

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Olefin metathesis is an established reaction, yet it is still growing and diversifying at a remarkable rate. Since 2000, there has been notable progress in a number of areas, especially the development of new catalysts, many of which have N‐heterocyclic carbenes modifying ruthenium. These include phosphine‐free ruthenium catalysts that broaden the scope of efficient ruthenium‐catalyzed olefin metathesis, as well as catalysts with N‐heterocyclic carbenes and electron‐poor phosphines having turnover frequencies >100‐fold faster than the original Grubbs catalyst. In concert with this, some excellent mechanistic experiments and theoretical work have better elucidated the structure‐reactivity relationship and subtle but important points about mechanism relative rates of phosphine. Association, dissociation, and formation of the metallacyclobutane of the ruthenium‐catalyzed reactions are leading the way to further improvements in ruthenium catalysts. Many methodological applications have also been developed, including improvements in the scope of hetereocycle and macrocycle formation. Cross metathesis (CM) has also undergone a transformation to a high yielding and stereoselective reaction that can be performed with predictable outcomes of yield and alkene stereochemistry. Great strides have been made in asymmetric olefin metathesis reactions, especially desymmetrization and kinetic resolution, with the majority of the results reported using molybdenum‐based catalysts with C 2 ‐symmetric chiral bisaryloxy based ligands. In addition, successful ruthenium‐based catalysts with C 2 ‐ and C 1 ‐symmetric ligands have been reported. Numerous reports of Tandem and sequential olefin metathesis reactions have been published, often in one‐pot, and sometimes utilizing the same metal complex for multiple operations, like ring closure/hydrogenation. A number of examples of tandem reactions utilizing a palladium catalyst and ruthenium‐catalyzed olefin metathesis have also been reported as very efficient routes to desirable organic building blocks. One of the areas that exploited olefin metathesis is natural product synthesis. There are an ever increasing number of reports that cite olefin metathesis as a key, often step saving, reaction in the successful completion of target molecules by ring closing or cross metathesis. The synthetic advantages the olefin metathesis reaction have also been employed by materials and polymer chemists as part of design strategies for constructing well‐defined polymers, substrates for combinatorial chemistry, and metal‐containing rings. The olefin metathesis catalysts have been attached to a variety of supports for the purpose of recycling. Many groups have examined methods for tethering both molybdenum and ruthenium‐based catalysts through reversibly coordinating ligands, the alkylidene and the backbone of nonlabile ligands, with reports of high efficiency recycling of up to 10 times.

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Total Synthesis and Conformational Analysis of the Antifungal Agent (−)-PF1163B

Cited by 24 publications

References 16 publications

Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Synthesis of Cyclic Peptides and Peptidomimetics by Metathesis Reactions

Synthesis of Natural Products Containing Macrocycles by Alkene Ring‐Closing Metathesis

Organic Synthesis Using Metal‐Mediated Metathesis Reactions

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