A flexible and unified strategy for syntheses of cladospolides A, B, C, and iso-cladospolide B

Si, Debjani; Sekar, Narayana M.; Kaliappan, Krishna P.

doi:10.1039/c1ob05787a

Cited by 29 publications

(13 citation statements)

References 89 publications

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“…43 It is worth noting that other approaches to this class of natural products have used olefin-metathesis, 44 Evans aldol reaction, 45 and Os-catalyzed dihydroxylation 46 transforms. (−)-Phoracantholide J ( 89 ) was previously constructed through either ring-closing metathesis or Ru-catalyzed hydroalkynylation.…”

Section: Methodsmentioning

confidence: 99%

Decarboxylative alkenylation

Edwards

Merchant

McClymont

et al. 2017

Nature

311

209

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Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or reductions, plays an essential role in the foundation of how organic matter is manipulated.1 Despite its importance, olefin synthesis still largely relies upon chemistry invented more than three decades ago, with metathesis2 being the most recent addition. Here we describe a simple method to access olefins with any substitution pattern or geometry from one of the most ubiquitous and variegated building blocks of chemistry: alkyl carboxylic acids. The same activating principles used in amide-bond synthesis can thus be employed, under Ni- or Fe-based catalysis, to extract CO2 from a carboxylic acid and economically replace it with an organozinc-derived olefin on mole scale. Over sixty olefins across a range of substrate classes are prepared, and the ability to simplify retrosynthetic analysis is exemplified with the preparation of sixteen different natural products across a range of ten different families.

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Section: Methodsmentioning

confidence: 99%

Decarboxylative alkenylation

Edwards

Merchant

McClymont

et al. 2017

Nature

311

209

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“…Utilizing synthons such as 134 – 136 resulted in the need for multiple olefination reactions and nonstrategic redox manipulations to access 133 . 44 The use of RCC on tartaric acid significantly streamlines such a plan. Thus, sequential coupling of organozincs 140 and 141 to tartartic acid derivative 139 provided a concise formal synthesis, which proceeds in half the number of steps, in an order of magnitude higher yield, and with complete diastereocontrol.…”

Section: Strategic Applications Of Radical Cross-couplingmentioning

confidence: 99%

Radical Retrosynthesis

2018

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In The Logic of Chemical Synthesis, E. J. Corey stated that the key to retrosynthetic analysis was a "wise choice of appropriate simplifying transforms" ( Corey , E. J. ; Cheng , X.-M. The Logic of Chemical Synthesis ; John Wiley : New York , 1989 ). Through the lens of "ideality", chemists can identify opportunities that can lead to more practical, scalable, and sustainable synthesis. The percent ideality of a synthesis is defined as [(no. of construction rxns) + (no. of strategic redox rxns)]/(total no. of steps) × 100. A direct consequence of designing "wise" or "ideal" plans is that new transformations often need invention. For example, if functional group interconversions are to be avoided, one is faced with the prospect of directly functionalizing C-H bonds ( Gutekunst , W. R. ; Baran , P. S. Chem. Soc. Rev. 2011 , 40 , 1976 ; Brückl , T. ; et al. Acc. Chem. Res. 2012 , 45 , 826 ). If protecting groups are minimized, methods testing the limits of chemoselectivity require invention ( Baran , P. S. ; et al. Nature 2007 , 446 , 404 ; Young , I. S. ; Baran , P. S. Nat. Chem. 2009 , 1 , 193 ). Finally, if extraneous redox manipulations are to be eliminated, methods directly generating key skeletal bonds result ( Burns , N. Z. ; et al. Angew. Chem., Int. Ed. 2009 , 48 , 2854 ). Such analyses applied to total synthesis have seen an explosion of interest in recent years. Thus, it is the interplay of aspirational strategic demands with the limits of available methods that can influence and inspire ingenuity. E. J. Corey's sage advice holds true when endeavoring in complex molecule synthesis, but together with the tenets of the "ideal" synthesis, avoiding concession steps leads to the most strategically and tactically optimal route ( Hendrickson , J. B. J. Am. Chem. Soc. 1975 , 97 , 5784 ; Gaich , T. ; Baran , P. S. J. Org. Chem. 2010 , 75 , 4657 ). Polar disconnections are intuitive and underlie much of retrosynthetic logic. Undergraduates exposed to multistep synthesis are often taught to assemble organic molecules through the combination of positively and negatively charged synthons because, after all, opposites attract. Indeed, the most employed two-electron C-C bond forming reactions today are those based upon either classical cross-coupling reactions (e.g., Suzuki, Negishi, or Heck) or polar additions (aldol, Michael, or Grignard). These reactions are the mainstay of modern synthesis and have revolutionized the way molecules are constructed due to their robust and predictable nature. In contrast, radical chemistry is sparsely covered beyond the basic principles of radical chain processes (i.e., radical halogenation). The historical perception of radicals as somewhat uncontrollable species does not help the situation. As a result, synthetic chemists are not prone to make radical-based strategic bond disconnections during first-pass retrosynthetic analyses. Recent interest in the use of one-electron radical cross-coupling (RCC) methods has been fueled by the realization of their uniquely chemoselective profiles a...

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“…Table shows some representative examples of syntheses of the Clad family, paying specific attention to the key intermediates employed and the method of ring closure. According to the literature, there have been ten reports of total syntheses of CladA since 1987. Five of these syntheses have intercepted an intermediate of type 107 .…”

Section: Other Examples Of 12‐membered Macrolactonesmentioning

confidence: 99%

“…Similarly, CladB and CladC have also received significant attention from synthetic chemists, both being the subject of several synthetic quests (Table ). The first reports of syntheses of CladB were in 2005 .…”

Section: Other Examples Of 12‐membered Macrolactonesmentioning

confidence: 99%

Twelve‐membered macrolactones: privileged scaffolds for the development of new therapeutics

Brzozowski

Wuest

2017

Chem Biol Drug Des

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Natural products commonly produced as secondary metabolites of various plants and micro-organisms represent a diverse chemical space of compounds. The diversity of natural products makes them an attractive target for interrogation by both chemists and biologists alike. Indeed, the study of 12-membered macrolactones has already led to the discovery of lead drug compounds and new biological targets, which has motivated the development of diverted total synthetic routes to libraries of analogs. This review explores the discovery, biological characterization, and synthesis of several 12-membered macrolactones, exploiting examples that underscore their importance in the drug discovery field. It is our hope that this review will motivate further interest in this class of natural products, a group of molecules that we think merit the classification of 'privileged scaffolds' within the medicinal chemistry community, to further investigate and develop novel compounds with promising bioactivity. K E Y W O R D Santibiotic, biosynthesis, diverted total synthesis, macrolactone, natural product

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A flexible and unified strategy for syntheses of cladospolides A, B, C, and iso-cladospolide B

Cited by 29 publications

References 89 publications

Decarboxylative alkenylation

Decarboxylative alkenylation

Radical Retrosynthesis

Twelve‐membered macrolactones: privileged scaffolds for the development of new therapeutics

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