Enantioselective total synthesis of iso-cladospolide B, cladospolide C and cladospolide B from tartaric acid

Prasad, Kavirayani R.; Gandi, Vasudeva Rao

doi:10.1016/j.tetasy.2011.02.018

Cited by 18 publications

(11 citation statements)

References 33 publications

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“…The same hydroxylated side-chain motif can be found in two other similar products prepared by RCM, botryolide E 24 [79,80], and isocladospolide B 25 [81] (Scheme 11). The first was extracted from cultures of a fungicolous isolate of Botryotrichum sp.…”

Section: The "Acrylate Approach": Synthesis Of Natural Productssupporting

confidence: 52%

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

Bassetti

D’Annibale

2015

Topics in Heterocyclic Chemistry

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Section: The "Acrylate Approach": Synthesis Of Natural Productssupporting

confidence: 52%

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

Bassetti

D’Annibale

2015

Topics in Heterocyclic Chemistry

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“…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%

“…In the same year, Kumar reported a synthesis of CladB that used Yamaguchi macrolactonization as the ring‐closing step, preceded by a linear synthesis to generate 110 . This intermediate was also intercepted by Prasad, thus constituting a formal synthesis. Moving through the early 2000s, many groups applied divergent approaches to synthesize multiple members of the Clad family.…”

Section: Other Examples Of 12‐membered Macrolactonesmentioning

confidence: 99%

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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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“…Eventually the desired acid 7 was obtained via hydrolysis of ester 15 using LiOH and H 2 O in 85% yield. 13 With the fragments 4 and 7 in hand, efforts towards the target compound were taken into account (Scheme 4). Esterification of alcohol 4 with 7 using DCC and DMAP furnished the desired ester 16 14 in 90% yield.…”

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confidence: 99%

Total Synthesis of 4-Ketoclonostachydiol

2014

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A facile total synthesis of nonsymmetrical 14-membered macrocyclic bis-lactone, 4-ketoclonostachydiol has been demonstrated in a convergent approach. The synthetic strategy has been unambiguously successful towards incorporating all the three stereogenic centers present in the molecule with an overall yield of 0.9%. The key synthetic step includes MacMillan hydroxylation and Grubbs ring-closing metathesis reactions to furnish the core skeleton.Since decades, isolated marine natural products have been a source of numerous pharmacologically active compounds. 1 Among their many classes, in particular, fungi are very well known to produce several active secondary metabolites. 2 Moreover, in 2006 Munro et al. have identified a marine alga-derived fungus from New Zealand as Gliocladium sp., which showed to contain the metabolite 4-ketoclonostachydiol (1), strongly cytotoxic against P388 cells (IC 50 0.55 μM). The studies also revealed that 1 has stronger antimicrobial activity than the known clonostachydiol (2) 3 ( Figure 1) against Bacillus subtilis, Trichophyton mentagrophytes, and Cladosporium resinae. 4 In 2009, She et al. 5 have revised and established the absolute configuration for 1 as 5S,10S,13S instead of 5R,10R,13R by chemical synthesis. The synthesis includes Yamaguchi lactonization, Mitsunobu, and Sharpless asymmetric dihydroxylation reactions as the key steps. 5 In continuation of our interest and effort towards the synthesis of biologically active marine natural products from such family, 6 the synthesis of 4-ketoclonostachydiol (1) was attempted in a facile and straightforward manner. Herein, we report a stereocontrolled total synthesis of 1 in a convergent fashion as depicted in the retrosynthetic strategy (Scheme 1). As outlined in the strategy, the formation of 14-membered macrocycle of 1 was envisaged by ring-closing metathesis (RCM) of 3, wherein all the required chiral centers are in place. Esterification reaction between the alcohol 4 and the acid 7 leads to compound 3. And to begin with, alcohol 5 and diethyl L-(+)-tartrate (6), respectively, would be used for the preparations of 4 and 7 using routine reaction steps. Figure 1 Structure of 4-ketoclonostachydiol (1) and clonostachydiol (2)We began our synthesis towards the intermediate 4 from the commercially available hex-1-enol (5) (Scheme 2). Aldehyde 8 was obtained in six reaction steps 7 from 5 in an overall yield of 42%. Then, aldehyde 8 was subjected to MacMillan α-hydroxylation 8 in the presence of L-proline and nitrosobenzene, followed by rapid reduction and cleavage of the N-O bond providing the desired diol 9 in high enantioselectivity of 97%.Selective tosylation of the primary alcohol 9 using tosyl chloride and triethylamine 9 furnished the alcohol 10 in 85% yield. The expected epoxide 11 was obtained using K 2 CO 3 in methanol in 90% yield. Subsequently, opening of the epoxide 11 by trimethlysulfonium methylide, which was prepared from trimethylsulfonium iodide and n-BuLi produced the required allylic alcohol 12 10 in 80% yield. The al...

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Enantioselective total synthesis of iso-cladospolide B, cladospolide C and cladospolide B from tartaric acid

Cited by 18 publications

References 33 publications

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

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

Total Synthesis of 4-Ketoclonostachydiol

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