Toward an Asymmetric Synthesis of the Dimeric Pyranonaphthoquinone Antibiotic Crisamicin A

Brimble, Margaret A.; Hassan, Najmah P.S.; Naysmith, Briar J.; Sperry, Jonathan

doi:10.1021/jo501344c

Cited by 28 publications

(19 citation statements)

References 20 publications

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“…[3] Them onomeric naphthoquinonopyrano-g-lactones (+ +)-kalafungin (1), [4,5] (+ +)-frenolicin B( 2), [6, 4c, 5c, 7] and (À)-griseusin A (3) [8,9] have been obtained by total synthesis.M uch less is known about the synthesis of naturally occurring naphthoquinonopyrano-g-lactone dimers.F or example,the combined synthetic efforts towards (À)-crisamycin A( 7a) [10] ended prematurely with the synthesis of dimeric precursors, [11] a1 :1 mixture-not referred to as such by the authors-of rac-crisamycin A(7b)and meso-crisamycin A(8b), [12] or the synthesis of acompound that resisted demethylation in what would have been the final step. [13] Endeavors towards g-actinorhodin (5)a nd actinorhodin (6)c ame to ah alt at the stage of precursors, [14] "half-sized molecules", [15] or earlier. [16] In fact, our total synthesis of g-actinorhodin (5) described in the following is the very first synthesis of ad imeric naphthoquinonopyrano-g-lactone natural product in isomerically pure form.…”

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confidence: 99%

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

Neumeyer

Brückner

2017

Angew Chem Int Ed

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We have accomplished the first total synthesis of an isomerically pure naphthoquinonopyrano-γ-lactone dimer, γ-actinorhodin, in eleven steps. Two steps exploit pairs of peri-MeO groups as unusual selectivity controls. The respective MeO groups convey the steric bulk of a bromo or iodo substituent located ortho to one MeO group as steric hindrance into the vicinity of the second MeO group. This relay effect was indispensable for exerting regiocontrol in an aromatic bromination and diastereocontrol in an oxa-Pictet-Spengler cyclization. The absolute configuration of our target compound was established in an asymmetric Sharpless dihydroxylation of a β,γ-unsaturated ester, which was synthesized in a Heck coupling of a bromoiodonaphthalene with ethyl vinylacetate. The dihydroxylation provided the γ-hydroxylactone moiety of the bromonaphthalene that was used as the substrate in the oxa-Pictet-Spengler cyclization. Dimerization to the core of γ-actinorhodin occurred by two Suzuki couplings.

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confidence: 99%

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

Neumeyer

Brückner

2017

Angew Chem Int Ed

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“…The next partner α, -unsaturated ketone 110 was synthesized from commercially available ethyl acetoacetate in four steps. [112] Further oxidative demethylation of 114 with CAN yielded the bis-quinone 7,7′-demethoxy-9,9′deoxycardinalin 3 (115), which represent the core structure of 1. Facile debenzylation of 111 (H 2 , Pd/C) delivered a phenol that underwent smooth triflate formation to give 112.…”

Section: Hauser-kraus Annulation Strategymentioning

confidence: 99%

“…[115] The cyanophthalide 130 was synthesized from Scheme 11. [115] The cyanophthalide 130 was synthesized from Scheme 11.…”

Section: Hauser-kraus Annulation Strategymentioning

confidence: 99%

Dimeric Pyranonaphthoquinones: Isolation, Bioactivity, and Synthetic Approaches

2016

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The dimeric pyranonaphthoquinones, “bis versions” of the naphtho[2,3‐c]pyran‐5,10‐dione moiety, comprises a group of antibiotics that have been isolated from a variety of sources including plants, bacteria, fungi, and insects. This review discusses the known naturally occurring dimeric pyranonaphthoquinones, their isolation and bioactivity, and synthetic approaches towards them that have helped to confirm their structures, as well as to resolve structural uncertainties such as stereochemistry. The major focus has been on the synthetic approaches adopted to complete the challenging total synthesis of the natural isolates and analogues.

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“…The correctness of the last structure elucidation was corroborated by an independent synthesis of the enantiomeric compound by Fernandes et al (Scheme , lower moiety) and by the fact that it is dextrorotatory. The key building blocks of that route are the Fischer carbene 215 and the alkyne 223 , derived from d ‐glucono‐δ‐lactone in six steps …”

Section: The Sharpless Asymmetric Dihydroxylation Of βγ‐Unsaturatmentioning

confidence: 99%

Nonracemic γ‐Lactones from the Sharpless Asymmetric Dihydroxylation of β,γ‐Unsaturated Carboxylic Esters

Neumeyer

Brückner

2016

Eur J Org Chem

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Since Sharpless' discovery of the asymmetric dihydroxylation of C=C double bonds in the late 1980s this reaction has become a powerful tool of synthetic organic chemistry. As a consequence, this transformation has been reviewed repeatedly and extensively. The present microreview focuses on Sharpless' asymmetric dihydroxylations (from here on “SADs”) of β,γ‐unsaturated carboxylic esters. These SADs differ from most others in that they provide not nonracemic 1,2‐diols but follow‐up products thereof. Bearing ester groups at appropriate distances, the SAD‐based 1,2‐diols obtained from β,γ‐unsaturated carboxylic esters lactonize readily under SAD conditions. Accordingly, SADs of β,γ‐unsaturated carboxylic esters furnish nonracemic β‐hydroxy‐γ‐lactones in a single operation. We show that this SAD route represents a – or even the most – potent easy‐to‐handle route to nonracemic butanolides and butenolides “of almost all kinds”. The span covered is from pioneering racemic work to applications in natural product synthesis. Some non‐butanolide and non‐butenolide target syntheses are included, especially those of tetrahydrofurans.

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Toward an Asymmetric Synthesis of the Dimeric Pyranonaphthoquinone Antibiotic Crisamicin A

Cited by 28 publications

References 20 publications

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

Dimeric Pyranonaphthoquinones: Isolation, Bioactivity, and Synthetic Approaches

Nonracemic γ‐Lactones from the Sharpless Asymmetric Dihydroxylation of β,γ‐Unsaturated Carboxylic Esters

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