Synthesis of a Protected (±)-Calicheamicinone Derivative by Sequential Introduction of Functionality into the Bicyclo[7.3.1]enediyne Core Structure

Magnus, Philip; Miknis, Gregory F.; Press, Neil J.; Grandjean, D.; Taylor, and G. Mark; Harling, John D.

doi:10.1021/ja970743t

Cited by 38 publications

(14 citation statements)

References 23 publications

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“…102 En route to the synthesis of (AE)-calicheamicinone derivatives, Magnus and co-workers treated the cyclic endione 33 with sodium azide. 103 In a solvent mixture 2,2,2-trifluoroethanol/ DMF they obtained the enaminone 35 in low (o10%) yield, which became even lower on ''larger'' (>10 mg) scale. This product clearly originates from a conjugate addition of the azide anion to the a,b-unsaturated ketone unit giving a-azido Scheme 1 Synthesis of a-azido ketones 2 by nucleophilic substitution.…”

Section: In Esiz)mentioning

confidence: 99%

Syntheses and transformations of α-azido ketones and related derivatives

2011

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Organic azides are known and utilized in the synthetic organic chemistry as amine precursors, potential sources of nitrenes, dipoles useful in 1,3-dipolar cycloadditions and starting materials of phosphoranes for a long time, and their literature has been overviewed by several authors. On the other hand, there are some special subclasses within the azides which possess peculiar and interesting properties differing from those of the majority and offering extra synthetic possibilities. In this critical review we wish to give an exhaustive overview on the synthesis and synthetic potential of α-azido ketones and related systems, an underestimated group of compounds. The enhanced acidity of the α-hydrogen offers various new synthetic applications including the creation of a new C-C bond, while the joint presence of the carbonyl and vinyl functions of α-azido-α,β-unsaturated ketones results in a special reactivity, too. Chemo- and stereoselectivity issues also represent important points which are discussed in detail. Finally, the usefulness of the titled derivatives in the synthesis of various heterocycles is reviewed (273 references).

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Section: In Esiz)mentioning

confidence: 99%

Syntheses and transformations of α-azido ketones and related derivatives

2011

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“…Direct oxidation with HIO 3 in DMSO [35] or 2-iodoxybenzoic acid (IBX) in DMSO [35] gave 35-40 % of a mixture of enedione and dienedione 11. Further procedures [36,37] again gave only mixtures of starting material 29, enedione, and dienedione 11, or poor yields.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis and NMR Investigations of Cylindramide

Cramer

Buchweitz

Frey

et al. 2006

Chemistry A European J

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Cylindramide (1) was built up from three components: a hydroxyornithine derivative 7, a tetrazolylsulfone 8, and a substituted pentalene subunit 9. Derivative 7 was prepared in a six-step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N-Boc-3-aminopropanal (12). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22. The synthesis of the pentalene fragment 9 started from cycloocta-1,5-diene 26, that was converted into enantiopure bicyclo[3.3.0]octanedione 29. The latter was functionalized to give derivative 9. The total synthesis was accomplished by inducing C-C bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia-Kocienski conditions, macrocyclization, and subsequent Lacey-Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1H and 13C NMR spectroscopic investigations (DQF-COSY, ROESY spectra), the stereochemistry of synthetic cylindramide (1) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest-energy structures for cylindramide.

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“…Magnus’ 1997 synthesis of a protected derivative of calicheamicinone ( 131 ) was also achieved with the help of a macroaldolization ( Scheme 26 ). 146 The conjugate addition of an aluminium thiophenolate to cyclohexenone 128 generated an enolate, which added to the cobalt-protected ynal moiety to provide the aldol product 129 under highly concentrated conditions. Further transformations led to 130 , which proved resistant to deprotection and further elaboration to the target compound 131 .…”

Section: Addition To Carbonylsmentioning

confidence: 99%

Unconventional Macrocyclizations in Natural Product Synthesis

2020

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Over the past several decades, macrocyclic compounds have emerged as increasingly significant therapeutic candidates in drug discovery. Their pharmacological activity hinges on their rotationally restricted three-dimensional orientation, resulting in a unique conformational preorganization and a high enthalpic gain as a consequence of high-affinity macrocycle–protein binding interactions. Synthetic access to macrocyclic drug candidates is therefore crucial. From a synthetic point of view, the efficiency of macrocyclization events commonly suffers from entropic penalties as well as undesired intermolecular couplings (oligomerization). Although over the past several decades ring-closing metathesis, macrolactonization, or macrolactamization have become strategies of choice, the toolbox of organic synthesis provides a great number of versatile transformations beyond the aforementioned. This Outlook focuses on a selection of examples employing what we term unconventional macrocyclizations toward the synthesis of natural products or analogues.

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Synthesis of a Protected (±)-Calicheamicinone Derivative by Sequential Introduction of Functionality into the Bicyclo[7.3.1]enediyne Core Structure

Cited by 38 publications

References 23 publications

Syntheses and transformations of α-azido ketones and related derivatives

Syntheses and transformations of α-azido ketones and related derivatives

Total Synthesis and NMR Investigations of Cylindramide

Unconventional Macrocyclizations in Natural Product Synthesis

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