Synthesis of Amino-1,4-benzoquinones and Their Use in Diels–Alder Approaches to the Aminonaphthoquinone Antibiotics

Nawrat, Christopher C.; Lewis, William; Moody, Christopher J.

doi:10.1021/jo201320g

Cited by 29 publications

(34 citation statements)

References 32 publications

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“…Synthetically, we envisioned rifsaliniketal and salinisporamycinwhich differ only by the presence or absence of a carboxylic acid at C4to be derived from combining a common saliniketal A fragment with an appropriately functionalized naphthoquinone fragment via two potential routes: (1) a condensation between saliniketal acid and aminonaphthoquinone Q or aminonaphthalene N (Scheme , X = NH 2 ) or (2) transition-metal-catalyzed C–N bond formation between saliniketal A and bromonaphthoquinone Q or bromonaphthalene N (Scheme , X = Br) . Because of the prevalence of highly substituted naphthoquinones in ansamycins such as rifamycin, several approaches for their synthesis have been reported. , Of those, we considered two approaches most pertinent for our goals. A Diels–Alder reaction between 46 and 47 , according to protocols explored by Trost and Roush, , would provide facile access to bromonaphthoquinone Q (X = Br, R = H), whereas a cycloaddition between in situ-generated benzyne 50 (from C 2 -symmetric dibromide 49 ) and furan as described by Kinoshita , would deliver oxygen-bridged cycloadduct 48 .…”

Section: Resultsmentioning

confidence: 99%

Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B

Feng

Carrasco

et al. 2016

J. Am. Chem. Soc.

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We describe the isolation, structure elucidation, and total synthesis of the novel marine natural product rifsaliniketal and the total synthesis of the structurally related variants salinisporamycin and saliniketals A and B. Rifsaliniketal was previously proposed, but not observed, as a diverted metabolite from a biosynthetic precursor to rifamycin S. Decarboxylation of rifamycin provides salinisporamycin, which upon truncation with loss of the naphthoquinone ring leads to saliniketals. Our synthetic strategy hinged upon a Pt(II)-catalyzed cycloisomerization of an alkynediol to set the dioxabicyclo[3.2.1]octane ring system and a fragmentation of an intermediate dihydropyranone to forge a stereochemically defined (E,Z)-dienamide unit. Multiple routes were explored to assemble fragments with high stereocontrol, an exercise that provided additional insights into acyclic stereocontrol during stereochemically complex fragment-assembly processes. The resulting 11-14 step synthesis of saliniketals then enabled us to explore strategies for the synthesis and coupling of highly substituted naphthoquinones or the corresponding naphthalene fragments. Whereas direct coupling with naphthoquinone fragments proved unsuccessful, both amidation and C-N bond formation tactics with the more electron-rich naphthalene congeners provided an efficient means to complete the first total synthesis of rifsaliniketal and salinisporamycin.

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Section: Resultsmentioning

confidence: 99%

Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B

Feng

Carrasco

et al. 2016

J. Am. Chem. Soc.

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“…was added to a flame-dried flask, followed by the addition of anhydrous THF (540 mL) and HMPA (15 mL) and the solution was cooled to 0 °C. Next, neat methyl 2-methyl-3-oxobutanoate (prepared according to the literature, 66 30.3 g, 234 mmol, 5.0 equiv.) was added slowly, causing the gas evolution and the grey suspension to thicken.…”

Section: Methodsmentioning

confidence: 99%

Toward a Unified Total Synthesis of the Xiamycin and Oridamycin Families of Indolosesquiterpenes

Trotta

2017

J. Org. Chem.

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A unified synthetic strategy toward the oridamycin and xiamycin families of natural products was designed, aiming to access several natural products from a common synthetic intermediate readily prepared from geranyl acetate. Part of this strategy was successfully realized, culminating in the synthesis of oridamycin A and oridamycin B. Key steps include a Mn(III)-mediated oxidative radical cyclization to construct the trans-decalin ring, and a 6π-electrocyclization/aromatization sequence to produce the 2,3-fused carbazole. Oridamycin B was accessed through a late-stage, C-H oxidation that converted the C16 methyl to a hydroxymethyl. A variety of strategies were explored to form a chelated radical intermediate en route to xiamycin A, including enolate SET oxidation, oxo-vanadium oxidation, and atom-transfer cyclization. Unfortunately, none of these strategies provided the desired C16-epimeric trans-decalin. Exploratory studies on photoredox-catalyzed radical cyclizations yielded interesting results, including the formation of a bicyclic lactone arising from oxidative termination of the photoredox-catalyzed radical cyclization, and a double 6-endo cyclization with catalyst loadings as low as 0.01 mol%.

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“…N ‐Allylbenzylamine42 and N ‐benzylbut‐3‐en‐1‐amine43 were prepared by following reported procedures. Compounds 3 ,44 4 ,45 5 ,46 6 ,46 7 ,40 8 ,40 10 ,47 11 ,48 13 ,20 14 a / 14 b ,20 17 a / 17 b ,21 18 ,49 19 ,49 20 ,24c 22 ,24c methyl 2‐methyl‐3‐oxobutanoate,50 methyl 1‐oxo‐1,2,3,4‐tetrahydronaphthalene‐2‐carboxylate,51 and methyl 1‐oxo‐2,3‐dihydro‐1 H ‐indene‐2‐carboxylate,52 were already described. Compounds 2 g and 21 were only detected by analysis of the crude reaction mixture and not isolated (in particular, 21 is unstable on silica).…”

Section: Methodsmentioning

confidence: 99%

Silver‐Free Two‐Component Approach in Gold Catalysis: Activation of [LAuCl] Complexes with Derivatives of Copper, Zinc, Indium, Bismuth, and Other Lewis Acids

Fang

Presset

Guérinot

et al. 2014

Chemistry A European J

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Complexes of type [LAuCl] (L = phosphine, phosphite, NHC and others) are widely employed in homogeneous catalysis, however, they are usually inactive as such and must be used jointly with a halide scavenger. To date, this role has mostly been entrusted to silver salts (AgSbF6 , AgPF6, AgBF4, AgOTf, etc.). However, silver salts can be the source of deactivation processes or side reactions, so it is sometimes advisable to use silver-free cationic gold complexes, which can be difficult to synthesize and to handle compared with the more robust chloride. We show in this study that various Lewis acids of the transition and main group metal families are expedient substitutes to silver salts. We have tested Cu(I), Cu(II), Zn(II), In(III), Si(IV), Bi(III), and other salts in a variety of typical Au(I)-catalyzed transformations, and the results have revealed that [LAuCl] can form active species in their presence.

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Synthesis of Amino-1,4-benzoquinones and Their Use in Diels–Alder Approaches to the Aminonaphthoquinone Antibiotics

Cited by 29 publications

References 32 publications

Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B

Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B

Toward a Unified Total Synthesis of the Xiamycin and Oridamycin Families of Indolosesquiterpenes

Silver‐Free Two‐Component Approach in Gold Catalysis: Activation of [LAuCl] Complexes with Derivatives of Copper, Zinc, Indium, Bismuth, and Other Lewis Acids

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