Free radical-mediated vinyl amination: a mild, general pyrrolidinyl enamine synthesis

Nugent, Benjamin M.; Williams, Amie L.; Prabhakaran, Erode N.; Johnston, Jeffrey N.

doi:10.1016/j.tet.2003.04.003

Cited by 31 publications

(17 citation statements)

References 40 publications

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“…Starting compound was N-(3-hydroxypropyl)phthalimide, which was oxidized with Dess-Martin periodinane to give the aldehyde 7 [14]. a-Bromination with Me 3 SiBr, and subsequent reaction of the product without purification, with 2,6-diaminopyrimidin-4-one furnished directly the phthalimido-protected preQ 1 base 8 with a yield of 85% [15].…”

Section: Scheme 1 Proposed Biosynthesis Of Queuosine-containing Trnamentioning

confidence: 99%

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)

Klepper

Polborn

Carell

2005

Helvetica Chimica Acta

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We describe robust and efficient synthetic methods for the synthesis of the preQ 0 and preQ 1 bases, which are the biosynthetic precursors of the hypermodified RNA nucleoside queuosine. The X-ray crystal-structure analysis of preQ 1 is also described.Introduction. -10 -25% of all nucleotides present in tRNA are modified [1]. Today, more than 80 different nucleotide modifications are known [2]. The nature of the observed nucleotide modifications varies strongly. Frequently, methylations of the nucleobase or of the sugar moieties are found. Sometimes, however, also strongly altered nucleotide structures, so called 'hypermodifications' of the canonical bases, are observed. The biological impact of the modified bases in tRNA is unknown but it is generally assumed that the modifications are needed for the fine tuning of the translational process at the ribosome [3]. The biosynthesis of the hypermodified bases is also only rudimentarily understood. To gain insight into the biosynthesis and the function of the modified bases in tRNA, the chemical synthesis of the modified bases via robust, efficient, and high-yielding methods is required.One of the most significant hypermodifications is the nucleoside queuosine (Q; (= 7-{[(3,4-trans-4,5-cis-4,5-dihydroxycyclopent-1-en-3-yl)amino]methyl}-7-deazaguanosine), which is generally found in the anticodon loop of the tRNAs encoding for the amino acids aspartate, asparagine, histidine, and tyrosine [4]. The nucleoside Q was initially discovered by Harada and Nishimura in 1972 [5]. The proposed biosynthesis of this unusual nucleoside via its biosynthetic precursors preQ 0 and preQ 1 is depicted in Scheme 1 [6] [7]. Today, it is clear that bacteria produce Q-nucleobase-modified tRNA directly by using the unmodified precursor tRNA as the substrate. The enzyme tRNA-guanine transglycosylase (TGT) removes in a first step a specific guanine from the tRNA by cleaving the glycosidic bond between the ribose and the nucleobase [8]. The abasic site, which is thus created, reacts in a second step with the preQ 1 nucleobase, which is biosynthesized by a recently discovered enzyme QueF from preQ 0 (= 7-cyano-7-deazaguanine) to generate a preQ 1 (= 7-(aminomethyl)-7-deazaguanine)-containing tRNA [9]. The tRNA containing preQ 1 base is subsequently further modified to give first epoxyqueuosine-containing tRNA by the action of the S-adenosylmethioninedependant enzyme QueA. Final conversion of epoxyqueuosine to queuosine is carried out by an unknown enzyme in a possibly vitamin B 12 -dependant reaction [10].

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Section: Scheme 1 Proposed Biosynthesis Of Queuosine-containing Trnamentioning

confidence: 99%

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)

Klepper

Polborn

Carell

2005

Helvetica Chimica Acta

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“…14 The stannane radical adds to the terminal position of the alkyne (as in 21a ) to form the vinyl radical ( 21b ). The 5- exo-trig cyclization of the vinyl radical onto the azomethine nitrogen provides a stabilized tertiary carbon radical adjacent to two phenyl groups ( 21c ).…”

Section: Resultsmentioning

confidence: 99%

“…The β-stannylenamine was synthesized by methodology developed earlier by us, involving a non-conventional radical-mediated 5- exo -trig cyclization of an imine. 14,15 The required imine ( 11d ) is accessible in three steps from the commercially available chloride 12 by a Gabriel amine synthesis. The acid chloride portion ( 8 ) was anticipated to be accessible from α,β-unsaturated aldehyde 10 using a Brown crotylation.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a β-Stannyl Enamine Linchpin

et al. 2012

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Serratezomine A is a member of the structurally diverse class of compounds known as the Lycopodium alkaloids. The key supporting studies and successful total synthesis of serratezomine A are described in this account. Significant features of the synthesis include the first application of free radical mediated vinyl amination and Hwu’s oxidative allylation in a total synthesis, and an intramolecular lactonization via a transannular SNi reaction. Minimal use of protecting groups and the highly diastereoselective formation of a hindered, quaternary stereocenter using an umpolung allylation are also highlights from a strategy perspective. Observation of quaternary carbon epimerization via a retro-Mannich/Mannich sequence highlights the additional challenge presented by the axial alcohol at C8 in serratezomine A.

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“…The synthesis commences with the condensation of dioxanone 6 with amine 7 14 in the presence of sodium sulfate (Scheme 2). Acylation of the resulting imine with acid chloride 8 15 gave amidodioxin 9 , which upon heating underwent a smooth retrocycloaddition and concomitant cycloaddition to afford a 4.5:1 mixture of exo -cycloadduct 12 and endo -cycloadduct 11 , respectively.…”

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confidence: 99%

Total synthesis of (±)-isophellibiline

Funk

Belmar

2012

Tetrahedron Letters

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The total synthesis of (±)-isophellibiline is described. This represents the first synthesis of a member of the nonaromatic homoerythrinan family of alkaloids. The tetracyclic ring system of the natural product was quickly assembled by a strategy that features a retrocycloaddition/cycloaddition reaction of an amidodioxin, an intramolecular Heck reaction and a 6π-electrocyclic ring closure of a dienoic acid.

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Free radical-mediated vinyl amination: a mild, general pyrrolidinyl enamine synthesis

Cited by 31 publications

References 40 publications

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)

Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a β-Stannyl Enamine Linchpin

Total synthesis of (±)-isophellibiline

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Free radical-mediated vinyl amination: a mild, general pyrrolidinyl enamine synthesis

Cited by 31 publications

References 40 publications

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ0 Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ1 Base)

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ0 Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ1 Base)

Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a β-Stannyl Enamine Linchpin

Total synthesis of (±)-isophellibiline

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Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)

Robust Synthesis and Crystal‐Structure Analysis of 7‐Cyano‐7‐deazaguanine (PreQ₀ Base) and 7‐(Aminomethyl)‐7‐deazaguanine (PreQ₁ Base)