A new stereoselective route to branched-chain nitro and amino sugars: synthesis of both enantiomers of decilonitrose and avidinosamine

Greven, R.; Juetten, Peter; Scharf, Hans‐Dieter

doi:10.1021/jo00066a029

Cited by 19 publications

(16 citation statements)

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“…This disconnection was, however, distinct from a biomimetic step, which formally involves polyketide chemistry rather than pericyclic processes. Finally, we anticipated that the aminosugar 8 could be readily obtained from the chiral pool 11 based on previous work27,28.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of marmycin A and investigation into its cellular activity

Cañeque¹,

Gomes²,

Thi³

et al. 2015

Nature Chem

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Anthracyclines such as doxorubicin are used extensively in the treatment of cancers. Anthraquinone-related angucyclines also exhibit antiproliferative properties and have been proposed to operate via similar mechanisms, including direct genome targeting. Here, we report the chemical synthesis of marmycin A and the study of its cellular activity. The aromatic core was constructed by means of a one-pot multistep reaction comprising a regioselective Diels-Alder cycloaddition, and the complex sugar backbone was introduced through a copper-catalysed Ullmann cross-coupling, followed by a challenging Friedel-Crafts cyclization. Remarkably, fluorescence microscopy revealed that marmycin A does not target the nucleus but instead accumulates in lysosomes, thereby promoting cell death independently of genome targeting. Furthermore, a synthetic dimer of marmycin A and the lysosome-targeting agent artesunate exhibited a synergistic activity against the invasive MDA-MB-231 cancer cell line. These findings shed light on the elusive pathways through which anthraquinone derivatives act in cells, pointing towards unanticipated biological and therapeutic applications.

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Section: Resultsmentioning

confidence: 99%

Synthesis of marmycin A and investigation into its cellular activity

Cañeque¹,

Gomes²,

Thi³

et al. 2015

Nature Chem

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“…Enzymatic sugar deoxygenation most often proceeds through a polar β-dehydration mechanism from an enol(ate) intermediate or via dehydration from a Schiff base intermediate in PMP-dependent enzymes. , Both of these pathways require a carbonyl functional group, necessitating substrate preactivation to a ketosugar intermediate. Synthetically, deoxygenation also requires substrate prefunctionalization, and is typically achieved through (a) activation and reductive displacement of one hydroxyl group − or (b) dehydration or deoxydehydration followed by olefin refunctionalization. − …”

Section: Enzymatic and Synthetic Deoxygenation Reactions Via 12-radic...mentioning

confidence: 99%

Selective Transformations of Carbohydrates Inspired by Radical-Based Enzymatic Mechanisms

2021

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Enzymes are a longstanding source of inspiration for synthetic reaction development. However, enzymatic reactivity and selectivity are frequently untenable in a synthetic context, as the principles that govern control in an enzymatic setting often do not translate to small molecule catalysis. Recent synthetic methods have revealed the viability of using small molecule catalysts to promote highly selective radical-mediated transformations of minimally protected sugar substrates. These transformations share conceptual similarities with radical SAM enzymes found in microbial carbohydrate biosynthesis and present opportunities for synthetic chemists to access microbial and unnatural carbohydrate building blocks without the need for protecting groups or lengthy synthetic sequences. Here, we highlight strategies through which radical reaction pathways can enable the site-, regio-, and diastereoselective transformation of minimally protected carbohydrates in both synthetic and enzymatic systems.

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“…Numerous approaches to the synthesis of deoxy sugars have been developed. − In many cases, deoxy sugar monosaccharide construction relies on de novo synthesis. − While there are a myriad of approaches to de novo synthesis, the majority of routes that have been reported are target specific. A more flexible approach relies on carrying out modifications on glycals, − which permits the generation of multiple different sugars from the same starting material. However, this strategy is cost-effective only when the glycal in question can be generated from readily available sugars, which is often not the case.…”

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confidence: 99%