Wittig Reaction: Domino Olefination and Stereoselectivity DFT Study. Synthesis of the Miharamycins’ Bicyclic Sugar Moiety

Cachatra, Vasco; Almeida, A. Filipa; Sardinha, João; Lucas, Susana D.; Gomes, Ana Coelho; Vaz, Pedro D.; Florêncio, M. Helena; Nunes, Rafael; Vila-Viçosa, Diogo; Rauter, Amélia P.

doi:10.1021/acs.orglett.5b02849

Cited by 20 publications

(14 citation statements)

References 19 publications

(25 reference statements)

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“…Methyl 2,3‐Di‐ O ‐benzyl‐4,6‐ O ‐benzylidene‐α‐ d ‐glucopyranoside (5) . To a solution of methyl 4,6‐ O ‐benzylidene‐α‐ d ‐glucopyranoside (3 g, 10.6 mmol) in DMF (200 mL), NaH (60 % oil suspension, 2.84 g, 42.4 mmol, 4 equiv.) was carefully added at 0 °C and the reaction was stirred for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus anthracis

et al. 2019

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The discovery of the bactericide dodecyl 2,6‐dideoxypyranoside reorganizing membrane phospholipid matrix of Bacillus species into a hexagonal phase, encouraged further research on glycone deoxygenation/bioactivity relationship. We now describe expedient syntheses of new 2‐, 3‐, 4‐deoxy, 2,3‐ and 3,4‐dideoxy glycosides in moderate to good yields. Interestingly, Amberlyst 15 is a key protagonist, efficiently applied for the transacetalation of alkyl deoxy glycosides and for ring contraction to access regioselectively hexofuranosides. The 2‐deoxy‐d‐arabino pyranoside affords the higher MIC values against two Bacillus spp. and Enterococcus faecalis, while a 4‐fold decrease or higher was found by inversion of configuration or by deoxygenation at C‐3. While 2,3‐ and 3,4‐dideoxygenation do not improve bioactivity, the 4,6‐dideoxy‐α‐d‐xylo‐hexopyranoside remains a promising glycoside, presenting low MIC values for all species tested, and low cytotoxicity in intestinal and liver cell models.

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Section: Methodsmentioning

confidence: 99%

Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus anthracis

et al. 2019

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“…Interestingly, while the total synthesis of amipurimycin was accomplished only recently, 16 some 40 years after the initial discovery of this PNA, a successful total synthesis of a miharamycin has yet to be reported. 17,18…”

Section: Introductionmentioning

confidence: 99%

The Amipurimycin and Miharamycin Biosynthetic Gene Clusters: Unraveling the Origins of 2-Aminopurinyl Peptidyl Nucleoside Antibiotics

et al. 2019

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Peptidyl nucleoside antibiotics (PNAs) are a diverse class of natural products with promising biomedical activities. These compounds have tripartite structures composed of a core saccharide, a nucleobase, and one or more amino acids. In particular, amipurimycin and the miharamycins are novel 2-aminopurinyl PNAs with complex nine-carbon core saccharides and include the unusual amino acids (–)-cispentacin and N5-hydroxyarginine, respectively. Despite their interesting structures and properties, these PNAs have heretofore eluded biochemical scrutiny. Herein is reported the discovery and initial characterization of the miharamycin gene cluster in Streptomyces miharaensis (mhr) and the amipurimycin gene cluster (amc) in Streptomyces novoguineensis and Streptomyces sp. SN-C1. The gene clusters were identified using a comparative genomics approach, and heterologous expression of the amc cluster as well as gene interruption experiments in the mhr cluster support their role in the biosynthesis of amipurimycin and the miharamycins, respectively. The mhr and amc biosynthetic gene clusters characterized encode enzymes typical of polyketide biosynthesis instead of enzymes commonly associated with PNA biosynthesis, which along with labeled precursor feeding studies, implies that the core saccharides found in the miharamycins and amipurimycin are partially assembled as polyketides rather than derived solely from carbohydrates. Furthermore, in vitro analysis of Mhr20 and Amc18 established their roles as ATP-grasp ligases involved in the attachment of the pendant amino acids found in these PNAs, and Mhr24 was found to be an unusual hydroxylase involved in the biosynthesis of N5-hydroxyarginine. Finally, analysis of the amc cluster and feeding studies also led to the proposal of a biosynthetic pathway for (–)-cispentacin.

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“…Whilst ketoses 10 αβ should be viewed as important synthetic intermediates for a wide range of potential applications, the next step in the route to KAR1 1 involved a Wittig reaction of 10 αβ using conditions reported by Rauter and Calhorda et al [44] In the first trial, the relatively abundant αanomer 10 α was reacted with Ph 3 P=CHCO 2 Et (1.5 equiv.) in MeCN at 75 °C for 72 h to give the isomeric cyclized products 14 α and 15 α in 55 % and 32 % isolated yields respectively (Scheme 2B and Figures S9 and S10).…”

Section: Resultsmentioning

confidence: 99%

From Biomass to the KarrikinsviaSelective Catalytic Oxidation of Hemicellulose‐Derived Butyl Xylosides and Glucosides

Xiao

Slawin

et al. 2022

Eur J Org Chem

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Members of the karrikin family of bioactive small molecules are known to promote germination of a range of plants following large scale fires. As a result, they are relevant and interesting compounds. This report describes their synthesis from a biomass‐derived product stream. During work to fractionate biomass with the goal of obtaining high quality lignins, an interesting co‐product stream derived from the hemicellulose in the biomass, was obtained. Whilst many applications of this co‐product stream can be proposed, in this case the major monosaccharides have been converted to relevant karrikins in short reaction sequences. Key results include a highly selective catalytic oxidation reaction, conversion of the resulting ketone to a butenolide by two alternative approaches, a selective acetal reductive opening reaction, X‐ray crystallographic analysis of two compounds and detailed comparison of the final products with previous literature reports. Only through successful use of all the components generated during biomass refining, can economic sustainability be potentially achieved.

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Wittig Reaction: Domino Olefination and Stereoselectivity DFT Study. Synthesis of the Miharamycins’ Bicyclic Sugar Moiety

Cited by 20 publications

References 19 publications

Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus anthracis

Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus anthracis

The Amipurimycin and Miharamycin Biosynthetic Gene Clusters: Unraveling the Origins of 2-Aminopurinyl Peptidyl Nucleoside Antibiotics

From Biomass to the KarrikinsviaSelective Catalytic Oxidation of Hemicellulose‐Derived Butyl Xylosides and Glucosides

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