Mitsunobu Reaction: A Powerful Tool for the Synthesis of Natural Products: A Review

Munawar, Saba; Zahoor, Ameer Fawad; Ali, Shafaqat; Javed, Sadia; Irfan, Muhammad; Irfan, Ali; Kotwica-Mojzych, Katarzyna

doi:10.3390/molecules27206953

Cited by 19 publications

(16 citation statements)

References 121 publications

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“…The diol could in principle also be reconverted to the carbonate and resubmitted to the kinetic resolution. The synthesis of chiral vicinal diols is of great relevance in synthetic chemistry [49,50] . One of the most common routes for their preparation is the Sharpless asymmetric dihydroxylation of alkenes with OsO 4 [51] .…”

Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Synthesis of Chiral Building Blocks Based on the Kinetic Resolution of Glycerol‐Derived Cyclic Carbonates

Terazzi,

Spannenberg,

von Langermann

et al. 2023

ChemCatChem

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The biocatalytic kinetic resolution of cyclic carbonates derived from glycerol is reported. A selection of 26 esterases and lipases was tested for the asymmetric hydrolysis of the model substrate (4‐(chloromethyl)‐1,3‐dioxolan‐2‐one) in aqueous medium. Among them, Pig Liver Esterase and Novozym® 435 showed the best selectivity with E = 38 and 49, respectively. Both enzymes were employed for the conversion of 12 glycerol derivatives under optimized conditions. The resolution of halogenated carbonates afforded the unconverted enantiomer in up to >99:1 er. Furthermore, Novozym® 435 was successfully recycled 10 times without significant loss of activity. Upscaling and isolation of a chiral carbonate was also demonstrated. Subsequent conversion of this chiral building block allowed the direct one‐pot synthesis of Guaifenesin, Mephenesin and Chlorphenesin in up to 89% yield and 94:6 er.

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Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Synthesis of Chiral Building Blocks Based on the Kinetic Resolution of Glycerol‐Derived Cyclic Carbonates

Terazzi,

Spannenberg,

von Langermann

et al. 2023

ChemCatChem

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“…9 The Mitsunobu reaction of (R)-4 with 4-nitrobenzoic acid in the presence of triphenyl phosphine and diisopropyl azodicarboxylate (DIAD) gave ester (S)-5. 16,17 (S)-5 was treated with sodium methoxide in methanol to deliver (S)-HPA ((S)-4). (S)-4 was then O-alkylated with tosylated hydroxymethylphosphonate diester (DESMP) in the presence of magnesium tert-butoxide (MTB) to deliver diethyl phosphonate (S)-6, which was treated with sodium bromide and trimethylsilyl chloride combination for diethyl removal to finally deliver (S)-3.…”

Section: Synthesis Of Reference Substancesmentioning

confidence: 99%

Chiral Analysis of the Key Intermediates of Tenofovir Alafenamide Fumarate

Zhou

Zhang

2023

Pharmaceutical Fronts

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Abstract(R)-Tenofovir phenyl ester ((R)-1) and (R)-tenofovir diphenyl ester ((R)-2) are key intermediates for the practical synthesis of tenofovir alafenamide fumarate, which is a mainstay antiretroviral for the treatment of chronic hepatitis B and HIV-1 infections. This article deals with the chiral analysis of (R)-1 and (R)-2 against their respective optical impurity (S)-tenofovir phenyl ester ((S)-1) and (S)-tenofovir diphenyl ester ((S)-2) using a polysaccharide-coated chiral stationary phase (CSP) by normal-phase high-performance liquid chromatography (HPLC). To this end, a chiral synthetic strategy for (S)-2 was efficiently executed capitalizing on a classical Mitsunobu reaction to stereospecifically invert the configuration of chiral carbon in readily accessible (R)-HPA ((R)-4) to deliver (S)-HPA ((S)-4), from which (S)--tenofovir ((S)-3) was in turn prepared and further transformed into (S)-2. With reference substance (S)-2 in hand, a chiral analytical method for (R)-2 using Chiralpak AD-H as CSP by normal-phase HPLC has been developed and validated. The validation results indicated that this chiral analytical method has been achieved with satisfactory separation effect, high sensitivity, and good precision and accuracy, and thus can be deployed for the determination of optical impurities in samples of (R)-1 (via derivation to (R)-2) and (R)-2.

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“…103,104 Dumpala et al in 2020 presented a concise and efficient synthetic route towards the first total synthesis of this heterocyclic scaffold 233 , with 8.0% overall yield (Scheme 26). 105 The main steps entailed Sharpless epoxidation, regioselective epoxide ring opening by Gilman reagent, Mitsunobu reaction, 37 Yamaguchi esterification, and amide coupling reaction. To accomplish this task, the easily available cinnamyl alcohol 226 was converted into epoxide 227 via Sharpless asymmetric epoxidation under given conditions with 97% yield.…”

Section: Review Of Literaturementioning

confidence: 99%