Beyond the Roche Ester: A New Approach to Polypropionate Stereotriad Synthesis

Foley, Corinne N.; Leighton, James L.

doi:10.1021/ol500051e

Cited by 12 publications

(13 citation statements)

References 17 publications

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“…Enantiomerically pure 2-substituted 3-hydroxycarboxylate esters are an important class of chiral building blocks widely used in organic synthesis. − For example, ( S )- and ( R )-methyl 3-hydroxy-2-methylpropanoate (i.e., Roche esters) are largely employed as precursors for the preparation of bioactive natural compounds and pharmaceuticals (e.g., discodermolide with potent antimitotic activity, epothilone analogue ZK-Epo (sagopilone), the ionophore antibiotic zincophorin, cytotoxic marine natural products auripyrones A and B, the depsipeptide stevastelin B3, and the antifungal polyketide soraphen A). − Other chiral 2-substituted 3-hydroxycarboxylate esters can be found in the preparation of peptide deformylase inhibitors (Figure ). , …”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation

Marín-Valls¹,

Hernández²,

Bolte

et al. 2019

ACS Catal.

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Chiral 2-substituted 3-hydroxycarboxylic acid derivatives are valuable building blocks for the preparation of naturally occurring and synthetic biologically active molecules. Current methodologies for the preparation of these compounds are still limited for large-scale production due to the high costs, limited microbial strains, low yields, difficult downstream processing, and limited range of structures. We report an effective chemoenzymatic method for the synthesis of enantiomerically pure 2-substituted 3-hydroxycarboxylic esters. The strategy comprises: (i) a stereoselective aldol addition of 2-oxoacids to methanal catalyzed by two enantiocomplementary 2-oxoacid aldolases, (ii) oxidative decarboxylation, and (iii) esterification. Compounds with S-configuration were obtained in 69–80% isolated yields (94–99% ee), and the R enantiomers in 57–88% (88–98% ee), using a substrate concentration range of 0.1–1.0 M. The method developed offers a versatile alternative route to this important class of chiral building blocks and highlights the exciting opportunities available for using natural enzymes with minimal active site modification.

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Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation

Marín-Valls¹,

Hernández²,

Bolte

et al. 2019

ACS Catal.

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“…26 Thus, silylformylation of 6-chlorohex-1-yne gave aldehyde 17 which was directly crotylated with ( S , S )- cis EZ-CrotylMix 20 to give 18 in 90% yield and 95% ee (Scheme 2). Tamao oxidation/ anti -diastereoselective tautomerization and protection of the aldehyde gave 19 in 66% yield over two steps.…”

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confidence: 99%

A “Methyl Extension” Strategy for Polyketide Natural Product Linker Site Validation and Its Application to Dictyostatin

Sackett

Leighton

2015

J. Am. Chem. Soc.

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An approach to the validation of linker strategies for polyketide natural products with few or no obvious handles for linker attachment, and its application to dictyostatin are described. Analogs in which the C(6) and C(12) methyl groups were replaced by 4-azidobutyl groups were prepared and shown to retain the low nM potency of dictyostatin. Further, conjugation of the C(6)-analog with a cyclooctyne resulted in only minor attenuations in potency. Together, these results shed light on the binding of dictyostatin to β-tubulin, establish a validated linker strategy for dictyostatin, and set the stage for the synthesis and study of dictyostatin conjugates.

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“…However, there are many natural products bearing a methyl group as the stereogenic center, and these aldehydes are important synthetic targets for natural product synthesis. These aldehydes are normally obtained using Evans' oxazolidinones or related auxiliaries,105 or obtained after various synthetic transformations from the commercially available Roche ester 106. By applying the organocatalytic procedure with the benzodithiolylium, followed by treatment with Raney® nickel, a quite simple and easy α‐alkylation of aldehydes can be performed.…”

Section: An Unexpected Journey: Carbenium Ions For Organocatalytic Snmentioning

confidence: 99%

“…These aldehydes are normally obtained using Evans' oxazolidinones or related auxiliaries, [105] or obtained after various synthetic transformations from the commercially available Roche ester. [106] By applying the organocatalytic procedure with the benzodithiolylium, followed by treatment with Raney V R nickel, a quite simple and easy a-alkylation of aldehydes can be performed. No dried solvents or strong bases are necessary for the alkylation, and the procedure can be successfully used by undergraduate students.…”

Section: Scheme 14mentioning

confidence: 99%

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

Gualandi

Mengozzi

Manoni

et al. 2016

The Chemical Record

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What do quantum cellular automata (QCA), "on water" reactions, and SN 1-type organocatalytic transformations have in common? The link between these distant arguments is the practical access to useful intermediates and key products through the use of stabilized carbenium ions. Over 10 years, starting with a carbenium ion bearing a ferrocenyl group, to the 1,3-benzodithiolylium carbenium ion, our group has exploited the use of these intermediates in useful and practical synthetic transformations. In particular, we have applied the use of carbenium ions to stereoselective organocatalytic alkylation reactions, showing a possible solution for the "holy grail of organocatalysis". Examples of the use of these quite stabilized intermediates are now also considered in organometallic chemistry. On the other hand, the stable carbenium ions are also applied to tailored molecules adapted to quantum cellular automata, a new possible paradigm for computation. Carbenium ions are not a problem, they can be a/the solution!

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Beyond the Roche Ester: A New Approach to Polypropionate Stereotriad Synthesis

Cited by 12 publications

References 17 publications

Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation

Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation

A “Methyl Extension” Strategy for Polyketide Natural Product Linker Site Validation and Its Application to Dictyostatin

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

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