Synthesis of Substrates for Aldolase-Catalysed Reactions: A Comparison of Methods for the Synthesis of Substituted Phenylacetaldehydes

Al-Smadi, Derar; Enugala, Thilak Reddy; Norberg, Thomas; Kihlberg, Jan; Widersten, Mikael

doi:10.1055/s-0036-1591963

Cited by 11 publications

(30 citation statements)

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“…A two-fold excess of the ketones were used due to their commercial availability and low cost, as opposed to aldehydes 1b-f that require preparation in two steps. 11 The direct aldol reactions were successful with the phenylsubstituted ketone 2c as donor, but gave poor yields when using 2a or 2b. Thus, reaction of 2-hydroxyacetophenone (2c) with 1b-f,…”

Section: Resultsmentioning

confidence: 99%

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Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di- and Tri-Hydroxypentanones

et al. 2019

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Polyhydroxylated compounds are building blocks for the synthesis of carbohydrates and other natural products. Their synthesis is mainly achieved by different synthetic versions of aldolcoupling reactions, catalyzed either by organocatalysts, enzymes or metal-organic catalysts. We have investigated the formation of 1,4-substituted 2,3-dihydroxybutan-1-one derivatives from para-and meta-substituted phenylacetaldehydes by three distinctly different strategies. The first involved a direct aldol reaction with hydroxyacetone, dihydroxyacetone or 2hydroxyacetophenone, catalyzed by the cinchona derivative cinchonine. The second was reductive cross-coupling with methyl or phenyl glyoxal promoted by SmI 2 resulting in either 5-substituted 3,4-dihydroxypentan-2-ones or 1,4 bis-phenyl substituted butanones, respectively. Finally, in the third case, aldolase catalysis was employed for synthesis of the corresponding 1 1,3,4-trihydroxylated pentan-2-one derivatives. The organocatalytic route with cinchonine generated distereomerically enriched syn products (de = 60−99 %), with moderate enantiomeric excesses (ee = 43−56%), but did not produce aldols with either hydroxyacetone or dihydroxyacetone as donor ketones. The SmI 2-promoted reductive cross-coupling generated product mixtures with diastereomeric and enantiomeric ratios close to unity. This route allowed for the production of both 1-methyl-and 1-phenylsubstituted 2,3-dihydroxybutanones, at yields between 40−60%. Finally, the biocatalytic approach resulted in enantiopure syn (3R,4S) 1,3,4trihydroxypentan-2-ones.

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Section: Resultsmentioning

confidence: 99%

“…The reactions of phenylglyoxal were faster, and gave higher total yields than those of methylglyoxal (3a, Table 1). The products (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) were mixtures of the anti and syn diastereomers, at ratios close to unity.…”

Section: Resultsmentioning

confidence: 99%

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di- and Tri-Hydroxypentanones

et al. 2019

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“…The acceptor aldehydes represent a structural series of para-and meta-substituted phenylacetaldehydes (1a-f, Figure 1) 11 containing both electron-withdrawing as well as electrondonating substituents. In the direct aldol reaction, hydroxyacetone (2a), dihydroxyacetone (2b), and 2-hydroxyacetophenone (2c) were tested as donor reactants.…”

Section: Resultsmentioning

confidence: 99%

Section: Samarium Diiodide Promoted Reductive Cross Couplingsmentioning

confidence: 99%

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones

Widersten¹,

Al-Smadi²,

Enugala³

et al. 2019

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<div>Polyhydroxylated compounds are building blocks for the synthesis of carbohydrates and other natural products. Their synthesis is mainly achieved by different synthetic versions of aldolcoupling reactions, catalyzed either by organocatalysts, enzymes or metal-organic catalysts. We have investigated the formation of 1,4-substituted 2,3-dihydroxybutan-1-one derivatives from para- and meta-substituted phenylacetaldehydes by three distinctly different strategies. The first involved a direct aldol reaction with hydroxyacetone, dihydroxyacetone or 2-hydroxyacetophenone, catalyzed by the cinchona derivative cinchonine. The second was reductive cross-coupling with methyl or phenyl glyoxal promoted by SmI2 resulting in either 5-substituted 3,4-dihydroxypentan-2-ones or 1,4 bis-phenyl substituted butanones, respectively.</div><div>Finally, in the third case, aldolase catalysis was employed for synthesis of the corresponding 1,3,4-trihydroxylated pentan-2-one derivatives. The organocatalytic route with cinchonine generated distereomerically enriched syn products (de = 60−99 %), with moderate enantiomeric excesses (ee = 43−56%), but did not produce aldols with either hydroxyacetone or dihydroxyacetone as donor ketones. The SmI2-promoted reductive cross-coupling generated product mixtures with diastereomeric and enantiomeric ratios close to unity. This route allowed for the production of both 1-methyl- and 1-phenylsubstituted 2,3-dihydroxybutanones, at yields between 40−60%. Finally, the biocatalytic approach resulted in enantiopure syn (3R,4S) 1,3,4-trihydroxypentan-2-ones.</div>

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Section: Samarium Diiodide Promoted Reductive Cross Couplingsmentioning

confidence: 99%

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones

Widersten¹,

Al-Smadi²,

Enugala³

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Polyhydroxylated compounds are building blocks for the synthesis of carbohydrates and other natural products. Their synthesis is mainly achieved by different synthetic versions of aldolcoupling reactions, catalyzed either by organocatalysts, enzymes or metal-organic catalysts. We have investigated the formation of 1,4-substituted 2,3-dihydroxybutan-1-one derivatives from para-and meta-substituted phenylacetaldehydes by three distinctly different strategies. The first involved a direct aldol reaction with hydroxyacetone, dihydroxyacetone or 2hydroxyacetophenone, catalyzed by the cinchona derivative cinchonine. The second was reductive cross-coupling with methyl or phenyl glyoxal promoted by SmI 2 resulting in either 5-substituted 3,4-dihydroxypentan-2-ones or 1,4 bis-phenyl substituted butanones, respectively.Finally, in the third case, aldolase catalysis was employed for synthesis of the corresponding 1 1,3,4-trihydroxylated pentan-2-one derivatives. The organocatalytic route with cinchonine generated distereomerically enriched syn products (de = 60−99 %), with moderate enantiomeric excesses (ee = 43−56%), but did not produce aldols with either hydroxyacetone or dihydroxyacetone as donor ketones. The SmI 2 -promoted reductive cross-coupling generated product mixtures with diastereomeric and enantiomeric ratios close to unity. This route allowed for the production of both 1-methyl-and 1-phenylsubstituted 2,3-dihydroxybutanones, at yields between 40−60%. Finally, the biocatalytic approach resulted in enantiopure syn (3R,4S) 1,3,4trihydroxypentan-2-ones.

show abstract

Synthesis of Substrates for Aldolase-Catalysed Reactions: A Comparison of Methods for the Synthesis of Substituted Phenylacetaldehydes

Cited by 11 publications

References 14 publications

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di- and Tri-Hydroxypentanones

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di- and Tri-Hydroxypentanones

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones

Chemical and Biochemical Approaches for the Synthesis of Substituted Dihydroxybutanones and Di-, and Tri-Hydroxypentanones

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