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Concise Chemoenzymatic Three Step Total Synthesis of Isosolenopsin Through Medium Engineering.

Simon RC, Fuchs CS, Lechner H, Zepeck F, Kroutil W - European J Org Chem (2013)

Bottom Line: A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved.Diastereostelective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound.The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee > 99%, d.r. = 99:1) with an overall yield of 64%.

View Article: PubMed Central - PubMed

Affiliation: ACIB GmbH, Heinrichstraße 28, 8010-Graz, Austria.

ABSTRACT
A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved. In the key step, a ω-transaminase catalyzed the regioselective mono-amination of the diketone pentadecane-2,6-dione which was obtained in a single step via Grignard reaction. Initial low conversions in the biotransformation could be overcome by optimisation of the reaction conditions employing suitable cosolvents. In the presence of 20 vol% DMF or n-heptane best results were obtained employing two enantio-complementary ω-transaminases originating from Arthrobacter between 30-40 °C; under these conditions conversions of >99% and perfect stereocontrol (ee > 99%) were achieved. Diastereostelective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound. The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee > 99%, d.r. = 99:1) with an overall yield of 64%.

No MeSH data available.


Related in: MedlinePlus

Reductive amination of diketone 3a in an aqueous two-phase system: (▪) (R)-Arthrobacter sp., (•) A. citreus. Reagents and conditions: diketone 3a (25 mm) dissolved in 5 vol.-% DMF, lyophilised E. coli cells containing the overexpressed ω-TA (20 mg), PLP (1 mm), NAD+ (1 mm), ammonium formate (150 mm), D- or L-alanine (500 mm), AlaDH (12 U), FDH (11 U), 5–40 vol.-% n-heptane, KPi buffer (100 mm, pH 7.0), 30 °C, 24 h, 700 rpm.
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fig07: Reductive amination of diketone 3a in an aqueous two-phase system: (▪) (R)-Arthrobacter sp., (•) A. citreus. Reagents and conditions: diketone 3a (25 mm) dissolved in 5 vol.-% DMF, lyophilised E. coli cells containing the overexpressed ω-TA (20 mg), PLP (1 mm), NAD+ (1 mm), ammonium formate (150 mm), D- or L-alanine (500 mm), AlaDH (12 U), FDH (11 U), 5–40 vol.-% n-heptane, KPi buffer (100 mm, pH 7.0), 30 °C, 24 h, 700 rpm.

Mentions: Although conversions above 95 % were achieved by employing the reaction conditions mentioned above, n-heptane was also investigated due to the similarity in polarity of the solvent to the starting material 3a (Figure 5). For solubility reasons, the substrate still needed to be predissolved in DMF (5 vol.-% final conc.). Despite the formation of a biphasic system, the reaction resulted in full conversion (> 99 %) at 20 vol.-% n-heptane for the ω-TA from (R)-Arthrobacter sp. and 85 % conversion for the (S)-ω-TA from Arthrobacter.


Concise Chemoenzymatic Three Step Total Synthesis of Isosolenopsin Through Medium Engineering.

Simon RC, Fuchs CS, Lechner H, Zepeck F, Kroutil W - European J Org Chem (2013)

Reductive amination of diketone 3a in an aqueous two-phase system: (▪) (R)-Arthrobacter sp., (•) A. citreus. Reagents and conditions: diketone 3a (25 mm) dissolved in 5 vol.-% DMF, lyophilised E. coli cells containing the overexpressed ω-TA (20 mg), PLP (1 mm), NAD+ (1 mm), ammonium formate (150 mm), D- or L-alanine (500 mm), AlaDH (12 U), FDH (11 U), 5–40 vol.-% n-heptane, KPi buffer (100 mm, pH 7.0), 30 °C, 24 h, 700 rpm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151137&req=5

fig07: Reductive amination of diketone 3a in an aqueous two-phase system: (▪) (R)-Arthrobacter sp., (•) A. citreus. Reagents and conditions: diketone 3a (25 mm) dissolved in 5 vol.-% DMF, lyophilised E. coli cells containing the overexpressed ω-TA (20 mg), PLP (1 mm), NAD+ (1 mm), ammonium formate (150 mm), D- or L-alanine (500 mm), AlaDH (12 U), FDH (11 U), 5–40 vol.-% n-heptane, KPi buffer (100 mm, pH 7.0), 30 °C, 24 h, 700 rpm.
Mentions: Although conversions above 95 % were achieved by employing the reaction conditions mentioned above, n-heptane was also investigated due to the similarity in polarity of the solvent to the starting material 3a (Figure 5). For solubility reasons, the substrate still needed to be predissolved in DMF (5 vol.-% final conc.). Despite the formation of a biphasic system, the reaction resulted in full conversion (> 99 %) at 20 vol.-% n-heptane for the ω-TA from (R)-Arthrobacter sp. and 85 % conversion for the (S)-ω-TA from Arthrobacter.

Bottom Line: A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved.Diastereostelective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound.The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee > 99%, d.r. = 99:1) with an overall yield of 64%.

View Article: PubMed Central - PubMed

Affiliation: ACIB GmbH, Heinrichstraße 28, 8010-Graz, Austria.

ABSTRACT
A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved. In the key step, a ω-transaminase catalyzed the regioselective mono-amination of the diketone pentadecane-2,6-dione which was obtained in a single step via Grignard reaction. Initial low conversions in the biotransformation could be overcome by optimisation of the reaction conditions employing suitable cosolvents. In the presence of 20 vol% DMF or n-heptane best results were obtained employing two enantio-complementary ω-transaminases originating from Arthrobacter between 30-40 °C; under these conditions conversions of >99% and perfect stereocontrol (ee > 99%) were achieved. Diastereostelective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound. The linear three step synthesis provided the natural product isosolenopsin in diastereomerically pure form (ee > 99%, d.r. = 99:1) with an overall yield of 64%.

No MeSH data available.


Related in: MedlinePlus