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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

Chemoenzymatic asymmetric synthesis of 2,6-disubstituted piperidines involving regio- and stereoselective monoamination.
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fig02: Chemoenzymatic asymmetric synthesis of 2,6-disubstituted piperidines involving regio- and stereoselective monoamination.

Mentions: Recently, we demonstrated that 2,6-diketones 3 serve as useful precursors for the synthesis of the optically pure 2,6-disubstituted piperidine scaffold 8 through enzymatic reductive amination (Scheme 1).7 A ω-transaminase (ω-TA)8–10 catalysed regio- and stereoselective monoamination of 3 at the sterically less demanding (ω-1)-keto moiety, yielding preferentially amino-ketone 4, which underwent spontaneous ring-closure to give the corresponding Δ1-piperideines 6 in enantiomerically pure form. Based on this concept, we now report an extension of this method for the total synthesis of isosolenopsin [(2S,6R)-1a] and its enantiomer (2R,6S)-1a.11


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)

Chemoenzymatic asymmetric synthesis of 2,6-disubstituted piperidines involving regio- and stereoselective monoamination.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Chemoenzymatic asymmetric synthesis of 2,6-disubstituted piperidines involving regio- and stereoselective monoamination.
Mentions: Recently, we demonstrated that 2,6-diketones 3 serve as useful precursors for the synthesis of the optically pure 2,6-disubstituted piperidine scaffold 8 through enzymatic reductive amination (Scheme 1).7 A ω-transaminase (ω-TA)8–10 catalysed regio- and stereoselective monoamination of 3 at the sterically less demanding (ω-1)-keto moiety, yielding preferentially amino-ketone 4, which underwent spontaneous ring-closure to give the corresponding Δ1-piperideines 6 in enantiomerically pure form. Based on this concept, we now report an extension of this method for the total synthesis of isosolenopsin [(2S,6R)-1a] and its enantiomer (2R,6S)-1a.11

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