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An improved biomimetic formal synthesis of abyssomicin C and atrop-abyssomicin C

An improved biomimetic formal synthesis of abyssomicin C and atrop-abyssomicin C
An improved biomimetic formal synthesis of abyssomicin C and atrop-abyssomicin C

Biomimetic approaches towards the synthesis of abysssomicin C and atrop-abyssomicin C are based on a powerful intramolecular Diels–Alder reaction (IMDA) of a butenolide derivative attached to a keto-triene side chain, where the stereogenic centers and the carbon framework are established in one step. The synthesis of the IMDA precursor is based on an ionic coupling of methyl γ-methylene-β-tetronate with various aldehydes. However, the low yields of the coupling and the high sensitivity of the precursor hampered the efficiency of the developed routes and should be met. In the present work, a modified aldehyde is coupled with methyl γ-methylene-β-tetronate, in a substantially higher yield. Asymmetric synthesis of this aldehyde is based on the use of the widely available and cheap Amano lipase AK. In addition, the development of a highly convenient one-pot oxidation-IMDA reaction protocol obviates the isolation of the sensitive IMDA-precursor and augments the yield towards the carbocyclic skeleton of abysssomicin C and atrop-abyssomicin C.

Biomimetic synthesis, Cycloaddition, Natural products, Polyketides, Spiro compounds
1434-193X
4547-4557
Vidali, Veroniki P.
b2e1bca5-8746-4827-a5af-6e4f95543a24
Canko, Aleksander
efcf7fa9-3b01-430f-9469-b7d97b68492a
Peroulias, Angelos D.
9a978d7e-02fa-4580-95f6-d0efd4c5a02a
Georgas, Evangelos T.
c6f8d952-2201-4d3d-9848-d8e5d4ac3f30
Bouzas, Emmanuel
c61394b0-2b74-48f3-b065-4ce9ec02d248
Herniman, Julie M.
530b1a36-1386-4602-8df7-defa6eb3512b
Couladouros, Elias A.
8d090bee-1ec2-43ef-8c3a-0a06e62a7293
Vidali, Veroniki P.
b2e1bca5-8746-4827-a5af-6e4f95543a24
Canko, Aleksander
efcf7fa9-3b01-430f-9469-b7d97b68492a
Peroulias, Angelos D.
9a978d7e-02fa-4580-95f6-d0efd4c5a02a
Georgas, Evangelos T.
c6f8d952-2201-4d3d-9848-d8e5d4ac3f30
Bouzas, Emmanuel
c61394b0-2b74-48f3-b065-4ce9ec02d248
Herniman, Julie M.
530b1a36-1386-4602-8df7-defa6eb3512b
Couladouros, Elias A.
8d090bee-1ec2-43ef-8c3a-0a06e62a7293

Vidali, Veroniki P., Canko, Aleksander, Peroulias, Angelos D., Georgas, Evangelos T., Bouzas, Emmanuel, Herniman, Julie M. and Couladouros, Elias A. (2020) An improved biomimetic formal synthesis of abyssomicin C and atrop-abyssomicin C. European Journal of Organic Chemistry, 2020 (29), 4547-4557. (doi:10.1002/ejoc.202000671).

Record type: Article

Abstract

Biomimetic approaches towards the synthesis of abysssomicin C and atrop-abyssomicin C are based on a powerful intramolecular Diels–Alder reaction (IMDA) of a butenolide derivative attached to a keto-triene side chain, where the stereogenic centers and the carbon framework are established in one step. The synthesis of the IMDA precursor is based on an ionic coupling of methyl γ-methylene-β-tetronate with various aldehydes. However, the low yields of the coupling and the high sensitivity of the precursor hampered the efficiency of the developed routes and should be met. In the present work, a modified aldehyde is coupled with methyl γ-methylene-β-tetronate, in a substantially higher yield. Asymmetric synthesis of this aldehyde is based on the use of the widely available and cheap Amano lipase AK. In addition, the development of a highly convenient one-pot oxidation-IMDA reaction protocol obviates the isolation of the sensitive IMDA-precursor and augments the yield towards the carbocyclic skeleton of abysssomicin C and atrop-abyssomicin C.

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Accepted/In Press date: 10 July 2020
e-pub ahead of print date: 10 July 2020
Published date: 9 August 2020
Keywords: Biomimetic synthesis, Cycloaddition, Natural products, Polyketides, Spiro compounds

Identifiers

Local EPrints ID: 443402
URI: http://eprints.soton.ac.uk/id/eprint/443402
ISSN: 1434-193X
PURE UUID: ab32db69-92df-44c0-8d12-337131a1f5ce
ORCID for Julie M. Herniman: ORCID iD orcid.org/0000-0003-4834-1093

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Date deposited: 24 Aug 2020 16:33
Last modified: 07 Oct 2020 01:42

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Contributors

Author: Veroniki P. Vidali
Author: Aleksander Canko
Author: Angelos D. Peroulias
Author: Evangelos T. Georgas
Author: Emmanuel Bouzas
Author: Elias A. Couladouros

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