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Dai M, Sims HS, de Andrade Horn P, et al. Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester. Angew Chem Int Ed Engl. 2021;doi: 10.1002/anie.202115633.
Dai, M., Sims, H. S., de Andrade Horn, P., Isshiki, R., Lim, M., Xu, Y., & Grubbs, R. H. (2021). Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester. Angewandte Chemie (International ed. in English), . https://doi.org/10.1002/anie.202115633
Dai, Mingji, et al. "Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester." Angewandte Chemie (International ed. in English) vol. (2021). doi: https://doi.org/10.1002/anie.202115633
Dai M, Sims HS, de Andrade Horn P, Isshiki R, Lim M, Xu Y, Grubbs RH. Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester. Angew Chem Int Ed Engl. 2021 Dec 06; doi: 10.1002/anie.202115633. Epub 2021 Dec 06. PMID: 34870881.
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Angew Chem Int Ed Engl. 2021 Dec 06; doi: 10.1002/anie.202115633. Epub 2021 Dec 06.

Catalysis-Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D2 Metabolite Methyl Ester.

Angewandte Chemie (International ed. in English)

Mingji Dai, Hunter S Sims, Pedro de Andrade Horn, Ryota Isshiki, Melissa Lim, Yan Xu, Robert H Grubbs

Affiliations

  1. Purdue University, Department of Chemistry, 560 Oval Drive, 47907, West Lafayette, UNITED STATES.
  2. Purdue University, Chemistry, UNITED STATES.
  3. Caltech: California Institute of Technology, Division of Chemistry and Chemical Engineering, UNITED STATES.

PMID: 34870881 DOI: 10.1002/anie.202115633

Abstract

A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D 2 metabolite (tricyclic-PGDM) methyl ester in racemic form was accomplished in 8 steps from a readily available known cyclopentene-diol derivative. The synthesis features a nickel-catalyzed Ueno-Stork-type dicarbofunctionalization to generate two consecutive stereocenters, a palladium-catalyzed carbonylative spirolactonization to build the core oxaspirolactone, and a Z -selective cross metathesis to introduce the ( Z )-3-butenoate side chain, a group challenging to introduce through traditional Wittig protocols and troublesome for the two previous total syntheses. A general Z -selective cross metathesis protocol to construct ( Z )-β,γ-unsaturated esters was also developed that has broad functional group tolerance and high stereoselectivity. Additionally, our synthesis already accumulated 75 mg of valuable material for an 18 O tricyclic-PGDM based assay used in clinical settings for inflammation.

© 2021 Wiley-VCH GmbH.

Keywords: carbonylation; nickel catalysis; olefin metathesis; prostaglandins; total synthesis

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