Stereocontrolled total synthesis of neuroprotectin D1/protectin D1 and its aspirin-triggered stereoisomer
Open accessAbstract
Neuroprotectin D1 / protectin D1, a potent anti-inflammatory, proresolving, and neuroprotective lipid mediator derived biosynthetically from docosahexaenoic acid, was prepared in enantiomerically pure form via total organic synthesis. The synthetic strategy is highly stereocontrolled and convergent, featuring epoxide opening of glycidol starting materials for the introduction of the 10(R) and 17(S) hydroxyl groups. The desired alkene Z geometry was secured via the cis-reduction of alkyne precursors, while the conjugated E,E,Z triene was introduced at the end, in order to minimize Z/E isomerization. The same strategy, was also employed for the total synthesis of aspirin-triggered neuroprotectin D1 / protectin D1 having the 17(R)-stereochemistry. Synthetic compounds obtained with the reported method were matched with endogenously derived materials, and helped establish their complete stereochemistry.
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The complete structures and stereochemistry of elovanoids ELV-N32 and ELV-N34 from neuronal cultures were established through a direct comparison with compounds prepared via stereocontrolled total organic synthesis.
“The complete structures and stereochemistry of elovanoids ELV-N32 and ELV-N34 from neuronal cultures were established through a direct comparison with compounds prepared via stereocontrolled total organic synthesis by adapting our previous method (Petasis et al., 2012).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Petasis et al., 2012
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- Authors
- Petasis, N. A., Yang, R., Winkler, J. W., Zhu, M., Uddin, J., Bazan, N. G., & Serhan, C. N.
- Affiliations
- University of Southern California (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Petasis, Nicos A.
- Venue
- Tetrahedron Letters
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 53
- Issue
- 14
- Pages
- 1695-1698
- ISSN
- 0040-4039 (ISSN-L)
- PMC
- PMC3370686
- OpenAlex
- W2087590528
- Cited by
- 45
- References
- 18
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 6 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 4 · 2015: 8 · 2014: 7 · 2013: 6 · 2012: 3
- FWCI
- 7.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Tetrahedron Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P50-DE016191, RC2-AT005909, P01-GM095467)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Physical Sciences › Chemistry › Organic Chemistry › Organic Chemistry Synthesis Methods
- Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
- Keywords
- neuroprotectin D1, protectin D1, total synthesis, stereoselective synthesis, epoxide ring opening, glycidol, cis-trans isomerization, stereochemistry determination, neuroprotection
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