Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene
- PMID: 36656952
- PMCID: PMC10462259
- DOI: 10.1126/science.ade0032
Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene
Abstract
Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate. This key step swiftly assembles the azadecalin framework of the natural product, allows for a succinct synthetic endgame, and enables a 12-step total synthesis (longest linear sequence; 0.8% overall yield). These studies demonstrate that strained cyclic allenes are versatile building blocks in chemical synthesis.
Conflict of interest statement
Figures




Similar articles
-
Total Synthesis of Lissodendoric Acid A.Angew Chem Int Ed Engl. 2024 Aug 5;63(32):e202406676. doi: 10.1002/anie.202406676. Epub 2024 Jul 3. Angew Chem Int Ed Engl. 2024. PMID: 38695853 Free PMC article.
-
Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B.Org Lett. 2023 Aug 4;25(30):5553-5557. doi: 10.1021/acs.orglett.3c01489. Epub 2023 Jun 30. Org Lett. 2023. PMID: 37387644 Free PMC article.
-
Diels-Alder cycloadditions of strained azacyclic allenes.Nat Chem. 2018 Sep;10(9):953-960. doi: 10.1038/s41557-018-0080-1. Epub 2018 Jul 30. Nat Chem. 2018. PMID: 30061614 Free PMC article.
-
Leveraging Fleeting Strained Intermediates to Access Complex Scaffolds.JACS Au. 2021 Jul 26;1(7):897-912. doi: 10.1021/jacsau.1c00214. Epub 2021 Jun 23. JACS Au. 2021. PMID: 34337603 Free PMC article. Review.
-
Radical transformations for allene synthesis.Chem Sci. 2022 Jun 29;13(29):8491-8506. doi: 10.1039/d2sc02573f. eCollection 2022 Jul 29. Chem Sci. 2022. PMID: 35974759 Free PMC article. Review.
Cited by
-
Diels-Alder Cycloadditions of Oxacyclic Allenes and α-Pyrones.Org Lett. 2024 Aug 2;26(30):6465-6470. doi: 10.1021/acs.orglett.4c02294. Epub 2024 Jul 24. Org Lett. 2024. PMID: 39046907 Free PMC article.
-
Access to Complex Scaffolds Through [2 + 2] Cycloadditions of Strained Cyclic Allenes.J Am Chem Soc. 2024 Jun 5;146(22):15420-15427. doi: 10.1021/jacs.4c03369. Epub 2024 May 20. J Am Chem Soc. 2024. PMID: 38768558 Free PMC article.
-
Recent advancements in the chemistry of Diels-Alder reaction for total synthesis of natural products: a comprehensive review (2020-2023).RSC Adv. 2025 Feb 10;15(6):4496-4525. doi: 10.1039/d4ra07989b. eCollection 2025 Feb 6. RSC Adv. 2025. PMID: 39931410 Free PMC article. Review.
-
Development of a Vinylated Cyclic Allene: A Fleeting Strained Diene for the Diels-Alder Reaction.Angew Chem Int Ed Engl. 2025 Aug 11;64(33):e202510319. doi: 10.1002/anie.202510319. Epub 2025 Jun 26. Angew Chem Int Ed Engl. 2025. PMID: 40525234 Free PMC article.
-
σ-Bond insertion reactions of two strained diradicaloids.Nature. 2025 Apr;640(8059):683-690. doi: 10.1038/s41586-025-08745-1. Epub 2025 Feb 12. Nature. 2025. PMID: 39938569
References
-
- Stoermer R, Kahlert B, Ber. Dtsch. Chem. Ges 35, 1633–1640 (1902).
-
- Roberts JD, Simmons HE Jr., L. A. Carlsmith, C. W. Vaughan, J. Am. Chem. Soc 75, 3290–3291 (1953).
-
- Wittig G, Pohmer L, Angew. Chem 67, 348 (1955).
-
- Scardiglia F, Roberts JD, Tetrahedron 1, 343–344 (1957).
-
- Wenk HH, Winkler M, Sander W, Angew. Chem. Int. Ed 42, 502–528 (2003). - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources