Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 19;89(14):9783-9788.
doi: 10.1021/acs.joc.4c00158. Epub 2024 Jul 11.

Synthesis of Simplified 2-Desmethyl Sanctolide A Analogs

Gihan C Dissanayake  1 , James B Martinez  1 , Gaurav Garg  1 , Cornelius Ndi  2 , Jana L Markley  2 , Paul R Hanson  1
Affiliations

Synthesis of Simplified 2-Desmethyl Sanctolide A Analogs

Gihan C Dissanayake et al. J Org Chem. .

Abstract

A one-pot, sequential phosphate tether-mediated method for the synthesis of simplified 2-desmethyl sanctolide A analogs is reported. Western side-chain diversification was achieved using a pot-efficient, sequential cross metathesis (CM)/ring-closing metathesis (RCM)/H2/dephosphorylation procedure. Further diversification was achieved by Me3Al-mediated amide formation, Yamaguchi esterification, and RCM macrocyclization to access five C11/C12 Z-configured, 2-des-methyl sanctolide A analogs with improved stability.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
RCM comparison between various phosphate trienes.
Scheme 1
Scheme 1
New protocol for one-pot, sequential strategy.
Scheme 2.
Scheme 2.
Our previous synthesis of sanctolide A
Scheme 3.
Scheme 3.
Synthesis of bicyclo[5.3.1]phosphate (S,S,Rp)-8.
Scheme 4.
Scheme 4.
Synthesis of lactone methyl ethers 12a and 12b.
Scheme 5.
Scheme 5.
Synthesis of dienes 18–20. aStep 7a. 2,4,6-trichlorobenzoyl chloride, DIPEA, 17a or 17b; THF, rt, 3 h; Step 7b. DMAP, 14 or 15; toluene, 0°C to rt, 12 h.
Scheme 6.
Scheme 6.
Synthesis of dienes 21 and 22. aStep 7a. 2,4,6-trichlorobenzoyl chloride, DIPEA, 17a or 17b; THF, rt, 3 h; Step 7b. DMAP, 16; toluene, 0°C → rt, 12 h.
Scheme 7.
Scheme 7.
Final RCM to synthesis of macrocycles 23–27.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Kang HS; Krunic A; Orjala J Sanctolide A, a 14-Membered PK-NRP Hybrid Macrolide from the Cultured Cyanobacterium Oscillatoria sancta (SAG 74.79). Tetrahedron Lett. 2012, 53, 3563–3567. - PMC - PubMed
    1. Yadav JS; Suresh B; Srihari P Stereoselective total synthesis of the marine macrolide sanctolide A. Eur. J. Org. Chem 2015, 2015, 5856–5863.
    1. Wadsworth AD; Furkert DP; Brimble MA Total Synthesis of the Macrocyclic N-Methyl Enamides Palmyrolide A and 2 S-Sanctolide A. J. Org. Chem 2014, 79, 11179–11193. - PubMed
    1. Dissanayake GC; Ndi CN; Markley JL; Martinez J; Hanson PR Total Synthesis of Sanctolide A and Formal Synthesis of (2S)-Sanctolide A. J. Org. Chem 2023, 88, 805–817. - PMC - PubMed
    2. Dissanayake GC, Phosphate Tether-Mediated Strategies for the Synthesis of Complex Polyols, Natural Products, and Analogs. Ph.D. Thesis, University of Kansas, Lawrence, KS, 2022.
    1. Pereira AR; Cao Z; Engene N; Soria-Mercado IE; Murray TF; Gerwick WH Palmyrolide A, an Unusually Stabilized Neuroactive Macrolide from Palmyra Atoll Cyanobacteria. Org. Lett 2010, 12, 4490–4493 - PMC - PubMed
    2. Tello-Aburto R; Johnson EM; Valdez KC; Maio WA Asymmetric Total Synthesis and Absolute Stereochemistry of the Neuroactive Marine Macrolide Palmyrolide A. Org. Lett 2012, 14, 2150–2153.s - PMC - PubMed

LinkOut - more resources