Stereoselective Total Synthesis of an Anti-Fouling Agent, C2-Symmetricnatural Macrolide Trichobotryside A
K. Nagi Reddy
Department of Chemistry, Mahatma Gandhi University, Nalgonda, Telangana - 508 254, INDIA
Mandala Jyothi
Department of Chemistry, KRR Government Arts and Science College (A), Kodad, Suryapet, Telangana, INDIA
23-32
Vol: 16, Issue: 1, 2026
Receiving Date:
2025-11-19
Acceptance Date:
2025-12-31
Publication Date:
2026-01-17
Download PDF
http://doi.org/10.37648/ijrst.v16i01.003
Abstract
A stereoselective total synthesis of 16-membered macrodiolide trichobotryside A has been successfully completed. The key features are: Evans’ Crotylation, regioselective epoxide opening, Wardsworth-Emmons-Horner Olefination and Mitsunobu Reaction.
Keywords:
Macrodiolide; anti-fouling agent; Evans’ Crotylation; Super Hydride; regioselective epoxide opening; Wardsworth-Emmons-Horner Olefination; Mitsunobu Reaction
References
- A curated open-access collection of method-focused reviews. (n.d.). PubMed Central. https://www.ncbi.nlm.nih.gov/pmc/
- Carroll, A. R., Copp, B. R., Grkovic, T., Keyzers, R. A., & Prinsep, M. R. (2024). Marine natural products. Natural Product Reports, *41*(1), 162–207. https://doi.org/10.1039/D3NP00061C
- Carroll, A. R., Copp, B. R., Grkovic, T., Keyzers, R. A., & Prinsep, M. R. (2026). Marine natural products. Natural Product Reports, Advance Article. https://doi.org/10.1039/D5NP00080G
- Chatterjee, A. K., & Grubbs, R. H. (1999). Synthesis of trisubstituted alkenes via olefin cross-metathesis. Organic Letters, *1*(11), 1751–1754. https://doi.org/10.1021/ol991023p
- Chatterjee, A. K., Grubbs, R. H., & Miller, S. J. (1999). Olefin metathesis in complex settings: Methods and troubleshooting. Organic Letters. https://doi.org/10.1021/ol991023p
- Croll, E. A., & Kwon, O. (2024). Mechanism of the Mitsunobu reaction: An ongoing mystery. Synthesis, *56*(11), 1843–1850. https://doi.org/10.1055/a-2232-8633
- Cross-metathesis troubleshooting and substrate scope reviews. (2015). In R. H. Grubbs (Ed.), Handbook of metathesis (2nd ed., Vol. 2). Wiley-VCH.
- Dess, D. B., & Martin, J. C. (1991). A useful 12-I-5 triacetoxyperiodinane (the Dess–Martin periodinane) for the selective oxidation of primary or secondary alcohols. Journal of the American Chemical Society, *113*(19), 7277–7287. https://doi.org/10.1021/ja00019a027
- Dodge, J. A., Trujillo, J. I., & Presnell, M. (1996). A general procedure for Mitsunobu inversion of sterically hindered alcohols. Organic Syntheses, *73*, 110. https://doi.org/10.15227/orgsyn.073.0110
- Evans, D. A. (1982). Studies in asymmetric synthesis. The development of practical chiral enolate synthons. Aldrichimica Acta, *15*(2), 23–32.
- General technique and characterization references. (n.d.). Bruker BioSpin. https://www.bruker.com/en/productsand-solutions/mr/nmr/nmr-software/topspin.html
- Hackman, B. M., & Hoveyda, D. A. (2004). Enantioselective reagents for aldehyde crotylation. Organic Letters, *6*(23), 4371–4374. https://doi.org/10.1021/ol0480731
- Humphrey, J. M., & Yates, J. T. S. (2003). Use and handling of LiEt3BH (Super-Hydride) in stereoselective reductions. Aldrichimica Acta, *36*(1), 3–12.
- Inanaga, J., Hirata, K., Saeki, H., Katsuki, T., & Yamaguchi, M. (1979). A rapid esterification by means of mixed anhydride and its application to large-ring lactonization. Bulletin of the Chemical Society of Japan, *52*(7), 1989–1993. https://doi.org/10.1246/bcsj.52.1989
- Ireland, R. E., & Reider, G. F. W. (1995). The Wadsworth–Emmons and related olefinations in complex molecule synthesis. In B. M. Trost & C. H. Heathcock (Eds.), Comprehensive organic synthesis (Vol. 1, pp. 91-128). Pergamon.
- Kaburagi, Y., & Kishi, Y. (2007). A safer, economical, and scalable TBAF-mediated desilylation of tertbutyldimethylsilyl ethers. Organic Letters, *9*(4), 723–726. https://doi.org/10.1021/ol0630458
- Katsuki, T., & Sharpless, K. B. (1980). The first practical method for asymmetric epoxidation. Journal of the American Chemical Society, *102*(18), 5974–5976. https://doi.org/10.1021/ja00538a077
- Mancuso, A. J., Huang, S. L., & Swern, D. (1978). Oxidation of long-chain and related alcohols to carbonyls by dimethyl sulfoxide activated by oxalyl chloride. The Journal of Organic Chemistry, *43*(12), 2480– 2482. https://doi.org/10.1021/jo00406a041
- Maryanoff, B. E., & Reitz, A. B. (1989). The Wittig olefination reaction and modifications involving phosphorylstabilized carbanions. Chemical Reviews, *89*(4), 863–927. https://doi.org/10.1021/cr00094a007
- Modern alternatives to Mitsunobu and improved reagents. (2023). In Organic synthesis. https://doi.org/10.1055/sos-SD-237-00123
- Munir, R. (2024). Yamaguchi esterification: A key step toward the synthesis of natural products and their analogs—A review. Molecules, *29*(8), 1707. https://doi.org/10.3390/molecules29081707
- Narala, S. G., Reddy, P. R., & Majji, K. C. (2018). First stereoselective total synthesis of an anti-fouling agent, C2-symmetric natural macrolide trichobotryside A. Arkivoc, *2018*(vii), 495– 508. https://doi.org/10.24820/ark.5550190.p010.795
- Nicolaou, K. C., Sorensen, E. J., & Winssinger, N. (1998). The art and science of organic and natural products synthesis. Journal of Chemical Education, *75*(10), 1225. https://doi.org/10.1021/ed075p1225
- Ohtani, I., Kusumi, T., Kashman, Y., & Kakisawa, H. (1991). High-field FT NMR application of Mosher's method. The absolute configurations of marine terpenoids. Journal of the American Chemical Society, *113*(11), 4092–4096. https://doi.org/10.1021/ja00011a006
- Organic Syntheses procedure for Dess–Martin periodinane and related protocols. (n.d.). Organic Syntheses. https://doi.org/10.15227/orgsyn.077.0141
- Practical guides for protecting group chemistry. (2022). In Organic synthesis: Strategy and control. John Wiley & Sons.
- Reviews and protocols for macrolactonization techniques. (2021). Chemical Reviews, *121*(14), 7121– 7160. https://doi.org/10.1021/acs.chemrev.0c01266
- Reznik, S. K., & Leighton, J. L. (2014). Complex fragment coupling by crotylation: A powerful tool. In Organic synthesis (pp. 1-13). John Wiley & Sons, Inc. https://doi.org/10.1002/0471264180.or086.01
- Sun, Y.-L., Zhang, X.-Y., Nong, X.-H., Xu, X.-Y., & Qi, S.-H. (2016). New antifouling macrodiolides from the deep-sea-derived fungus Trichobotrys effuse DFFSCS021. Tetrahedron Letters, *57*(3), 366– 370. https://doi.org/10.1016/j.tetlet.2015.12.026
- Swern/Parikh-Doering comparisons and practical guides. (n.d.). Organic Chemistry Portal. https://www.organicchemistry.org/namedreactions/parikh-doering-oxidation.shtm
- Toste, F. D., & McClory, A. (2007). N-Iodosuccinimide (NIS) in electrophilic transformations/iodofunctionalization. In Encyclopedia of reagents for organic synthesis. https://doi.org/10.1002/047084289X.rn00800
- Voigtritter, K., Ghorai, S., & Lipshutz, B. H. (2011). Rate-enhanced olefin cross-metathesis reactions: The copper iodide effect. The Journal of Organic Chemistry, *76*(11), 4697–4702. https://doi.org/10.1021/jo200360s
- Wadsworth, W. S., Jr., & Emmons, W. D. (1961). The utility of phosphonate carbanions in olefin synthesis. Journal of the American Chemical Society, *83*(7), 1733–1738. https://doi.org/10.1021/ja01468a042
- Williams, D. R., & Benbow, J. W. (1990). Sharpless asymmetric epoxidation: Mechanistic and synthetic studies. In S. Patai (Ed.), The chemistry of the functional groups. John Wiley & Sons.
- Wuts, P. G. M. (2014). Greene's protective groups in organic synthesis (5th ed.). John Wiley & Sons.
Back