Retrosynthetic Analysis and Design for the Total Synthesis of Astellolide S

Guanbing Chen; Zitong Wang; Zheng Shi

doi:10.54254/2755-2721/2026.KA28726

Applied and Computational EngineeringOpen access

Retrosynthetic Analysis and Design for the Total Synthesis of Astellolide S

Research Article

Open Access

Retrosynthetic Analysis and Design for the Total Synthesis of Astellolide S

Guanbing Chen ^1* Zitong Wang ², Zheng Shi ³

¹ Sun Yat-sen University

² Shenzhen Middle School (Nigang Campus (Headquarters))

³ South China University of Technology

^*Corresponding author: chengb39@mail2.sysu.edu.cn

Published on 28 October 2025

ACE Vol.200

ISSN (Print): 2755-273X

ISSN (Online): 2755-2721

ISBN (Print): 978-1-80590-491-5

ISBN (Online): 978-1-80590-492-2

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Abstract

This study addresses the total synthesis of Astellolide S, a structurally complex sesquiterpenoid natural product featuring a rare nicotinic acid unit and four chiral centres. Three distinct retrosynthetic pathways and their corresponding forward strategies are systematically proposed and evaluated. Route 1 incrementally constructs the decalin skeleton via key cyclization and Wittig reactions. Route 2 innovatively leverages a vicinal tricarbonyl system and a di-epoxide-enol tandem reaction for efficient core assembly, complemented by Pd-catalysed carbonylation for lactone formation. Route 3 designs intermolecular coupling and cyclization based on oxidation state analysis. The advantages and challenges of each route regarding molecular simplification, feasibility of key steps, stereo control, and byproduct mitigation are critically compared. This work provides a theoretical foundation for the eventual efficient and stereoselective total synthesis of Astellolide S and future bioactivity studies.

Keywords:

Astellolide S, Total synthesis, Retrosynthetic analysis, Synthetic Route design

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References

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References

[2]. Aminudin N I, Ridzuan M, Susanti D, et al. Biotransformation of sesquiterpenoids: a recent insight [J]. Journal of Asian Natural Products Research, 2021, 24(2): 103-45.

[4]. Cao H, Liu Y, Li Y, et al. N-heterocyclic carbene promoted one-pot synthesis of 1, 2-diols and ɑ-Hydroxyketones from simple aldehydes [J]. Molecular Catalysis, 2024, 564.

[5]. Andringa R L H, Marinus N, Bunt D V, et al. Total synthesis of dissectol A, using an enediolate-based Tsuji–Trost reaction [J]. Chemical Science, 2024, 15(27): 10541-6.

[6]. Sugimoto K, Kobayashi Y, Hori A, et al. Syntheses of aza-analogues of macrosphelides via RCM strategy and their biological evaluation [J]. Tetrahedron, 2011, 67(40): 7681-5.

[7]. PARR H H W A J. The Chemistry of Vicinal Tricarbonyls and Related Systems [J]. ACCOUNTS OF CHEMICAL RESEARCH, 2004: 37: 687-701.

[10]. Shinohara Y, Takahashi S, Osada H, et al. Identification of a novel sesquiterpene biosynthetic machinery involved in astellolide biosynthesis [J]. Sci Rep-Uk, 2016, 6(1).

Cite this article

Chen,G.;Wang,Z.;Shi,Z. (2025). Retrosynthetic Analysis and Design for the Total Synthesis of Astellolide S. Applied and Computational Engineering,200,7-24.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of CONF-MCEE 2026 Symposium: Advances in Sustainable Aviation and Aerospace Vehicle Automation

ISBN: 978-1-80590-491-5(Print) / 978-1-80590-492-2(Online)

Editor: Ömer Burak İSTANBULLU

Conference website: https://2025.confmcee.org/kayseri.html

Conference date: 14 November 2025

Series: Applied and Computational Engineering

Volume number: Vol.200

ISSN: 2755-2721(Print) / 2755-273X(Online)

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