A Total Synthesis of Aculeatiols A-C: Lovastatin Derivatives Extracted from Aspergillus Aculeatus

Research Article
Open access

A Total Synthesis of Aculeatiols A-C: Lovastatin Derivatives Extracted from Aspergillus Aculeatus

Jiahao Zhang 1*
  • 1 Science College, Civil Aviation University of China, Tianjin 300300, People’s Republic of China    
  • *corresponding author 1050779611@qq.com
Published on 20 June 2025 | https://doi.org/10.54254/2755-2721/2025.24248
ACE Vol.168
ISSN (Print): 2755-273X
ISSN (Online): 2755-2721
ISBN (Print): 978-1-80590-205-8
ISBN (Online): 978-1-80590-206-5

Abstract

As research into lovastatin derivatives continues to advance, exploring their structural diversity and potential therapeutic applications has become increasingly significant in pharmaceutical chemistry. This paper focuses on the total synthesis of aculeatiols A-C, derived from Aspergillus aculeatus, and provides a comprehensive account of the key strategies and steps employed throughout the synthesis process. Initially, a linearization analysis was conducted, identifying 35 potential structures, from which the most suitable linearized structure was selected for synthesis. The core reactions utilized in this study included Robinson annulation, olefin metathesis, and asymmetric synthesis, which were crucial for constructing the complex molecular framework and ensuring the accurate stereochemical features of the target compounds. Furthermore, applying the "chiral pool" concept facilitated the optimization of the synthetic pathway, enhancing the efficiency of the synthesis. This research not only offers effective methodologies for the synthesis of novel lovastatin derivatives but also contributes valuable insights into their structure-activity relationships. The findings underscore the importance of continued exploration in this area, as they promise to develop more effective cholesterol-lowering therapies and personalized medicine approaches, ultimately benefiting patient care and treatment outcomes.

Keywords:

lovastatin, Aculeatiols, total synthesis, Robinson annulation, stereochemistry, linearization, chiral synthesis

Zhang,J. (2025). A Total Synthesis of Aculeatiols A-C: Lovastatin Derivatives Extracted from Aspergillus Aculeatus. Applied and Computational Engineering,168,26-33.
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References

[1]. Grundy, S. M. (2018). AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Journal of the American College of Cardiology, 73(24), e285-e350.

[2]. Alberts, A. W., et al. (1980). Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proceedings of the National Academy of Sciences, 77(7), 3957-3961.

[3]. Endo, A. (1985). The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research, 33(11), 1569-1582.

[4]. Goldstein, J. L., & Brown, M. S. (1990). Regulation of the mevalonate pathway. Nature, 343(6257), 425-430.

[5]. Taylor, F., et al. (2013). Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, (1).

[6]. Davignon, J. (2004). Beneficial cardiovascular pleiotropic effects of statins. Circulation, 109(23_suppl_1), III-39.

[7]. Clendening, J. W., & Penn, L. Z. (2012). Targeting tumor cell metabolism with statins. Oncogene, 31(48), 4967-4978.

[8]. Zhang, X., et al. (2015). Statins, autophagy and cancer metastasis. International Journal of Biological Sciences, 11(7), 921-929.

[9]. Joy, T. R., & Hegele, R. A. (2009). Narrative review: statin-related myopathy. Annals of Internal Medicine, 150(12), 858-868.

[10]. Silva, M., Matthews, M. L., Jarvis, C., Nolan, N. M., Belliveau, P., & Malloy, M. (2007). Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clinical Therapeutics, 29(2), 253-260.

[11]. Xie, X., et al. (2014). Regulation of lovastatin production by HMG-CoA reductase in Aspergillus terreus. Applied Microbiology and Biotechnology, 98(2), 705-715.

[12]. Kennedy, J., Auclair, K., Kendrew, S. G., Park, C., Vederas, J. C., & Hutchinson, C. R. (1999). Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science, 284(5418), 1368-1372.

[13]. Liu F, Qiao X, Li Q, Zhou J, Gao J, He F, Wu P, Chen C, Sun W, Zhu H, Zhang Y. (2024) Aculeatiols A-G: Lovastatin Derivatives Extracted from Aspergillus aculeatus. J Nat Prod., 87(4):753-763.

Cite this article

Zhang,J. (2025). A Total Synthesis of Aculeatiols A-C: Lovastatin Derivatives Extracted from Aspergillus Aculeatus. Applied and Computational Engineering,168,26-33.

Data availability

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

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About volume

Volume title: Proceedings of the 5th International Conference on Materials Chemistry and Environmental Engineering

ISBN：978-1-80590-205-8(Print) / 978-1-80590-206-5(Online)
Editor：Harun CELIK
Conference website: https://2025.confmcee.org/
Conference date: 17 January 2025
Series: Applied and Computational Engineering
Volume number: Vol.168
ISSN：2755-2721(Print) / 2755-273X(Online)

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References

[1]. Grundy, S. M. (2018). AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Journal of the American College of Cardiology, 73(24), e285-e350.

[2]. Alberts, A. W., et al. (1980). Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proceedings of the National Academy of Sciences, 77(7), 3957-3961.

[3]. Endo, A. (1985). The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research, 33(11), 1569-1582.

[4]. Goldstein, J. L., & Brown, M. S. (1990). Regulation of the mevalonate pathway. Nature, 343(6257), 425-430.

[5]. Taylor, F., et al. (2013). Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, (1).

[6]. Davignon, J. (2004). Beneficial cardiovascular pleiotropic effects of statins. Circulation, 109(23_suppl_1), III-39.

[7]. Clendening, J. W., & Penn, L. Z. (2012). Targeting tumor cell metabolism with statins. Oncogene, 31(48), 4967-4978.

[8]. Zhang, X., et al. (2015). Statins, autophagy and cancer metastasis. International Journal of Biological Sciences, 11(7), 921-929.

[9]. Joy, T. R., & Hegele, R. A. (2009). Narrative review: statin-related myopathy. Annals of Internal Medicine, 150(12), 858-868.

[10]. Silva, M., Matthews, M. L., Jarvis, C., Nolan, N. M., Belliveau, P., & Malloy, M. (2007). Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clinical Therapeutics, 29(2), 253-260.

[11]. Xie, X., et al. (2014). Regulation of lovastatin production by HMG-CoA reductase in Aspergillus terreus. Applied Microbiology and Biotechnology, 98(2), 705-715.

[12]. Kennedy, J., Auclair, K., Kendrew, S. G., Park, C., Vederas, J. C., & Hutchinson, C. R. (1999). Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science, 284(5418), 1368-1372.

[13]. Liu F, Qiao X, Li Q, Zhou J, Gao J, He F, Wu P, Chen C, Sun W, Zhu H, Zhang Y. (2024) Aculeatiols A-G: Lovastatin Derivatives Extracted from Aspergillus aculeatus. J Nat Prod., 87(4):753-763.

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