Nature-Inspired Tetrahydropentalene Building Blocks: Scalable Synthesis for Medicinal Chemistry Needs-Reference-Cited by-同舟云学术

Nature-Inspired Tetrahydropentalene Building Blocks: Scalable Synthesis for Medicinal Chemistry Needs

Published:2023-12-10 Issue:4 Volume:21 Page:43-50
ISSN:2518-1548
Container-title:Journal of Organic and Pharmaceutical Chemistry
language:
Short-container-title:J. Org. Pharm. Chem.

Author:

Smyrnov Oleh K.¹^ORCID,Pashenko Olexandr Ye.²^ORCID

Affiliation:

1. Taras Shevchenko National University of Kyiv, Ukraine

2. Taras Shevchenko National University of Kyiv; Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine

Abstract

Inspired by the bioactivity of natural compounds with a bicyclo[3.3.0]octane core, the study focuses on developing tetrahydropentalene-2,5-dione (2,5-THP-dione) derivatives as potential building blocks for the use in medicinal chemistry. Using the commercially available 2,5-THP-dione, a number of alkylated derivatives and a monofunctional ketone were synthesized. Using optimized protocols for synthesis, target compounds were obtained with high yields on a multigram scale. These compounds are promising derivatives for further chemical derivatization and therapeutic use, and thus highlight the value of 2,5-THP-dione in creating complex molecular structures for drug discovery, as well as the importance of tetrahydropentalene derivatives as valuable building blocks in synthetic chemistry.

Publisher

National University of Pharmacy

Reference14 articles.

1. Deimling, M.; Zens, A.; Park, N.; Hess, C.; Klenk, S.; Dilruba, Z.; Baro, A.; Laschat, S. Adventures and Detours in the Synthesis of Hydropentalenes. Synlett 2021, 32 (02), 119-139. https://doi.org/10.1055/s-0040-1707226.

2. Cho, T. P.; Gang, L. Z.; Long, Y. F.; Yang, W.; Qian, W.; Lei, Z.; Jing, L. J.; Ying, F.; Ke, Y. P.; Ying, L.; Jun, F. Synthesis and biological evaluation of bicyclo[3.3.0] octane derivatives as dipeptidyl peptidase 4 inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett. 2010, 20 (12), 3521-3525. https://doi.org/10.1016/j.bmcl.2010.04.138.

3. Mitcheltree, M. J.; Li, D.; Achab, A.; Beard, A.; Chakravarthy, K.; Cheng, M.; Cho, H.; Eangoor, P.; Fan, P.; Gathiaka, S.; Kim, H.-Y.; Lesburg, C. A.; Lyons, T. W.; Martinot, T. A.; Miller, J. R.; McMinn, S.; O’Neil, J.; Palani, A.; Palte, R. L.; Saurí, J.; Sloman, D. L.; Zhang, H.; Cumming, J. N.; Fischer, C. Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy. ACS Med. Chem. Lett. 2020, 11 (4), 582-588. https://doi.org/10.1021/acsmedchemlett.0c00058.

4. Anderl, T.; Emo, M.; Laschat, S.; Baro, A.; Frey, W. Synthesis of Functionalized Pentalenes via Carbonyl-Ene Reaction and Enzymatic Kinetic Resolution. Synthesis 2008, 2008 (10), 1619-1627. https://doi.org/10.1055/s-2008-1067012.

5. Kashima, H.; Kawashima, T.; Wakasugi, D.; Satoh, T. A method for synthesis of bicyclo[3.3.0]oct-1-en-3-ones from cyclobutanones with one-carbon ring expansion and its application to a formal synthesis of racemic 1-desoxyhypnophilin. Tetrahedron 2007, 63 (19), 3953-3963. https://doi.org/10.1016/j.tet.2007.03.019.