Thailanstatin A
[CAS# 1426953-21-0]

Identification

• Classification: Organic raw materials >> Heterocyclic compound
• Name: Thailanstatin A
• Synonyms: 2-[(3R,4R,5R,7S)-5-[(1E,3E)-5-[(2S,3S,5R,6R)-5-[[(Z,4S)-4-acetyloxypent-2-enoyl]amino]-3,6-dimethyloxan-2-yl]-3-methylpenta-1,3-dienyl]-4-hydroxy-1,6-dioxaspiro[2.5]octan-7-yl]acetic acid
• Molecular Formula: C₂₈H₄₁NO₉
• Molecular Weight: 535.63
• CAS Registry Number: 1426953-21-0
• SMILES: C[C@H]1C[C@H]([C@H](O[C@H]1C/C=C(C)/C=C/[C@@H]2[C@H]([C@@]3(C[C@H](O2)CC(=O)O)CO3)O)C)NC(=O)/C=C[C@H](C)OC(=O)C

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.556, Calc.^*
• Boiling Point: 757.3±60.0 °C (760 mmHg), Calc.^*
• Flash Point: 411.8±32.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS0i7;GHS0i8 Warning
• Risk Statements: H315-H319-H351
• Safety Statements: P501-P202-P201-P264-P280-P308+P313-P337+P313-P305+P351+P338-P332+P313-P405

Discovery and Applications

Thailanstatin A is a potent cytotoxic compound that has become a valuable asset in the fields of natural product discovery and drug development. Thailanstatin A was first isolated and characterized from Streptomyces strain CMB-TL029 collected from soil samples in Thailand. The discovery of this interesting molecule was reported in the early 2000s by a research team led by Dr. Kazuro Shiomi of Okayama University in Japan. The complex structure of Thailanstatin A consists of a highly oxidized macrolide core and a unique spiracetal moiety.

Thailanstatin A exerts its cytotoxic effects by inhibiting the function of the spliceosome, a cellular complex involved in pre-mRNA splicing. By disrupting this important process of gene expression, Thailanstatin A can interfere with cancer cell proliferation and survival, making it a promising candidate for anti-cancer treatment. Thailanstatin A selectively targets the spliceosome pathway, distinguishing it from traditional chemotherapy drugs and offering potential advantages in efficacy and reduction of side effects. Thailanstatin A shows promise in targeting cancers with aberrant splicing patterns, such as certain hematological malignancies and solid tumors. Research efforts are ongoing to further elucidate its mechanism of action and explore its therapeutic potential in preclinical and clinical settings. The complex structure of Thailanstatin A poses challenges to its chemical synthesis, limiting its availability for research and development. However, advances in synthetic organic chemistry have made the total synthesis of telantatin A and its analogs possible, promoting structure-activity relationship studies and the exploration of structure-guided modifications to enhance their pharmacological properties. The ability of Thailanstatin A to selectively target the spliceosomal pathway provides new insights into the molecular mechanisms of cancer progression and drug resistance.

References

2021. Spliceostatins and derivatives: chemical syntheses and biological properties of potent splicing inhibitors. Journal of Natural Products, 84(5).
DOI: 10.1021/acs.jnatprod.1c00100

2018. Total syntheses of Thailanstatins A-C, spliceostatin D, and analogues thereof. Stereodivergent synthesis of tetrasubstituted dihydro- and tetrahydropyrans and design, synthesis, biological evaluation, and discovery of potent antitumor agents. Journal of the American Chemical Society, 140(26).
DOI: 10.1021/jacs.8b04634

2016. Total synthesis of Thailanstatin A. Journal of the American Chemical Society, 138(24).
DOI: 10.1021/jacs.6b04781