Chemistry:Antarlide
Antarlides are a family of macrocyclic polyketide natural products (antarlides A–H) isolated from Streptomyces sp. BB47.[1][2] These compounds are notable for their potent activity as androgen receptor (AR) antagonists, including activity against mutant ARs associated with resistance to clinically used antiandrogens.[1]
Biological activity
Antarlides act as androgen receptor antagonists, inhibiting both wild-type and clinically relevant mutant ARs in vitro. This activity is significant for the treatment of prostate cancer, particularly in cases where resistance to standard AR antagonists has developed.[1]
Synthesis
The complex structure of antarlides has inspired synthetic efforts. A recent report describes a practical and efficient synthesis of the C8–C23 fragment of antarlides A–H, incorporating six stereocenters and a conjugated diene. This synthesis utilized CBS reduction, Evans' aldol reaction, Keck–Maruoka allylation, and enzymatic resolution, demonstrating the feasibility of assembling key structural motifs of the antarlides.[3]
References
- ↑ 1.0 1.1 1.2 Saito, Shun; Fujimaki, Takahiro; Panbangred, Watanalai; Igarashi, Yasuhiro; Imoto, Masaya (2016-02-18). "Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR-Targeted Therapy". Angewandte Chemie (International ed. In English) 55 (8): 2728–2732. doi:10.1002/anie.201510079. ISSN 1521-3773. PMID 26805525. Bibcode: 2016ACIE...55.2728S.
- ↑ Saito, Shun; Fujimaki, Takahiro; Panbangred, Watanalai; Sawa, Ryuichi; Igarashi, Yasuhiro; Imoto, Masaya (2017). "Antarlides F–H, new members of the antarlide family produced by Streptomyces sp. BB47". The Journal of Antibiotics 70 (5): 595–600. doi:10.1038/ja.2017.6. PMID 28174422.
- ↑ Ghosh, Palash; Das, Pralay; Mainkar, Prathama S.; Kumaraguru, Thenkrishnan; Madhavachary, Rudrakshula; Chandrasekhar, Srivari (2024-07-17). "Stereo flexible synthesis of the C8–C23 fragment of antarlides, androgen receptor antagonists" (in en). Organic & Biomolecular Chemistry 22 (28): 5797–5802. doi:10.1039/D4OB00852A. ISSN 1477-0539. PMID 38946203. https://pubs.rsc.org/en/content/articlelanding/2024/ob/d4ob00852a.
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