Antarlide
Macrocyclic natural products and androgen receptor antagonists
From Wikipedia, the free encyclopedia
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]