A201A is a structurally distinctive nucleoside antibiotic, characterized by a furanose unit that contains an exo-ene ether—a structural feature not observed in any other natural product. Discovered in 1976 by Eli Lilly and Company from *Streptomyces capreolus* NRRL 3817, A201A exhibits potent antibacterial activity against Gram-positive bacteria and many anaerobic Gram-negative species. Its mechanism of action is believed to involve the ribosome's A site, as it contains a 3'-amido nucleoside fragment that mimics the end of tRNA, thereby interfering with protein synthesis.
In 2012, the Jianhua Group at the South China Sea Institute of Oceanology, Chinese Academy of Sciences, accidentally isolated A201A from *Actinomycetes thermotolerans*, a strain obtained from the seabed of the South China Sea. This discovery sparked interest in studying its unique biosynthetic pathway, offering new insights into the natural production of such rare compounds.
More recently, Yu Yu from the State Key Laboratory of Bioorganic Chemistry at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, achieved the first full chemical synthesis of A201A (J. Am. Chem. Soc., 2014, 136, 4157–4160). The synthesis employed a linear strategy, assembling five distinct blocks through glycosidation and amidation. A key challenge was the stereoselective formation of the 1,2-cis-glucosidic bond in the furanose ring, which was successfully accomplished using Mitsunobu glycosidation. Additionally, the E-enol methyl ether was optimized for stereoselectivity under improved reaction conditions.
The synthesis also featured a valency-promoted glycosidation method to achieve N-glycosylation of hydrazine, and a robust approach for glycosylating complex substrates containing acid-sensitive groups and basic nitrogen atoms. This modular and linear synthetic strategy not only enabled the efficient total synthesis of A201A but also opens up new possibilities for the divergent synthesis of analogs, facilitating further studies on structure-activity relationships.
Skin Essence,Firming Repair Essence,Brightening Anti-Aging Serum,Anti Aging Vitaoil Serum
RYEOGLOBAL Co,.LTD , https://www.ryeolab.com