Stereoselective Synthesis of the Cotylenin A Aglycone Carbon Skeleton
Stereoselective Convergent Synthesis of Carbon Skeleton of Cotylenin A Aglycone: M. Kuwabara, A. Matsuo, S. Kamo, A. Matsuzawa, K. Sugita
Synthesis 2021, 53, DOI: 10.1055/s-0040-1706684
Cotylenin A, originally isolated in 1975 from the fungal strain Cladosporium sp. 501-7W, has been reported to modulate biological signals by stabilizing protein–protein interactions involved in the stabilization of p53, a tumor suppressor, thus enhancing its antitumor activity. However, Cladosporium sp. 501-7W has now lost the ability to produce cotylenin A, so the only source of this compound can be based on chemical synthesis. A total synthesis has been described for both the aglycone and cotylenin A itself, which also confirmed its stereochemistry and structure. However, an improved synthetic approach to the title compound could facilitate access to this natural product, allowing for more detailed biological studies.
Recently, the group of Professor Kazuyuki Sugita from Hoshi University (Tokyo, Japan) reported a stereoselective convergent synthesis of the carbon skeleton of cotylenin A aglycone in 5.9% yield, with the longest linear sequence of 17 steps from commercially available (R)-limonene oxide.
Professor Sugita said: “We expect that this synthetic strategy will lead to an effective total synthesis of cotylenin A. Furthermore, it might be applicable for the synthesis of derivatives for medicinal chemistry.”