The Scripps Research Institute

Seijiro Hosokawa

Kyriacos Costa Nicolaou

Dionisios Vourloumis

Nicolas Winssinger

Tianhu Li

Sanghee Kim

Floris VanDelft

Jin-You Xu

Jeff Pfefferkorn

Takashi Ohshima

Sarcodictyin A and B, eleutherobin, and bioactive analogs thereof synthesized using solid phase and solution phase chemistries. The synthetic method employs an attachment of common precursors, e.g., compounds 1880 or 200, on a solid support for generating conjugates 230 and 240, followed by standard chemical manipulations. A combinatorial library of sarcodictyins and eletherobin analogs was constructed with modified C-8 ester, C-15 ester and C-4 ketal functionalities and was screened for activity with respect to tubulin polymerization and cytotoxic activity against tumor cells, including Taxol-resistant lines. Compounds 600, 610, 630, 660-700, 730, 760, 850, and 920 were identified to be of equal or superior biological activities as compared to their corresponding natural product.

Analogs of sarcodictyin and eleutherobin

Growing community of inventors

Tokyo, Japan

Seijiro Hosokawa