Abstract

As a part of our continuous efforts in synthesizing potent anti-cancer natural product cephalostatin 1 and its analogues using a symmetrical bits-steroidal diketone, progress in the chemoselective distinction of the two parts is reported. The first strategy involves the highly chemoselective reductive opening of the spiroketal moiety (ring-F) of nonsymmetrical diol precursor. Thus, the protected 12β,12´α-diol underwent a chemoselective ketal opening using the catechol-borane complex yielding mono-opened spiroketal product with high chemoselctivity. Additionally, 11α-methoxy diketone derivative led to the corresponding mono-opened spiroketal product when treated with 4-methylcatecholborane, a modified reducing complex. The same derivative underwent a chemo- and regioselective hydration of the D-ring double bond using diaminobenzonitrile-borane complex. These key developments pave the way to prepare cephalostatin 1 and analogues.

Keywords: Cephalostatins, chemoselectivity, spiroketal ring-opening, selective D-ring hydration, spiroketal reconstruction, transformation.

Graphical Abstract