Title:Progress in Chemo- and Regioselective Transformations of Symmetrical Cephalostatin Analogues
Volume: 15
Issue: 2
Author(s): Mansour Nawasreh*
Affiliation:
- Physics and Basic Sciences Department, Faculty of Eng. Techn./Al-Balqa Applied University, P.B. 15008, Marka 11134, Amman,Jordan
Keywords:
Cephalostatins, chemoselectivity, spiroketal ring-opening, selective D-ring hydration, spiroketal reconstruction,
transformation.
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.
