Enantioselective Synthesis of (+)-Cephalostatin 1
Fortner, K. C.; Kato, D.; Tanaka, Y.; Shair, M. D. J. Am. Chem. Soc. 2010, 132, 275-280.
Cephalostatin is an agent with selective cancer killing characteristics.
One important step in this synthesis is kinetic spiroketalization.
Pinky: "Gee, Brain, what do you want to do tonight?"
The Brain: "The same thing we do every night, Pinky—try to take over the world!"
One eerily dark night at Acme laboratories, the Brain startled awake and exclaimed “Yes, I have finally found the fool proof plan to take over the world!”. He wakes Pinky and in his excitedly monotone voice describes a molecule that is cytotoxic to cancer cells—a molecule that he apparently saw in his dream (a dream that was probably the product of side effects from when his genes were spliced). He called this molecule cephalostatin. The Brain believed that he had found the cure for cancer in this molecule and that he could patent and sell it and become the richest mouse in the world and with this money, he could proceed to take over the world (a difficult task for a lab rat). Enlisting Pinky’s help, he devises a scheme—a mechanism of sorts—for creating this molecule. He had most of the mechanism completed when Pinky spilled hydrochloric acid all over the write up. Fuming with anger, the Brain hits Pinky over the head, then notices that only one part of the mechanism could be salvaged….