30 July 2009
Thinking about synthetic cannabinoids (see earlier post) I came across, HU-210. From the wikipedia link,
"HU-210 is a synthetic cannabinoid that was first synthesized in 1988 by the group led by Professor Raphael Mechoulam at the Hebrew University. HU-210 is 100 to 800 times more potent than natural THC from cannabis and has an extended duration of action."
The synthesis began1 with a derivative of alpha-pinene, [1S, 5R]-myrtenol. The primary alcohol was protected as a pivaloyl ester; oxidised to the ketone and reduced to the alcohol shown in the picture above.
Reaction with the rescorcinol in the presence of boron trifluoride etherate gave the product after deprotection.
The mechanism must go as shown. Firstly a Friedel-Crafts reaction (the authors had isolated a non-cyclised species when p-TSA is used instead of boron trifluoride etherate) followed by attack at the tertiary carbon followed by bond migration.
Can anyone think of a better way of synthesising the compound?
1 Tetrahedron Asymmetry 1990, 1, 315.