Conformational control in activation of an enediyne.
In the bicyclo[7.3.1]tridec-4-ene-2,6-diyne framework characteristic of calicheamicin, DFT calculations predict that the chair conformer should be much more reactive toward cycloaromatization compared to the boat form. A functionalized derivative of this framework with an added two-atom bridge to enforce the boat conformation was synthesized and shown to be stable at 23 degrees C. Cleavage of the bridge releases the conformational lock and cycloaromatization proceeds with t1/2 42.5 min/23 degrees C, presumably through the chair conformation. This confirms the prediction based on computation and points to a new principle for triggering the enediyne toxins.
Semmelhack
M F
MF
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA. mfshack@princeton.edu
Wu
Lingyun
L
Pascal
Robert A
RA
Ho
Douglas M
DM
D000480:Alkynes / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry; D008968:Molecular Conformation; D013816:Thermodynamics
D000480:Alkynes; D001952:Bridged-Ring Compounds; D003510:Cyclohexanes