Synthesis of a Ribose-Incorporating Medium Ring Scaffold via a Challenging Ring-Closing Metathesis Reaction.
Date
2016-09-01Author
Rankin, SS
Caldwell, JJ
Cronin, NB
van Montfort, RLM
Collins, I
Type
Journal Article
Metadata
Show full item recordAbstract
A practical synthesis of a novel oxabicyclo[6.2.1]undecenetriol useful as a medicinal chemistry scaffold has been developed starting from l-ribose. The sequence involves an oxidation/Grignard addition sequence and a challenging ring-closing metathesis (RCM) reaction as the ring forming step. Exploration of the RCM substrate protecting groups revealed the key factor for successful nine-membered medium ring formation to be conformational bias of the reacting alkenes of the RCM substrate by very bulky silyl ether protecting groups. The synthesis also allowed access to an epimeric triol and saturated and unsaturated variants of the nine-membered ring. The medium ring conformation of the oxabicyclo[6.2.1]undecenetriol was determined by X-ray crystallography and correlated to the solution state conformation by NMR experiments.
Collections
Research team
Medicinal Chemistry 2
Hit Discovery & Structural Design
Language
eng
Date accepted
2016-07-21
License start date
2016-09
Citation
European journal of organic chemistry, 2016, 2016 (26), pp. 4496 - 4507
Publisher
WILEY-V C H VERLAG GMBH