Synthesis of a Ribose-Incorporating Medium Ring Scaffold via a Challenging Ring-Closing Metathesis Reaction.
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Authors
Rankin, SS
Caldwell, JJ
Cronin, NB
van Montfort, RLM
Collins, I
Caldwell, JJ
Cronin, NB
van Montfort, RLM
Collins, I
Document Type
Journal Article
Date
2016-09-01
Date Accepted
2016-07-21
Abstract
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.
Citation
European journal of organic chemistry, 2016, 2016 (26), pp. 4496 - 4507
Source Title
Publisher
WILEY-V C H VERLAG GMBH
ISSN
1434-193X
eISSN
Collections
Research Team
Medicinal Chemistry 2
Hit Discovery & Structural Design
Hit Discovery & Structural Design