title: Synthesis of a Ribose-Incorporating Medium Ring Scaffold via a Challenging Ring-Closing Metathesis Reaction.
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.
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit The Institute of Cancer Research SM2 5NG London United Kingdom.
authors.forename: Stuart S
authors.identifier: 0000-0002-6234-7355
authors.initials: SS
authors.lastname: Rankin
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit The Institute of Cancer Research SM2 5NG London United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: Caldwell
authors.affiliation: Division of Structural Biology The Institute of Cancer Research SW7 3RP London United Kingdom.
authors.forename: Nora B
authors.initials: NB
authors.lastname: Cronin
authors.affiliation: Division of Structural Biology The Institute of Cancer Research SW7 3RP London United Kingdom.
authors.forename: Rob L M
authors.initials: RL
authors.lastname: van Montfort
authors.affiliation: Cancer Research UK Cancer Therapeutics Unit The Institute of Cancer Research SM2 5NG London United Kingdom.
authors.forename: Ian
authors.identifier: 0000-0002-8143-8498
authors.initials: I
authors.lastname: Collins
keywords: Carbohydrates; Cyclization; Fused‐ring systems; Medium‐ring compounds; Metathesis