Asymmetric synthesis, structure, and reactivity of unexpectedly stable spiroepoxy-beta-lactones including facile conversion to tetronic acids: application to (+)-maculalactone A.

ABSTRACT: A novel class of small spirocyclic heterocycles, spiroepoxy-beta-lactones (1,4-dioxaspiro[2.3]-hexan-5-ones), is described that exhibit a number of interesting reactivity patterns. These spiroheterocycles, including an optically active series, are readily synthesized by epoxidation of ketene dimers (4-alkylidene-2-oxetanones) available from homo- or heteroketene dimerization. An analysis of bond lengths in these systems by X-ray crystallography and comparison to data for known spirocycles and those determined computationally suggest that anomeric effects in these systems may be more pronounced due to their rigidity and may contribute to their surprising stability. The synthetic utility of spiroepoxy-beta-lactones was explored, and one facile rearrangement identified under several conditions provides a three-step route from acid chlorides to optically active tetronic acids, ubiquitous heterocycles in bioactive natural products. The addition of various nucleophiles to these spirocycles leads primarily to addition at C5 and C2. The utility of an optically active spiroepoxy-beta-lactone was demonstrated in the concise, enantioselective synthesis of the antifouling agent, (+)-maculalactone A, which proceeds in five steps from hydrocinnamoyl chloride by way of a tetronic acid intermediate.

SUBMITTER: Duffy RJ 

PROVIDER: S-EPMC2745962 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature