Base-catalyzed epimerization of the butenolide in annonaceous acetogenins

Synthesis of (+)-Hypoxylactone through Allenoate γ-Addition: Revision of Stereochemistry

“…Methyl epoxybutanoate 10 was prepared from the modified literature procedure . To a mixture of l -threonine (2 g, 16.8 mmol) and KBr (7.03 g, 59.1 mmol) in aq H 2 SO 4 (1.25 M, 35 mL, 43.7 mmol) was added NaNO 2 (1.88 g, 27.2 mmol) in portions over 30 min at 0 °C.…”

“…The final epoxidation of a chlorohydrin unit in 3 was conducted under various basic conditions. However, reactions always produced 1 along with a mixture of inseparable diastereomers mainly due to an epimerization at C4 of the γ-lactone unit . Epoxidations at low temperatures turned out to be inefficient in terms of chemical conversion and purity in the desired product.…”

NMR Determination of Absolute Configuration of Butenolides of Annonaceous Type

“…For the structural determinations of the (>350) known acetogenins of the Annonaceae , extensive spectroscopic methods have been used; however, only scarce reports have been dealing with the absolute configuration determination of the butenolide part (based on specific rotation comparisons, circular dichroism, or analyzes of degradation metabolites such as lactic acid) 1h. Furthermore, total syntheses have been reported, and most of the strategies used thereof are based on an aldolisation, lactonisation and dehydration sequence,2 although we,3 and others,4, 5 have reported the difficulties in performing these three chemical transformations without epimerisation of the chiral center of the butenolide. We wish to report the first applicable NMR method for the determination of the absolute configuration of the butenolide (without derivatisation or immolation of the substrate) 6…”