Indian Journal of Chemistry Vol. 53B, August 2014, pp 1140-1142 Synthesis of chenopanone Prashant S Deore & Narshinha P Argade* Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune 411 008, India E-mail: np.argade@ncl.res.in Received 7 November 2013; accepted (revised) 14 June 2014 Starting from glyoxalic acid, a facile three step approach to chenopanone has been described utilizing the Barbier reaction as a key step. Keywords: Glyoxalic acid, isovaleraldehyde, condensation, Barbier reaction, acid hydrolysis, synthesis, chenopanone The genus Chenopodium consists of 120 plus species which are imperative due to their wide range of medicinal properties 1-3 . The crude extract of C. ambrosioides is known to possess antifungal acitity 4,5 . Hence in search of an active ingredient, chenopanpone was isolated in the year 2000 from an Egyptian collection of aerial parts of C. ambrosioides L. (Chenopodiaceae) extract 6 . Its structure was established as 4-isopropyl-5-(2-oxopropyl)furan-2(5H)-one 1 on the basis of MS and NMR spectroscopic data. Large number of bioactive natural and unnatural -lactones with broad assortment of substituents is well known in the literature 7a-c . They have been designed by employing several elegant new carbon-carbon or carbon-oxygen bond forming reactions. In this context, now it is herein reported the first synthesis of target compound (Scheme I). In continuance with the studies on cyclic anhydrides and derivatives to bioactive natural products, it was reasoned that isopropylmaleic anhydride or its equivalent would be a potential precursor for the synthesis of chenopanone 8a-c . Hence for a simplicity reasons, it was decided to start the synthesis from readily available glyoxalic acid to design the requisite hydroxylactone 9 . The morpholinium hydrochloride induced reaction of glyoxalic acid with 3-methylbutanal (isovaleraldehyde) exclusively furnished the desired lactol 4 in 78% yield via a selective dehydrative intermolecular condensation and intramolecular cyclization pathway. Such type of lactols display ring-chain tautomerism. The selective zinc promoted Barbier reaction 10 of propargyl bromide with a ring opened aldehyde form of 4 formed the inisolable secondary alcohol intermediate, which on an in situ lactonization gave the required acetylenic -lactone 5 in 87% yield. The present Barbier reaction of masked aldehyde 4 results in overall substitution of hydroxy group in the lactol by a propargyl group. The structure of product 5 was confirmed on the basis of analytical and spectral data. Finally, the acid catalyzed hydration of an acetylenic unit in product 5 to the corresponding ketone unit provided the desired chenopanone 1 in 97% yield. The analytical and spectral data obtained for synthetic 1 were in complete agreement with the reported data 6,11 . In the present study, assignment for -positive carbon at δ 172.4 (proton decoupled 13 C NMR) for synthetic chenopanone is also in accordance with the literature reports 8d,12-14 . The natural product 1 was obtained in three steps with 66% overall yield. In summary, a practical synthesis of chenopanone has been described. The present approach to chenopanone is general in nature and will be useful to design the focused mini-library of its analogues and congeners for SAR studies. Experimental Section Melting points are uncorrected. The 1 H NMR spectra were recorded in CDCl 3 using TMS as an internal standard on 200 MHz NMR spectrometer. 13 C NMR spectra were recorded on 200 MHz NMR spectrometer (50 MHz). Mass spectra were obtained on MS-TOF mass spectrometer. HRMS was obtained on ESI mass spectrometer. IR spectra were recorded on a FT-IR spectrometer. Column chromatographic separations were carried out over silica gel (60-120 and 200-400 mesh). Commercially available glyoxalic acid, isovaleraldehyde, zinc powder and propargyl bromide were used. 5-Hydroxy-4-isopropylfuran-2(5H)-one, 4. To a stirred homogeneous suspension of glyoxylic acid hydrate (920 mg, 10.00 mmol) and powdered morpholinium hydrochloride (1.36 g, 11.00 mmol) in dioxane (5 mL) and water (0.50 mL) mixture was added isovaleraldehyde (860 mg, 10.00 mmol). The reaction mixture was stirred at RT for 1 hr and then refluxed for 24 hr. The solvent was evaporated to dryness under vacuum and the residue was extracted with ethyl acetate (3 × 80 mL). The organic layer was dried over anhyd. Na 2 SO 4 and concentrated in vacuo. The obtained residue was purified by silica gel column