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ItemStudies towards the synthesis of mulberry Diels-Alder adductsGUNAWAN, CHRISTIAN ( 2011)The synthetic studies of mulberry Diels-Alder adducts are described. Two dehydroprenylarylbenzofuran adducts, mulberrofuran C hexamethyl ether (325) and mulberrofuran J hexamethyl ether (326) were obtained from the cycloaddition Diels-Alder reaction between diene dehydroprenylarylbenzofuran (118) and chalcone dienophile 264. Chalcomoracin hexamethyl ether (330) and mongolicin F hexamethyl ether (331) were also obtained from cycloaddition Diels-Alder reaction between the arylbenzofuran diene 118 and prenyl chalcone 267. Prenyl chalcone 267 was synthesised from commercially available 2,4-dihydroxyacetophenone 175 and 2,4-dihydroxybenzaldehyde 176 in four steps. An aldol condensation between methyl ethers acetophenone 262 and benzaldehyde 263 using Claisen-Schmidt condition afforded chalcone 264. Ortho-prenylation and [1,3]- rearrangement successfully furnished the desired chalcone 267. The dehydroprenylarylbenzofuran 118 was synthesised from a Suzuki coupling reaction between arylbenzofuran iodide 315 and dienylboronate 322. The key step in the synthesis of arylbenzofuran iodide 315 is the Sonogashira coupling reaction between alkyne 306 and iodide 310. Methanolysis of 313, followed by TBAF-induced cyclisation afforded the arylbenzofuran iodide 315 in good yield. Alkyne 306 was synthesised from commercially available 3,5-dihydroxybenzoic acid (262) in five steps. The iodide partner 310 was prepared from commercially available 3-methoxyphenol 311 in three steps. The stereochemistry of the endo adduct was confirmed by direct 1H NMR signals comparison of the product which was obtained from permethylation of chalcomoracin hexamethyl ether (330), with an authentic sample of chalcomoracin (47). The cis, trans-configuration of the endo adducts, mulberrofuran C hexamethyl ether (325) and chalcomoracin hexamethyl ether (330) was confirmed by 2D NMR spectroscopic analysis. From the analysis of variable temperature 1H NMR spectra, the exo adducts, mulberrofuran J hexamethyl ether (326) and mongolicin F hexamethyl ether (331) showed a significant restricted rotation. The deydroprenylchalcone adducts, kuwanon J heptamethyl ether (339) and kuwanon I heptamethyl ether (340) were also synthesised from a cycloaddition Diels-Alder reaction between a dehydroprenylchalcone 338 and a chalcone dienophile 267. The key Suzuki coupling reaction chalcone-iodide 337 and dienylboronate 322 afforded dehydroprenylchalcone 338. The chalcone iodide 337 was prepared from an aldol condensation between methyl ether derivatives of acetophenone 335 and benzaldehyde 263. The exo adduct, kuwanon I heptamethyl ether (340) appeared as a mixture of atropisomers as a result of significant restricted C3”-C4” rotation. This phenomenon was confirmed by 1H NMR variable temperature experiments. Since the global deprotection of mulberrofuran C hexamethyl ether (325) only led to incomplete demethylation and decomposition, orthogonal protecting groups were also investigated for the synthesis of mulberry Diels-Alder adducts. Debenzylation of adduct 368 using a Lewis acid, BCl3 and C6HMe5 at -78 °C gave the monobenzylated product 370. However, when the reaction was allowed to warm from -40 °C to 0 °C, an undesired product whose structure could not be determined was isolated. MOM deprotection of kuwanon V (77) was achieved using HCl to afford the cyclised product 407 which was found to be unstable. Attempts at deprotection of benzyl, methyl and MOM ether derivative of kuwanon V 415 were not successful.