| Marine microorganisms are widely viewed as an emerging source of novel natural products.A variety of butenolides [or furan-2(5H )-ones], featured with an alpha,beta-unsaturated lactone core,are isolated from different marine fungi, bacteria, and gorgonians, to name a few. Thosemarine-derived butenolides possess a variety of bioactivities including antifouling bydisrupting quorum sensing systems. Butenolides with a long side chain, as the importantmembers of butenolide family, are suffered from the problem in determination of theirabsolute configuration, especially the remote stereogenic center(s) on the side chain. Thisthesis presents the efforts and results for the synthesis of four butenolides with remotechirality on the side chain, and for the determination of their absolute configurations. It alsoincludes the attempted study on the total synthesis of cladospolide B via a ring-closingmetathesis (RCM) strategy and the preliminary results on the unexpected [1,2]-Wittigrearrangement of chiral boron enolates observed in the syn-selective glycolate aldol reaction.;An introduction to the general background, including isolation, structures, and bioactivityof butenolide natural products is given in chapter 1. It is followed by an illustration of theselected methods for construction of the butenolide core. Also discussed are the typicalmethods for and problems in stereochemistry determination of some selected natural productswhich possess remote pair(s) of stereogenic centers.;The results on the total synthesis of 5-(6-hydroxy-6-methyloctyl)-furan-2(5 H)-one arecompiled in chapter 2. A double Wittig olefination--hydrogenation strategy was used toconstruct the side chains possessing the stereochemically defined tertiary alcohol at C10. ARCM reaction was used to assemble the butenolide core. Two diastereomeric butenolides, with opposite configuration at C10, have been synthesized in this work and the absolutionconfiguration of the naturally occurring compound produced by Streptomycete strain B 5632has been determined to be (4S,10S) by comparison of the optical rotation data.;Cladospolides are the 12-membered ring macrolides possessing a conjugate enoate moietyand two free hydroxy groups. Among them, cladospolide B likely shares the samebiosynthesis precursor with iso-cladospolide B, which has a butenolide core with the (11R)stereogenic center on the side chain. The corresponding (11S)-epimer, i.e. 11- epi-iso-cladospolideB, has also been isolated from a marine fungal species. As summarized inchapters 3 and 4, a diverted total synthesis strategy based on use of an advanced commonintermediate has been investigated in the current work. The synthesis started from a chiralaldehyde followed by a syn-selective glycolate aldol reaction to secure the (4S, 5S)-configuration. The butenolide core was assembled by the RCM protocol to afford iso-cladospolideB. On the other hand, 11-epi-iso-cladospolide B was synthesized by inversion ofthe (11R)-intermediate through the Mitsunobu reaction. Attempted efforts on total synthesisof cladospolide B via a RCM strategy are discussed.;As described in chapter 5, an unexpected [1,2]-Wittig rearrangement of chiral boronenolates, derived from the p-methoxybenzyl glycolate of the norephedrine derivative, wasobserved in the syn-selective glycolate aldol reaction when excess amounts of Hex2BOTfwere used. The reaction temperatures were optimized and the absolute configuration of therearranged product was determined by chemical transformation into the known 2-hydroxy-3-(4-methoxyphenyl)propanoic acid. Chiral boron enolates of other electron-rich arylmethylglycolates were found to undergo the same [1,2]-Wittig rearrangement. These findings mayprovide further mechanistic insights on this [1,2]-Wittig rearrangement.;The main experimental procedures, the characterization data for the key intermediates andthe cited references are found at the end of the thesis. Copies of the original 1H and 13C NMRspectra of some key intermediates are given in the Appendix. |
