The synthesis of kibdelone C, a polycyclic natural xanthone isolated from a soil actinomycete, was achieved through a convergent approach. A 6π-electrocyclization was applied to construct the highly substituted dihydrophenanthrenol fragment (B-C-D ring). InBr-promoted lactonization was employed to build the isocoumarin ring, which served as a common precursor for the formation of isoquinolinone ring (A-B ring). A key DMAP-mediated oxa-Michael/aldol cascade reaction was developed to install the tetrahydroxanthone fragment (E-F ring). This approach provides a new solution to prepare its derivatives and structurally related natural products.

The first concise and efficient total synthesis of (±)-cassumunin C has been accomplished with a longest linear sequence of seven steps in 11.7% yield. The key steps involve aromatic propargylation and stereoselective reduction of alkynylphenol to the corresponding (E)-alkenylphenol.Over the last few decades, curcumin (1, Figure 1) has been studied extensively and has been shown to exhibit various biological properties including anti-inflammatory, antioxidant, antimicrobial, anti-HIV, and anticancer activities. 1 However, these activities are not strong enough to compare with vitamin E, 2 which may limit the interest of curcumin as a useful antioxidant for human health. New curcuminoid antioxidants, cassumunin A-C (2-4) ( Figure 1) were isolated from the rhizomes of a medicinal ginger Zingiber cassumunar by Masuda and co-workers in 1993. 3 These three curcuminoids were found to perform better antioxidant activity and anti-inflammatory activity than curcumin. 4 Subsequently, the synthesis of cassumunin A and B was accomplished in nine steps by Masuda et al. in 1998 using conjugated addition of Me 2 CuLi and thermoelimination of an acetyl group as key steps. 5 Moreover, the activities of synthetic 2 and 3 are nearly five times more efficient than curcumin against H 2 O 2 -induced cell death. To the best of our knowledge, no total synthesis of cassumunin C has been reported. In order to study the relationship between the structure and the bioactivity of the compound, we describe here the first total synthesis of cassumunin C.The structure of cassumunin C has a curcumin core with an (E)-1,1-diarylbut-2-ene fragment. As shown in our retrosynthetic analysis (Scheme 1), cassumunin C could be assembled by aldol condensation of compound 12 with aldehyde 11. The aldehyde group in 11 could be introduced by Reimer-Tiemann Reaction, and the E-olefin could be obtained by the reduction of intermediate 7, which would be derived from aromatic propargylation of 6 with veratrole.Our synthesis commenced with the preparation of the intermediate 7 from commercially available o-vanillin (Scheme 2). Thus, protection of the phenolic hydroxyl group was accomplished using tert-butyldimethylsilyl chloride (TBSCl) in DMF to afford the aromatic aldehyde 5 in 93% yield. 6 Treatment of 5 with prop-1-ynylmagnesium bromide gave the alcohol 6 in 92% yield. Propargylation of aromatic compounds with propargylic alcohols usually requires metal complexes of ruthenium, rhenium, or gold as a catalyst. 7 Differently, Srihari et al. reported an efficient procedure for propargylation by using iodine as a cheap and eco-friendly catalyst. 8 As expected, the iodine-catalyzed propargylation of 6 with veratrole by using the reported procedure 8 gave alkyne 7 as a single product in 93% yield. Reduction of 7 with Lindlar catalyst afforded the Z-configured olefin 8 in 92% yield. With intermediate 8 in hand, the construction of E-olefin was investigated. For Z-E interconversion of olefin 8, heating, reaction with I 2 , and other conditions like Ph 2 S 2 /hν have b...

The first total synthesis of (±)-latifolin has been accomplished in six steps and 47.8% overall yield. To understand the relative importance of phenolic O-H and benzhydryl C-H hydrogen on the antioxidant activity of latifolin, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and density functional theory (DFT) studies were carried out. On scavenging DPPH radical in ethanol, the activity of latifolin (1) bearing phenolic hydrogen is remarkably higher than analogue 10 bearing no phenolic hydrogen. Therefore, Phenolic hydrogen is responsible for latifolin's antioxidant activity rather than benzhydryl C-H hydrogen. Furthermore, the 5-OH BDE is lower than 2'-OH and 7-CH BDEs by a DFT calculation, respectively. Based on theoretical results it is definitely concluded that the phenolic 5-OH plays a major role in the antioxidant activity of latifolin.

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