## 3 Results and Discussion  
The retrosynthetic analysis for olercones is outlined in Scheme 1. Homoisoflavone skeleton was anticipated to be efficiently prepared via a deoxybenzoic route, one of the most popular synthetic methods used for the preparation of isoflavoids [19]. Therefore, homoisoflavone **2** and its \(O\)-demethylated analog **1** were planned to be obtained from dihydrochalcone **3**. Oleracone E (**3**) was anticipated to be prepared via an aldol condensation between commercially available 4,6-dimethoxy-2-hydroxybenzophenone **4** and 2-(benzyl)benzaldehyde **5**.  
Our synthesis was commenced with an aldol condensation between commercially available 4,6-dimethoxy-2-hydroxybenzophenone **4** and 2-(benzyloxy)benzaldehyde **5** to give chalcone **6** (Scheme 2). Concurrent hydrogenation and hydrogenolysis of the \(O\)-benzyl group in chalcone **6** using 5% activated Pd on carbon under H\({}_{2}\) atmosphere led to olereacone E (**3**) in 88% yield.  
We envisaged the construction of the homoisoflavone skeleton of **1** and **2** via a selective intramolecular oxa-Michael addition reaction of an enone moiety by the phenol group at the 2\"-position rather than the 2\"-position of intermediate **6**, resulting from condensation reaction between **3** and a formyl reagent. According to our expectation, olercone F (**2**) was obtained in high yield (90%) upon stirring with \(N\),\(N\)-dimethylformamide dimethyl acetal [20] in toluene under reflux condition, and no regioisomeric by-products were observed. The high regiooselectivity observed in the reaction was attributed to the enhanced nucleophilicity of the phenol group at the 2\"-position compared to that at the 2\"-position in **3**, which can be supported by the electron-withdrawing effect of the carbonyl group. Finally, selective \(O\)-demethylation of **2** using BCl\({}_{3}\) afforded oleracone D (**1**) in high yield (80%).  
The spectral data obtained for olercones D-F (**1-3**) were consistent with those previously reported data [16; 17].  
With the olercones D-F (**1-3**) in hand, we examined their effects on the longevity of nematodes. To test whether olercones exhibit lifespan-extension activity, we performed a lifespan assay using wild-type N2 nematodes at 20 \({}^{\circ}\)C, as described previously [21]. As shown in Figure 2A,B, all of the olercones tested could prolong the lifespan of the nematodes under standard culture conditions, although the effectiveness of each compound was somewhat variable. At the maximum concentration studied (20 \(\mu\)M), treatment with **3** and **2** extended the lifespan of nematodes by 13.8 and 11.8%, respectively, compared with the control, while the efficacy of **1** (4.3% extension) was inferior to that of **2** and **3**. Interestingly, the longevity effect of **1-3** on nematodes did not show any correlation with their radical scavenging activities (IC\({}_{50}\) values: 11.73, 13.17, and 17.78 \(\mu\)M, respectively) [16; 17]. These results suggest the possibility that modulating aging-related factors may also cooperate with the direct radical scavenging activity that produces the anti-aging effect. However, detailed information on the underlying mechanism of the lifespan-extension properties of oler