53(P-25) Euryleneとその類縁体の不斉全合成 : イオン輸送能とその細胞毒性の関係(ポスター発表の部)

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Eurylene (1) and 14-deacetyl eurylene (2) are triterpene polyethers isolated by Itokawa et al. from the wood of Eurycoma longifolia. In addition to the structure of 1 and 2, Itokawa et al. discussed the relation between the cytotoxic activity and conformation of these triterpene polyethers on the basis of the findings that 1 has extended conformation and exhibits essentially no cytotoxic activity (IC_<50> for KB cell: >100mg/mL), whereas 2 existing as a folded conformation possesses potent cytotoxicity (IC_<50> of 2 for KB cell: 0.52mg/mL). In the course of our synthetic studies of natural products using baker's yeast reduction as the chirality induction method, we achieved the enantioselective synthesis of 8 eurylene derivatives. We attempted to clarify the relationship between ionophoric complexing nature and cytotoxic activities. The (R)-allylic alcohol 11, obtained in more than 99% ee by using baker's yeast reduction, was first converted into the epoxide 12. Treatement of 12 with mCPBA afforded, as desired, two tetrahydrofuran derivatives 13 and 14 in almost equal amounts. They were converted to the right and left half segments respectively. Coupling reaction of the lithio-anion of 20 and 18 followed by the reductive desufonylation and NaBH_4 reduction afforded ca. 1: 1 mixture of epimeric alcohols. The mixture was acetylated and then separated to pure 22 and 23. Deprotection of MPM group on 22, 23 gave 2 and 4 which were acetylated to complete the synthesis of 1 and 3. The eurylene analogues 5 - 8, which have no prenyl side chains were also prepared in the same manner as 1-4. With 8 eurylene analogues in hand, we next studied the relation between their ion transport abilities and cytotoxic activities. Eurylene (1) and C20 analogues 5 - 8 showed no cytotoxic activities. On the other hand, 2, 3, and 4 exhibited moderate activities. The ionophoric nature was evaluated in combination with ion-selective electrodes and liposomes. Eurylene (1) had no ability to transport any ions essentially, while the other derivatives 2, 3, and 4 were found to act as K^+-selective ionophores. The complexation with, K^+ may be related to the cytotoxic activitiy. (Table 1)
天然有機化合物討論会の論文
2004-10-01

53(P-25) Euryleneとその類縁体の不斉全合成 : イオン輸送能とその細胞毒性の関係(ポスター発表の部)

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