P-27 パラジウム触媒を利用したAmphidinolide T1の合成研究(ポスター発表の部)

抄録

Amphidinolide T1 (1), a 19-membered macrolide isolated from the marine dinoflagellates Amphidinium sp., has shown potent activity against murine lymphoma L1210 and human epidermoid carcinoma KB coll lines. Synthesis of 1 was studied using palladium catalyzed hydrogenolysis of sulfonyloxirance as a key reaction to construct vicinal stereogenic centers. We have planned to synthesize 1 by coupling of tetrahydrofuran segment 4 and sulfone 5 via Julia-Kocienski reaction, followed by alkylation with TBS-enol segment 3, and macrolactonization of 2. The hydrogemolysis of sulfonyloxirane 6, which was synthesized from known alcohol 8, was carried out using palladium-HCO_2H and gave alcohol 11 with high stereoselectivity. After protection and reduction of the double bond, 12 was coupled with optically active epoxide 13 using n-BuLi and BF_3OEt_2. Protection of alcohol and Julia methylenation gave 15. Using similar procedures, sulfonyloxirane 7, enantiomer of 6, was synthesized. Hydrogenolysis of 7 with plladium-HCO_2H gave alcohol 17, followed by reduction and protection. Treating 18 with t-BuLi and HCO_2Et, deprotecton and introduction of azide gave 21. We could construct tetrahydrofuran moiety by treating 21 with BF_3OEt_2 and formed desired intermediate 4. Segment 5 was synthesized from (S)-4-Benzyl-2-oxazolidinone by stereoselective methylaton and introduction of phenyl tetrazole sulfone. Total synthesis of 1 using the synthetic segments 3, 4, 5 is under way.