95(P-52) SmI_2を用いる環化反応を利用した抗腫瘍活性アセトゲニン、ムコシンの全合成(ポスター発表の部)

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Recently, we have developed a highly efficient method for the synthesis of tetrahydropyrans and oxepanes based on a SmI_2-induced reductive cyclization. In order to demonstrate the utility of the method, we have planed total synthesis of mucocin (1), a powerful antitumor acetogenin. Our synthetic strategy directed toward 1 was based on the convergent process involving a coupling reaction of two building blocks 2 and 3. Initially, C_2-symmetric tetraol 10, prepared by the Sharpless asymmetric dihydroxylation of the corresponding diene, was converted into a bis-formyl ester 5 via hydroxy protection-deprotection sequence including internal acetalization. Treatment of 5 with 3.0 eq. of SmI_2 in the presence of methanol (4.4 eq.) effected radical-mediated reductive cyclization, giving a 2,6-syn-2,3-trans-3-hydroxytetrahydropyran 14 as a single stereoisomer (87% yield). After installation of the long side chain on the tetrahydropyran ring, one carbon unit was introduced to afford an exo-methylene derivative 4. Oxidative cyclization of 4 with Co(modp)_2 and O_2 provided stereoselectively a 2,5-anti-tetrahydrofuran derivative 17, which was subject to an ethynylation to afford a left half segment 2. On the other hand, an α-substituted γ-lactone moiety 3 corresponding to the right half segment of 1 was synthesized through an aldol condensation of a chiral γ-hydroxy ester 7 and (2S)-2-O-(tetrahydropyranyloxy)propanal 8. Finally, a palladium-catalyzed cross coupling reaction of 2 and 3, and subsequent two-step sequence led to 1.
天然有機化合物討論会の論文
2001-09-01

95(P-52) SmI_2を用いる環化反応を利用した抗腫瘍活性アセトゲニン、ムコシンの全合成(ポスター発表の部)

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