P-40 渡環Diels-Alder反応を鍵とするツベラクトマイシンAおよびEの全合成(ポスター発表の部)

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Tubelactomicins (1-4) are tricyclic macrolide antibiotics, isolated from the culture broth of Nocardia sp., which consist of an octahydronaphthalene substructure with six contiguous stereogenic centers, and a 16-membered lactone. We have explored the total synthesis of tubelactomicins by utilizing a biosynthesis-based transannular Diels-Alder (TADA) reaction as the key step. The substrates for the macrocyclization reaction were synthesized by a multi-step sequence, including Horner-Wadsworth-Emmons reaction from known 11 and 10. The intramolecular Sonogashira coupling of substrate 14 proceeded at room temprature to provide two TADA adducts (16-endo and 16-exo), which were considered to form after the Sonogashira reaction proceeded. This TADA reaction proceeded with complete π-facial selectivity to provide one endo- and one exo-adduct in an equal ratio. Then we tried to synthesize the 24-membered lactone 5 having a conjugated tetraene structure as substrate for TADA reaction. For this new macrocyclization strategy, the intramolecular Hiyama coupling and ring-closing metathesis (RCM) were employed. The Hiyama coupling reaction conducted using substrate 6 (R=SiMe_3), having both an iodo-olefin unit and a trimethylsilylvinyl unit, proceeded at 60℃ to provide two TADA adducts (19-endo and 19-exo, ca. 1: 1). The RCM of substrate 7, obtained from iodide 13 by a 3-step sequence, was proceeded at 40℃ to provide the two cycloadducts (19-endo and 19-exo) equally. The endo-cycloadduct 19-endo possesses the same stereochemistry as that of natural tubelactomicins. Therefore, through a few-step transformation, tubelactomicin A (1) and E (4) were synthesized from 19-endo.
天然有機化合物討論会の論文
2007-08-24

P-40 渡環Diels-Alder反応を鍵とするツベラクトマイシンAおよびEの全合成(ポスター発表の部)

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