20 新規3環性マクロリド、ツベラクトマイシン類の全合成(口頭発表の部)

概要

論文の詳細を見る
Tubelactomicin A, B, D, and E (1-4) are novel macrolide antibiotics, isolated from the culture bloth of Nocardia sp. These antibiotics show potent and specific antibacterial activities against acid-fast bacteria including drug-registant strains. Tubelactomicins are tricyclic macrolides, consisting of a trans-fused octahydronaphthalene substructure (the lower-half part) with six contiguous stereogenic centers, and a highly functionalized 16-membered lactone (the upper-half part). Interested in these unique structures and biological activities, we involved in studies on the total synthesis of tubelactomicins, which have been completed recently. Each tubelactomicin is expected to be synthesized in a convergent manner by an assembly of the 16-membered lactone unit 5 or 6 and an octahydronaphthalene unit 7, 8 or 9, respectively. The syntheses of the upper-half segments 5 and 6 are as follows. Methyl (R)-lactate was converted into a hexanal derivative 10. Compound 10 was then subjected to a Baylis-Hillman reaction or a Wittig reaction to introduce the two kinds of trisubstituted olefin parts. The resulting compounds 11 and 15 were transformed into the upper-half segments 5 and 6, respectively, by standard functional group manipulations, including a syn-stereoselective Evans aldol reaction. The lower-half segments 7-9 were synthesized from diethyl (R)-malate. As a key step for the construction of the highly functionalized trans-fused octahydronaphthalene, an intramolecular Diels-Alder (IMDA) approach was adopted. The substrates for the IMDA reaction were synthesized by a six-step sequence, including Horner-Emmons reaction of aldehyde 29 with phosphonates 24 or 27. In all cases, the IMDA reactions provided an endo-cycloadduct with excellent π-facial selectivity and good endo-selectivity. The lower-half segments 7-9 were synthesized from the endo-cycloadducts 36-endo or 37-endo. The assemblies of the upper-half segments 5 or 6 and the lower-half segments 7, 8 or 9 were achieved by a sequence of Stille coupling and macrolactonization. Finally, thus obtained macrolides 43-46 were converted into (+)-tubelactomicin A, B, D, and E (1-4).
天然有機化合物討論会の論文
2005-09-15

20 新規3環性マクロリド、ツベラクトマイシン類の全合成(口頭発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク