Stereoselective total synthesis of (-)-borrelidin.
Stereoselective total synthesis of (-)-borrelidin.
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DOI：
10.1002/anie.200460203
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发表时间：
2004-07
影响因子：
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通讯作者：
B. Vong;S. H. Kim;Sunny Abraham;E. Theodorakis
中科院分区：
文献类型：
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作者：
B. Vong;S. H. Kim;Sunny Abraham;E. Theodorakis
Borrelidin (treponemycin, 1) is a biologically intriguing and structurally unique macrolide, first isolated by Berger et al. from a soil sample of Streptomyces rochei and subsequently identified in other related Streptomyces species.[1] Initial biological screening indicated that 1 exhibits broad antiviral [2] and antibacterial [3] activity, which presumably arises from its inhibition of threonyl-tRNA synthetase and protein synthesis.[4] More recently, borrelidin was found to inhibit cyclindependent kinase (CDK) and thus display potent antimitotic properties at low μm concentrations.[5] Equally impressive are reports that 1 inhibits angiogenesis in rat aorta models at subnanomolar concentrations (IC50= 0.4 ng mLÀ1) through a yet unknown mechanism of action.[6] These results underline the significant potential of borrelidin as a lead compound for the development of novel antiangiogenesis drugs. Chemical degradation [7] and crystallographic studies [8] revealed that borrelidin is an 18-membered macrolide with an unprecedented structure, composed of a repeated isopropyl subunit (C4–C10),[9] a conjugated cyanodiene fragment (C12–C15), and a cyclopentane carboxylic acid substituent (C18–C23).[10] The unique structure of 1 has spurred the development of several synthetic routes,[11] which recently led to two elegant syntheses by the Morken [12] and Hanessian [13] research groups. Inspired by the structural and biological uniqueness of borrelidin, we devised a strategy toward its
