Synthesis of the QRSTU domain of maitotoxin and its 85-epi- and 86-epi-diastereoisomers.
Synthesis of the QRSTU domain of maitotoxin and its 85-epi- and 86-epi-diastereoisomers.
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麦毒毒素 QRSTU 结构域及其 85-表观-和 86-表观-非对映异构体的合成。
DOI：
10.1021/ja103708j
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发表时间：
2010
影响因子：
15
通讯作者：
Umezawa,Taiki
中科院分区：
文献类型：
--
作者：
Nicolaou,KC;Gelin,ChristineF;Seo,JaeHong;Huang,Zhihong;Umezawa,Taiki
针对海洋衍生生物毒素maitotoxin（1）的QRSTU环系统4设计的合成策略，除了4之外，还提供了其非对映异构体85-epi-QRSTU和86-epi-QRSTU环系统5和6。这些maitotoxin片段的会聚途径涉及UT和Q结构单元9（从2-脱氧-d-核糖获得）和10（从d-核糖获得）的偶联，然后通过闭环复分解得到烯醇醚8，其加工成靶向QRSTU环系统4需要其转化为羟基酮7。后一种化合物（7）通过羟基二硫代缩酮环化转化为最终产物，然后通过所得O，S-混合缩酮的氧化/甲基化以安装目标分子（4）内所含的五个甲基中的最后一个。和6，并与maitotoxin的比较，为天然产物的QRSTU结构域的最初指定的结构提供了强有力的支持。
A devised synthetic strategy toward the QRSTU ring system4of the marine-derived biotoxin maitotoxin (1) delivered, in addition to4, its diastereoisomers 85-epi-QRSTU and 86-epi-QRSTU ring systems5and6. The convergent route to these maitotoxin fragments involved coupling of UT and Q building blocks9(obtained from 2-deoxy-d-ribose) and10(obtained fromd-ribose) followed by ring-closing metathesis to afford enol ether8, whose elaboration to the targeted QRSTU ring system4required its conversion to hydroxy ketone7. The latter compound (7) was transformed to the final product through a hydroxy dithioketal cyclization, followed by oxidation/methylation of the resultingO,S-mixed ketal to install the last of the five methyl groups contained within the target molecule (4).13C NMR spectroscopic analysis of synthesized fragments4,5, and6and comparisons with maitotoxin provided strong support for the originally assigned structure of the QRSTU domain of the natural product.