Synthetic Efforts and Ultimate Limitation to an Asymmetric Achmatowicz Approach Toward EBC-23
Synthetic Efforts and Ultimate Limitation to an Asymmetric Achmatowicz Approach Toward EBC-23
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DOI：
10.1021/acs.joc.2c00262
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发表时间：
2022-05-06
影响因子：
3.6
通讯作者：
O'Doherty，George A.
中科院分区：
文献类型：
--
作者：
Wang，Yanping;O'Doherty，George A.
报道了聚酮类天然产物EBC-23的全合成方法。不对称方法是收敛的，并使用后期类似Claisen的烯酸酯/酸性氯化物偶联来建立关键的1，3-二酮中间体。1，3-二酮靶标是水合天然产物的一种氧化形式，不能螺旋酮化。收敛的不对称合成使用β-呋喃酮酯的不对称Noyori转移氢化来对映体选择性地形成手性呋喃醇。采用Achmatowicz/Jones/Luche三步反应序列，立体选择性地将呋喃醇转化为5-羟基-吡喃-2-酮。通过Leighton烯丙基化反应建立了1，3-多元醇片段的绝对立体化学。随后的格拉布斯交叉复分解和Evans缩醛被用于安装1，3-二醇立体化学。
An effort toward the total synthesis of the polyketide natural product EBC-23 is reported. The asymmetric approach is convergent and uses a late-stage Claisen-like enolate/acid chloride coupling to establish a key 1,3-diketone intermediate. The 1,3-diketone target is an oxidized form of the hydrated natural product, which fails to spiroketalize. The convergent asymmetric synthesis uses an asymmetric Noyori transfer hydrogenation of a β-furyl ketoester to enantioselectively form a chiral furyl alcohol. An Achmatowicz/Jones/Luche three-step reaction sequence was used to stereoselectively convert the furyl alcohol into the 5-hydroxy-pyran-2-one. The absolute stereochemistry of the 1,3-polyol fragment was established by a Leighton allylation. A subsequent Grubbs cross-metathesis, and Evans acetalation were used to install the 1,3-syn-diol stereochemistry.