Heliquinomycin和Griseorhodin类活性天然产物的不对称全合成及其关键步骤高价碘催化的不对称螺环化反应研究

Heliquinomycins and Griseorhodins are a series of natural compounds characterized with highly-functionalized fused- / spiro- multicycles and remarkable bioactivities, which made their total synthesis to be great challenges. There is still no report on their asymmetric total synthesis, which is the attention of this project. A convergent strategy was designed for these natural product based on hypoiodite-catalyzed asymmetric spiroketalization,a widely concerned transformation. Initially, we will explored detailedly and systematically the hypoiodite-catalyzed asymmetric cycloetherification and spiroketalization. Then the synthesis will be carried out using naphoquinone furanone and isocoumarin moiety as starting materials through Aldol condensation and hypoiodite-catalyzed asymmetric spiroketalization as key steps. For the request of total synthesis, more efficient and elegant synthesis was designed respectively for naphoquinone furanone using Danieshefsky-type Diels-Alder reaction as key step and for isocoumarin moiety using Claison rearrangement / Seyferth-Gilbert reaction as key strategy. This project will also make sure the chiral centers' configurations of these natural peoducts through the total synthesis. Using the synthesized natural products, their stereoisomers, precursors, analogs, and intermediates, the sturture-activity relationship will be explored, too. The exploration will provide a strategy and referrnce for their analogs, along with hypoiodite-catalysis transforamtion and a new catalytic application of hypoiodite reagents, and will be essenetial for the further investigation on these kind of compounds.

Heliquinomycin和Griseorhodins是一类官能团密集、活性显著的多稠环和螺环的天然产物，其全合成是一个巨大挑战，不对称合成尚未见报道。本课题将采用近年备受关注的高价碘催化的反应作为关键步骤，以完全汇聚的策略开展它们的不对称全合成，为该类天然产物的不对称合成和深入研究打下基础。首先，本课题计划深入研究手性碘化物和碘盐作为手性高价碘源催化的不对称环醚化和螺环化反应；然后，本课题以该反应为核心，通过萘醌并呋喃酮和异香豆素乙醛的Aldol缩合、高价碘催化的不对称螺环化反应合成天然产物。对于全合成所需的关键中间体苯并呋喃酮和异香豆素片断本课题设计了新的合成路线，分别采用Danieshefsky-type Diels-Alder和Claison Condensation /Seyferth-Gilbert反应为关键步骤进行合成。本课题还将确定天然物物绝对构形，开展构效关系研究。

Heliquinomycin和Griseorhodins是rubromycin类天然产物，是一类官能团密集、活性显著的多稠环和螺环的天然产物，其全合成是一个巨大挑战，不对称合成尚未见报道。本课题将采用近年备受关注的高价碘催化的反应作为关键步骤，以完全汇聚的策略开展它们的不对称全合成，为该类天然产物的不对称合成和深入研究打下基础。首先，本课题通过系统的深入研究发现了构筑手性螺环缩酮的三个不同的策略：手性碘盐在氧化剂作用下催化2-取代苯并呋喃酮环化得到双苯并螺环缩酮；手性胺与高价碘催化的2-取代-苯并呋喃酮环化得到双苯并螺环缩酮；手性2-甲叉基-2-羟基苯并呋喃醇与邻甲叉基醌发生D-A反应得到双苯并螺环缩酮。这些反应选择性，效率较高。然后，本课题以该反应为关键步骤，通过萘醌并呋喃酮和异香豆素乙醛的Aldol缩合、高价碘催化的不对称螺环化反应合成天然产物rubromycin。对于全合成所需的关键中间体苯并呋喃酮和异香豆素片断本课题设计并实施了新的合成路线，分别采用Danieshefsky-type Diels-Alder Claison Condensation /Seyferth-Gilbert反应为关键步骤进行合成，较好的得到了这两个片段。给予新的合成萘醌片段和异香豆素片段的路线的Heliquinomycin个Griseorhodin的全合成还在进行中。.本课题完成了螺环缩酮的方法学研究，对于合成各种类型的螺环缩酮、呋喃环、吡喃环具有十分重要的价值。.本课题对于天然产物的合成探索，得到了萘醌片段和异香豆素片段的新的合成路线，对于含有这两个片段的化合物的合成具有十分重要的意义。