Qin Tian, Skraba-Joiner Sarah L, Khalil Zeinab G, Johnson Richard P, Capon Robert J, Porco John A
Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts 02215, USA.
Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
Nat Chem. 2015 Mar;7(3):234-40. doi: 10.1038/nchem.2173. Epub 2015 Feb 2.
Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.
含有复杂结构和有趣生物学特性的手性二聚体天然产物几十年来一直启发着化学家和生物学家。本文描述了轴向手性二聚体四氢呫吨酮天然产物rugulotrosin A的七步全合成。该合成采用一锅法铃木偶联/二聚化反应来生成所需的2,2'-联芳基键。使用钯催化和非手性膦配体实现了高度选择性的点到轴向手性转移。获得了单晶X射线衍射数据以确认rugulotrosin A的阻转异构体构型和绝对立体化学。描述了计算研究以合理化在关键二聚化步骤中观察到的阻转选择性。将粗制真菌提取物与合成的rugulotrosin A及其阻转异构体进行比较，证实了自然界产生的是该天然产物的单一阻转异构体。
