Department of Chemistry "Ugo Schiff", University of Firenze , Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy.
Institut für Chemie und Biochemie, Freie Universität Berlin , Takustrasse 3, 14195 Berlin, Germany.
J Org Chem. 2017 Jun 2;82(11):5835-5844. doi: 10.1021/acs.joc.7b00667. Epub 2017 May 16.
Hyacinthacines are members of the class of polyhydroxylated pyrrolizidines exhibiting outstanding biological activity as glycosidases inhibitors. Their structural complexity is embodied in the densely functionalized core, possessing a series of contiguous stereogenic centers. In this synthetic study we report a route to the more complex congeners of this class of alkaloids exploiting the diastereoselective addition of an axially chiral lithiated alkoxyallene to an enantiopure cyclic nitrone. Our stereodivergent approach enabled the installation of the targeted configuration at the ring A by minimal synthetic manipulations and at ring B by using stage dependent selective functionalizations. The versatility and robustness of this methodology were demonstrated by the syntheses of (-)-hyacinthacine B and of two epimers of (+)-hyacinthacine C, allowing a suggestion of the likely structure of the isolated natural product.
靛红烷类是多羟基吡咯里西啶类化合物的成员，作为糖苷酶抑制剂具有出色的生物活性。它们的结构复杂性体现在其密集的功能化核心上，具有一系列连续的手性中心。在这项合成研究中，我们报告了一种利用轴向手性锂化烷氧基丙二烯与对映纯环状硝酮的非对映选择性加成来制备此类生物碱的更复杂同系物的方法。我们的立体定向方法通过最小的合成操作在环 A 上安装目标构型，通过使用阶段相关的选择性官能化在环 B 上安装目标构型。该方法的多功能性和稳健性通过 (-)-靛红烷 B 和 (+)-靛红烷 C 的两个差向异构体的合成得到了证明，这为分离的天然产物的可能结构提供了一个线索。
