Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104, Freiburg im Breisgau, Germany.
Angew Chem Int Ed Engl. 2016 May 4;55(19):5765-9. doi: 10.1002/anie.201600632. Epub 2016 Apr 4.
Natural products of polyketide origin, in particular small-sized lactones often possess a very broad range of impressive biological activities. An efficient way to demonstrate the concise access to six-membered lactones was emphasized as part of a stereodivergent and protecting-group-free synthesis of all three representatives of the helicascolide family. This strategy features an atom-economical and highly diastereoselective rhodium-catalyzed "head-to-tail" lactonization by an intramolecular addition of ω-allenyl-substituted carboxylic acids to terminal allenes, including the selective construction of a new stereocenter in the newly formed core structures. The excellent selectivities with which the helicascolide precursors were obtained are remarkable, thus resulting in an expeditious and highly efficient natural product synthesis.
天然产物中的聚酮类化合物，特别是小分子量的内酯，通常具有非常广泛的令人印象深刻的生物活性。作为一种立体发散且无保护基团的合成方法的一部分，高效地展示了获得六元内酯的简洁方法，该方法合成了所有三种海鞘内酯家族的代表物。这种策略具有原子经济性和高度非对映选择性的铑催化“头到尾”内酯化反应，通过ω-烯丙基取代的羧酸与末端丙二烯的分子内加成，包括在新形成的核心结构中选择性构建新的立体中心。海鞘内酯前体获得的优异选择性非常显著，从而导致快速高效的天然产物合成。
