Abstract:
Terpene synthesis stands at the forefront of modern synthetic chemistry and represents the state-of-the-art in the chemist\'s toolbox. Notwithstanding, these endeavors are inherently tied to the current availability of natural cyclic building blocks. Addressing this limitation, the stereocontrolled cyclization of abundant unbiased linear terpenes emerges as a valuable tool, which is still difficult to achieve with chemical catalysts. In this study, we showcase the remarkable capabilities of squalene-hopene cyclases (SHCs) in the chemoenzymatic synthesis of head-to-tail-fused terpenes. By combining engineered SHCs and a practical reaction setup, we generate ten chiral scaffolds with >99% ee and de, at up to decagram scale. Our mechanistic insights suggest how cyclodextrin encapsulation of terpenes may influence the performance of the membrane-bound enzyme. Moreover, we transform the chiral templates to valuable (mero)-terpenes using interdisciplinary synthetic methods, including a catalytic ring-contraction of enol-ethers facilitated by cooperative iodine/lipase catalysis.
摘要:
萜烯合成处于现代合成化学的最前沿,代表着化学家工具箱中最先进的技术。尽管如此,这些努力与当前天然循环积木的可用性有着内在的联系。解决这一限制,大量无偏线性萜烯的立体控制环化成为一种有价值的工具,用化学催化剂仍然难以实现。在这项研究中,我们展示了角鲨烯-hopene环化酶(SHCs)在头对尾融合萜烯的化学酶法合成中的显着能力。通过结合工程SHCs和实际的反应设置,我们产生10个手性支架,>99%ee和de,达到decram规模。我们的机械见解表明,萜烯的环糊精封装如何影响膜结合酶的性能。此外,我们使用跨学科合成方法将手性模板转化为有价值的(mero)-萜烯,包括通过协同碘/脂肪酶催化促进的烯醇醚的催化环收缩。