Computational and Synthetic Investigation of Cationic Rearrangement in the Putative Biosynthesis of Justicane Triterpenoids

Abstract

A biomimetic cationic structural rearrangement of the oleanolic acid framework is reported for the gram-scale synthesis and structural reassignment of justicioside E aglycone. The mechanism of the putative biosynthetic rearrangement is investigated with kinetic, computational, and synthetic approaches. The precursor to rearrangement was accessed through two strategic advancements: (1) synthesis of a 1,3-diketone via oxidation of a β-silyl enone, and (2) diastereoselective 1,3-diketone reduction to form a syn-1,3-diol using SmI2 with PhSH as a key additive.

Towards Knowledge Maintenance in Scientific Digital Libraries with the Keystone Framework

“…Support conformational analysis [9,22] "Conformational analysis of 4 was performed with Schrödinger MacroModel 2016 by following the method of Willoughby et al [35]." Successful example [53] "The successful characterization of karlotoxin 2 (KmTx2) followed by KmTx8 [17,28,33,40] "Therefore, we turned to a protocol that relies on density functional theory-based computations of 1H and 13C NMR chemical shifts and the use of statistical tools to assign the experimental data to the correct isomer of a compound [28]. "…”

“…The remaining four papers [17,28,33,40] stated that they used the WH protocol to calculate the theoretical NMR chemical shift and thus could be significantly impacted, because the theoretical NMR chemical shifts supported findings that went into abstracts or the conclusion section. We say "could be" because the nonreproducibility comes from the protocol's implementation rather than the protocol itself.…”

“…2006's Refs [15][16][17][18][19] that had reported the reduction of PSD-95 early in neurodegeneration (including in Alzheimer's disease). However, unlike the pass-through keystone citations seen in the first case study, which are tangentially supported by main findings (though not of the cited paper itself), in this case, this support comes from an informal literature review, Zhao's introduction, which is cited for the statement "PSD-95 decreases early in neurodegeneration.…”

Dreyfus‐Preis und Camille‐Dreyfus‐Teacher‐Scholar‐Preise 2019

“…Newhouse und seine Gruppe beschäftigen sich mit chemischen und theoretischen Studien, die kurze Synthesen strukturell komplexer Naturstoffe mit Anwendungspotenzial in den Neurowissenschaften zum Ziel haben. In einer Angewandte‐Chemie ‐ Zuschrift berichteten sie über eine kationische Umlagerung in einer vorgeschlagenen Biosynthese von Justican‐Triterpenoiden …”

Dreyfus Prize and Camille Dreyfus Teacher‐Scholar Awards 2019

“…The Newhouse group develops chemical technologies and computational approaches to enable the step‐efficient synthesis of structurally complex natural products with potential applications to neuroscience. In a Communication in Angewandte Chemie , they reported on a cationic rearrangement in the putative biosynthesis of justicane triterpenoids …”