Effect of Isotopically Sensitive Branching on Product Distribution for Pentalenene Synthase: Support for a Mechanism Predicted by Quantum Chemistry

Mechanistic proposals for the carbocation cascade reaction leading to the tricyclic sesquiterpene pentalenene are assessed in light of the results of isotopically sensitive branching experiments with the H309A mutant of pentalenene synthase. These experimental results support a mechanism for pentalenene formation involving a 7-protoilludyl cation whose intermediacy was first predicted using quantum-chemical calculations

Collective total synthesis of stereoisomeric yohimbine alkaloids

Abstract Stereoisomeric polycyclic natural products are important for drug discovery-based screening campaigns, due to the close correlation of stereochemistry with diversified bioactivities. Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the ten-carbon building block. In this work, we reset the stage by the development of a bioinspired coupling, in which the rapid construction of the entire pentacyclic skeleton and the complete control of all five stereogenic centers are achieved through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate. The stereochemical diversification from a common intermediate allows for the divergent and collective synthesis of all four stereoisomeric subfamilies of yohimbine alkaloids through orchestrated tackling of thermodynamic and kinetic preference

Pericyclic or Pseudopericyclic? Deep Mechanism Insight into The Mi-gration Selectivity of Cb-Substituted-4aH-Carbazoles: Competition between Orbital Interaction and Electrostatic Interaction

The migration selectivity of Cb-substituted-4aH-carbazoles has been studied by DFT methods. For n-Bu and Ph substituted sub-strates, C4 migration and Ca-C1 migration are all pericyclic. C4 migration is favorable for more aromatic transition states. For halo-gen substituted substrates, C4 migration locates in the junction zone of pericyclic reactions and pseudopericyclic reactions while Ca-C1 migration is pseudopericyclic. Ca-C1 migration is favorable due to more positive NPA charges and LUMO distributions on Ca than C4. The acid catalysts with large steric hindrance can adjust the reaction selectivity through to some extent

Rapid Assembly of Functionalized Hydrodibenzofurans via Semipinacol Rearrangements

A distinct strategy via unprecedented semipinacol rearrangements for the synthesis of functionalized hydrodibenzofurans is reported. The versatile reactivity of benzofuran-3-one as a building block enabled the convergent coupling of simple starting materials and, thus, allowed for the facile variation of R group and the construction of hydrodibenzofurans with fused rings

Unified Total Syntheses of Structurally Diverse Akuammiline Alkaloids

The unified total syntheses of structurally diverse akuammiline alkaloids deformylcorymine (<b>1</b>), strictamine (<b>2</b>), and calophyline A (<b>3</b>) are reported. The strategy mimics the biosynthesis in nature at a strategic level, which allows for structural diversification from a common synthetic precursor by late-stage ring migrations

Effect of Isotopically Sensitive Branching on Product Distribution for Pentalenene Synthase: Support for a Mechanism Predicted by Quantum Chemistry

Mechanistic proposals for the carbocation cascade reaction leading to the tricyclic sesquiterpene pentalenene are assessed in light of the results of isotopically sensitive branching experiments with the H309A mutant of pentalenene synthase. These experimental results support a mechanism for pentalenene formation involving a 7-protoilludyl cation whose intermediacy was first predicted using quantum-chemical calculations.Reprinted with permission from Journal of the American Chemical Society 134 (2012): 11369, doi:10.1021/ja3043245. Copyright 2012 American Chemical Society.</p

Efficient Assembly of Polysubstituted Pyrroles via a (3 + 2) Cycloaddition/Skeletal Rearrangement/Redox Isomerization Cascade Reaction

An unprecedented cascade strategy, used in conjunction with a redox isomerization, for the synthesis of 3-allyl pyrroles is reported. In a single step, readily accessible simple starting materials are transformed into highly substituted pyrroles with high efficiency. The products obtained contain allyl substituents, which can be readily elaborated to other useful functional groups. The reaction proceeds through an unusual (3 + 2) cycloaddition/skeletal rearrangement/redox isomerization pathway

Total Synthesis of (±)-Grandilodine B

The first total synthesis of the opened-type <i>Kopsia</i> alkaloid grandilodine B is reported. Four stereocenters of this alkaloid, three of them quaternary, are stereoselectively generated by a Diels–Alder reaction, a diastereoselective cyanation of tertiary alcohol, and a facial-selective nitrone 1,3-dipolar cycloaddition