Asymmetric Total Synthesis of (2R)-Hydroxynorneomajucin, a Norsesquiterpene from Illicium jiadifengpi.

We report the first total synthesis of (2R)-hydroxynorneomajucin, a norsesquiterpene derived from the Illicium genus. This natural product displays neurotrophic properties. Small molecule neurotrophins have potential as therapeutics in neurodegenerative diseases. Key steps of our synthesis include a Tsuji-Trost reaction, a Pauson-Khand cyclization, and a Nagata hydrocyanation. A simple sequence of reductions and a Mukaiyama hydration introduce the A-ring substituents with the correct configurations. The overall synthesis was completed in 17 steps (longest linear sequence, LLS).

Using the Competing Enantioselective Conversion Method to Assign the Absolute Configuration of Cyclic Amines with Bode's Acylation Reagents.

The competing enantioselective conversion (CEC) method is a quick and reliable means to determine absolute configuration. Previously, Bode's chiral acylated hydroxamic acids were used to determine the stereochemistry of primary amines, as well as cyclic and acyclic secondary amines. The enantioselective acylation has been evaluated for 4-, 5-, and 6-membered cyclic secondary amines, including medicinally relevant compounds. The limitations of the method were studied through computational analysis and experimental results. Piperidines with substituents at the 2-position did not behave well unless the axial conformer was energetically accessible, which is consistent with the transition state geometries proposed by Bode and Kozlowski. Control experiments were performed to investigate the cause of degrading selectivity under the CEC reaction conditions. The present study expands the scope of the CEC method for secondary amines and provides a better understanding of the reaction profile.

Relative and Absolute Structure Assignments of Alkenes Using Crystalline Osmate Derivatives for X-ray Analysis.

Osmium tetroxide and TMEDA form stable crystalline adducts with alkenes. The structure of liquid alkenes can be determined through the X-ray analysis of these derivatives. Osmium, a heavy atom, facilitates the crystallographic analysis and the determination of the absolute configuration using common Mo X-ray sources. The utility of this method for assigning structures and absolute configurations was demonstrated on a number of unsaturated substrates that include simple alkenes, enones, enol ethers, and silyl enol ethers.