The Total Synthesis of Cycloheximide¹

A comparative study on the reaction mechanisms of Cp2MH2 (M = Cr, Mo, W) with HBF4

“…Cp 2 WH 3 ·BF 4 is stable, while Cp 2 MoH 3 ·BF 4 is unstable and can liberate hydrogen and alkanes over time. [10,11] To illustrate the experimental results, reaction mechanism calculations were performed. The optimized geometric parameters of the reactants, transition states, intermediates and products on the potential energy surfaces (PES) are listed in Table 3.…”

“…Unlike the stable Cp 2 WH 2 adducts, some of the Cp 2 MoH 2 adducts were reported to be unstable and could liberate hydrogen and alkanes over time. [10,11] Although these studies have passed decade years, the proton transfer between a transition-metal hydride (M-H) and a protic hydrogen moiety (H-A) continues to be a topic extensively studied at present. [12][13][14][15] The experimental and theoretical studies show that proton transfer is not a simple process but very sensitive to the nature of both the proton donor and the transition-metal hydride, as well as to the solvent.…”

Synthesis and Antimicrobial Activity of Optically Active trans-Cycloheximide Isomers

“…MPLC were performed on the same instrument using a glass column packed with a silica-gel (Lichroprep Si 60, 40", 63 .urn) and using the same solvent system. 2) Aldol condensation of the lithium enolate 7b with the aldehyde 6. To a stirred solution of LDA in 50 ml of dry tetrahydrofuran, prepared from 5.7 mmol of n-butyllithium and 5.7 mmol of diisopropylamine, was added 720 mg (5.7 mmol) of the ketone 5b and then 880 mg (5.7 mmol) of the aldehyde 6 5 ) at -70°C.…”

“…NaHC0 3 , brine and dried over anhyd. 6. To a solution of tin tetrachloride (1 M, 2.0ml) in methylene chloride, 350mg of the TMS ether 7e (1.…”

Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation

“…Based on the structure of 1 bound to the human ribosome, [9b] we hypothesized that installation of electrophilic functionality extending from the cyclohexanone of 1 may allow covalent interception of nearby lysine residues of RPL36a, ar ibosomal protein that comprises the E-site,a nd subsequent irreversible inhibition of translation ( Figure 2A). Such astrategy would require alteration of the cyclohexanone of 1 without disrupting the activity of 1,b ut the relative contribution of the substituents on the cyclohexanone to the activity of 1 remains elusive.T he lack of information could potentially be attributed to the strategy employed in the only reported synthesis of 1, [20] wherein the cyclohexanone moiety was prepared in the first stage.S ince the importance of glutarimide and C8 À OH of 1 has already been established, [21] we devised an alternative route to 1 which would allow latestage stereodivergent assembly of C11 and C13 substituents. We envisioned the cyclohexene 5 as ak ey intermediate for incorporating different functionality and stereochemistry across the alkene.T oa ccess 1 from 5,t he desired C13 stereocenter could be installed by directed hydrogenation.…”