Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations

Biomimetic synthesis of Cbz-(S)-dolaphenine

“…19-25 By far the greatest synthetic challenge to the synthesis of dolaphenine has been the ability to secure the stereochemical purity of the stereocenter adjacent to the C-2 position of the thiazole unit, either by its introduction with chiral auxiliaries or by its retention, starting from enantiomerically pure substrates. The majority of the successful approaches have been geared toward the former given the facile lability of this stereocenter.…”

Antineoplastic Agents. 592. Highly Effective Cancer Cell Growth Inhibitory Structural Modifications of Dolastatin 10

“…To a solution of Boc-Dap 15 ( 6 , 0.49 g, 1.71 mmol) in dry DMF (3 mL) that was stirring at 20 °C was added 1-hydroxybenzotriazole (HOBT, 0.37 g, 2.74 mmol). Diisopropylethylamine (DIEA, 0.95 mL, 5.48 mmol) was added, followed by N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDCI), and the reaction mixture was stirred for 10 min before the addition of tyramine (0.28 g, 2.05 mmol).…”

“…To a solution of Boc-Dap 15 ( 6 , 0.172 g; 0.6 mmol) in CH 2 Cl 2 (3 mL) was added 2-aminoquinoline (82.8 mg; 0.57 mmol), and the mixture was stirred and cooled to 0 °C under argon. Triethylamine (TEA, 0.3 mL; 2.1 mmol) and diethylcyanophosphonate (DEPC; 0.2 mL; 1.2 mmol) were added, and the resultant yellow solution was allowed to warm to room temperature (rt) and was stirred under argon for 6 h. Removal of solvent yielded a dark orange-brown residue that was fractioned under pressure on silica gel [eluent: hexane–acetone (7:2 to 2:3)] to give the product as a colorless solid (90.8 mg, 0.22 mmol, 36.6%, based on recovery of starting material): 1 H NMR (CDCl 3 , 300 MHz) δ 8.43 (1H, dd, J = 8.7.…”

“…To a stirring solution of Boc-Dap 15 ( 6 , 87.2 mg; 0.3 mmol) in DMF (2 mL) and pyridine (0.1 mL) was added Boc 2 O (0.183 g; 0.84 mmol). After 10 min, 6-aminoquinoline (6-AQ; 50.4 mg; 0.35 mmol) was added to the solution, and stirring was continued for 64 h, at which time starting material was still present.…”

Enantioselective, Ketoreductase-Based Entry into Pharmaceutical Building Blocks: Ethanol as Tunable Nicotinamide Reductant

“…In the former case, Genet has reported the use of stoichiometric DIP-Cl (92% ee), 18 whereas Masui employs a diphenylprolinol-ligated borane reagent (92% ee). 19 The highly enantioselective reductions seen here (KREDs 108 and 132) open up alternative “green” processes.…”