Asymmetric Total Synthesis of (-)-Quinocarcin

(-)-Quinocarcin (I) has been synthesized in a longest linear sequence of 22 steps from 3-hydroxybenzaldehyde in 16% overall yield. The Pictet-Spengler reaction of L-tert-butyl-2-bromo-5-hydroxy phenylalanate, synthesized according to Corey-Lygo's enantioselective alkylation process, with benzoxyacetaldehyde under mild acidic conditions afforded 1,3-cis tetrahydroisoquinoline as an only isolable stereomer in 91% yield. The diazabicycle[3,2,1]-octane ring system of II was constructed by a silver tetrafluoroborate-promoted intramol. Mannich reaction using amino thioether as a latent N-acyliminium species and tethered silyl enol ether as a nucleophile. Using amino thioether instead of aminal as a precursor of N-acyliminium was of high importance to the success of this otherwise disfavored 5-endo-Trig cyclization. A Hf(OTf)4-catalyzed (0.1 equiv) transformation of aminal to amino thioether was uncovered in the course of this study, allowing the conversion of a tricyclic aminal to an amino thioether to be realized in high yield. From the bridged tetracyclic compd. III, a sequence of oxidn. of aldehyde to acid, global deprotection under hydrogenolysis conditions, and one-pot partial redn. of lactam to aminal/oxazolidine formation completed the total synthesis of the pentacyclic (-)-quinocarcin. [on SciFinder (R)]

Published in:
Journal of the American Chemical Society, 130, 22, 7148-7152
CAN 149:10162
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
written in English.
200132-54-3 Role: CAT (Catalyst use), USES (Uses) (asym. total synthesis of (-)-quinocarcin); 56-86-0 (L-Glutamic acid); 100-83-4; 60656-87-3; 81477-94-3 Role: RCT (Reactant), RACT (Reactant or reagent) (asym. total synthesis of (-)-quinocarcin); 67436-17-3P; 96013-77-3P; 164513-32-0P; 699020-18-3P; 1030029-42-5P; 1030029-43-6P; 1030029-44-7P; 1030029-45-8P; 1030029-46-9P; 1030029-47-0P; 1030029-50-5P; 1030029-51-6P; 1030029-52-7P; 1030029-53-8P; 1030029-54-9P; 1030029-55-0P; 1030029-56-1P; 1030029-57-2P; 1030029-58-3P; 1030029-59-4P; 1030029-60-7P; 1030029-61-8P; 1030029-62-9P; 1030029-64-1P; 1030029-65-2P; 1030029-66-3P; 1030029-67-4P; 1030029-68-5P; 1030029-70-9P; 1030029-72-1P; 1030029-74-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (asym. total synthesis of (-)-quinocarcin); 84573-33-1P; 1030029-48-1P; 1030029-49-2P; 1030029-63-0P Role: SPN (Synthetic preparation), PREP (Preparation) (asym. total synthesis of (-)-quinocarcin)

 Record created 2010-11-25, last modified 2018-03-17

Rate this document:

Rate this document:
(Not yet reviewed)