Synthetic Studies on (-)-Lemonomycin: An Efficient Asymmetric Synthesis of Lemonomycinone Amide
Asym. synthesis of lemonomycinone amide was accomplished from readily accessible starting materials. Enantioselective alkylation of N-(diphenylmethylene)glycine tert-Bu ester by 5-tert-butyldimethylsilyloxy-2,4-dimethoxy-3-methylbenzyl bromide in the presence of Corey-Lygo's phase transfer catalyst [O-(9)-ally-N-(9'-anthracenylmethyl) cinchonidium bromide, 0.1 equiv] afforded, after chemoselective hydrolysis of the imine function (THF/H2O/AcOH), the substituted L-tert-Bu phenylalanate in 85% yield. A Pictet-Spengler reaction with benzyloxyacetaldehyde provided the 1,3-cis-disubstituted tetrahydroisoquinoline in 85% yield as a single diastereomer. Coupling of hindered secondary amine with amino acid was accomplished under carefully controlled conditions to furnish the amide, which was in turn converted to hemi-aminal. A hafnium triflate catalyzed conversion of hemi-aminal to alpha -amino thioether followed by a silver tetrafluoroborate promoted intramol. Mannich reaction of 26 afforded the tetracycle in excellent overall yields. Debenzylation of the tetracycle [Pd(OH)2, H2, MeOH, 0 DegC], removal of N-Boc function (aq. 3 N HCl, MeOH/H2O), and oxidn. of hydroquinone to quinone [(NH4)2Ce(NO3)6, H2O, rt] afforded the lemonomycinone amide in 76% yield over three steps. [on SciFinder (R)]
Cite this item
Wu, Y.-C., Bernadat, G., Masson, G., Couturier, C., Schlama, T., & Zhu, J. (2009). Synthetic Studies on (-)-Lemonomycin: An Efficient Asymmetric Synthesis of Lemonomycinone Amide. The Journal of Organic Chemistry, 74(5), 2046–2052. https://doi.org/10.1021/jo8027449
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2009
74
5
2046
2052
CAN 150:283309
33-7
Carbohydrates
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
written in English.
7790-86-5 (Cerium chloride); 14104-20-2 (Silvertetrafluoroborate); 161337-67-3 (Hafnium triflate); 200132-54-3 Role: CAT (Catalyst use), USES (Uses) (synthetic studies on (-)-Lemonomycin and efficient asym. synthesis of lemonomycinone amide via Corey-Lygo's phase transfer-catalyzed enantioselective alkylation and Pictet-Spengler cyclocondensation reactions); 56-86-0 (L-Glutamic acid); 75-08-1 (Ethanethiol); 3966-32-3; 5673-07-4; 24424-99-5; 26164-26-1; 60656-87-3; 80522-42-5; 81477-94-3 Role: RCT (Reactant), RACT (Reactant or reagent) (synthetic studies on (-)-Lemonomycin and efficient asym. synthesis of lemonomycinone amide via Corey-Lygo's phase transfer-catalyzed enantioselective alkylation and Pictet-Spengler cyclocondensation reactions); 7149-92-0P; 19676-67-6P; 59279-60-6P; 206128-03-2P; 225938-52-3P; 367968-06-7P; 869190-20-5P; 871108-91-7P; 871108-92-8P; 871108-94-0P; 912655-01-7P; 1124171-88-5P; 1124171-89-6P; 1124171-91-0P; 1124171-92-1P; 1124171-94-3P; 1124171-95-4P; 1124171-96-5P; 1124171-97-6P; 1124171-98-7P; 1124171-99-8P; 1124172-00-4P; 1124172-01-5P; 1124172-03-7P; 1124172-06-0P; 1124172-07-1P; 1124172-08-2P; 1124172-09-3P; 1124172-10-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (synthetic studies on (-)-Lemonomycin and efficient asym. synthesis of lemonomycinone amide via Corey-Lygo's phase transfer-catalyzed enantioselective alkylation and Pictet-Spengler cyclocondensation reactions); 10139-51-2 Role: RGT (Reagent), RACT (Reactant or reagent) (synthetic studies on (-)-Lemonomycin and efficient asym. synthesis of lemonomycinone amide via Corey-Lygo's phase transfer-catalyzed enantioselective alkylation and Pictet-Spengler cyclocondensation reactions); 276248-62-5P (Lemonomycin); 1124171-87-4P; 1124172-02-6P; 1124172-04-8P Role: SPN (Synthetic preparation), PREP (Preparation) (synthetic studies on (-)-Lemonomycin and efficient asym. synthesis of lemonomycinone amide via Corey-Lygo's phase transfer-catalyzed enantioselective alkylation and Pictet-Spengler cyclocondensation reactions)
REVIEWED
OTHER