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Asymmetric aldol reactions between acetone and benzaldehydes catalyzed by chiral Zn2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane: fine-tuning of the amino-acid side chains and a revised reaction mechanism.
Chem Asian J. 2013 Sep; 8(9):2125-35.CA

Abstract

We previously reported that chiral Zn(2+) complexes that were designed to mimic the actions of class-I and class-II aldolases catalyzed the enantioselective aldol reactions of acetone and its analogues thereof with benzaldehyde derivatives. Herein, we report the synthesis of new chiral Zn(2+) complexes that contain Zn(2+)-tetraazacyclododecane (Zn(2+)-[12]aneN4) moieties and amino acids that contain aliphatic, aromatic, anionic, cationic, and dipeptide side chains. The chemical and optical yields of the aldol reaction were improved (up to 96 % ee) by using ZnL complexes of L-decanylglycyl-pendant [12]aneN4 (L-ZnL(7)), L-naphthylalanyl-pendant [12]aneN4 (L-ZnL(10)), L-biphenylalanyl-pendant [12]aneN4 (L-ZnL(11)), and L-phenylethylglycyl-pendant [12]aneN4 ligands (L-ZnL(12)). UV/Vis and circular dichroism (CD) titrations of acetylacetone (acac) with ZnL complexes confirmed that a ZnL-(acac)(-) complex was exclusively formed and not the enaminone of ZnL and acac, as we had previously proposed. Moreover, the results of stopped-flow experiments indicated that the complexation of (acac)(-) with ZnL was complete within milliseconds, whereas the formation of an enaminone required several hours. X-ray crystal-structure analysis of L-ZnL(10) and the ZnL complex of L-diphenylalanyl-pendant [12]aneN4 (L-ZnL(13)) shows that the NH2 groups of the amino-acid side chains of these ligands are coordinated to the Zn(2+) center as the fourth coordination site, in addition to three nitrogen atoms of the [12]aneN4 rings. The reaction mechanism of these aldol reactions is discussed and some corrections are made to our previous mechanistic hypothesis.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Itoh S
Production Technology Laboratories, Kaken Pharmaceutical Co. Ltd. 301 Gensuke, Fujieda, Shizuoka 426-8646, Japan.
Tokunaga T
No affiliation info available
Sonoike S
No affiliation info available
Kitamura M
No affiliation info available
Yamano A
No affiliation info available
Aoki S
No affiliation info available

MeSH

AcetoneAldehydesAmino AcidsBenzaldehydesCatalysisCoordination ComplexesCrystallography, X-RayHeterocyclic CompoundsLigandsMolecular ConformationStereoisomerismZinc

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23780779

Citation

Itoh, Susumu, et al. "Asymmetric Aldol Reactions Between Acetone and Benzaldehydes Catalyzed By Chiral Zn2+ Complexes of Aminoacyl 1,4,7,10-tetraazacyclododecane: Fine-tuning of the Amino-acid Side Chains and a Revised Reaction Mechanism." Chemistry, an Asian Journal, vol. 8, no. 9, 2013, pp. 2125-35.
Itoh S, Tokunaga T, Sonoike S, et al. Asymmetric aldol reactions between acetone and benzaldehydes catalyzed by chiral Zn2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane: fine-tuning of the amino-acid side chains and a revised reaction mechanism. Chem Asian J. 2013;8(9):2125-35.
Itoh, S., Tokunaga, T., Sonoike, S., Kitamura, M., Yamano, A., & Aoki, S. (2013). Asymmetric aldol reactions between acetone and benzaldehydes catalyzed by chiral Zn2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane: fine-tuning of the amino-acid side chains and a revised reaction mechanism. Chemistry, an Asian Journal, 8(9), 2125-35. https://doi.org/10.1002/asia.201300308
Itoh S, et al. Asymmetric Aldol Reactions Between Acetone and Benzaldehydes Catalyzed By Chiral Zn2+ Complexes of Aminoacyl 1,4,7,10-tetraazacyclododecane: Fine-tuning of the Amino-acid Side Chains and a Revised Reaction Mechanism. Chem Asian J. 2013;8(9):2125-35. PubMed PMID: 23780779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asymmetric aldol reactions between acetone and benzaldehydes catalyzed by chiral Zn2+ complexes of aminoacyl 1,4,7,10-tetraazacyclododecane: fine-tuning of the amino-acid side chains and a revised reaction mechanism. AU - Itoh,Susumu, AU - Tokunaga,Takuya, AU - Sonoike,Shotaro, AU - Kitamura,Masanori, AU - Yamano,Akihito, AU - Aoki,Shin, Y1 - 2013/06/18/ PY - 2013/03/08/received PY - 2013/04/29/revised PY - 2013/6/20/entrez PY - 2013/6/20/pubmed PY - 2014/3/22/medline KW - aldol reaction KW - asymmetric catalysis KW - enzyme models KW - macrocyclic ligands KW - zinc SP - 2125 EP - 35 JF - Chemistry, an Asian journal JO - Chem Asian J VL - 8 IS - 9 N2 - We previously reported that chiral Zn(2+) complexes that were designed to mimic the actions of class-I and class-II aldolases catalyzed the enantioselective aldol reactions of acetone and its analogues thereof with benzaldehyde derivatives. Herein, we report the synthesis of new chiral Zn(2+) complexes that contain Zn(2+)-tetraazacyclododecane (Zn(2+)-[12]aneN4) moieties and amino acids that contain aliphatic, aromatic, anionic, cationic, and dipeptide side chains. The chemical and optical yields of the aldol reaction were improved (up to 96 % ee) by using ZnL complexes of L-decanylglycyl-pendant [12]aneN4 (L-ZnL(7)), L-naphthylalanyl-pendant [12]aneN4 (L-ZnL(10)), L-biphenylalanyl-pendant [12]aneN4 (L-ZnL(11)), and L-phenylethylglycyl-pendant [12]aneN4 ligands (L-ZnL(12)). UV/Vis and circular dichroism (CD) titrations of acetylacetone (acac) with ZnL complexes confirmed that a ZnL-(acac)(-) complex was exclusively formed and not the enaminone of ZnL and acac, as we had previously proposed. Moreover, the results of stopped-flow experiments indicated that the complexation of (acac)(-) with ZnL was complete within milliseconds, whereas the formation of an enaminone required several hours. X-ray crystal-structure analysis of L-ZnL(10) and the ZnL complex of L-diphenylalanyl-pendant [12]aneN4 (L-ZnL(13)) shows that the NH2 groups of the amino-acid side chains of these ligands are coordinated to the Zn(2+) center as the fourth coordination site, in addition to three nitrogen atoms of the [12]aneN4 rings. The reaction mechanism of these aldol reactions is discussed and some corrections are made to our previous mechanistic hypothesis. SN - 1861-471X UR - https://www.unboundmedicine.com/medline/citation/23780779/Asymmetric_aldol_reactions_between_acetone_and_benzaldehydes_catalyzed_by_chiral_Zn2+_complexes_of_aminoacyl_14710_tetraazacyclododecane:_fine_tuning_of_the_amino_acid_side_chains_and_a_revised_reaction_mechanism_ L2 - https://doi.org/10.1002/asia.201300308 DB - PRIME DP - Unbound Medicine ER -