Catalytic Asymmetric Direct Aldol Reaction of alpha-Alkyl Azlactones and Aliphatic Aldehydes for the Synthesis of Protected beta-Hydroxy-alpha-Amino Acids

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dc.contributor.advisor Deng, Li
dc.contributor.author Zheng, Yang
dc.date.accessioned 2015-03-02T16:09:41Z
dc.date.available 2015-03-02T16:09:41Z
dc.date.issued 2015
dc.identifier.uri http://hdl.handle.net/10192/29094
dc.description.abstract Optically active beta-hydroxy-alpha-amino acids are an important class of amino acids as they exist as structural components of many biologically active natural products such as vancomycin, katanosins, cyclosporin, ustiloxins, lactacystin, myriocin, mycestericins, threonine and sphingosine. Furthermore, these beta-hydroxy-alpha-amino acids are also useful chiral building blocks in organic synthesis, as illustrated by their transformations into beta-lactams, beta-halo-alpha-amino acids, and aziridines. The catalytic asymmetric synthesis of beta-hydroxy-alpha-amino acids and their derivatives has been realized by different catalytic methods. For the catalytic asymmetric synthesis of beta-hydroxy-alpha-amino acids and their derivatives with tertiary beta-centers and quaternary alpha-centers, there were two unsolved problems: 1) high diastereoselectivity when both tertiary beta-center and quaternary alpha-center have alkyl substituents; 2) high anti-diastereoselectivity. These problems have been solved by our new catalytic asymmetric direct aldol reaction of alpha-alkyl azlactones and aliphatic aldehydes. To the best of our knowledge, this is the first time that a direct aldol reaction of the azlactone and the aldehyde is reported. No similar direct aldol reactions with nucleophilic amino acid equivalents other than azlactones are available for making aldol products with free beta-hydroxy groups. This is also the first time that the protected beta-hydroxy-alpha-amino acid bearing alkyl substituents at both tertiary beta-center and quaternary alpha-center is synthesized by a catalytic asymmetric approach with high enantioselectivity and diastereoselectivity. The high anti-diastereoselectivity obtained for the synthesis of protected beta-hydroxy-alpha-amino acids having tertiary beta-centers and quaternary alpha-centers is unprecedented for a catalytic asymmetric approach with a general scope. This new method has enabled us to achieve an unprecedented scope in the synthesis of protected beta-hydroxy-alpha-amino acids. This promising method could be applied to the synthesis of highly immunosuppressant mycestericin natural products and sphingosine analogs in search of new drug leads.
dc.description.sponsorship Brandeis University, Graduate School of Arts and Sciences
dc.format.mimetype application/pdf
dc.language English
dc.language.iso eng
dc.publisher Brandeis University
dc.relation.ispartofseries Brandeis University Theses and Dissertations
dc.rights Copyright by Yang Zheng 2015
dc.subject Cinchona Alkaloid
dc.subject beta-Hydroxy-alpha-Amino Acid
dc.subject Asymmetric Catalysis
dc.subject Direct Aldol Reaction
dc.subject alpha-Alkyl Azlactone
dc.subject mycestericin natural products
dc.subject immunosuppressant
dc.subject sphingosine analogs
dc.title Catalytic Asymmetric Direct Aldol Reaction of alpha-Alkyl Azlactones and Aliphatic Aldehydes for the Synthesis of Protected beta-Hydroxy-alpha-Amino Acids
dc.type Thesis
dc.contributor.department Department of Chemistry
dc.degree.name PhD
dc.degree.level Doctoral
dc.degree.discipline Chemistry
dc.degree.grantor Brandeis University, Graduate School of Arts and Sciences


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