Highly Functionalized 1,2–Diamino Compounds through Reductive Amination of Amino Acid-Derived β–Keto Esters

A synthetic strategy for the preparation of two orthogonally protected methyl esters of the non-proteinogenic amino acid 2,3-l-diaminopropanoic acid (l-Dap) was developed. In these structures, the base-labile protecting group 9-fluorenylmethyloxycarbonyl (Fmoc) was paired to the p-toluensulfonyl (tosyl, Ts) or acid-labile tert-butyloxycarbonyl (Boc) moieties. The synthetic approach to protected l-Dap methyl esters uses appropriately masked 2,3-diaminopropanols, which are obtained via reductive amination of an aldehyde prepared from the commercial amino acid Nα-Fmoc-O-tert-butyl-d-serine, used as the starting material. Reductive amination is carried out with primary amines and sulfonamides, and the process is assisted by the Lewis acid Ti(OiPr)4. The required carboxyl group is installed by oxidizing the alcoholic function of 2,3-diaminopropanols bearing the tosyl or benzyl protecting group on the 3-NH2 site. The procedure can easily be applied using the crude product obtained after each step, minimizing the need for chromatographic purifications. Chirality of the carbon atom of the starting d-serine template is preserved throughout all synthetic steps.

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Reductive Amination of Biobased Levulinic Acid to Unnatural Chiral γ-Amino Acid Using an Engineered Amine Dehydrogenase

ACS Sustainable Chemistry & Engineering ◽

10.1021/acssuschemeng.0c04647 ◽

2020 ◽

Vol 8 (46) ◽

pp. 17054-17061

Author(s):

Rui-Feng Cai ◽

Lei Liu ◽

Fei-Fei Chen ◽

Aitao Li ◽

Jian-He Xu ◽

...

Keyword(s):

Amino Acid ◽

Levulinic Acid ◽

Reductive Amination ◽

Amine Dehydrogenase

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A new retro-aza-ene reaction: formal reductive amination of an α-keto acid to an α-amino acid

Tetrahedron ◽

10.1016/s0040-4020(01)88730-5 ◽

1992 ◽

Vol 48 (9) ◽

pp. 1715-1728 ◽

Cited By ~ 4

Author(s):

David B. Berkowitz ◽

W. Bernd Schweizer

Keyword(s):

Amino Acid ◽

Reductive Amination ◽

Keto Acid ◽

Ene Reaction

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ChemInform Abstract: Photosensitized NAD(P)H Regeneration Systems; Application in the Reduction of Butan-2-one, Pyruvic, and Acetoacetic Acids and in the Reductive Amination of Pyruvic and Oxoglutaric Acid to Amino Acid.

Chemischer Informationsdienst ◽

10.1002/chin.198639138 ◽

1986 ◽

Vol 17 (39) ◽

Author(s):

D. MANDLER ◽

I. WILLNER

Keyword(s):

Amino Acid ◽

Reductive Amination ◽

Regeneration Systems

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Facile Formation of Novel Carbohydrate-Amino Acid Conjugates by Reductive Amination.

ChemInform ◽

10.1002/chin.200341209 ◽

2003 ◽

Vol 34 (41) ◽

Author(s):

Saskia Weingarten ◽

Joachim Thiem

Keyword(s):

Amino Acid ◽

Reductive Amination ◽

Amino Acid Conjugates

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Scope and limitations in the use of N-(PhF)serine-derived cyclic sulfamidates for amino acid synthesis

Canadian Journal of Chemistry ◽

10.1139/v00-176 ◽

2001 ◽

Vol 79 (1) ◽

pp. 94-104 ◽

Cited By ~ 38

Author(s):

Lan Wei ◽

William D Lubell

Keyword(s):

Amino Acid ◽

Sodium Azide ◽

Ring Opening ◽

Acid Synthesis ◽

Potassium Thiocyanate ◽

Dimethyl Malonate ◽

Amino Acid Synthesis ◽

Keto Ester ◽

Keto Esters ◽

Nucleophilic Displacement

Ring-opening of N-(PhF)serine-derived cyclic sulfamidate 17 was achieved with different nucleophiles (β-keto esters, β-keto ketones, dimethyl malonate, nitroethane, sodium azide, imidazole, and potassium thiocyanate) to prepare a variety of amino acid analogs. Two different pathways for ring opening of 17 were elucidated: direct nucleophilic displacement, as well as β-elimination followed by Michael addition. Furthermore, β-keto ester and β-keto ketone products 18k,18m, and 18i were converted to prolines and pyrazole amino acids.Key words: glutamate, amino acid, cyclic sulfamidate, proline.

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