Abstract
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.
Highlights
The Role of l-Dap in Natural and Synthetic Compounds2,3-l-Diaminopropanoic acid (l-Dap) is a non-proteinogenic amino acid produced by numerous plants and bacteria [1]
Protected l-Diaminopropanoic acid (l-Dap) derivatives were proposed as powerful inhibitors of the formation of advanced glycosylation end-products (AGEs), which are implicated in the development of diabetes mellitus and neurodegenerative Alzheimer’s and Parkinson’s diseases [17]
The scope of the present work was an investigation of a preparative route to appropriately protected l-Dap methyl esters, which may further be employed in branching, alkylation, cyclization, cross-linking, and solid-phase peptide synthesis
Summary
2,3-l-Diaminopropanoic acid (l-Dap) is a non-proteinogenic amino acid produced by numerous plants and bacteria [1]. It is the main structural motif of albizziine, a natural non-proteinaceous free amino acid which is ubiquitously present in higher plants and in seeds [2]. Advanced lipid peroxidation end-product (ALE) formation can be modulated by the same l-Dap derivatives used to control AGE cascades, against the endogenous peroxidation of polyunsaturated fatty acids [17]. The identification of l-Dap in the Murchison chondritic meteorite [33] suggested the possible role of this non-proteinogenic amino acid as a selective molecular target to investigate prebiotic polycondensation processes of importance in establishing the appearance of life on Earth [34]
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