Name: N3-Dab(Boc)-OH
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

(S)-2-azido-4-[Boc-amino]butanoic acid; Azido-L-Dab(Boc)-OH

IUPAC Name

(2S)-2-azido-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid

Canonical SMILES

CC(C)(C)OC(=O)NCCC(C(=O)O)N=[N+]=[N-]

InChI

InChI=1S/C9H16N4O4/c1-9(2,3)17-8(16)11-5-4-6(7(14)15)12-13-10/h6H,4-5H2,1-3H3,(H,11,16)(H,14,15)/t6-/m0/s1

InChIKey

JLMWKZYQNHSSAD-LURJTMIESA-N

Melting Point

91-92°C

Appearance

White crystalline powder

Storage

Store at 2-8 °C

N3-Dab(Boc)-OH, also known as N3-Boc-3-amino-1,4-diaminobutane, is a key intermediate in organic and medicinal chemistry, commonly used in the synthesis of peptides, peptide mimetics, and other bioactive compounds. The Boc (tert-butoxycarbonyl) protecting group is widely used to protect amino groups during peptide synthesis, making N3-Dab(Boc)-OH an important building block in the development of peptide-based therapeutics. Its structure allows for easy modification and integration into larger peptide sequences, facilitating the design of compounds with specific biological activity.

One of the primary applications of N3-Dab(Boc)-OH is in peptide synthesis, particularly when synthesizing peptides with complex sequences or those requiring specific modifications. The Boc group protects the amino group, preventing unwanted reactions during peptide elongation. N3-Dab(Boc)-OH is used as a precursor for incorporating the 3-amino-1,4-diaminobutane (Dab) unit into peptides, which is valuable in the creation of peptides with enhanced stability, cell permeability, or resistance to enzymatic degradation. This makes N3-Dab(Boc)-OH essential for developing peptides for pharmaceutical applications, including targeted therapies and hormone mimetics.

N3-Dab(Boc)-OH is also crucial in the design of peptide conjugates, where it can be used to link peptides to other molecules such as drugs, diagnostic agents, or targeting ligands. The reactive amine group in N3-Dab(Boc)-OH allows for the conjugation of various bioactive compounds, creating peptide-drug conjugates (PDCs) or peptide-targeting agents. These conjugates can improve the pharmacokinetics, selectivity, and efficacy of the therapeutic peptides, making N3-Dab(Boc)-OH an important tool in the development of novel drug delivery systems.

Another significant application of N3-Dab(Boc)-OH is in the synthesis of peptide mimetics and small molecule inhibitors. By incorporating the Dab unit into non-peptidic frameworks, researchers can design peptide-like molecules that retain the biological activity of the original peptides while offering improved stability and oral bioavailability. N3-Dab(Boc)-OH serves as a key precursor for creating these mimetics, which are often used in drug discovery to develop inhibitors of protein-protein interactions, enzymes, or receptors. This enhances the versatility of N3-Dab(Boc)-OH in pharmaceutical research.

In addition, N3-Dab(Boc)-OH plays a role in the synthesis of functionalized polymers and materials. By incorporating the Dab unit into polymeric chains, it is possible to design polymers with specific bioactivity or controlled release properties. N3-Dab(Boc)-OH is often used as a monomer in the preparation of functional polymers for drug delivery, tissue engineering, or biosensors. The amine group in the Dab residue allows for further functionalization, making these materials versatile for biomedical and industrial applications.

1. Solid-phase synthesis of D-fructose-derived Heyns peptides utilizing Nα-Fmoc-Lysin[Nε-(2-deoxy-D-glucos-2-yl),Nε-Boc]-OH as building block

Sebastian Schmutzler, Daniel Knappe, Andreas Marx, Ralf Hoffmann Amino Acids. 2021 Jun;53(6):881-891. doi: 10.1007/s00726-021-02989-7. Epub 2021 May 2.

Aldoses and ketoses can glycate proteins yielding isomeric Amadori and Heyns products, respectively. Evidently, D-fructose is more involved in glycoxidation than D-glucose favoring the formation of advanced glycation endproducts (AGEs). While Amadori products and glucation have been studied extensively, the in vivo effects of fructation are largely unknown. The characterization of isomeric Amadori and Heyns peptides requires sufficient quantities of pure peptides. Thus, the glycated building block Nα-Fmoc-Lys[Nε-(2-deoxy-D-glucos-2-yl),Nε-Boc]-OH (Fmoc-Lys(Glc,Boc)-OH), which was synthesized in two steps starting from unprotected D-fructose and Fmoc-L-lysine hydrochloride, was site-specifically incorporated during solid-phase peptide synthesis. The building block allowed the synthesis of a peptide identified in tryptic digests of human serum albumin containing the reported glycation site at Lys233. The structure of the glycated amino acid derivatives and the peptide was confirmed by mass spectrometry and NMR spectroscopy. Importantly, the unprotected sugar moiety showed neither notable epimerization nor undesired side reactions during peptide elongation, allowing the incorporation of epimerically pure glucosyllysine. Upon acidic treatment, the building block as well as the resin-bound peptide formed one major byproduct due to incomplete Boc-deprotection, which was well separated by reversed-phase chromatography. Expectedly, the tandem mass spectra of the fructated amino acid and peptide were dominated by signals indicating neutral losses of 18, 36, 54, 84 and 96 m/z-units generating pyrylium and furylium ions.

2. Synthesis of ( +) -( R)-Tiruchanduramine

Zahraa S Al-Taie, et al. Molecules. 2022 Feb 16;27(4):1338. doi: 10.3390/molecules27041338.

The absolute stereochemistry of the marine alkaloid (+)-(R)-tiruchanduramine was established via a convergent total synthesis in six steps and 15.5% overall yield from Fmoc-D-Dab(Boc)-OH.

3. A high-yielding solid-phase total synthesis of daptomycin using a Fmoc SPPS stable kynurenine synthon

Ryan Moreira, Jacob Wolfe, Scott D Taylor Org Biomol Chem. 2021 Apr 14;19(14):3144-3153. doi: 10.1039/d0ob02504f. Epub 2021 Jan 28.

A high-yielding total synthesis of daptomycin, an important clinical antibiotic, is described. Key to the development of this synthesis was the elucidation of a Camps cyclization reaction that occurs in the solid-phase when conventionally used kynurenine (Kyn) synthons, such as Fmoc-l-Kyn(Boc,CHO)-OH and Fmoc-l-Kyn(CHO,CHO)-OH, are exposed to 20% 2-methylpiperidine (2MP)/DMF. During the synthesis of daptomycin, this side reaction was accompanied by intractable peptide decomposition, which resulted in a low yield of Dap and a 4-quinolone containing peptide. The Camps cyclization was found to occur in solution when Boc-l-Kyn(Boc,CHO)-Ot-Bu and Boc-l-Kyn(CHO,CHO)-OMe were exposed to 20% 2MP/DMF giving the corresponding 4-quinolone amino acid. In contrast, Boc-l-Kyn(CHO)-OMe was stable under these conditions, demonstrating that removing one of the electron withdrawing groups from the aforementioned building blocks prevents enolization in 2MP/DMF. Hence, a new synthesis of daptomycin was developed using Fmoc-l-Kyn(Boc)-OH, which is prepared in two steps from Fmoc-l-Trp(Boc)-OH, that proceeded with an unprecedented 22% overall yield. The simplicity and efficiency of this synthesis will facilitate the preparation of analogs of daptomycin. In addition, the elucidation of this side reaction will simplify preparation of other Kyn-containing natural products via Fmoc SPPS.