Boc-Dab(Z)-OH DCHA: Properties, Handling & Lab Use Guide

Boc-dab(z)-oh dcha is a fully side-chain- and alpha-amine-protected derivative of L-2,4-diaminobutyric acid supplied as its dicyclohexylamine salt, widely used as a building block in Boc-strategy solid-phase and solution-phase peptide synthesis.

Full Name

Nα-Boc-Nγ-Z-L-2,4-diaminobutyric acid dicyclohexylamine salt

SKU

B182001

Protection Scheme

Alpha-amine: Boc (acid-labile); gamma-amine: Z/Cbz (hydrogenolysis-labile); carboxyl: free acid stabilised as DCHA salt

Primary Application

Building block for incorporation of L-Dab residues in Boc-SPPS and solution-phase peptide synthesis

Recommended Storage

Store tightly sealed at 2–8 °C, protected from moisture and light

Supplier

Aladdin Scientific

Chemical Identity and Structural Features

Boc-Dab(Z)-OH DCHA is a doubly protected derivative of the non-proteinogenic amino acid L-2,4-diaminobutyric acid (L-Dab). The alpha-amine is masked with a tert-butyloxycarbonyl (Boc) group, which is selectively removed by dilute trifluoroacetic acid (TFA) or anhydrous HCl in an organic solvent. The side-chain gamma-amine bears a benzyloxycarbonyl (Z or Cbz) group, orthogonally removable by catalytic hydrogenolysis (e.g., Pd/C, H₂) or by strong acid conditions (HF, HBr/AcOH) in classical Boc-strategy synthesis. The carboxylic acid is presented as the dicyclohexylamine (DCHA) salt to enhance crystallinity, long-term stability, and ease of handling; the free acid is liberated by partitioning between ethyl acetate and dilute aqueous acid prior to coupling reactions.

The compound is characterised by its short two-carbon side chain terminating in a primary amine, making it a valuable scaffold for introducing cationic residues, lactam bridges, or bioconjugation handles into peptide targets.

Reconstitution and Solution Preparation

Before use in coupling reactions, the DCHA salt must be converted to the free acid. The recommended procedure is as follows:

1. Dissolve the DCHA salt in ethyl acetate (EtOAc) at an appropriate concentration (typically 0.1–0.5 M).
2. Wash the organic layer twice with cold 10% citric acid solution or 1 M KHSO₄ to protonate and extract the DCHA base into the aqueous phase.
3. Wash the organic layer with saturated brine, dry over anhydrous Na₂SO₄ or MgSO₄, filter, and concentrate under reduced pressure to yield the free Boc-Dab(Z)-OH.

The liberated free acid can then be dissolved in DMF, NMP, or DCM for standard coupling protocols using reagents such as HATU, HBTU, DIC/HOBt, or PyBOP. Prepare solutions freshly and avoid prolonged exposure to moisture to prevent Boc hydrolysis.

Applications in Peptide Synthesis

Boc-Dab(Z)-OH DCHA is primarily employed in the following synthetic contexts:

• Boc-SPPS: Sequential incorporation of L-Dab residues into peptide chains assembled on a resin, where the Boc group is removed at each cycle with TFA/DCM and the Z group is retained until global deprotection (typically with HF or TFMSA).
• Cyclic and branched peptides: The orthogonally protected gamma-amine enables selective deprotection and on-resin cyclisation to form lactam bridges or branching points without affecting the backbone.
• Antimicrobial peptide analogues: L-Dab is a key residue in natural antimicrobial peptides such as polymyxins and colistin; Boc-Dab(Z)-OH DCHA facilitates the synthesis of structural analogues and SAR studies.
• Bioconjugation handles: After global deprotection, the free side-chain amine can be selectively acylated, PEGylated, or conjugated to payloads for drug delivery applications.

Storage, Stability and Safety Guidance

Storage: Store at 2–8 °C in a tightly sealed container, away from moisture, heat, and direct light. Under these conditions the compound is expected to maintain specification-level purity for an extended period; consult the certificate of analysis (CoA) for the specific expiry date of your lot.

Stability considerations: The Boc group is sensitive to protic acids and prolonged exposure to humid air; avoid repeated freeze-thaw cycles and reseal the container immediately after use. The Z group is stable under normal storage conditions but will cleave under hydrogenolytic conditions.

Safety: Refer to the Safety Data Sheet (SDS) provided by Aladdin Scientific before handling. As with most peptide synthesis reagents, use appropriate PPE including lab coat, nitrile gloves, and safety glasses. Work in a well-ventilated area or fume hood. The DCHA component may cause skin and eye irritation; avoid inhalation of dust.

Disposal: Dispose of residues and solutions in accordance with local institutional and regulatory guidelines for organic chemical waste.

Frequently asked questions

How do I convert Boc-Dab(Z)-OH DCHA to the free acid before a coupling reaction?

Dissolve the DCHA salt in ethyl acetate, then extract twice with cold 10% citric acid or 1 M KHSO4 aqueous solution to remove the dicyclohexylamine base. Wash the organic phase with brine, dry, and evaporate under reduced pressure to obtain Boc-Dab(Z)-OH as a free acid ready for coupling.

Are Boc and Z protecting groups on this compound truly orthogonal?

Yes, they are considered orthogonal: the Boc group is selectively cleaved by mild protic acid (e.g., 20–50% TFA in DCM or 4 M HCl in dioxane) while the Z group remains intact. Conversely, the Z group is removed by catalytic hydrogenolysis (H2/Pd-C) or strong acid (HF, HBr/AcOH), conditions under which the Boc group would also be removed. In Boc-SPPS, the Z group therefore serves as a semi-permanent protecting group removed only during final global deprotection.

What is the significance of L-Dab in antimicrobial peptide research?

L-2,4-diaminobutyric acid (L-Dab) is a key residue found in clinically important lipopeptide antibiotics such as polymyxin B and colistin (polymyxin E). Its positively charged side-chain amine is critical for electrostatic interaction with the lipopolysaccharide of Gram-negative bacterial membranes. Boc-Dab(Z)-OH DCHA enables researchers to synthesise polymyxin analogues and other Dab-containing peptides for structure-activity relationship studies aimed at improving antibacterial potency and reducing nephrotoxicity.

Can this reagent be used in Fmoc-SPPS as well as Boc-SPPS?

Boc-Dab(Z)-OH DCHA is specifically designed for Boc-strategy synthesis; the Boc group is incompatible as an alpha-amine protecting group in Fmoc-SPPS cycles, which use piperidine for Fmoc removal — conditions that are not harmful to Boc but the alpha-amine is never Fmoc here. For Fmoc-SPPS, the corresponding Fmoc-Dab(Boc)-OH or Fmoc-Dab(ivDde)-OH building blocks should be used instead.

References

1. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149–2154. doi:10.1021/ja00897a025
2. Bodanszky, M.; Bodanszky, A. The Practice of Peptide Synthesis, 2nd ed.; Springer: Berlin, 1994.
3. Velkov, T.; Thompson, P. E.; Nation, R. L.; Li, J. Structure-activity relationships of polymyxin antibiotics. J. Med. Chem. 2010, 53, 1898–1916. doi:10.1021/jm900999h
4. Aladdin Scientific. Product Information Sheet: Boc-Dab(Z)-OH DCHA, SKU B182001. Aladdin Scientific, Shanghai.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.