Fmoc-dab(boc)-oh

• CAS: 125238-99-5
• Catalog Number: ACM125238995
• Category: Main Products
• Molecular Weight: 440.49
• Molecular Formula: C₂₄H₂₈N₂O₆
• Synonyms: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid; (S)-4-(Boc-amino)-2-(Fmoc-amino)butyric acid; (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-4-((tert-butoxycarbonyl)amino)butanoic acid; Fmoc-Dab(Boc)-OH
• IUPAC Name: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoicacid
• SMILES: CC(C)(C)OC(=O)NCCC(C(=O)O)NC(=O)OCC1C2=CC=CC=C2C3=CC=CC=C13
• InChI Key: LIWKOFAHRLBNMG-FQEVSTJZSA-N
• Boiling Point: 670.9ºC at 760 mmHg
• Flash Point: 359.6ºC
• Density: 1.243g/cm³
• Appearance: white powder
• Exact Mass: 440.19500
• Hazard Statements: Xi
• WGK Germany: 3

Case Study

Fmoc-Dab(Boc)-OH Used in the Synthesis of Polymyxin Mimetic Peptide

Su, Ma, et al. Chemical Communications, 2019, 55(87), 13104-13107.

This work designed several polymyxin derivatives as broad-spectrum antibiotics. Among them, the lead compound P1 can quickly destroy bacterial membranes without developing drug resistance and inhibit the biofilm formed by Escherichia coli. Fmoc-Dab(Boc)-OH can be used in the synthesis process of the polymyxin mimetic peptide lead compound P1.
Synthesis of polymyxin mimic peptide
· Initially, the CTC resin was reacted with Fmoc-Thr(tBu)-OH and DIPEA in DCM solution followed by washing and capping in methanol. The attachment of Fmoc-Dab(Boc)-OH to the resin was achieved by adding Fmoc-Dab(Boc)-OH, DIC, and HOBt in DMF solution, followed by washing.
· Subsequently, the Fmoc protection group was removed using piperidine/DMF solution, and Fmoc-Dab(Boc)-OH was added again. This process was repeated with Fmoc-L-leucine until the desired building blocks were attached.
· After removal of the Fmoc group, palmitic acid was added, followed by removal of the alloc protein group using Pd(PPh3)4 and Me2NH.BH3. The compound was then cleaved using a cocktail of TFE, acetic acid, and DCM. Cyclization was achieved by adding HOBt, TBTU, and DMAP in DCM solvent overnight.
· Finally, the remaining protecting groups were removed using a cocktail of TFA and DCM, and the resulting solution was collected, purified using HPLC, and lyophilized to obtain the pure product compound P1.

Application of Fmoc-Dab(Boc)-OH in the Solid-Phase Synthesis of Polymyxins

Xu, Wei-Liang, et al. Tetrahedron letters, 2015, 56(33), 4796-4799.

A new strategy for the solid-phase synthesis of polymyxins and their analogs that is more convenient and more effective has been developed. The method is to first anchor the amine side chain of Dab9 to the resin and then cyclize it on the resin. Among them, Fmoc-Dab(Boc)-OH is used in the key step of synthesizing moc-Dab(Boc)-OAll.
Synthesis procedure of polymyxin E2
· The Fmoc-Dab(Boc)-OH was reacted with allyl bromide using tricaprylmethylammonium chloride and NaHCO3 to produce Fmoc-Dab(Boc)-OAll, which was then converted to Fmoc-Dab-OAll with a high yield of 81% after removing the Boc group using trifluoroacetic acid (TFA).
· The Fmoc-Dab-OAll was attached to 2CTC resin with N,N-diisopropylethylamine (DIEA) to create compound 1. Next, a linear fully protected peptide 2 was synthesized through solid-phase peptide synthesis (SPPS), using 20% piperidine in DMF for Fmoc deprotection and 1-[Bis(dimethylamino)methylen]-5-chlorobenzotriazolium 3-oxide hexafluorophosphate (HCTU)/DIEA in DMF for coupling.
· After removing the N-(1-(4,4-dimethyl-2,6-dioxocylohexylidene) ethyl (Dde) group with 3% NH2NH2 in DMF, Fmoc-Thr(tBu)-OH was added to the side chain of Dab4 to produce compound 4. The allyl group on Dab9 was then eliminated with Pd(PPh3)4/PhSiH3, followed by Fmoc removal on Thr10.
· The cyclization between Thr10 and Dab9 was achieved using PyAOP with N-methyl morpholine (NMM) and 1-hydroxy-7-azabenzotriazole (HOAt). Finally, the cyclic peptide was released from the 2CTC resin using a cleavage cocktail (TFA/H2O/triisopropylsilane (TIPS) in a ratio of 95/2.5/2.5).

Orthogonal Protecting, Peptidomimetic Scaffolding and Oligosaccharyl Transferase Inhibitory Properties of Fmoc-Dab(Boc)-OH

eerapana E, Imperiali B. Organic & Biomolecular Chemistry, 2003, 1(1): 93-99.

The synthetic reactivity and glycobiological functional properties of Fmoc-Dab(Boc)-OH (orthogonally protected 2,4-diaminobutanoic acid monomer) were studied via solid-phase peptide synthesis workflows and yeast/mammalian microsome oligosaccharyl transferase (OT) enzyme inhibition assays. Fmoc terminal amine protecting group and Boc side-chain amine protecting group form dual orthogonal masking fragments, with the Dab 1,4-diamino aliphatic carbon skeleton as the core structural unit for constructing competitive OT inhibitory peptidomimetic backbones.
Fmoc-Dab(Boc)-OH exhibited prominent orthogonal dual amine protection performance for modular solid-phase assembly: Under standard Fmoc SPPS deprotection (20% piperidine/DMF), only the N-terminal Fmoc carbamate group underwent quantitative cleavage, while the side-chain Boc moiety remained fully intact without premature deprotection; concentrated trifluoroacetic acid (95% TFA) final cleavage selectively removed Boc groups to expose free Dab side-chain primary amines, realizing independent control of two distinct amine sites during multi-step inhibitor chain elongation. It demonstrated critical peptidomimetic scaffold-building capacity as the core consensus residue for OT inhibitor lead synthesis: When incorporated into the parent hexapeptide sequence Bz-Dab-Ala-Thr-Val-Thr-Nph-NH₂, the Dab fragment replaced native asparagine's amide side chain to form a potent competitive OT inhibitor with a yeast microsome Kᵢ value of 69 nM, far exceeding weak inhibitory activity of simple Asn-based tripeptide substrates (Kₘ = 20 μM). Additionally, Fmoc-Dab(Boc)-OH supported advanced conformation-locked cyclized inhibitor construction via selective side-chain modification: Orthogonal Alloc side-chain protection exchange from Boc enabled selective installation of nitrobenzyl aromatic substituents on Dab's amine terminus, while cysteine cross-linking with alkyl bromide linkers constructed macrocyclic Asx-turn constrained peptidomimetics (cyclic inhibitor 11, Kᵢ = 130 nM) with enhanced membrane permeability and proteolytic resistance compared to linear peptide analogs. HPLC and mass spectrometry characterization of synthetic intermediates confirmed no side-chain premature deprotection or intramolecular cyclization side reactions during sequential coupling of threonine, norvaline and aminobenzoic acid isostere residues using HATU/PyBOP coupling reagents. These studies demonstrate that Fmoc-Dab(Boc)-OH possesses significant orthogonal amine protection, peptidomimetic backbone scaffolding and target oligosaccharyl transferase inhibitory structural properties for rational glycobiology inhibitor design.
The comprehensive synthetic and enzymatic evaluation experiment adopted uniform Fmoc-based solid-phase peptide synthesis (SPPS) platforms, divided into four core test groups: unprotected free Dab control group, single Fmoc-protected Dab group, single Boc-protected Dab group, and dual orthogonally protected Fmoc-Dab(Boc)-OH experimental group. Parallel testing modules included orthogonal deprotection stability assays (piperidine Fmoc removal, TFA Boc cleavage), solid-phase chain elongation intermediate HPLC-MS identification, linear OT inhibitor synthesis and yeast/mammalian liver microsome competitive inhibition Kᵢ quantification. For deprotection stability testing, each protected Dab derivative was separately incubated in piperidine deprotection solution (20 min) and concentrated TFA cleavage cocktail (2 h); crude products were purified by C18 preparative HPLC and characterized via electrospray mass spectrometry to quantify deprotection selectivity. For inhibitor construction testing, Fmoc-Dab(Boc)-OH was sequentially coupled with Fmoc-Thr(t-Bu)-OH, Fmoc-Ala/Nva-OH and Alloc-protected aminobenzoic acid dipeptide isosteres on PAL-PEG or aldehyde-functionalized FMPE resins; after full chain assembly, orthogonal deprotection and side-chain reductive amination/cyclization modifications were executed to generate linear and cyclic peptidomimetics. Radiolabeled OT enzymatic assays with [³H]-dolichol pyrophosphate substrate were performed to calculate competitive inhibition constants Kᵢ for all Dab-containing inhibitors, with data averaged from duplicate incubation replicates and processed via one-way ANOVA at p<0.05 significance threshold. The results verified that Fmoc-Dab(Boc)-OH's dual orthogonal protecting groups enable precise, stepwise manipulation of Dab's two amine sites, providing an essential modular building block for assembling nanomolar-potency, cell-permeable oligosaccharyl transferase peptidomimetic inhibitors.

Orthogonal Dual-Protecting, Peptide Scaffolding and Polymyxin Synthetic Properties of Fmoc-Dab(Boc)-OH

Yamada K, Urakawa H, Oku H, et al.Journal of Peptide Research, 2004, 64: 43-50.

The synthetic structural and peptide-building characteristics of Fmoc-Dab(Boc)-OH (orthogonally protected L-α,γ-diaminobutyric acid monomer) were studied via aqueous Hofmann rearrangement synthesis workflows and solution-phase polymyxin B heptapeptide (PMBH) total synthesis assays. Fmoc Nα-terminal protecting group and Boc γ-side chain protecting group form orthogonal masking fragments, while the linear 4-carbon Dab aliphatic skeleton acts as the core structural unit for constructing polymyxin-class antimicrobial peptide backbones.
Fmoc-Dab(Boc)-OH exhibited unique orthogonal amine protection stability: Comparative solvent compatibility tests showed precursor Fmoc-Gln-OH cannot undergo PSDIB-mediated aqueous Hofmann rearrangement due to complete insolubility in water, whereas Z-Gln-OH and Boc-Gln-OH afforded single-protected Dab intermediates in 83% and 87% yields respectively; two-step derivatization from Z-Dab-OH produced target Fmoc-Dab(Boc)-OH with a total isolated yield of 54%, with no cross-deprotection observed during sequential Fmoc installation and Z-group hydrogenolysis. It demonstrated superior peptide assembly capacity as a key building block for polymyxin derivatives: In stepwise solution-phase PMBH synthesis, Fmoc-Dab(Boc)-OH enabled controlled side-chain amine manipulation, where Boc groups remained intact during Fmoc removal under mild alkaline conditions, and selective γ-NH₂ exposure after TFA deprotection supported intramolecular cyclization of linear peptide precursors. After cyclization via HATU coupling under diluted DMF conditions, fully protected PMBH intermediate was obtained in 89% cyclization yield, and global deprotection delivered pure PMBH with HPLC retention time fixed at 5.43 min, matching standard peptide chromatographic profiles. Additionally, Fmoc-Dab(Boc)-OH avoided toxic iodobenzene by-product generation compared to traditional soluble PIDA/PIFA hypervalent iodine reagents; polymer-supported PSDIB reagent used in upstream Dab precursor synthesis was recyclable, retaining 85% conversion efficiency after regeneration with peracetic acid, significantly lowering synthetic waste and side lactam impurity formation. ESI-MS, optical rotation and HPLC characterization confirmed Fmoc-Dab(Boc)-OH maintained L-amino acid stereochemical purity without racemization throughout multi-step derivatization and peptide elongation procedures. These studies demonstrate that Fmoc-Dab(Boc)-OH possesses significant orthogonal dual amine protecting, polymyxin peptide scaffolding and eco-friendly synthetic precursor properties for constructing lipopolysaccharide-targeting antimicrobial oligopeptides.
The comprehensive synthetic evaluation experiment was split into two parallel testing modules: PSDIB-mediated Dab precursor synthesis and PMBH peptide total synthesis, divided into five comparative groups: unmodified L-Gln raw material group, single Boc-protected Boc-Dab-OH group, single Z-protected Z-Dab-OH group, soluble PIDA reagent control group, and Fmoc-Dab(Boc)-OH experimental monomer group. For Hofmann rearrangement testing, uniform 1 mmol amino acid substrate dosage and 3.0 g PSDIB polymer reagent were applied, with solvent gradients of pure water, DMF-water mixed solvent and organic ester solvent systems screened, reaction completion tracked via silica thin-layer chromatography and crude products purified by ether recrystallization. For peptide synthesis validation, Fmoc-Dab(Boc)-OH was sequentially coupled with Fmoc-Thr, Fmoc-Leu and D-Phe residues using EDC/HATU condensation reagents; linear protected heptapeptide was cyclized at low peptide concentration to suppress intermolecular cross-linking, then full deprotection with TFMSA-TFA cocktail and Sephadex LH-20 gel filtration purification were carried out. Final PMBH purity was quantified by reversed-phase HPLC (ODS column, 65% aqueous methanol mobile phase, UV 210 nm detection), all synthetic yields, optical rotation values and MS mass spectra recorded in three parallel experimental replicates, data processed via one-way ANOVA at p<0.05 significance threshold. The results verified that Fmoc-Dab(Boc)-OH's orthogonal Fmoc/Boc dual protection system enables precise independent manipulation of α and γ amino groups of Dab residues, serving as an indispensable modular monomer for scalable, high-purity synthesis of polymyxin heptapeptide and related outer-membrane permeabilizing peptide analogs.

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Custom Q&A

What is the molecular formula of fmoc-dab(boc)-oh?

The molecular formula of fmoc-dab(boc)-oh is C24H28N2O6.

What is the molecular weight of fmoc-dab(boc)-oh?

The molecular weight of fmoc-dab(boc)-oh is 440.5 g/mol.

What are the physical and chemical properties of fmoc-dab(boc)-oh?

Fmoc-dab(boc)-oh is a white or light yellow crystalline solid.

What is the melting point of fmoc-dab(boc)-oh?

The melting point of fmoc-dab(boc)-oh is about 54-56℃.

What is the boiling point of fmoc-dab(boc)-oh?

The boiling point of fmoc-dab(boc)-oh is about 287.8℃.

How is fmoc-dab(boc)-oh extracted or synthesized from natural sources?

Fmoc-dab(boc)-oh is not a naturally occurring compound, it needs to be synthesized by chemical or biological methods.

What is the main application field of fmoc-dab(boc)-oh?

Fmoc-dab(boc)-oh is mainly used as a building block for peptide synthesis, which can be used to synthesize peptides or protein containing L-2,4- diaminobutyric acid residues.

What is security of fmoc-dab(boc)-oh?

Fmoc-dab(boc)-oh is irritating and corrosive, which may cause irritation or damage to skin, eyes, respiratory tract or digestive tract.

What are the precautions of fmoc-dab(boc)-oh?

Wear appropriate protective equipment when using or handling fmoc-dab(boc)-oh, and avoid direct contact or swallowing.

What are the storage conditions of fmoc-dab(boc)-oh?

Fmoc-dab(boc)-oh needs to be stored in a cool and dry place, away from light sources, heat sources and fire sources, and avoid contact with strong oxidants, strong acids, strong bases and other substances.