1-(Cbz-amino)cyclohexanecarboxylic Acid: Properties & Uses

1-(Cbz-amino)cyclohexanecarboxylic acid is a Cbz (benzyloxycarbonyl)-protected quaternary alpha-amino acid building block widely used in peptide synthesis and medicinal chemistry research.

CAS Number

132622-69-6 (needs verification)

SKU

C182055

Molecular Formula

C₁₅H₁₉NO₄

Molecular Weight

281.32 g/mol (needs verification)

Protecting Group

Cbz (benzyloxycarbonyl) on the amine nitrogen

Core Structure

Quaternary carbon alpha-amino acid with cyclohexane ring

Recommended Storage

Cool, dry conditions away from light (needs verification)

Chemical Structure and Key Properties

1-(Cbz-amino)cyclohexanecarboxylic acid belongs to the class of N-protected quaternary alpha-amino acids. Its defining structural feature is a cyclohexane ring bearing both an amino group and a carboxylic acid at the same (C-1) carbon, creating a fully substituted, achiral quaternary carbon center. The amino group is protected with a benzyloxycarbonyl (Cbz or Z) group, one of the most commonly employed and versatile amine-protecting groups in synthetic chemistry.

The Cbz group confers stability under basic and mild acidic conditions while remaining readily removable by hydrogenolysis (H₂, Pd/C) or strong acids such as HBr/AcOH. This orthogonal deprotection profile makes it highly compatible with Fmoc and Boc solid-phase peptide synthesis (SPPS) strategies.

The quaternary carbon architecture of this compound eliminates the conventional chiral center found in most natural alpha-amino acids, simplifying stereochemical considerations in synthesis while simultaneously imposing significant conformational restriction on any peptide chain into which it is incorporated.

Applications in Peptide Synthesis and Medicinal Chemistry

The primary application of 1-(Cbz-amino)cyclohexanecarboxylic acid is as a building block in the synthesis of peptidomimetics and constrained peptide analogs. Quaternary alpha-amino acids derived from alicyclic scaffolds such as cyclohexane are well-established tools for inducing conformational rigidity in peptide backbones, which can enhance proteolytic stability, receptor selectivity, and oral bioavailability of peptide-based drug candidates.

In medicinal chemistry, incorporating a 1-aminocyclohexane-1-carboxylic acid (Acc) residue — with or without N-protection — into a peptide sequence is a recognized strategy to enforce specific secondary structures such as helices or beta-turns, depending on the ring size and substitution pattern. The Cbz-protected form is specifically suited for use in solution-phase and solid-phase synthesis as an intermediate that can be deprotected at the appropriate stage of assembly.

The compound may also serve as a synthetic intermediate in the preparation of pharmacologically relevant spirocyclic or bridged heterocyclic frameworks, and as a starting material for the synthesis of Cbz-protected analogs of 1-aminocyclohexane-1-carboxylic acid derivatives used in structure-activity relationship (SAR) studies.

Handling, Storage, and Safety Considerations

As with most N-protected amino acid derivatives, 1-(Cbz-amino)cyclohexanecarboxylic acid should be handled following standard laboratory safety practices for organic reagents. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for specific hazard classifications, GHS pictograms, and first-aid measures before use.

The compound should be stored under cool, dry conditions, protected from moisture and direct light, to maintain long-term stability of both the carboxylic acid functionality and the Cbz protecting group. Proper sealing of the container after each use is recommended to prevent hygroscopic degradation.

When performing Cbz deprotection via catalytic hydrogenolysis, standard precautions for working with flammable hydrogen gas and pyrophoric palladium catalysts must be strictly observed. All waste containing palladium catalyst should be disposed of according to institutional and local regulatory requirements.

Ordering and Product Specifications

1-(Cbz-amino)cyclohexanecarboxylic acid is available from Aladdin Scientific under SKU C182055. Researchers requiring purity certificates (CoA), spectral data (NMR, HPLC), or bulk quantities are encouraged to contact Aladdin Scientific's technical support or sales team directly through the product page.

When placing an order, verify that the required quantity, purity grade, and packaging format meet your experimental requirements. For applications demanding the highest analytical rigor — such as reference standard preparation or GMP-adjacent research — please request the relevant batch-specific analytical documentation prior to purchase.

Frequently asked questions

What is the purpose of the Cbz protecting group in this compound?

The Cbz (benzyloxycarbonyl) group protects the amine nitrogen from unwanted side reactions during multi-step synthesis. It can be cleanly removed by catalytic hydrogenolysis (H₂, Pd/C) or treatment with strong acids such as HBr in acetic acid, revealing the free amine for subsequent coupling or functionalization steps.

Is 1-(Cbz-amino)cyclohexanecarboxylic acid chiral?

No. Because the C-1 carbon of the cyclohexane ring bears two identical ring carbons (C-2 and C-6 of the ring) in addition to the amino and carboxyl substituents, the alpha-carbon is a quaternary center that is achiral. This simplifies synthesis by eliminating the need for asymmetric methods or chiral resolution.

How can this compound be incorporated into solid-phase peptide synthesis (SPPS)?

The free carboxylic acid group can be activated using standard coupling reagents (e.g., HATU, DIC/HOBt) and coupled to the free amine of a resin-bound peptide. The Cbz group on the amine can be retained as a permanent N-terminal protecting group or removed selectively by hydrogenolysis after synthesis is complete, depending on the overall protecting group strategy employed.

What solvents are typically used to dissolve N-protected amino acids like this compound?

N-protected amino acids of this type are generally soluble in polar aprotic solvents such as DMF, DMSO, and dichloromethane (DCM), as well as in ethyl acetate and methanol. Solubility in water is typically low due to the lipophilic Cbz group. Researchers should verify solubility experimentally for their specific conditions.

References

1. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2007.
2. Toniolo, C.; Crisma, M.; Formaggio, F.; Peggion, C. Control of peptide conformation by the Thorpe-Ingold effect (Cα-tetrasubstitution). Biopolymers (Peptide Science) 2001, 60, 396–419.
3. Aladdin Scientific Product Page: 1-(Cbz-amino)cyclohexanecarboxylic acid, SKU C182055.

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