Cbz-trans-3-hydroxy-L-proline is the N-benzyloxycarbonyl (Cbz) protected form of trans-3-hydroxy-L-proline, used as a chiral building block and intermediate in macrocyclic peptide synthesis. Hzymes supplies it with a COA reporting chiral purity (ee above 99%) and residual palladium.

Cbz-trans-3-hydroxy-L-proline carries a benzyloxycarbonyl group on the ring nitrogen of trans-3-hydroxy-L-proline. The Cbz group is stable to the TFA and piperidine conditions used to remove Boc and Fmoc groups and is typically removed by catalytic hydrogenolysis, which makes it a practical choice when orthogonal protection is needed. Hzymes lists this compound at purity above 99.5% in its Enlicitide (MK-0616) building-block series, and its COA includes chiral purity (ee above 99%) and residual palladium.

Product Overview

This N-protected derivative of trans-3-hydroxy-L-proline is intended as an intermediate for peptide and macrocycle synthesis, where the ring nitrogen must be masked during coupling steps.

Because palladium chemistry is widely used with Cbz-protected compounds and residual metal limits matter for pharmaceutical intermediates, Hzymes reports residual Pd on the COA alongside chiral purity.

Key Features

Cbz-Protected Hydroxyproline Building Block

The Cbz group effectively protects the amino functionality while leaving the side-chain hydroxyl group available for further functionalization. This makes the product a useful solid phase peptide synthesis building block for incorporating hydroxyproline structures into peptide sequences.

Orthogonal Protection Strategy

The combination of Cbz-protected amino functionality and a free hydroxyl group provide flexibility in multi-step synthesis. It can be incorporated into synthetic routes requiring Cbz/Fmoc orthogonal protection, depending on the overall protecting-group strategy and reaction conditions.

Practical Cbz Deprotection

The Cbz group can be removed by Pd catalyzed Cbz removal, most commonly through catalytic hydrogenation using Pd/C. Acidic systems such as HBr/AcOH can also be considered depending on the requirements of the synthetic route.

This provides a practical hydrogenolysis deprotection Cbz option for downstream synthesis.

Favorable Crystallinity and Purification

Compared with the corresponding unprotected amino acid, the protected derivative offers favorable crystallization and handling characteristics, facilitating isolation and purification during synthetic workflows.

Consistent Quality for Research and Development

Controlled manufacturing and purification processes support reliable quality and batch-to-batch consistency, making the product suitable for peptide research, pharmaceutical intermediate development, and other demanding synthetic applications.

Applications

Solid-Phase Peptide Synthesis

Cbz-trans-3-hydroxy-L-proline can be used as a solid phase peptide synthesis building block for introducing a trans-3-hydroxyproline motif into peptide sequences.

Its protected amino group and free hydroxyl functionality can provide additional flexibility when designing selective coupling and deprotection sequences.

Note: Cbz-trans-3-hydroxy-L-proline is a Cbz-protected amino acid and should not be considered equivalent to an Fmoc-protected amino acid. Compatibility with a specific SPPS strategy should be evaluated based on the selected protecting-group system.

Solution-Phase Peptide Synthesis

The product is also applicable to solution phase peptide synthesis Cbz strategies, particularly where Cbz protection is preferred for controlling amino-group reactivity during fragment synthesis and coupling.

Natural Product and Antibiotic Synthesis

Cbz-trans-3-hydroxy-L-proline can serve as a synthetic building block for hydroxy-L-proline-containing natural products, antibiotics, and their analogues, especially in routes requiring selective protection of the amino group.

Pharmaceutical and Peptide Intermediate Synthesis

The product can be incorporated into the synthesis of structurally complex pharmaceutical intermediates and peptide-based molecules where controlled amino-group protection and downstream deprotection are important.

Functional Peptide Materials

Hydroxyproline-containing structures can contribute to specific conformational and self-assembly properties. Cbz-trans-3-hydroxy-L-proline may therefore be used as an intermediate for developing functional peptide materials and related biomolecular structures.

•     Cbz removal: catalytic hydrogenolysis (H₂, Pd/C) or strong acid such as HBr in acetic acid.

•     Stable to TFA (Boc removal) and piperidine (Fmoc removal) conditions.

•     Check solubility data in the COA package before choosing a reaction solvent.

Customer Case

University Organic Synthesis Laboratory — Total Synthesis of a Marine Alkaloid

A university organic synthesis laboratory encountered significant polymerization and purification problems when using the corresponding unprotected amino acid in the total synthesis of a marine alkaloid.

After switching to Cbz-trans-3-hydroxy-L-proline, the team improved the coupling reaction yield from 60% to 85%. The improved reaction performance also reduced purification time by approximately two weeks, enabling successful gram-scale preparation of the target natural product.

The case demonstrates how an appropriately Cbz protected amino acid can help improve reaction control and purification efficiency in challenging multi-step synthesis.

FAQ

What is Cbz-trans-3-hydroxy-L-proline?

It is trans-3-hydroxy-L-proline with a benzyloxycarbonyl (Cbz) protecting group on the ring nitrogen, used as a chiral building block and intermediate in peptide and macrocycle synthesis.

How is the Cbz group removed?

Typically by catalytic hydrogenolysis (H2 with Pd/C) or by strong acid such as HBr in acetic acid. It is stable to the TFA and piperidine conditions used to remove Boc and Fmoc groups, which is why it is useful when orthogonal protection is needed.

Why does the COA report residual palladium?

Palladium catalysts are widely used in Cbz chemistry, for example in hydrogenolysis, and residual metal limits matter for pharmaceutical intermediates. Hzymes reports residual Pd on the COA.

What chiral purity does the product have?

The COA reports chiral purity, with enantiomeric excess above 99%.

Should I choose the Cbz or the Boc derivative?

Choose by deprotection strategy. Use the Cbz form when hydrogenolysis or orthogonal protection is needed, and the Boc form when acid-labile removal (TFA or HCl) fits your route. Both derive from trans-3-hydroxy-L-proline.