In chemistry, stories of molecular discovery often show how simple ideas have huge impacts. Trans-4-Phenyl-L-Proline stepped into the limelight as chemists searched for proline derivatives to help assemble complex peptides and pharmaceuticals. Early research focused on proline’s role in protein folding. Adding a phenyl ring at the 4-position was about seeing how side chains affect behavior, not about drug development, but it quickly found its place in medicinal chemistry toolkits. Labs first produced the compound in small batches for basic research, but as demand in peptide synthesis grew, chemical suppliers ramped up production and standardized manufacturing. Large companies published technical sheets about it before 2000, and soon patents appeared using Trans-4-Phenyl-L-Proline in drug synthesis. The molecule now serves as a workhorse for researchers and companies looking to design new drugs with improved biological properties.
Trans-4-Phenyl-L-Proline is an amino acid derivative that’s recognized by a unique twist in its structure: the four-membered proline ring gets a phenyl group stuck on at carbon four, defining the "trans" orientation. Off-white powder, sometimes crystalline, it dissolves easily in water and polar solvents. More rigid than plain proline, it resists flattening under stress, holding shapes that lock in special combinations during peptide formation. Chemical suppliers sell it in both small research vials and bulk drums for industrial use. The compound is available as a stable, shelf-friendly solid and ships under room temperature conditions. Labels usually list CAS number 3077-48-1, purity of 98% or higher, and sometimes even optical rotation values, since chirality defines the whole point of this molecule.
You can spot the physical traits of Trans-4-Phenyl-L-Proline pretty easily. The molecular weight comes in at 203.25 g/mol, and the melting range hovers around 203-206°C. Its chirality makes it optically active — rotate polarized light through a dissolved sample and you can see those degrees shift based on the L-isomeric purity. The rigid ring adopts a puckered conformation, adding to the stability of peptides built with this amino acid. Basic solubility works best in water and methanol, with some compatibility with DMSO for demanding synthetic reactions. Chemically, the compound resists hydrolysis under normal lab conditions but reacts neatly with activators during peptide coupling. Since phenyl groups are hydrophobic, this molecule slightly boosts nonpolar character when part of a peptide chain.
Chemists working with Trans-4-Phenyl-L-Proline pay attention to manufacturer data sheets, focusing on several technical details. Purity usually exceeds 98%, often determined by HPLC or NMR. Moisture content is kept under 0.5% by weight, and labels mention the specific optical rotation, an important factor for chiral purity. The major supplier codes and product catalog numbers keep reappearing in the literature, making it easy to trace and compare batches. Labels include recommended storage conditions – typically room temperature in a tightly sealed container, away from sources of moisture. The molecular formula C11H13NO2 and InChI key also pop up for database searches. Compliance with international standards like ISO or REACH forms a point of trust for buyers handling sensitive medical research.
Most commercial production runs start from L-proline itself, using a stepwise synthesis to tack on the needed phenyl group at the fourth position. One common route uses palladium-catalyzed coupling reactions, where the proline ring gets functionalized and the phenyl ring attaches via an arylation. Protecting groups shield the amino and carboxylic acid sites, stopping unwanted reactions at those spots. Deprotection steps at the end bring the molecule to its final form. Reaction conditions must be just right — temperature, solvent, catalyst loading all get carefully tuned to prevent racemization and maximize yield. Labs usually perform purification by recrystallization, then check purity on HPLC before distribution. Larger production lines might favor continuous or flow-based synthesis for better control and consistency across big orders.
Trans-4-Phenyl-L-Proline heads straight into peptide coupling reactions, often reacting with carboxylic acid-activating agents like DCC (dicyclohexylcarbodiimide) or EDC (ethyl(dimethylaminopropyl) carbodiimide). The rigid backbone and bulky side chain steer peptide folding and introduce new turns or breaks in the finished polymer. On the bench, you can run standard protection/deprotection schemes from peptide chemistry on both the amine and carboxyl groups. That means Fmoc or Boc strategies fit, so it’s compatible with automated peptide synthesizers. Reduced forms of the amino acid (making the phenyl group a cyclohexyl, for example) and additional substitutions let chemists create libraries of derivatives. Its phenyl ring invites aromatic substitutions or cross-coupling for further molecular modifications, expanding the playground for drug design.
Researchers, catalogues, and suppliers tag this substance with a slew of names: (2S,4S)-4-Phenylpyrrolidine-2-carboxylic acid, Trans-4-Phenyl-L-proline, and the short code 4-Ph-L-Pro. Sometimes you’ll see the short-hand "trans-PP," and the compound’s presence in pharmaceutical intermediates leads to further alphanumeric cataloging, especially in inventory management. Brands in the chemical supply world give it their own stock numbers, and some academic papers use abbreviations based on the three-letter amino acid code system — although "Phe-Pro" might mislead, so accuracy means checking the full IUPAC naming on chemical registries.
Handling Trans-4-Phenyl-L-Proline in the lab never gets taken lightly. Users check the SDS (Safety Data Sheet) before scooping out even a milligram, since good lab practice demands clear information about risks. It’s classified as relatively safe among amino acid derivatives, though like most powders, it poses an inhalation risk if not handled with proper ventilation or a mask. Skin or eye contact may cause mild irritation, and gloves remain standard to avoid repeated exposure. Material safety protocols require storing away from acids and bases that could degrade the aromatic or proline rings. Disposing of unused material goes by local chemical waste guidelines, and bulk handlers use fume hoods and eye protection as a matter of routine. For pharmaceutical use, GMP (Good Manufacturing Practice) certification comes into play, making sure every step from raw material to final batch meets health and safety laws.
In peptide science, Trans-4-Phenyl-L-Proline serves as a specialty tool for building in structure and hydrophobicity where regular proline falls short. Researchers use it to modify sequences in synthetic peptides, trying to improve drug properties like metabolic stability or specific receptor binding. The increased ring rigidity can slow down degradation by proteases — helpful for peptides aiming for a longer lifespan in the human body. Drug hunters testing new small molecules sometimes plug Trans-4-Phenyl-L-Proline into lead structure optimization, searching for that perfect balance between absorption and selectivity.
Academic labs also pick this compound for biomimetic chemistry, trying to copy or tweak natural proteins for new materials or biocatalysts. In recent years, it cropped up in the chemical biology field, where the altered backbone gets used to force peptides into unusual folds, helping map out protein interactions with new precision.
Active research keeps finding new roles for Trans-4-Phenyl-L-Proline in both the therapeutic and biotechnological worlds. Analytical studies measure how its presence warps peptide backbone geometry, offering a route to more resistant or targeted biopharmaceuticals. Some teams look at immune-active peptides, injecting this amino acid to see how folding changes antigen recognition. Other groups engineer enzymes using modified prolines like the trans-4-phenyl variant, aiming to tweak catalytic power for green chemistry purposes. On the technical front, improvements in asymmetric synthesis of this compound lower cost and boost access for labs without industrial-sized budgets. Newer work also considers “green chemistry” production, testing catalysts and solvents that avoid hazardous byproducts and cut down on waste.
So far, toxicity studies suggest Trans-4-Phenyl-L-Proline remains safer than many of the highly reactive amino acid derivatives crowding synthetic chemistry. Oral and dermal exposure in animals points to low toxicity, but data on chronic or high-dose exposure still falls short of what’s needed for regulatory comfort. Studies check for mutagenicity and reproductive toxicity to keep pharmaceutical development on the right side of safety standards. Every batch used in regulated drug production goes through purity and contaminant screening, keeping unexpected side products out of the supply chain. As more of this compound moves toward clinical use, both company and independent research teams will need to dig deeper on long-term impacts and metabolic fate in humans, especially if it enters the bloodstream as part of new drugs.
Trans-4-Phenyl-L-Proline will see heavier use as peptide therapeutics carve out a bigger space in medicine. Drug designers hunt for building blocks offering just enough steric bulk to tilt activity without breaking compatibility with established synthesis methods. As companies push into personalized and precision medicine, demand for boutique amino acids like this will increase. Improvements in catalytic arylation and biocatalyst-driven synthesis promise lower costs, cleaner production, and faster path to market. Researchers already tap into the molecule’s backbone-rigidifying power for molecular probes, enzyme inhibitors, and even next-generation biomaterials. Ongoing collaboration between academic chemists and industrial manufacturers can speed up safety testing, standardization, and access — cornerstones for scaling lab curiosity into real-world solutions.
