(2R,4S)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid
[CAS 1012341-50-2]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Cyclic carboxylic acid
• Name: (2R,4S)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid
• Molecular Formula: C₂₃H₂₉NO₄
• Molecular Weight: 383.48
• CAS Registry Number: 1012341-50-2
• EC Number: 695-674-1
• SMILES: C[C@H](C[C@@H](CC1=CC=C(C=C1)C2=CC=CC=C2)NC(=O)OC(C)(C)C)C(=O)O

Properties

• Solubility: Insoluble (3.1E^-3 g/L) (25 °C), Calc.^*
• Density: 1.115±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Boiling point: 582.6±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 306.2±30.1 °C (Calc.)^*
• Index of refraction: 1.546 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335-H413
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413

Discovery and Applications

(2R,4S)-5-(Biphenyl-4-yl)-4-[(tert-butoxycarbonyl)amino]-2-methylpentanoic acid is a stereochemically defined amino acid derivative containing a protected amine group, a carboxylic acid functionality, and a hydrophobic biphenyl substituent. The structure is based on a substituted pentanoic acid backbone with multiple functional modifications that introduce both rigidity and pronounced amphiphilic character.

The central framework of the molecule is a five-carbon aliphatic chain terminating in a carboxylic acid group. Carboxylic acids contain a carbonyl group directly bonded to a hydroxyl group, forming a strongly polar and acidic functional group capable of hydrogen bonding and ionization depending on pH. This group represents one of the primary polar sites in the molecule and significantly influences its physicochemical behavior in aqueous environments.

At the 4-position of the pentanoic backbone is a tert-butoxycarbonyl-protected amino group. The tert-butoxycarbonyl (Boc) group is a widely used protecting group in organic synthesis for amines. It consists of a carbamate linkage in which the nitrogen is attached to a carbonyl group that is further connected to a tert-butyl substituent. The carbamate carbonyl is stabilized by resonance with the nitrogen atom, giving the functional group partial double-bond character and reducing the basicity of the nitrogen.

The tert-butyl portion of the Boc group introduces significant steric bulk and hydrophobicity. This bulky substituent increases the spatial shielding around the nitrogen, making the protected amine less reactive under many conditions. Boc groups are typically stable under neutral and basic conditions but can be cleaved under acidic conditions, regenerating the free amine.

At the 2-position of the pentanoic acid backbone is a methyl substituent, which introduces a stereogenic center and increases steric complexity. At the 4-position, where the Boc-protected amine is located, another stereogenic center is present. The (2R,4S) configuration specifies the absolute three-dimensional arrangement of these substituents, which determines the overall shape of the molecule and influences how functional groups are oriented in space.

At the 5-position of the carbon chain, the molecule bears a biphenyl-4-yl substituent. Biphenyl consists of two connected benzene rings, forming an extended aromatic system with significant hydrophobic character and π-electron density. The 4-substitution pattern indicates that the attachment occurs at the para position of one phenyl ring. The biphenyl group introduces a large hydrophobic surface area and contributes strongly to aromatic stacking interactions in molecular environments.

From a conformational perspective, the biphenyl moiety can exhibit restricted rotation around the inter-ring single bond due to steric hindrance between ortho hydrogen atoms, although it is not fully rigid. The aliphatic backbone of the molecule retains some flexibility, but the presence of stereocenters constrains its overall three-dimensional arrangement.

Physicochemically, the molecule contains both strongly polar and strongly nonpolar regions. The carboxylic acid group provides high polarity and potential for ionic formation, while the Boc-protected amine contributes moderate polarity and hydrogen-bonding capability through its carbonyl oxygen. In contrast, the biphenyl substituent is highly hydrophobic and dominates the nonpolar character of the molecule. This combination yields a strongly amphiphilic compound with distinct polar and aromatic domains.

Chemically, the carboxylic acid is the most reactive functional group under typical conditions, capable of forming salts, esters, and amide derivatives. The Boc protecting group is stable under non-acidic conditions but can be selectively removed under acidic treatment. The aromatic biphenyl system is generally chemically stable but can undergo electrophilic substitution under appropriate conditions.

Without specific literature confirming biological or functional roles for this exact compound, no application claims can be made. Based solely on structural characteristics, it is best described as a stereochemically defined amino acid derivative featuring a protected amine, a biphenyl hydrophobic substituent, and a carboxylic acid group arranged on a constrained pentanoic acid backbone, resulting in a structurally diverse amphiphilic molecule.

References

2016. Diastereoselective Synthesis of an Industrially Relevant 4-Aminopentanoic Acid by Asymmetric Catalytic Hydrogenation in a Biphasic­ System Using Aqueous Sodium Hydroxide as Substrate Phase. Synthesis.
DOI: 10.1055/s-0036-1588910

2016. Sacubitril. Pharmaceutical Substances.