Question

Cysteine is the only amino acid that has \(\mathrm{L}\) stereochemistry but an \(R\) configuration. Make up a structure for another \(L\) amino acid of your own creation that also has an \(R\) configuration.

Short answer

Design an amino acid with a high-priority side chain, such as sulfur, for R configuration, while maintaining L-stereochemistry by placing the amino group on the left.

Step-by-step solution

Understand Amino Acid Stereochemistry

Amino acids have a general formula involving a central carbon (the alpha-carbon) linked to an amino group, a carboxyl group, a hydrogen atom, and a distinctive side chain (R group). The configuration around this central carbon determines its stereochemistry.

Recall L and R Definitions

In amino acids, the Fischer projection places the carboxyl group at the top, the amino group to the left for L-configuration, and the hydrogen to the right. Compounds with L-configuration are usually S (except certain cases like cysteine due to atomic priorities). 'R' refers to the absolute configuration using Cahn–Ingold–Prelog priority rules.

Prioritize Groups Using Cahn–Ingold–Prelog Rules

To determine if R or S, assign priorities based on atomic number. Usually, NH2 > COOH > side chain (R) > H. If the lowest priority is in the back, draw circles from highest to lowest to determine configuration R (clockwise) or S (counterclockwise).

Design Side Chain for Expected Priority

Create a unique amino acid with an unconventional side chain to alter the typical atomic priority leading to an 'R' configuration. One way is by modifying the side chain with a higher priority component like a sulfur atom.

Create New Amino Acid Structure

Design the amino acid by placing the unique high-priority side chain strategically. For instance, replace a carbon in the side chain with sulfur, making its atomic number higher than the standard CH group.

Ensure L-Amino Acid with R Configuration

Verify your created amino acid configuration. It should adhere to L due to amino group on the left in Fischer projection, and R due to the unique priority of the new side chain, making the circle from high to low priority clockwise.

Key concepts

L configuration

The concept of stereochemistry in amino acids revolves mainly around the central alpha carbon, which is connected to four different groups: an amino group, a carboxyl group, a hydrogen atom, and a unique side chain known as the R group. The orientation of these groups in space leads to different stereochemical configurations, designated as 'L' or 'D'. When it comes to amino acids, naturally occurring ones are usually in the 'L' configuration.

Understanding this configuration better, the Fischer projection is a commonly used method to visualize stereochemistry. In this projection:

• The carboxyl group is placed at the top.
• The amino group is placed on the left.
• The hydrogen atom is placed on the right.

For 'L' amino acids, this specific arrangement is typical, marking them as the mirror image or enantiomer, different from 'D' which would have its amino group on the right side in Fischer projection. Keep in mind that the 'L' nomenclature does not directly indicate the optical activity nor the absolute configuration (like R or S), which is another story.

Thus, L-amino acids have this left orientation of the amino group by convention, which is crucial in differentiating them from their counterparts, especially since biological systems predominantly incorporate L-forms.

Cahn–Ingold–Prelog rules

In stereochemistry, the Cahn–Ingold–Prelog (CIP) priority rules are a system to name stereoisomers based on the spatial arrangement of the substituents around chiral centers. To determine the chirality as 'R' (rectus, or right) or 'S' (sinister, or left), certain steps are followed:

1. **Assign Priorities**: Each substituent attached to a chiral center is assigned a priority based on the atomic number of the atoms directly attached to the chiral atom. The higher the atomic number, the higher the priority. For example: - Nitrogen (amino group, NH2) typically has the highest priority. - Carboxyl group (COOH) follows. - A side chain (e.g., R group) is generally next. - Hydrogen (H) has the lowest priority. 2. **Orient the Molecule**: Arrange the molecule in such a way that the group with the lowest priority (often the hydrogen) is directed away from you. 3. **Determine the Configuration**: Look at the three remaining groups and trace a path from the highest priority to the lowest. If the path is clockwise, the configuration is 'R'. If it's counterclockwise, the configuration is 'S'.

These rules are essential for accurately describing the three-dimensional orientation of molecules, especially in distinguishing between enantiomers. In some amino acids, like Cysteine, this leads to an interesting scenario where it maintains an L-form but holds an R configuration due to its unique side chain.

R and S configuration

The 'R' and 'S' notations are used to describe the absolute configuration of a chiral molecule's stereocenters, determined by the Cahn–Ingold–Prelog rules. This system is crucial for understanding the molecular geometry of stereoisomers and for predicting their interactions in biochemical environments.

To break it down simply:

• **'R' Configuration** - When you look at the prioritized atomic groups around a chiral center, if the path from highest to shortest (not showing hydrogen) is clockwise, the molecule has an 'R' configuration.
• **'S' Configuration** - Conversely, if that path is counterclockwise, then it's an 'S' configuration.

Many amino acids naturally exhibit an 'S' configuration due to the conventional atomic priorities assigned to amino groups, carboxyl groups, and side chains. However, exceptions like cysteine exist, where due to the presence of higher priority atoms in the side chain (like sulfur), the typical priority order changes. Here, it retains the L-amino acid classification (because of placement in a Fischer projection) but adopts an R configuration.

This nuanced distinction illustrates keen aspects of molecular geometry, highlighting how seemingly minor changes at the atomic level can lead to significant differences in molecular behavior and properties.