Amino Acids and Derivatives

This course covers synthetic methods used to produce enantiopure amino acids, as well as the use of chiral amino acids in the synthesis of other enantiopure compounds.

These amino acids are the building blocks of peptides. The various physicochemical properties resulting from the nature of these amino acids will enable the development of strategies for synthesizing peptides of interest and characterizing them.

Hourly Volumes*:

CM: 3:00 p.m.

TD: 5 H

Knowledge:

Methods for Obtaining Enantiopure Amino Acids

Use of Amino Acids in Asymmetric Synthesis

Structure and Biological Role of Natural Peptides

Conformational Analysis

Synthesis of Peptides and Modified Peptides

Introduction to Supported Peptide Synthesis

Characterization Methods

Skills:

Mastery of the Synthesis of Enantiopure Amino Acids

The Use of Amino Acids in Organic Synthesis

Implementation of a Peptide Synthesis Strategy

Overview of Expected Results Based on the Selected Strategies

L3 Level in Organic Chemistry

2-hour final written exam

- Permitted documents: no

- Non-graphing calculators allowed: yes

- Internet: not allowed

Course (15 hours): Materials available on the digital learning platform (Moodle): Course materials, tutorial materials, past exam questions, and reference publications.

Part 1: Synthesis, Characterization, and Reactivity of Chiral Amino Acids (7.5 hours of lectures and 2.5 hours of lab sessions)

 I. Synthesis of Amino Acids by Racemate Resolution (1.5 hours)

I.1.—Spontaneous splitting

I.2.—Splitting via the formation of diastereoisomers

I.3.—Separation by chiral chromatography

I.4.—Kinetic splitting

 II. Synthesis of Amino Acids from a Chiral Substrate: Utilization of the Chiral Pool (1.5 hours)

III. Asymmetric Synthesis of Amino Acids from a Prochiral Substrate (7h)

III.1.—Reactions Controlled by the Substrate Structure: Chiral Auxiliaries Derived from an Amino Acid

            III.1.1.—Alkylation of Cyclic Enolates

            III.1.2.—Chiral auxiliaries for aldolization reactions

III.2.—Reactions Controlled by the Structure of the Reagent:

            III.2.1.—Reactions Controlled by the Structure of a Chiral Reagent

            III.2.2.—Reactions Catalyzed by an Amino Acid-Derived Catalyst

                        a-Chiral transition metal complexes

                        b-Organocatalysts

Part 2: Peptide Synthesis (7.5 hours of lectures and 2.5 hours of lab sessions)

I. Introduction (2 hours)

I.1 Definition, Classification, and Nomenclature

I.2 The Peptide Bond

I.3 Biological Applications

II. Peptide Synthesis (3 hours)

II.1 Biosynthetic Approach

II.2 Chemical Approach

II.3 The Problem of Racemization

Integrated Problem: Synthesis of a Dipeptide

III- Synthesis Strategies (3 hours)

III.1 Permanent and Semipermanent Protections/Orthogonality

III.2 Strategic Approaches / Activation-Coupling

III.3 Characterization Methods (NMR, MS)

Application to the Synthesis of Linear and Cyclic Oligopeptides

IV. Implementation (2 hours)

IV.1 Introduction to Synthesis Using Automated Tools and Methods

IV.2 Examples of Peptide Applications (CPP, Short Peptide Self-Assembly, etc.)

IV.3 Non-canonical Amino Acids: An Introduction to Bioconjugation Strategies

TD (5 hours): Study of methods for synthesizing amino acids and their use in asymmetric synthesis. Case studies: application of synthetic strategies to peptides of interest; review of publications.