Amino acids and derivatives

This course covers synthesis methods applied to obtaining enantiopure amino acids, as well as the use of chiral amino acids for the synthesis of other enantiopure compounds.

These amino acids are the basic building blocks of peptides. The different physicochemical properties induced by the nature of these amino acids will enable the definition of strategies for synthesizing peptides of interest and their characterization.

Hourly volumes*:

CM: 3 p.m.

Tutorial: 5 hours

Knowledge:

Methods for obtaining enantiopure amino acids

Use of amino acids in asymmetric synthesis

Structure and biological role of natural peptides

Conformation analysis

Synthesis of peptides and modified peptides

Introduction to supported peptide synthesis

Characterization methods

Skills:

Mastery of the synthesis of enantiopure amino acids

Use of amino acids in organic synthesis

Implementation of a peptide synthesis strategy

Presentation of expected results based on the chosen strategies

Level L3 in organic chemistry

Final written exam, 2 hours

- Authorized documents: no

- Non-graphing calculator permitted: yes

- Internet: not permitted

Course (15 hours): Materials available on the digital workspace (Moodle): Course documents, tutorial documents, past exam papers, and reference publications.

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

 I.-Synthesis of amino acids by racemic separation (1.5 hours)

I.1.-Spontaneous splitting

I.2.-Splitting by formation of diastereoisomers

I.3.-Separation by chiral chromatography

I.4.-Kinetic splitting

 II.-Synthesis of amino acids from a chiral substrate: use of the chiral fund or reservoir (1.5 hours)

III.-Asymmetric synthesis of amino acids from a prochiral substrate (7h)

III.1.-Reactions controlled by 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 controlled by a catalyst derived from an amino acid

                        a-Chiral transition metal complexes

                        b-Organocatalysts

Part 2: Peptide synthesis (7.5 hours of lectures and 2.5 hours of tutorials)

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 semi-permanent protections/orthogonality

III.2 Strategic Approaches/Activation-Coupling

III.3 Characterization methods (NMR, MS)

Application on the synthesis of linear and cyclic oligopeptides

IV- Implementation (2 hours)

IV.1 Introduction to the summary on Automated Support/Methods

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

IV.3 Non-canonical amino acids: Introduction to bioconjugation strategies

Tutorial (5 hours): Study of amino acid synthesis methods and their use in asymmetric synthesis. Case studies: application of synthesis strategies for peptides of interest, study of publications.