Amino acids and derivatives

This course discusses synthetic methods applied to obtain 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 elements of peptides. The different physico-chemical properties induced by the nature of these amino acids will allow to define strategies for the synthesis of peptides of interest and their characterization.

Hourly volumes* :

CM : 15 H

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 peptide synthesis on carrier

Methods of characterization

Skills:

Control of the synthesis of enantiopure amino acids

Use of amino acids in organic synthesis

Implementation of a peptide synthesis strategy

Presentation of the expected results according to the chosen strategies

L3 level in organic chemistry

Final written exam 2h

- Authorized documents: no

- Non-graphic calculator allowed: yes

- Internet: not allowed

Course (15h): Support(s) available on ENT (Moodle) : Course documents, TD documents, exam annals and reference publications.

Part 1: Synthesis, Characterization and Reactivity of chiral amino acids (7.5h CM and 2.5h TD)

 I.-Synthesis of amino acids by racemate splitting (1.5h)

I.1.-Spontaneous duplication

I.2.-Doubling by formation of diastereomers

I.3.-Doubling by chiral chromatography

I.4.-Kinetic duplication

 II - Synthesis of amino acids from a chiral substrate: use of the chiral reservoir (1.5h)

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 Structure controlled reactions 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 (7.5h CM and 2.5h TD)

I- Introduction (2h)

I.1 Definition. Classification and nomenclature

I.2 The peptide bond

I.3 Biological applications

II- Peptide synthesis (3h)

II.1 Biosynthetic approach

II.2 Chemical approach

II.3 The problem of racemization

Integrated Problem: Synthesis of a dipeptide

III- Synthesis strategies (3h)

III.1 Permanent and semi-permanent 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 (2h)

IV.1 Introduction to Supported Synthesis/Automated Methods

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

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

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