Level of study
BAC +4
ECTS
2 credits
Component
Faculty of Science
Description
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
Objectives
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
Necessary pre-requisites
L3 level in organic chemistry
Knowledge control
Final written exam 2h
- Authorized documents: no
- Non-graphic calculator allowed: yes
- Internet: not allowed
Syllabus
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.