Chemical synthesis of the peptide

February 6, 2018AdminUncategorized

The assignment is to provide a detailed solid phase chemical synthesis of the peptide. For full marks please follow the below requirements

Provide the structures of all reagents and intermediates in the synthesis (excluding the solid support but including the linker). Once a structure has been given you can use an acronym for the remainder of the synthesis.

Use the standard protecting groups for the 20 common amino acids. The synthesis of these does not need to be shown. Standard amino acids you may begin with are found in the following link AND at the end of the assignment. https://www.sigmaaldrich.com/chemistry/chemistry-html?TablePage=111084330

For unnatural amino acids you need to synthesize these from achiral starting materials and install the necessary protecting groups. You can use any achiral starting material available from Sigma Aldrich (http://www.sigmaaldrich.com/canada-english.html – include CAS number of each reagent used). Be sure to include chiral resolution as a step if required

Be sure to include the chirality of all chiral compounds

Mechanisms are not necessary.

You are expected to work on this assignment individually.

Assignment is due in seminar on Wednesday Feb 7th. Hand written assignments are perfectly acceptable, or you may upload a file onto blackboard.

*Each peptide contains a single unnatural amino acid, 4 standard amino acids and a cyclized sidechain(s). It is recommended that you identify each amino acid in your peptide before planning a synthes:

Alternative protected amino acids you may use and their cleavage conditions

Sigma has a wide range of variably protected amino acids found at the following link: https://www.sigmaaldrich.com/chemistry/chemistry-products.html?TablePage=16255239 I’ve provided a couple handy ones below.

Aspartic Acid:

https://www.sigmaaldrich.com/catalog/product/aldrich/47593?lang=en&region=CA

OBzl (benzoyl) group removed by hydrogenation (H2/Pd)

https://www.sigmaaldrich.com/catalog/product/aldrich/47579?lang=en&region=CA

OAll (allyl) group removed by Pd(Ph3)4 (0.1eq) and PhSiH3 (10 Eq)

Glutamic Acid:

https://www.sigmaaldrich.com/catalog/product/aldrich/47703?lang=en&region=CA

OAll (allyl) group removed by Pd(Ph3)4 (0.1eq) and PhSiH3 (10 Eq)

https://www.sigmaaldrich.com/catalog/product/aldrich/47571?lang=en&region=CA

OBzl (benzoyl) group removed by hydrogenation (H2/Pd)

Lysine

https://www.sigmaaldrich.com/catalog/product/mm/852065?lang=en&region=CA