Lecture 13 - Combinatorial Chemistry 1

Question 1

What is combinatorial chemistry?

Answer 1

It involves reacting one set of compounds with a second set simultaneously to create a new set called a combinatorial library

Combining reagents; to make ABC, firstly A+B then add AB+C

If A1-3 and B1-3 and C1-3 were reacted, 27 unique compounds are made.

Question 2

What are the advantages and disadvantages of solid phase reactions?

Answer 2

Advantages:
- Reagent can be used in excess to drive to completion
- Easy to purify the product by washing the resin support
- Easy to automate

Disadvantages:
- Fewer solid supported reactions
- Expensive to scale up
- Research to find solid support and linker can be slow

Question 3

Solution phase reactions

Answer 3

Advantages:
- Limitless organic reactions
- Scaling up is easier and cheaper
- Rate limiting step is the optimisation of chemistry; relatively quick

Disadvantages:
- Reagents not used in excess unless there is additional purification
- Difficult to wash
- Hard to automate

Question 4

Merrifield’s Resin (what reactions occur?)

Answer 4

One of the earliest solid support resins (won the Nobel)

[RESIN]-Ph-MeCl

PhMeCl is called the “linker”

SN2 reactions occur at Cl

Question 5

Tentagel Resin

Answer 5

[RESIN]-Me-PEG-MeX

PEG = Polyethylene glycol
X = NH2, OH, SH, Br, COOH so can be nucleophilic or electrophilic

Question 6

Houghton’s Teabag Procedure

Answer 6

Parallel synthesis
- teabag consists of polymeric support resin in a propylene mesh
- three teabags are added separately to three (in PowerPoint, could be more) amino acids
- these teabags and amino acid solutions are then combined and deprotected into a larger vessel
- teabags are then separately added to three new amino acids
- they are combined and deprotected again
- teabags are then cleaved from resin and purified