Chapter 6 Multiple Choice Questions

. Combinatorial chemistry or parallel synthesis can be useful at various stages of the drug design / development process. Which of the following is NOT such a stage?

finding a lead compound

optimising a lead compound

structure determination of the lead compound

structure-activity relationships of the lead compound

. Solid phase synthesis is frequently used in combinatorial chemistry. What is meant by solid phase synthesis?

reactions are carried out without solvent

reagents and reactants are attached to a solid phase support

reagents are used in the solid phase

molecules are constructed on a solid phase support

. There are several advantages of solid phase synthesis over conventional synthesis. Which of the following statements is NOT an advantage?

excess reagents can be used to force the equilibrium of a reaction to products

impurities and by products are easily removed

intermediates do not need to be isolated and purified

structures can be strongly linked to the solid support such that they cannot be removed

. Which of the following statements regarding linkers is wrong?

the link between the molecule and the solid support must be stable to the reaction conditions used in the synthesis

the link between the molecule and the solid support must be easily cleaved under specific conditions

the choice of linker used depends on the functional groups available on the first molecule to be attached

the linker must be on the outer surface of the resin bead if a molecule is to become attached to it

. A pharmaceutical laboratory wishes to synthesise all the possible dipeptides containing the amino acids (Thr, Ile, Phe, Tyr, Ser). How would you carry out these syntheses using combinatorial techniques?

mix all five amino acids together and add the mixture to a resin such that the amino acids are attached to the resin, then add another mixture of the five amino acids such that dipeptides are formed on the resin

split the resin between five vessels and add a different amino acid to each vessel such that the amino acid is attached to the resin. Mix the resin beads from all the vessels and resplit the beads back into five vessels, then add a different amino acid to each vessel to form dipeptides on each resin

split the resin between five vessels and add a different amino acid to each vessel such that it is attached to the resin, then add a different amino acid to each vessel to form dipeptides on each resin

split the resin between five vessels and add a different amino acid to each vessel such that it is attached to the resin, then add a mixture of the five amino acids to each vessel to form dipeptides on each resin.

. Which of the following statements is true?

parallel synthesis involves the synthesis of a large number of compounds using the same reaction sequence, where there is a mixture of compounds in each reaction vessel

parallel synthesis involves the synthesis of a large number of compounds using the same reaction sequence, where there is a different, single compound formed in each reaction vessel

combinatorial synthesis involves the synthesis of a large number of compounds using a variety of different synthetic routes to produce a mixture of compounds in each reaction vessel

a parallel synthesis carried out in a specified number of vessels will produce more compounds than a mixed combinatorial synthesis.

. Consider the following synthesis

Molecular tags (A-I) are constructed on the resin bead as the synthesis is carried out in order to identify R, R' and R". The tagging molecules are used to create an encryption code as follows

On completion of the synthesis, the molecular tags are released from a set of resin beads and identified by gas chromatography as shown below.

What structure has been formed on the bead?

R= n-butyl; R'= isopropyl; R" methyl

R= ethyl; R'= propyl; R" benzyl

R= n-butyl; R'= isopropyl; R" benzyl

R= n-butyl; R'= ethyl; R" ethyl

. Dynamic combinatorial chemistry is an alternative method of producing compounds other than the classic mix and split method. Which of the following statements is true about dynamic combinatorial chemistry?

the target should be absent from the reaction flask

there is no scope for amplification

it is necessary to 'freeze' the equilibrium reaction to identify active compounds

the reactions involved should be irreversible

. Which statement best describes the aim of diversity-orientated synthesis?

To produce a compound library where the structures are 'globular'' in nature and structurally diverse

To produce a compound library using as many different reagents as possible

To produce a compound library using as many different reactions as possible

To produce a compound with as many different structures as possible

. Which description best identifies a catch and release strategy in parallel synthesis?

A starting material is linked to a solid support, then modified in a series of reactions before the final product is released into solution

A reagent is attached to a solid support and reacts with a structure to remove it from solution. A second structure reacts with this intermediate and the product is released into solution.

A solid support is used to remove impurities that might have been formed in a reaction carried out in solution

Tiny volumes of solutions are introduced to microreactors containing microfluidic channels and mixed on microchips. Products are formed and the resulting solutions are released from the chip and analyzed.

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