Lecture 4 Concept Notes

Question 1

Geometric Isomers

Answer 1

Isomers that arise to a restricted rotation around bonds like doublebonds (olefins)
and cyclic compounds

Question 2

Properties of geometric isomers

Answer 2

Do not show optical isomerism unless they are chiral

Question 3

Properties of geometric isomers:
physical and chemical properties

Answer 3

Geometric isomers exhibit differences in physical and chemical properties

Question 4

E/Z terminology

Answer 4

Z= on the same side
E= on different sides

Usually used for complex structures

Question 5

cis/trans

Answer 5

Cis = same side
Trans = different side

Question 6

Conformational Isomers

Answer 6

Rotations about a single bond

Question 7

Eclipsed and Staggered bonds

Answer 7

Eclipsed: H-bonds -> in a Newman projection, the bonds are all closer together

Staggered- H bonds -> in a Newman Projection, the bonds are spread apart equally

Question 8

Eclipsed

Answer 8

High energy conformation
Less preferred because of how high energy it is

Newman projection: Bonds are close together

Question 9

Staggered

Answer 9

Low energy conformation
More preferred because of how low energy it is.

Staggered: Bonds are far apart

Question 10

Rank the Newman projections from most to least preferred

Answer 10

Most:
Staggered
Partially eclipsed
Gauche/skew
Fully eclipsed
Least

Question 11

Sometimes a IMHB is more favorable than a projection confirmation. Why?

Answer 11

The H bonds are so favorable and stabilizing to the molecule, that it takes priority over the more preferred Newman projection conformation

Question 12

Cyclic or ring hydrocarbons

Answer 12

They provide more rigidity to a drug than acyclic systems

Question 13

Bioactive conformations

Answer 13

this is in relation to the receptor’s binding site

Question 14

T/F: the bioactive conformer needs to be the lowest energy conformer

Answer 14

False. It can be a higher energy conformer.W

Question 15

What problems do we run into when the bioactive conformer is a high energy conformer?

Answer 15

The drug does not have a high concentration of that conformer and the Kd of the molecule will be high, which means that the binding affinity is low

Question 16

High Kd means what

Answer 16

Means that the binding affinity is low

Question 17

Low Kd means

Answer 17

Binding affinity is high, and this is good for our drug

Question 18

How can we fix when the bioactive conformer is a high energy conformer?

Answer 18

Synthesize a rigid analog of the drug

Question 19

How can we synthesize a rigid analog of the drug?

Answer 19

Add ring structures
Add H bonding
Add double or triple bonds
Add more steric functional groups

Question 20

Why do stereoisomers have diff. biological responses?

Answer 20

Active transport & binding involve asymmetric receptors which would prefer one isomer over another

enzymes or biological targets are also chiral and their active sites may exhibit stereospecificity.

Question 21

In diastereomers, why are there different biological responses?

Answer 21

The diastereomers inherently have diff. physical and chemical properties anyway

Question 22

Easson-Stedman hypothesis

Answer 22

3 intermolecular interactions are needed for an enantiomer to be considered the more active one.

Question 23

R/S on Fischer Projections

Answer 23

Any time the lowest priority group is on a horizontal bond, make the switch.

Question 24

Enantiomers can differ in activity. What does this mean?

Answer 24

One enantiomer may be the more active form.
Enantiomers may also interconvert to the more toxic form, which makes the drug unusable as a whole

Question 25

Product selectivity

Answer 25

R and S enantiomers can affect which part of the drug are metabolized

Question 26

Racemic switch

Answer 26

Purifying drugs into one enantiomer is expensive. Drug companies can use racemic mixes (50/50 mix, even if one is inactive) for a patent, and then as the patent expires, file a new one for a “new” drug that only contains one enantiomer of the drug.

Question 27

Examples of racemic switch

Answer 27

Celexa to Lexapro
or
Zopiclone to Eszopiclone

Question 28

Which will create a more rigid drug? A drug with a ring or a drug without?

Answer 28

A drug with a ring. Rings provide rigidity to the structure in comparison to a structure without a ring

Question 29

The _____ the ring the _____ flexible

Answer 29

The bigger the ring, the more flexible
The smaller the ring, the more rigid