Med Chem - Natural Products

Question 1

What is the structure of a Tropane?

Answer 1

Fused bicyclic heterocycle, containing a basic nitrogen. And it is an alkaloid.

Question 2

What are alkaloids?

Answer 2

1. Nitrogen organic compound
2. Of plant origin
3. Has physiological action on humans.

Question 3

What is the product of partial hydrolysis of cocaine?

Answer 3

Methylecgonine

Question 4

What is the product of complete hydrolysis of cocaine?

Answer 4

Ecgonine

Question 5

What can you tell about the solubility of cocaine in the solvent below?
1) Ethanol - 1g/6.5ml
2) Chloroform - 1g/0.7ml

Answer 5

more soluble in chloroform than ethanol

Question 6

Which method of extraction is suitable for extraction of cocaine from Coca leaves?

Answer 6

Maceration; Soxhlet extraction

Question 7

What are the constituents of the extraction from Coca leaves called? (hint: plant-related substances)

Answer 7

Phytochemicals

Question 8

What is the degree of ionization for the difference between pH and pKa of 1, 2 and 3?

Answer 8

1 = 90%
2 = 99%
3 = 99.9%

Question 9

What are the essential functional groups in Cocaine?

Answer 9

1. Aromatic carboxylic acid ester
2. Basic amino group
3. Lipophilic hydrocarbon ring

Question 10

Why remove carbomethoxy (COOCH3) group from Cocaine?

Answer 10

to reduce addiction potential

Question 11

What are the parts of the SAR for Local anesthetics? What is their purpose?

Answer 11

1. Aromatic part (lipophilic) - facilitates permeation;
2. Intermediate chain (ester vs amide bond w/ 1-3C chain) - chemical stability and duration of action;
3. Amino group (hydrophilic, 2/3 amine or heterocycle) - basic, ionisable, use as injectable, pKa of 7.5-9)

Question 12

What are the 2 desirable physicochemical characteristics of a LA?

Answer 12

1. High lipid solubility (promotes permeation)
2. Higher pKa for base (promotes ionisation)

Question 13

List 3 characteristics of an Ideal Local Anesthetic agent.

Answer 13

• Reversible blockade
• Selective for sensory neurons over motor neurons
• Rapid onset
• Sufficient duration of action
• Chemically stable when sterilized
• no systemic toxicity
• wide margin of safety
• Compatible w/ other drugs
• absence of AE
• Inexpensive

Question 14

What structural modifications in an Opium Alkaloid can help with less addiction potential?

Answer 14

1. Removal of ether bridge
2. Removal of cyclohexene ring
3. Addition of large groups to piperidine ring / opening the ring