1. Sulfa Drug Group Project Chemistry 258 Loyd D. Bastin

2. Brief History 1932-I.G. Farben (dye company in Germany) 1932-I.G. Farben (dye company in Germany) 1933-Prontosil used against staphylococcal septicemia 1933-Prontosil used against staphylococcal septicemia (blood infection) 1935-Gerhard Domagk 1935-Gerhard Domagk Prontosil cured streptococcal infections in mice and rabbits Prontosil cured streptococcal infections in mice and rabbits Later shown to have an even broader application Later shown to have an even broader application 1939-Domagk earned Nobel Prize in medicine 1939-Domagk earned Nobel Prize in medicine Hitler did not allow him to accept Hitler did not allow him to accept Was later awarded the prize Was later awarded the prize

3. More History 1935-J. Tréfouël 1935-J. Tréfouël In vivo (in animals) prontosil effective In vivo (in animals) prontosil effective In vitro (petri dish) prontosil ineffective In vitro (petri dish) prontosil ineffectiveWHY? Tréfouël showed that prontosil was metabolized to sulfanilamide in the body Tréfouël showed that prontosil was metabolized to sulfanilamide in the body Sulfanilamide shown to have in vivo and in vitro activity Sulfanilamide shown to have in vivo and in vitro activity Led to an explosion in the synthesis of sulfanilamide analogs Led to an explosion in the synthesis of sulfanilamide analogs Became the wonder drug of the 30s and early 40s Became the wonder drug of the 30s and early 40s (referred to as sulfa drugs) (referred to as sulfa drugs)

4. A Little More History 1929-Alexander Fleming discovers Penicillin G 1929-Alexander Fleming discovers Penicillin G 1941-Penicillin G shown to be successful antibacterial agent in humans 1941-Penicillin G shown to be successful antibacterial agent in humans Leads to a decline in use of sulfa drugs Leads to a decline in use of sulfa drugs However, sulfa drugs are still used for malaria, tuberculosis, leprosy, meningitus, pneumonia, scarlet fever, plague, respiratory, infections, and intestinal/urinary tract infections However, sulfa drugs are still used for malaria, tuberculosis, leprosy, meningitus, pneumonia, scarlet fever, plague, respiratory, infections, and intestinal/urinary tract infections

5. Synthesis

6. Your Task Groups of 3 or 4 Groups of 3 or 4 Select groups Select groups Weekly group meetings with instructor to discuss your progress and future plans Weekly group meetings with instructor to discuss your progress and future plans You are a team and it is your job to work together and synthesize the appropriate number of sulfa drugs. You are a team and it is your job to work together and synthesize the appropriate number of sulfa drugs. Choose the R groups and synthesize 3 (or 4) different sulfanilamide analogs. Choose the R groups and synthesize 3 (or 4) different sulfanilamide analogs. Group of 3 – synthesize 3 different sulfanilamide analogs Group of 3 – synthesize 3 different sulfanilamide analogs Group of 4 – synthesize 4 different sulfanilamide analogs Group of 4 – synthesize 4 different sulfanilamide analogs Design a “greener” method for one of your group C sulfanilamide analogs Design a “greener” method for one of your group C sulfanilamide analogs If you change your plan, it must be submitted in writing and signed by all group members. If you change your plan, it must be submitted in writing and signed by all group members. You MUST prove the identity and purity of your compound using mp, 1 H-NMR, IR, and/or TLC to receive full credit You MUST prove the identity and purity of your compound using mp, 1 H-NMR, IR, and/or TLC to receive full credit We will do 1 H-NMR once you have purified your product. We will do 1 H-NMR once you have purified your product. Finally, you will test the antibacterial activity of your drugs against E. coli. Finally, you will test the antibacterial activity of your drugs against E. coli.

7. Your Task Continued Here are your possible R groups Here are your possible R groups It is your job to make the synthesis work. Use the procedures in the lab manual as GUIDELINES. Modifications may/will be necessary. Could be as simple as changing T and/or solvent, or it could require some research on your part. Use your time wisely and multi-task. It is your job to make the synthesis work. Use the procedures in the lab manual as GUIDELINES. Modifications may/will be necessary. Could be as simple as changing T and/or solvent, or it could require some research on your part. Use your time wisely and multi-task. Your group must submit IN WRITING during the first lab meeting, which molecules you plan to synthesize, 2-3 procedures that the group will initially dry, and a list of IR peaks you will use to indicate if a reaction occurred. If you have trouble with compounds from Groups B or C, you can update your target molecules and methods. However, you can NOT upgrade your target group after the first lab meeting. We want to be GREEN. Your group must submit IN WRITING during the first lab meeting, which molecules you plan to synthesize, 2-3 procedures that the group will initially dry, and a list of IR peaks you will use to indicate if a reaction occurred. If you have trouble with compounds from Groups B or C, you can update your target molecules and methods. However, you can NOT upgrade your target group after the first lab meeting. We want to be GREEN.

8. Rough Schedule Week 1 Groups must submit in writing within the first 1.5 hours of the 1 st lab meeting. List of Group Members List of Group Members Amines to be used initially and reasoning behind those choices Amines to be used initially and reasoning behind those choices 2-3 procedures that the group will try initially and the reasoning behind those choices 2-3 procedures that the group will try initially and the reasoning behind those choices List of IR peaks that your group will use to indicate if a reaction has occurred. List of IR peaks that your group will use to indicate if a reaction has occurred. Weeks 1, 2, and 3 Work on step 1. Group meetings Week 4 Work on hydrolysis step. Group meetings Weeks 5 and 6 Work on greener method. Group meetings Week 7 Test antibacterial activity of sulfa drugs. Finish any characterization

9. Final Report Each group will submit ONE report. Each group will submit ONE report. Each member will submit a peer evaluation sheet for each member of their group Each member will submit a peer evaluation sheet for each member of their group The written lab report 60 pts (total possible) Successful synthesis of drug from group A: 4 pts Successful synthesis of drug from group B: 8 pts Successful synthesis of drug from group C: 12 pts Successful “greener” synthesis of a sulfa drug:12 pts Peer evaluation of group work:8 pts Instructor evaluation of group work:4 pts Total points for the report120 points Examples: The total points possible for doing an amine from group A and 2 amines from group C and devising a greener method would be 112 points (60 + 4 + 12 +12 + 12 + 8 + 4). Total possible for doing 3 amines from group A and devising a greener method would be 96 points (60 + 4 + 4 + 4 + 4 + 8 + 4). For details please see pg. 181 in the lab manual and then ask me if you have any questions. For details please see pg. 181 in the lab manual and then ask me if you have any questions.