Nice work! I was wondering if you did any of the docking/modeling as well as the synthesis. Also, you talk about adding a hydroxymethyl at C6 and that's what seems to be in the docked structure, but on slide 12 your product looks like it has a hydroxyethyl. Is that a typo (they happen!) or am I misunderstanding something? Thanks!
To answer your first question, Rahul and I worked directly on the docking/modeling of the molecule. This is directly shown in slide 17 as we model the interaction between the enzyme and our proposed carbapenem structure on WINCOOT. We came to the hydroxymethyl group after several replacements of the C-6 position with different functional groups. This was actually the first step of the entire project as we were the ones who proposed the specific replacement after having looked at the orientation of several functional groups at different positions on the ring at the active site. As for the synthesis of the molecule, we independently worked on the first two steps, which involved the Gilman reaction and the subsequent oxidation reaction. However, we did receive guidance for the next four reactions as we struggled with the addition of the thiol side chain as well as the simultaneously removal of the PNB ester and PNB amino protecting groups.
As for the second question, you are not misunderstanding anything! We are terribly sorry for the mistake. It was not a typo, but we put in the same schemes for both mentioned molecules! I hope the recent edit reflects your concern.
Nice work! I was wondering if you did any of the docking/modeling as well as the synthesis. Also, you talk about adding a hydroxymethyl at C6 and that's what seems to be in the docked structure, but on slide 12 your product looks like it has a hydroxyethyl. Is that a typo (they happen!) or am I misunderstanding something? Thanks!
ReplyDeleteThank you for the kind note.
ReplyDeleteTo answer your first question, Rahul and I worked directly on the docking/modeling of the molecule. This is directly shown in slide 17 as we model the interaction between the enzyme and our proposed carbapenem structure on WINCOOT. We came to the hydroxymethyl group after several replacements of the C-6 position with different functional groups. This was actually the first step of the entire project as we were the ones who proposed the specific replacement after having looked at the orientation of several functional groups at different positions on the ring at the active site. As for the synthesis of the molecule, we independently worked on the first two steps, which involved the Gilman reaction and the subsequent oxidation reaction. However, we did receive guidance for the next four reactions as we struggled with the addition of the thiol side chain as well as the simultaneously removal of the PNB ester and PNB amino protecting groups.
As for the second question, you are not misunderstanding anything! We are terribly sorry for the mistake. It was not a typo, but we put in the same schemes for both mentioned molecules! I hope the recent edit reflects your concern.