Objective

To synthesize seven dipeptides via a 4 component Ugi Reaction. The dipeptides were ranked with in the top 20 list of Sortase inhibitors, from the docking experiment D-EXP016 spreadsheet-1

Results

IMGUCExp228-a
IMGUCExp228-b
IMGUCExp228-3
IMGUCExp228-4
IMGUCExp228-5
IMGUCExp228-6
IMGUCExp228-7
Spreadsheet UCExp228

Discussion

Vials 228-1 and 228-2 did not form a homogeneous solution when boc-tryptophan was added to them, therefore isocyanides were not added to these vials and they were aborted.
However clear solutions were obtained in the remaining vials. These vials were left at room temperature for two days, yet none of them developed any any solid in them.

Conclusion

None of the reactions vials yielded any ppts.

Log

2009-05-26
17:00 Labeled seven vials 228-1, 228-2, 228-3, 228-4, 228-5, 228-6 and 228-7.
17:20 Weighed-out 4,7-dimethoxy-1-naphthaldehyde (0.1mmol, 21.6mg) in vial 228-1, 3-hydroxybenzal dehyde (0.1mmol,12.2mg) in vial 228-2, and 4-(Dimethylamino)benzaldehyde (0.1mmol, 15mg) in vial 228-5.
17:45 Pipetted out 2,4-dimethylbenzaldehyde (0.1mmol, 14uL) in vial 228-3, benzaldehyde (0.1mmol, 10.1uL) in vial 228-4, 4-(Trifluoromethyl)benzaldehyde (0.1mmol, 13.6uL) in vial 228-6 and 4-methylbenzaldehyde (0.1mmol, 11.7uL) in vial 228-7.
18:15 Obtained a 2M solution of Boc-Tryptophan (500uL) in methanol from Exp229 [prepared by David Bulger] labeled (b-Try)
18:20 Weighed Octadecyl amine (0.1mmol, 26.9mg x 4), added the amine to the first four vials (228-1 to 228-4). Vortexed vials with liquid aldehydes for 1min, was unable to obtain a clear solution.
18:30 Added 100uL methanol to vials 228-1, 228-2, 228-3 and 228-4..this was required because the solid amine did not go in to the solution....After the addition of methanol, the solutions were vortexed for ~1min each...obtained a clear solution in vial 228-3 and 228-4, however a the solutions in vials 228-1 and 228-2 did turn clear.Therefore added more methanol (100uL) to vials 228-1 and 228-2, vortexed for 1min, still unable to obtain a clear solution.
18:45 Pipetted-out hexylamine (0.1mmol, 13.2uL) to vial 228-5, 5-methylfurfurylamine (0.1mmol, 11.1uL) in vial 228-6 and methylamine / THF 2.0M solution (0.1mmol, 50uLuL) in vial 228-7. Soon after the addition, each vial was vortexed for ~1min..was unable to obtain a clear solution in vial 228-5, therefore added 100uL methanol and vortexed for 1min, solution cleared-up quickly. Reactants in vial 228-6 formed a hazy solution, therefore 100uL of methanol was added to this vial also, vortexed and formed a clear solution.
19:10 Added 50uL of the 2M Boc-Tryptophan solution in methanol to vials 228-1 through 228-6...Each vial was vortexed for ~1min..Vial 228-1 immediately formed an orange precipitate..and vial 228-2 formed a white ppt...remaining vials after vortexing contained a homogenous solution. Added 100uL methanol to vials 228-1 and 228-2, vortexed for 1min, unable to obtain a clear solution.
19:20 Left the vials 228-1 and 228-2 in a sonicator, with water bath at 23C.
19:25 Added 1-pyrenebutyric acid (0.1mmol, 28.8mg) to vial 228-7, vortexed the solution for 1min, unable to obtain clear solution, therefore added 100uL of THF to this vial, vortexed again for 1min and obtained clear solution.
19:40 Removed vials 228-1and 228-2 from the sonicator. The ppts did not dissolve...Therefore the reactions in these vials are aborted.
20:35 Pipetted-out butyl isocyanide (0.1mmol, 10.4uL) to vials 228-3, 228-4 and 228-6...[Vial 228-4 should have used t-butylisocyanide, made a mistake here by adding n-butylisocyanide, therefore if any product is formed from this reaction would be an UNLISTED ugi product. Vials were vortexed for ~1min. Clear solutions obtained.
20:50 Added t-butylisocyanide (0.1mmol, 11.3uL) to vial 228-7. Vortexed for about 1min, homogeneous solution obtained.
21:00 Weighed-out TOSMIC (0.1mmol, 19.5mg), added it to vial 228-5, vortexed for 1min, unable to obtain a clear solution, added 100uL methanol, vortexed for about 30s and obtained a clear solution.
21:20 Obtained pictures of vials, IMGUCExp228-a and IMGUCExp228-b.
2009-05-27
20:45 Obtained a picture of the solutions indvidually IMGUCExp228-3, IMGUCExp228-4, IMGUCExp228-5, IMGUCExp228-6, IMGUCExp228-7. no precipitates observed in any vials.