Objective

To synthesize two new Ugi Products.

Procedure

Based on the sortase inhibitor predictions in D-EXP016, two (D16-4 and D16-17) out of the top twenty Ugi products were picked for synthesis based on availability of reactants. In order to synthesize D16-4, 0.1 mmol each of N-boc-L-tryptophan, octadecylamine, p-tolualdehyde, and t-butylisocyanide were combined in methanol to create 0.15-mL final 0.75 M solution. For D16-17, 0.1 mmol each of N-boc-L-tryptophan, hexylamine, benzaldehyde, and n-butylisocyanide were combined in methanol to create 0.10-mL final 1.00 M solution. Final solutions were then sonicated for 35 min to stimulate crystal formation.

Results

Pictures

UC229-1
UC229-2
UC229-3
UC229-4
UC229-5
UC229-6

Spreadsheets

UCExp229


Conclusion

As no precipitate was observed in UC229-6, using 0.10-mL final 1.00 M [the CombiUgi sheet calculates the final concentrations to be 0.67M - why the discrepancy? JCB] solution for these ugi reactions does not seem feasible for synthesizing and precipitating the expected ugi products.

Log

5 May 2009
16:40 Weighed 1-mL volumetric flask (15.582 6 g)
16:40 Added 0.304 1 g of N-boc-L-tryptophan to flask
17:13 Weighed (15.892 0 g)
17:26 Added 258.8 uL methanol to create 0.5 mL 2M solution
17:35 Vortexed for 30 sec
17:35 Sonicated (23 degrees Celsius) for 15 min
17:50 Photo (UC229-1)
17:52 Temperature in sonicator is 29 degrees Celsius
18:15 Labeled flask (b-Try), vial for D16-4 Ugi Product (UC229-1), and vial for D16-17 Ugi Product (UC229-2)
18:16 Weighed vials
Vial
Mass (g)
UC229-1
2.409 4
UC229-2
2.427 3
18:25 Added 11.8 uL of p-tolualdehyde to UC229-1 and weighed (2.421 5 g)
18:32 Added 33.2 mg of octadecylamine to UC229-1 and weighed (2.426 4 g)
18:35 Sample aborted as only 27.0 mg of octadecylamine should have been added
18:40 Vial UC229-1 cleaned and dried
18:50 Weighed empty vial UC229-1 (2.409 1 g)
18:51 Added 27.0 mg of octadecylamine to UC229-1 and weighed (2.436 9 g)
19:05 Added 11.8 uL of p-tolualdehyde to UC229-1 and weighed (2.448 2 g)
19:09 Added 22.0 uL of methanol to UC229-1
19:10 Vortexed for 10 sec
19:10 Added 22.0 uL of methanol to UC229-1
19:11 Vortexed for 10 sec
19:13 Added 50 uL of 2M N-boc-L-tryptophan solution to UC229-1 (Note: Khalid used same solution for Exp228 and had transferred solution to a 1-dram vial - although some evaporation of solvent did occur)
19:15 Vortexed about 3 min until solution was clear
19:21 Photo (UC229-2)
19:22 Weighed (2.511 0 g)
19:25 Added 11.3 uL of t-butylisocyanide to UC229-1
19:26 Vortexed for 10 sec
19:27 Weighed (2.513 0 g)
19:28 Photo (UC229-3)
19:29 Parafilmed UC229-1
19:31 Weighed vial UC229-2 (2.426 7 g)
19:32 Added 10.2 uL of benzaldehyde to UC229-2 and weighed (2.438 9 g)
19:34 Added 13.2 uL of hexylamine to UC229-2 - Note: Vial heated up and white vapor observed (possibly solvent evaporating)
19:36 Vortexed for 10 sec and weighed (2.448 2 g)
19:37 Added 50 uL of 2M N-boc-L-tryptophan solution to UC229-2
19:39 Vortexed for 10 sec and weighed (2.487 4 g)
19:40 Added 10.5 uL of n-butylisocyanide to UC229-2 and weighed (2.492 6 g)
19:45 Vortexed for 10 sec
19:45 Photo (UC229-4)
19:46 Parafilmed UC229-2
19:47 Photo (UC229-5)
19:55 Sonicated for 35 min (40 degrees Celsius)
20:48 Temperature in sonicator is 32 degrees Celsius - Note: Possibly cooled down during the 18 min following sonication.
20:48 Photo (UC229-6)