Exp130-i.JPG

Objective

To synthesize nine different Ugi adducts following the EXPLAN005 . The compounds will contribute toward a library for enoyl reductase inhibitors.
Comp ID/ Lib Rank
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
131-1
veratraldehyde (0.5mmol, 83.1mg)
furfurylamine (0.5mmol, 44.2uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-butyl isocyanide (0.5mmol, 52.3uL)
No
131-2
veratraldehyde (0.5mmol, 83.1mg)
furfurylamine (0.5mmol, 44.2uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-pentylisocyanide (0.5mmol, 62.9uL)
No
131-3
veratraldehyde (0.5mmol, 83.1mg)
5-methyl furfurylamine (0.5mmol, 55.7uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-pentylisocyanide (0.5mmol, 62.9uL)
No
131-4
o-Vanillin (0.5mmol, 76.1mg)
heptylamine (0.5mmol, 74.1uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
benzyl isocyanide (0.5mmol, 60.9uL)
No
131-5
o-Vanillin (0.5mmol, 76.1mg)
n-Octylamine (0.5mmol, 82.6uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
benzyl isocyanide (0.5mmol, 60.9uL)
No
131-6
o-Vanillin (0.5mmol, 76.1mg)
hexylamine (0.5mmol, 50.6uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-butyl isocyanide (0.5mmol, 52.3uL)
No
131-7
o-Vanillin (0.5mmol, 76.1mg)
hexylamine (0.5mmol, 50.6uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-pentylisocyanide (0.5mmol, 62.9uL)
No
131-8
o-Vanillin (0.5mmol, 76.1mg)
heptylamine (0.5mmol, 74.1uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-butyl isocyanide (0.5mmol, 52.3uL)
No
131-9
o-Vanillin (0.5mmol, 76.1mg)
heptylamine (0.5mmol, 74.1uL)
Boc-Trp-OH (0.5mmol, 152.1mg)
n-pentylisocyanide (0.5mmol, 62.9uL)
No

Procedure

Nine Ugi reactions were carried out in 1 dram vials labeled 1, 2, 3, 4, 5, 6, 7, 8, and 9. Vial 1 contained methanol (500uL), veratraldehyde (0.5mmol, 83.1mg), furfurylamine (0.5mmol, 44.2uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-butyl isocyanide (0.5mmol, 52.3uL), added in that order. Vial 2 contained methanol (500uL), veratraldehyde (0.5mmol, 83.1mg), furfurylamine (0.5mmol, 44.2uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-pentylisocyanide (0.5mmol, 62.9uL), added in that order. Vial 3 contained methanol (500 uL), veratraldehyde (0.5mmol, 83.1mg), 5-methyl furfurylamine (0.5mmol, 55.7uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-pentyl isocyanide (0.5mmol, 62.9 uL) added in that order. Vial 4 contained o-vanillin (0.5mmol, 76.1mg), heptylamine (0.5mmol, 74.1uL), Boc-Trp-OH (0.5mmol, 152.1mg), and benzylisocyanide (0.5mmol, 60.9uL), added in that order. Vial 5 contained o-Vanillin (0.5mmol, 76.1mg), n-Octylamine (0.5mmol, 82.6uL), Boc-Trp-OH (0.5mmol, 152.1mg), and benzyl isocyanide (0.5mmol, 60.9uL), added in that order. Vial 6 contained o-Vanillin (0.5mmol, 76.1mg), hexylamine (0.5mmol, 50.6uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-butylisocyanide (0.5mmol, 52.3uL), added in that order. Vial 7 contained o-Vanillin (0.5mmol, 76.1mg), hexylamine (0.5mmol, 50.6uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-pentylisocyanide (0.5mmol, 62.9 uL), added in that order. Vial 8 contained o-Vanillin (0.5mmol, 76.1mg), heptylamine (0.5mmol, 74.1uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-butylisocyanide (0.5mmol, 52.3uL), added in that order. Vial 9 contained o-Vanillin (0.5mmol, 76.1mg), heptylamine (0.5mmol, 74.1uL), Boc-Trp-OH (0.5mmol, 152.1mg), and n-pentylisocyanide (0.5mmol, 62.9 uL), added in that order. After each addition the solution was vortexed for 15s and made sure a homogeneous solution was obtained. The formation or absence of precipitate was noted. The dram vials were left at room temperature.

Results

Picture of solutions soon after the addition of all components
exp131before.JPG

Picture of solutions - next day
exp131after.JPG

Discussion

Solutions - Soon after addition of all components.
The patterns seen in the color variation amongst the samples could involve a number of factors. For Samples 1-3, veratraldehyde was used for the aldehyde component, while for samples 4-9 o-vanillin was used as the aldehyde component. There appears to be a darker tint across the last six samples than the first three samples. However, this may also be attributed to the amines involved in the reaction. For samples 1-3, the amines used are furfurylamine or 5-methylfurfurylamine while for samples 4-9, the amine used is hexylamine, heptylamine, and octylamine. The variation in lightness and darkness may also very well be attributed to a combination of the amine and aldehyde variation across these samples. When looking even closer, there appears to be a much darker tint in samples 6-9 than any of the reactions. There is no observable pattern here as there are no components exlclusive to these samples.
Solutions - Next Day
The next day, there is notable color change in all the samples except sample 3. Vial 1 appears to have lost some of its inital yellow color, appearing clearer than immediately after the reaction. Vial 2 appears to have acquired a barely visible off-white color from its initial clear appearance. Vial 3 shows the same basic color pattern. Vials 4 and 5 show an ever darker appearance the next day. Both these samples were the only ones to have benzylisocyanide, which is likely responsible for there similar color changes. Vials 6, 7, 8, and 9 all appear a bit lighter with an orange-brown color. There is no observable pattern as to why these samples experience similar color changes.
Vials were not vortexed or sonicated prior to taking the picture one day after mixing. Sometimes this is required to induce precipitation.

Conclusion

Despite notable color changes indicating that the reactions were carried out, there was no precipitate formation in any of the vials.

Log

2007-09-11

16:50: Weighed out veratraldehyde (83.1mg) and o-Vanillin (76.1mg) directly into dram vials.
17:30: Weighed out Boc-Trp-OH (152.1mg) on weighing paper
17:53: Added methanol (500uL) into the dram vials, followed by 30 seconds vortexing.
18:00: Added amine into the dram vials, followed by 15 seconds vortexing.
18:10: Added acid into the dram vials, followed by 30 second vortexing.
18:42: Added isocyanide into the dram vials followed by 15 second vortexing
18:52: Took Digital Still picture of all 9 vials.
18:54: Let vials sit in fume hood overnight.

2007-09-12

13:32: Took Digital Still picture of all 9 vials.

2007-09-18

17:20: Transferred dram vials without precipitate (1, 2, 3, 4, 5, 6, 7, 8, and 9) onto watch glasses to allow them to evaporate overnight.

Tags

o-vanillin InChI=1/C5H11NS2.Na/c1-3-6(4-2)5(7)8;/h3-4H2,1-2H3,(H,7,8);/q;+1/p-1/fC5H10NS2.Na/q-1;m
veratraldehyde InChI=1/C14H10/c1-2-6-12-10-14-8-4-3-7-13(14)9-11(12)5-1/h1-10H
5-methyl-furfurylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
Boc-trp-OH InChI=1/C16H20N2O4/c1-16(2,3)22-15(21)18-13(14(19)20)8-10-9-17-12-7-5-4-6-11(10)12/h4-7,9,13,17H,8H2,1-3H3,(H,18,21)(H,19,20)
n-butylisocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3
hexylamine InChI=1/C6H15N/c1-2-3-4-5-6-7/h2-7H2,1H3
heptylamine InChI=1/C7H17N/c1-2-3-4-5-6-7-8/h2-8H2,1H3
octylamine InChI=1/C8H19N/c1-2-3-4-5-6-7-8-9/h2-9H2,1H3
n-pentylisocyanide InChI=1/C6H11N/c1-3-4-5-6-7-2/h3-6H2,1H3
furfurylamine InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2