The Development of Novel Antibiotics Using ... - Jacobs University

H. F. Nour, A. M. Lopez-Periago and N. Kuhnert
Table 1. ESI-TOF MS data in the positive ion mode for the intermediates using terephthaldehyde 2, forming trianglimine 4
Entry Calcd. m/z Measured m/z Molecular formula
Error
[ppm]
4 637.4013 637.4012 C 42 H 48 N 6 0.2
7 231.1492 231.1491 C 14 H 18 N 2 O 0.2
8 327.2543 327.2544 C 20 H 30 N 4 0.3
9 347.1754 347.1746 C 22 H 22 N 2 O 2 2.3
10 443.2805 443.2813 C 28 H 34 N 4 O 1.7
11 539.3857 539.3867 C 34 H 46 N 6 1.8
12 655.4119 655.4115 C 42 H 50 N 6 O 0.6
Table 2. ESI-TOF mass spectrometry data in the positive ion mode for the intermediates using isophthaldehyde 3, forming
trianglimine 5
Entry Calcd. m/z Measured m/z Molecular formula
Error
[ppm]
6 425.2700 425.2715 C 28 H 32 N 4 3.7
13 231.1492 231.1489 C 14 H 18 N 2 O 1.3
14 327.2543 327.2537 C 20 H 30 N 4 2
15 347.1745 347.1745 C 22 H 22 N 2 O 2 2.7
16 443.2805 443.2807 C 28 H 34 N 4 O 0.4
17 539.3857 539.3846 C 34 H 46 N 6 2
18* 655.4119 655.4114 C 42 H 50 N 6 O 0.7
*Intermediate was detected after 30 min from the start of the reaction.
Figure 4. A plot of relative intensity for intermediates 7–18 versus reaction time (a)
reaction of (1R,2R)-1,2-diaminocyclohexane 1 with terephthaldehyde 2 (6 h), (b) reaction
of (1R,2R)-1,2-diaminocyclohexane 1 with isophthaldehyde 3 (2 h), and (c) reaction
of (1R,2R)-1,2-diaminocyclohexane 1 with isophthaldehyde 3 (12 h).
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while the intensities for the rest of intermediates decreased.
Furthermore, the peaks corresponding to all intermediates
disappeared after 6 h.
In the case of isophthaldehyde, the intensity of the peak
corresponding to trianglimine 5 goes through a maximum
value after 10 h and later decreases at the expense of the
smaller macrocycle 6. This is in line with our earlier observations
that in this case the [3+3]-macrocycle is the kinetic product
of the reaction and the [2+2]-macrocycle appears as the
thermodynamically stable product. In this particular case we
could only obtain a maximum of 50% yield for the [3+3]-
cyclocondensation product and not the reported quantitative
wileyonlinelibrary.com/journal/rcm Copyright © 2012 John Wiley & Sons, Ltd. Rapid Commun. Mass Spectrom. 2012, 26, 1070–1080