Biological Chemistry Synthesis of N heterocycle from amino acid precursor Hetero
ID: 553162 • Letter: B
Question
Biological Chemistry Synthesis of N heterocycle from amino acid precursor Heterocycles are common motifs in biologically active natural products and biomimetic drug molecules. Pyrrole rings are particularly common. One route to destroying cancer cells or viruses is to target DNA function and/or synthesis. A number of natural products that contain the pyrrole functional group, such as the peptides distamycin and netropsin, have been found to bind in the minor groove of DNA1 and disrupting DNA replication and transcription. This disruption of DNA function and processing leads to cell death in the cancer and viral cells. These naturally occurring poly-pyrrole compounds are essentially peptides, and are most likely biosynthesised from amino acid precursors. So, it seems logical that to produce these types of compounds in a laboratory environment we might want to begin with amino acid starting materials The synthesis you will be performing today has been adapted from the work of Kolar and Tišler. You will be starting from a simple, cheap, readily available amino acid precursor and, in two distinct steps, synthesising a pyrrole that has a number of useful synthetic 'handles', i.e. it can serve as the basis for making a range of possible small molecules (or even large polymeric ones) that will contain a pyrrole moiety. Note that we will be using phenyl alanine today, i.e. the R group in () is a benzene ring but this procedure should work with any amino acid starting material. R- akyl, aryl, heteroaryl R, methyl, ethyl Synthetic procedure L-Phenylalanine ethyl ester (I, R benzyl, R1 ethyl) Dissolve Lphenylalanine ethyl ester hydrochloride (2.57 g, how many moles is this?) in 25 mL of water, cool on ice bath to 0 °C, and neutralise with a solution of 0.45 g of sodium hydroxide in 10 mL of water. Extract neutralised solution 4-5 times with 15-ml portions of diethyl ether, combine extracts, dry with anhydrous sodium sulphate, and evaporate in vacuo (using rotary evaporator). You should end up with a colourless oily product. Record the weight of your product before proceeding to the next step.Explanation / Answer
C/N number
13C
1H
IR (Range)
1-NH
11.9 (bs)
3300-3500 cm-1
2
119
1500 – 1600 ( C=C)
3
114.8
1500 – 1600 ( C=C)
4
111
1500 – 1600 ( C=C)
4-OH
15.28 (bs)
3500 – 3700 (broad)
5
135
1500 – 1600 ( C=C)
6
28.5
3.85 (s)
2850 - 2970
7
138.5
8
129
7.23 (d)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
9
128.5
7.28 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
10
125.5
7.20 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
11
128.5
7.28 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
12
129
7.23 (d)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
13
165
13-COOH
12.20 (bs)
1690 – 1760 (C=O) , 1030 – 175 (C-O)
14
169
14-COOH
12.75 (bs)
1690 – 1760 (C=O) , 1030 – 175 (C-O)
C/N number
13C
1H
IR (Range)
1-NH
11.9 (bs)
3300-3500 cm-1
2
119
1500 – 1600 ( C=C)
3
114.8
1500 – 1600 ( C=C)
4
111
1500 – 1600 ( C=C)
4-OH
15.28 (bs)
3500 – 3700 (broad)
5
135
1500 – 1600 ( C=C)
6
28.5
3.85 (s)
2850 - 2970
7
138.5
8
129
7.23 (d)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
9
128.5
7.28 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
10
125.5
7.20 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
11
128.5
7.28 (t)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
12
129
7.23 (d)
3010 – 3095 (C-H), 1500 – 1600 ( C=C)
13
165
13-COOH
12.20 (bs)
1690 – 1760 (C=O) , 1030 – 175 (C-O)
14
169
14-COOH
12.75 (bs)
1690 – 1760 (C=O) , 1030 – 175 (C-O)
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