Many organic compounds are chiral and they are useful because of the biological
activities associated with them. The biological activities of chiral compounds are often
linked to absolute configuration, i.e. a compound and its mirror image can have different
biological activities. For example, one enantiomer can be toxic whereas the other
enantiomer is non-toxic. Enantioselective synthesis plays a significant role in the
synthesis of biologically active compounds. The activity of tetrahydroisoquinolines
prompted us to investigate the stereoselective synthesis of selected 1-substituted
tetrahydroisoquinolines.
The objectives of this project were to investigate stereoselective synthesis of some 1-
substituted tetrahydroisoquinolines and compare different chiral auxiliaries used in the
Bischler-Napieralski and Pictet-Spengler reactions and finally to optimize the number of
steps needed to prepare the target compounds. The main challenge encountered in the
Pictet-Spengler method was the decomposition of the phenylacetaldehyde. The
successfully used method was the Bischler-Napieralski reaction because it does not
involve the use of a phenylacetaldehyde.
Using the Bischler-Napieralski method, non-stereoselective and stereoselective syntheses
of tetrahydroisoquinolines have been achieved. The racemic tetrahydroisoquinolines have
been synthesized in a three-step procedure starting from 3,4-dimethoxyphenylethylamine
whereas the chiral tetrahydroisoquinolines were synthesized from vanillin in a seven-step
reaction procedure. The R and S enantiomers of α-methylbenzylamine were successfully
employed in the synthesis of 1-benzyltetrahydroisoquinolines. However, the Renantiomer
of 1,2,3,4-tetrahydro-1-naphthylamine could be used to form a chiral
phenylethylamine, while ring closure in a Biscler-Napieralski reaction was not successful
under similar reaction conditions.
The diastereoselectivity of the reactions to form the chiral tetrahydroisoquinolines was
determined using NMR spectroscopy and was found to be 96% and 90% de for the (R)-
and (S)-1-benzyl-6,7-dimethoxy-N-(1-phenylethyl)-1,2,3,4-tetrahydroisoquinoline, respectively. The stereochemistry of the final products was found to be similar to that of
the chiral auxiliary starting material for each of the synthesized chiral
tetrahydroisoquinolines. Yields for the precursors were good to moderate, especially on
the final stages of the synthesis. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2014.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/11217 |
| Date | 15 September 2014 |
| Creators | Zungu, Vezekile Princess. |
| Contributors | Van Heerden, Fanie R. |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
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