Dissertation/Thesis Abstract

Isolierung, Strukturaufklärung und Totalsynthese von Alkaloiden aus Stenus Käfern und der Seeanemone Heteractis aurora
by Müller, Tobias, Ph.D., Universitaet Bayreuth (Germany), 2011, 133; 27610507
Abstract (Summary)

Two new pyridine alkaloids (Z)- and (E)-3-(2-methyl-1-butenyl)-pyridine were detected as main compounds in the pygidial glands of the Stenus species Stenus solutus and S. similis, respectively. The corresponding nor-compound 3-(1-isobutenyl)-pyridine was found as a minor ingredient in S. solutus, S. cicindeloides, S. binotatus and S. pubescens. The structures of the new alkaloids could be elucidated by means of NMR spectroscopy and a final comparison with authentic references. These compounds were obtained by WITTIG-olefination from nicotinic aldehyde and the corresponding phosphonium salt in one single step. A new synthetic route, leading to all stereoisomers of the well-known spreading and defensive alkaloid stenusine, which can be found in most Stenus species, was developed. This alkaloid plays a somewhat special role in nature, since depending on the observed species, all stereoisomers occur naturally in rather pure form or as a mixture of all four compounds. All known synthetic routes to stenusine, as well as the SAMP/RAMP approach by ENDERS et al, give only a direct access to the stereoisomers showing (S)-configuration in the side chain. Therefore a new synthetic route, providing a straightforward access to all stereosiomers, was developed. The stereogenic center in the piperidine ring is generated by an auxiliary-mediated asymmetric hydrogenation, whereas the chiral side chain derives either from the chiral pool in form of compound (S)-2-methylbutanol–identical to the ENDERS protocol – or is constructed by means of a novel chemoenzymatic approach. Especially the (2S,3R)- and (2S,3S)-isomers can be obtained starting from 3-bromopyridine and (S)-2-methylbutylbromide via a very short 4 step sequence in good yields by this new synthetic route. Furthermore, the synthesis as a whole can be carried out free of protecting groups. The employed EVANS-auxiliary is recovered unchanged after the final hydrogenation. The new alkaloid cicindeloine has been isolated from Stenus beetles of the species S. cicindeloides and its structure was elucidated by combined analytic methods like NMR-spectroscopy, EI- and ESI-mass spectrometry. The absolute configuration of the natural alkaloid could be assigned by GC-comparison on a chiral phase with an authentic reference obtained by stereoselective total synthesis. For this purpose, a stereoselective synthetic route was developed, comprising a linear sequence of 12 steps which an excellent total yield of 20%.

Indexing (document details)
School: Universitaet Bayreuth (Germany)
School Location: Germany
Source: DAI-C 81/4(E), Dissertation Abstracts International
Subjects: Biology
Publication Number: 27610507
ISBN: 9781392727522
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