Fat‐Derived Aziridines and Their N‐Substituted Derivatives: Biologically Active Compounds Based on Renewable Raw Materials

Abstract

The first successful preparation of the aziridines methyl (9Z,12S,13R)‐12,13‐epimino‐9‐octadecenoate (10), derived from vernolic acid, and methyl (9R,10S,12R)‐9,10‐epimino‐12‐hydroxyoctadecanoate (12a) and methyl (9S,10R,12R)‐9,10‐epimino‐12‐hydroxyoctadecanoate (12b), both derived from ricinoleic acid, is reported. These are the first examples of enantiomerically pure fat‐derived aziridines. Treatment of the corresponding epoxides with sodium azide and ammonium chloride in ethanol in the presence of water yielded the new azido hydroxy compounds, which could be treated in an improved way with polymer‐bound triphenylphosphane to afford the aziridines in good yields. The intermediate azido hydroxy compounds could easily be reduced and so offer access to a variety of interesting β‐amino alcohols 17−21. The synthesis of various N‐substituted aziridine derivatives 22−29 by treatment of methyl cis‐9,10‐epiminooctadecanoate (3) with phenyl isocyanate and isothiocyanate, acetyl chloride, alkyl and aryl chloroformates and acrylonitrile is described. Finally, the fat‐derived 2,5‐dialkyl‐substituted pyrrole methyl 9‐(5‐pentyl‐1H‐pyrrol‐2‐yl)nonanoate (9) was obtained. The previously reported bis(aziridine) methyl cis‐9,10;cis‐12,13‐diepiminooctadecanoate, derived from linoleic acid, and tris(aziridine) methyl cis‐9,10;cis‐12,13;cis‐15,16‐triepiminooctadecanoate, derived from linolenic acid,1 have been subjected to different biological tests and showed cytotoxic and antimicrobial activity as well as remarkable antitumour‐promoting and good neuroprotective effects. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Applications of Chiral Three-membered Rings for Total Synthesis: A Review

“…In the same area, Metzger and Fürmeier reported the first preparation of chiral fat-derived aziridines, with the aim of gaining insight into their biological properties [28]. The same methodology as described in Scheme 16, based on the use of resin-bound PPh 3 , was applied to the enantiopure azido alcohol 37 derived from chiral methyl vernolate (Scheme 17).…”

Bioglycerol-based Sulphonic Acid Functionalized Carbon: An Efficient and Recyclable, Solid Acid Catalyst for the Regioselective Azidolysis of Epoxides in Aqueous Acetonitrile

“…Derivatives of vegetable oils and fatty esters with diethyl azidodicarboxylate 46 , azides 47 , aziridines and their N-substituted derivatives 48 are gaining significance as biologically active compounds. 10-Undecenoic acid prepared from pyrolysis of castor oil is a potential intermediate for the production of several industrial products like nylon-11, perfumery compounds and other specialty chemicals 49 .…”

Fette und Öle als nachwachsende Rohstoffe in der Chemie

“…[64] Vernolsäuremethylester (12 b) diente als Ausgangsmaterial für die Synthese eines Bolaamphiphils, das sich möglicher-weise für den gezielten Transport von Pharmaka in das Gehirn nutzen lässt. [65] Auch enantiomerenreine Aziridine ließen sich ausgehend von 12 b erhalten (Schema 4): [66] Nachwachsende Rohstoffe Angewandte Chemie sowie bemerkenswerte cytostatische Eigenschaften in Kombination mit neuroprotektiven Wirkungen. [66] Weiterhin wurde cis-9,10-Epoxyoctadecansäuremethylester für die Synthese fettsäurestämmiger Heterocyclen wie 4,5-Dihydrooxazolen, Oxazolidinen, Imidazolen, Oxazolen und Imidazolinthionen verwendet.…”

“…[65] Auch enantiomerenreine Aziridine ließen sich ausgehend von 12 b erhalten (Schema 4): [66] Nachwachsende Rohstoffe Angewandte Chemie sowie bemerkenswerte cytostatische Eigenschaften in Kombination mit neuroprotektiven Wirkungen. [66] Weiterhin wurde cis-9,10-Epoxyoctadecansäuremethylester für die Synthese fettsäurestämmiger Heterocyclen wie 4,5-Dihydrooxazolen, Oxazolidinen, Imidazolen, Oxazolen und Imidazolinthionen verwendet. [67] Um Oleochemikalien mit verbessertem Fließverhalten bei niedriger Temperatur zu gewinnen, wurden Epoxide verschiedener Ölsäurealkylester mit Alkansäuren in 72-83 % Ausbeute in die Diester umgewandelt.…”