Synthesis and biological activity of amination products of the alkaloid securinine

Synthesis of Suffranidine B

“…As part of our synthetic program aiming for high-order and high-oxidation state securinega alkaloids, biomimetic synthesis of flueggeacosine A ( 9 ) was investigated by conducting a 1,6-conjugate addition of 2,3-dehydroallosecurinine ( 6 ), obtained via our previously developed regioselective Polonovski reaction, to allosecurinine ( 8 ). However, in contrast to the previously reported facile 1,6-conjugate addition to the securinega scaffold, − no desired product was observed when 6 and 8 were refluxed in acetonitrile in the presence of bismuth­(III) triflate. Despite extensive experimentation, only 14% and 15% of flueggeacosine A ( 9 ) were obtained upon microwave irradiation of the neat mixtures or ionic liquid solution, respectively.…”

“…Finally, the mechanism of the epimerization of episuffranidine B (25) to suffranidine B (2) was investigated. Subjecting epi-suffranidine B (25) to 1 M D 2 SO 4 in D 2 O furnished suffranidine B that is deuterated at C3, C1′′, and C5′′ positions.…”

Unique indolizidine alkaloid securinine is a promising scaffold for the development of neuroprotective and antitumor drugs

“…As a result of nucleophilic addition of amines to securinine, hybrid molecules containing a fragment of the alkaloid securinine and various pharmacophoric amines can be obtained. Thus, a stereospecic method for the production of amino derivatives of securinine 14,30,31,[33][34][35] was developed under the conditions of Lewis acid catalysis (Scheme 1). Various primary, secondary, and cyclic amines have been used to obtain amino derivatives.…”

“…This may be due to both the antioxidant effect of allomargaritarine and its ability to increase mitochondrial resistance to the induction of mitochondrial permeability transition. 35 It is known that securinine is an antagonist of GABA receptors 13,14 and has been previously used as a neurostimulating agent in the treatment of various diseases, in particular, amyotrophic lateral sclerosis. However, its undesirable side effect, the pro-convulsive action, is also associated with the effect on the same target.…”

“…It is a selective antagonist of GABA (gamma aminobutyric acid) receptors. 13,14 It has been shown that securinine can be used in the treatment of neurological diseases such as amyotrophic lateral 15 and multiple sclerosis. 13,16 In ref.…”