The chemistry of Stemona alkaloids: An update

Abstract

In the review period, 97 new representatives of Stemona alkaloids were described, bringing the total reported so far to 139. In this review, we discuss their isolation, structural elucidation, structural classification, biological activities, semi-synthesis and total syntheses. These alkaloids are classified into seven groups displaying either a pyrrolo[1,2-a]azepine or a pyrido[1,2-a]azepine core, and a miscellaneous group comprising those alkaloids without these structural motifs, together with those that are the sole representative of a new group. It displays a ring A pyrrole unit, and its relative stereochemistry resembles that of tuberostemonine J (5), except for H-18 which is proposed to be aoriented in epi-bisdehydroneotuberostemonine J (10) while it is b-oriented in tuberostemonine J (5) and in most of the other Stemona alkaloids bearing the a-methyl-g-butyrolactone moiety attached to C-3. Its absolute chemical structure was claimed to have been established by X-ray crystallographic analysis. 1 9a-Bisdehydrotuberostemonine (11) also displays a pyrrole ring and it was isolated from the roots of S. tuberosa. 15 Its structure was assigned as the 9a epimer of bisdehydrotuberostemonine, also known as didehydrotuberostemonine, 4 by Fig. 2 Stemona alkaloids of the stenine group (1-14).

Alkaloids from the roots of Stemona javanica (Kunth) Engl. (Stemonaceae) and their anti-malarial, acetylcholinesterase inhibitory and cytotoxic activities

“…While compound 4 had the same molecular formula, and related structure features, to isoprotostemonine 2 and protostemonine there were notable differences in their NMR spectroscopic data (Wang et al, 2007). The aforementioned two known alkaloids had very similar However, we have tentatively assign the 3R, 18S, 20R configuration to 4 since the 18S configuration is the most commonly found absolute configuration of the Stemona alkaloids (Greger 2006;Kongkiatpaiboon, 2001;Pilli et al, 2010Pilli et al, , 2005. The lack of a NOESY correlations between the OMe group and the protons on the C-ring was consistent the Econfiguration of the C-11−C-12 alkene.…”

“…The ROESY correlations between H-18 and H-19and; H-19 and H-20; and H-19 and H-22 stereocentres from molecular modelling and ROESY NMR studies. However, we have tentatively assign the 3S, 18S, 20S configuration to 3 since this is the most commonly found absolute configuration of the Stemona alkaloids (Greger 2006;Kongkiatpaiboon, 2001;Pilli et al, 2010Pilli et al, , 2005. The configurations assigned to C-11 and C-12 in 3 were based on ROESY correlations and the magnitude of J 11,12 when compared to the known Stemona alkaloids 11S,12S-saxorumamide (ROESY correlation between H-12 and H-17, and J 11,12 = 2.0 Hz) and 11S,12R-isosaxorumamide (ROESY correlation between H-10 and H-13, and J 11,12 = 6.9 Hz) (Wang et al, 2007) and related dihydrostemofoline alkaloids (Mungkornasawakul et al, 2004b).…”

“…Extracts of the roots of the Stemona species have been used in traditional medicine to treat the symptoms of bronchitis, pertussis and tuberculosis and as anti-parasitics on humans and animals (Greger, 2006;Kongkiatpaiboon, 2001, Pilli et al, 2010, 2005. More than 190 unique Stemona alkaloids have been isolated, some of these have significant antitussive activity (Chung et al, 2003;Lin et al, 2008aLin et al, , 2008bLin et al, , 2006Xu et al, 2010Xu et al, , 2006Yang et al, 2009;Zhou et al, 2009;), as well as insect toxicity, antifeedant, and repellent activities (Brem et al, 2002;Jiwajinda et al, 2001;Kaltenegger et al, 2003;Kongkiatpaiboon et al, 2013Kongkiatpaiboon et al, , 2012Mungkornasawakul et al, 2009Mungkornasawakul et al, , 2004aPhattharaphan et al, 2010;Sanguanpong and Hummel, 2008;Sakata et al, 1978;Tang et al, 2008).…”

6-Hydroxy-5,6-seco-stemocurtisine: A novel seco-stemocurtisine-type alkaloid

“…The root extracts have also been used in the treatment of various respiratory diseases and have been used as anticough agents in China and Japan [Greger, 2006;Pilli et al 2000Pilli et al , 2005Pilli et al , 2010. To date over 130 different Stemona alkaloids have been isolated with the majority of alkaloids having the pyrrolo[1,2-a]azepine base structure [Pilli et al 2010]. In 2003, we reported the first pyrido[1,2-a]azepine based Stemona alkaloid, stemocurtisine 1 (Scheme 1), which was isolated from the roots of Stemona curtisii found in Trang Province, Thailand [Mungkornasawakul et al, 2003].…”

Tuberostemonine O from the Roots of Stemona tuberosa

“…[2][3][4] There have been several reports that S. tuberosa containes stichoneurine-and croomine-types alkaloids such as tuberostemonine, neotuberostemonine, and stemoninine, while non-tuberosa group contains protostemonine type alkaloids.…”