Phytochemical Investigations of Stemona curtisii and Synthetic Studies on Stemocurtisine Alkaloids

Abstract

The isolation of two new Stemona alkaloids, 1-hydroxyprotostemonine and stemocurtisine N-oxide, and a new benzofuran, stemofuran L, from the root extracts of Stemona curtisii is reported. The major known alkaloids from this plant extract, stemocurtisine, stemocurtisinol, and oxyprotostemonine, were also isolated along with oxystemokerrine N-oxide. The nonalkaloid components of this extract included a new benzofuran derivative, stemofuran L, the known stemofurans F, J, and K, dihydro-γ-tocopherol, and stigmasterol. Stemocurtisine and stemocurtisinol were converted to their respective N-oxides by oxidation. Stemocurtisine was converted to a tetracyclic derivative by oxidative cleavage of the γ-butyrolactone ring, while stemocurtisinol gave a novel lactam derivative by oxidative cleavage of the C-4 side chain under basic conditions. The acetylcholinesterase inhibitory activities of some known and new alkaloids and their derivatives are also reported. All were 10-20 times less active as acetylcholinesterase inhibitors than the pyrrolo[1,2-a]azepine Stemona alkaloids stemofoline and 1',2'-didehydrostemofoline. None of the stemofuran compounds showed significant antibacterial or antifungal activities.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…Interestingly,exposure of 32 to air resulted in rapid formation of oxidative fragmentation product 34 in 24 %y ield from 20.F ormation of 34 from 32 can be rationalized by initial air oxidation at C2 followed by intramolecular cyclization of the resulting hydroperoxide intermediate to produce the dioxetane 33. [27,28] Thedioxetane moiety in 33 can then undergo ar ing opening and be transformed into the lactam and carboxylic acid moiety present in 34. [29] Notably,r ecently isolated natural product flueggeacosine B(35) [30] consists of the molecular framework of 34 and hints at the plausibility of as imilar oxidative ringcleavage event during its biosynthesis.F urthermore,t he experimentally discovered inherent chemical propensity of 32 to undergo facile air oxidation and subsequent bond scission undermined the originally proposed biosynthetic pathway of 13,apathway that involves the C2-epimer of 32 (see Scheme S1).…”

Structural classification and biological activities of Stemona alkaloids

“…It was found that didehydrostemofoline (173) and (3 0 S)-hydroxystemofoline (166) were clearly the most active (Baird et al 2009). By contrast, the pyridoazepine alkaloids stemocurtisinol (188), stemocurtisine (191) and four synthetic analogues as well as the pyrroloazepine oxyprotostemonine (141) where shown to be 10-20 times less active (Chaiyong et al 2010). Starting with the highly active 173 the same working group prepared a number of related analogues with modifications in the C-3 butyl side chain and screened their AChE inhibitory reverse multidrug resistance through inhibition of permeability glycoprotein (P-gp) function (Umsumarng et al 2015) the cage-type structure is pivotal for the high insecticidal activity acting as agonist at nicotinic acetylcholine receptors (Tang et al 2008) acetylcholinesterase-inhibiting activity is 10-20 times higher than that of pyridoazepine-type derivatives (Chaiyong et al 2010) Fig.…”

“…In continuation of previous investigations on insecticidal activities (Sakata et al 1978;Jiwajinda et al 2001;Brem et al 2002;Kaltenegger et al 2003) follow-up studies focused on the mode of action by using biochemical and electrophysiological approaches (Tang et al 2008). With regard to the acetylcholinesterase inhibiting properties of Stemona alkaloids, bioassays with naturally-occurring as well as synthetically prepared derivatives informed about structure-activity relationships (Wang et al 2007a;Baird et al 2009;Chaiyong et al 2010;Sastraruji et al 2010Sastraruji et al , 2012Ramli et al 2013Ramli et al , 2014Lai et al 2013). Following the first report on multidrug resistance properties of an ethanolic extract of Stemona aphylla (Limtrakul et al 2007), a series of studies evaluated the synergistic growth inhibitory effect of Stemona alkaloids with cancer chemotherapeutic agents (Chanmahasathien et al 2011a, b;Umsumarng et al 2013Umsumarng et al , 2015Umsumarng et al , 2017Umsumarng et al , 2018.…”

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…Interestingly, exposure of 32 to air resulted in rapid formation of oxidative fragmentation product 34 in 24 % yield from 20 . Formation of 34 from 32 can be rationalized by initial air oxidation at C2 followed by intramolecular cyclization of the resulting hydroperoxide intermediate to produce the dioxetane 33 . The dioxetane moiety in 33 can then undergo a ring opening and be transformed into the lactam and carboxylic acid moiety present in 34 .…”