6-Deoxy- and 11-Hydroxytolypodiols: Meroterpenoids from the Cyanobacterium HT-58-2

Abstract

Chemical investigation of cyanobacterial strain HT-58-2, which most closely aligns with the genus Brasilomena, has led to the isolation of two compounds related to tolypodiol. The structures and absolute configuration of 6-deoxytolypodiol (1) and 11-hydroxytolypodiol (2) were elucidated by spectroscopic and spectrometric analysis. While tolypodiol previously showed anti-inflammatory activity in a mouse ear edema assay, only 2 reduced in vitro thromboxane B2 and superoxide anion (O2 –) generation from Escherichia coli lipopolysaccharide-activated rat neonatal microglia to any appreciable degree.

Marine natural products

“…Chemical investigation of a cyanobacterial strain most closely aligned with the genus Brasilomena , led to the identification of meroterpenoids, 6-deoxytolypodiol 294 and 11-hydroxytolypodiol 295 . 119 A cyclic carbonate-containing sesquiterpenoid named eudesmacarbonate 296 was isolated from cyanobacterial mats that were implicated in intoxications of captive bottlenose dolphins following ingestion. Sequencing of 16S rDNA showed the mats were composed of closely related Oscillatoriaceae species including a previously unreported species of Neolyngbya .…”

Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

“…Moreover 6-deoxytolypodiol (428) and 11-hydroxytolypodiol (429) were produced by cyanobacterial sources. Only compound 430 displayed potent antiinflammatory effects with IC 50 : 0.1 µM while the same compound possessed similar levels of TXB 2 inhibitory effects as NSAID flurbiprofen [131]. Hyperprins A (431) and B (432) were produced by Hypericum przewalskii and both compounds featured a 6/6/6/6/5/5 hexacyclic core and a 6/8/6/6 tetracyclic system respectively [132].…”

Natural Product Gene Clusters in the Filamentous Nostocales Cyanobacterium HT-58-2

“…Tolyporphin A was found to inhibit efflux pump activity and thereby reverse multidrug resistance (MDR) in tumor cells [1,3,4]. Tolypodiols and analogues were evaluated for anti-inflammatory properties germane to neurological disorders [13,14]. In contrast with the intriguing reports concerning bioactive properties, the biosynthetic pathways to tolyporphins and tolypodiols have been little explored, and essentially nothing is known concerning the functional roles of these natural products in the cyanobacterium and associated community bacteria.…”

“…Recently, two tolypodiol analogues, 6-deoxytolypodiol and 11-hydroxytolypodiol, were also found in extracts from the HT-58-2 culture. The structures and absolute configuration of the two tolypodiol analogues were determined, and the compounds were assayed for anti-inflammatory activity [14]. Prior work [9] annotating the genome of the Nostocales HT-58-2 suggested numerous genes for diverse functions, but did not delve deeply into the BGCs of natural products, including those for tolypodiols.…”