Lycophlegmarinines A–F, new Lycopodium alkaloids from Phlegmariurus phlegmaria

Jiang, Jia-Meng; Xia, Dan; Zhu, Xin-Liu; Zhu, Dan; Yang, Xue-Wen; Pan, Ke

doi:10.1016/j.tet.2022.132782

Cited by 7 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…( 21 ) However, Pt 2OGD-3 did not consume 13 , and thus we hypothesized that N -deacetylation must precede this desaturation. Accordingly, we found an alpha/beta hydrolase family enzyme ( Pt ABH-1) within cluster131 that consumed 13 to produce the N -deacetylated compound lycophlegmarinine D ( 14 ),( 41 ) which verified the positioning of the carbonyl and double bond installed by Pt 2OGD-4 and Pt 2OGD-5, respectively ( Fig S11 ). Addition of Pt 2OGD-3 to the transiently co-expressed combination of Pt 2OGD-4, Pt 2OGD-5, and Pt ABH-1 led to the consumption of 14 and the formation of huperzine B ( 15 ) ( Fig S12 ), and the subsequent addition of Pt 2OGD-1 and Pt 2OGD-2 allowed for the complete stepwise conversion to huperzine C ( 16 ), and ultimately, 17 ( Fig 4a, Fig S13 ).…”

Section: Main Textmentioning

confidence: 64%

“…A selection of these results are compiled and listed in Fig 5. References for each of the IC 50 values for each of the compounds are cited as follows: lycophlegmarinine D ( 14 ) ( 41 ), huperzine B ( 15 ) ( 52 ), huperzine C ( 16 )( 52 ), huperzine A ( 17 ) ( 53 ), des- N -methyl-a-obscurine ( 18 ) ( 54 ), des-N-methyl-b-obscurine ( 19 ) ( 55 ), casuarinine H ( 20 ) ( 56 ), 8,15-dihydrohuperzine A ( 21 ) ( 57 ), lycoplatyrine B ( 24 ) ( 40 ). Compounds annotated as “low/not detected” were not found to have AChE inhibition within the detectable range of each experiment in question (typically, IC 50 values in these experiments were not measurable, or were greater than 30 µM).…”

Section: Methodsmentioning

confidence: 99%

“…(-)-allosedridine) were provided by Professor Paul Evans (University College Dublin). An authentic standard of lycophlegmarinine D ( 14) isolated from Phlegmariurus phlegmaria (41) was provided by Professor Ke Pan (China Pharmaceutical University) and 8,15-dihydrohuperzine (21) was provided by Professor Richmond Sarpong (University of California, Berkeley). (15) The following Lycopodium alkaloids were previously isolated from Lycopodium platyrhizoma (40): flabellidine (10), des-N-methyl-alpha-obscurine (18), des-N-methyl-beta-obscurine (19), casuarinine H (20), and lycoplatyrine B (24).…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

See 2 more Smart Citations

Neofunctionalized carbonic anhydrases in the biosynthesis of neuroactive plant alkaloids

Nett

Dho

Tsai

et al. 2022

Preprint

View full text Add to dashboard Cite

Plants synthesize numerous alkaloids that mimic animal neurotransmitters. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds. However, many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known. By studying highly coordinated, tissue-specific gene expression in plants that produce neuroactive Lycopodium alkaloids, we identified a new enzyme class for alkaloid biosynthesis: neofunctionalized α-carbonic anhydrases (CAHs). We show that three CAH-like (CAL) enzymes are involved in a cryptic biosynthetic route to a key bicyclic precursor of the Lycopodium alkaloids, and additionally, we describe a series of oxidative tailoring steps that generate the optimized acetylcholinesterase inhibition activity of huperzine A. Our findings suggest a broader involvement of CAL enzymes in specialized metabolism and provide an example for how successive scaffold tailoring steps can drive potency against a natural protein target of interest.

show abstract

Section: Main Textmentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Chemicals and Reagentsmentioning

confidence: 99%

See 1 more Smart Citation

Neofunctionalized carbonic anhydrases in the biosynthesis of neuroactive plant alkaloids

Nett

Dho

Tsai

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The twelve known LAs (2-13) were identified as phlegmariurine B (2), [16,18] lycopodatine C (3), [19] lycoposerramine-K (4), [20] lycodine (5), lycophlegmarinine E (6), [21] huperzine A (7), huperzine C (8), [22] fawcettidine (9), lycoflexine (10), [23] 14,15-dehydrolycoflexine (11), carinatine A ( 12), and huperzine W (13) [24] by comparing the reported 1D NMR data in literature.…”

Section: Resultsmentioning

confidence: 99%

Lycopodium Alkaloids from Phlegmariurus carinatus with Cytotoxic and Neuroprotective Effects

Wang,

Zheng,

Jiang

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

One new fawcettimine‐type alkaloid, phlecarinadine A (1), and twelve known ones (2–13) were isolated from the whole plant of Phlegmariurus carinatus. Their chemical structures were unambiguously established by extensive spectroscopic analyses, including nuclear magnetic resonance (NMR) spectroscopic and high resolution electrospray ionization mass spectrometry (HR‐ESI‐MS). The absolute configuration of 1 was elucidated by the electronic circular dichroism (ECD) technique. These compounds were tested for their cytotoxic and neuroprotective activities. None of these compounds revealed cytotoxic activity against five tumor cells. Phlegmariurine B (2) exhibited potential neuroprotective effects against hemin‐induced HT22 cell damage, with a 17.76% increase in cell survival at 10 μM. In further study, 2 can ameliorate hemin‐induced neuronal cell death via an anti‐apoptotic pathway. These findings suggest that 2 might be a valuable lead compound with neuroprotective activity.

show abstract

“…2 Lycophlegmarinine A 3 , from Phlegmariurus phlegmaria , is a cleaved Lycodpodium alkaloid with a new ring system. 3 Massinidine 4 is an antiplasmodial metabolite of Massilia sp. NR 4-1 with an unusual structure.…”

mentioning

confidence: 99%