Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. J Nat Prod. 2022 Sep 23;85(9):2199-2206. doi: 10.1021/acs.jnatprod.2c00588.
Epub  2022 Aug 22.

Isolation and Biological Activity of 9-epiTetrodotoxin and Isolation of Tb-242B, 
Possible Biosynthetic Shunt Products of Tetrodotoxin from Pufferfish.

Yaegashi Y(1), Kudo Y(1)(2), Ueyama N(1), Onodera KI(3), Cho Y(1), Konoki K(1), 
Yotsu-Yamashita M(1).

Author information:
(1)Graduate School of Agricultural Science, Tohoku University, 468-1 
Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi 980-8572, Japan.
(2)Frontier Research Institute for Interdisciplinary Sciences, Tohoku 
University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
(3)Faculty of Agriculture and Marine Sciences, Kochi University, 200 Otsu, 
Monobe, Nankoku, Kochi 783-8502, Japan.

Tetrodotoxin (TTX, 1) is a potent voltage-gated sodium channel blocker detected 
in certain marine and terrestrial organisms. We report here a new TTX analogue, 
9-epiTTX (2), and a TTX-related compound, Tb-242B (4), isolated from the 
pufferfish Takifugu flavipterus and Dichotomyctere ocellatus, respectively. NMR 
analysis suggested that 2 exists as a mixture of hemilactal and 10,8-lactone 
forms, whereas other reported TTX analogues are commonly present as an 
equilibrium mixture of hemilactal and 10,7-lactone forms. Compound 2 and TTX 
were confirmed not to convert to each other by incubation under neutral and 
acidic conditions at 37 °C for 24 h. Compound 4 was identified as the 9-epimer 
of Tb-242A (3), previously reported as a possible biosynthetic precursor of TTX. 
Compound 4 was partially converted to 3 by incubation in a neutral buffer at 37 
°C for 7 days, whereas 3 was not converted to 4 under this condition. Compound 2 
was detected in several TTX-containing marine animals and a newt. Mice injected 
with 600 ng of 2 by intraperitoneal injection did not show any adverse symptoms, 
suggesting that the C-9 configuration in TTX is critical for its biological 
activity. Based on the structures, 2 and 4 were predicted to be shunt products 
for TTX biosynthesis.

DOI: 10.1021/acs.jnatprod.2c00588
PMID: 35994072 [Indexed for MEDLINE]


2. Chem Commun (Camb). 2016 Jan 18;52(5):1002-5. doi: 10.1039/c5cc08324a.

The total synthesis and stereochemical assignment of scytonemin A.

Liu J(1), Wang L(2), Zhang J(2), Xu Z(2), Ye T(1).

Author information:
(1)Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, 
University Town, Xili, Shenzhen, 518055, China. yet@pkusz.edu.cn 
xuzs@pkusz.edu.cn and Department of Applied Biology & Chemical Technology, The 
Hong Kong Polytechnic University, Hong Kong, China.
(2)Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, 
University Town, Xili, Shenzhen, 518055, China. yet@pkusz.edu.cn 
xuzs@pkusz.edu.cn.

The total synthesis of scytonemin A and its C-9 epimer, as well as elucidation 
of the absolute stereochemistry of natural scytonemin A is described.

DOI: 10.1039/c5cc08324a
PMID: 26593048 [Indexed for MEDLINE]


3. J Org Chem. 2013 Mar 15;78(6):2213-47. doi: 10.1021/jo3026077. Epub 2013 Feb
13.

Amphidinolide B: total synthesis, structural investigation, and biological 
evaluation.

Lu L(1), Zhang W, Nam S, Horne DA, Jove R, Carter RG.

Author information:
(1)Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, 
United States.

The total syntheses of amphidinolide B1 and the proposed structure of 
amphidinolide B2 have been accomplished. Key aspects of this work include the 
development of a practical, non-transition-metal-mediated method for the 
construction of the C13-C15 diene, the identification of α-chelation and dipole 
minimization models for diastereoselective methyl ketone aldol reactions, the 
discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, 
and the development of a novel late stage method for construction of an allylic 
epoxide moiety. The originally proposed structure for amphidinolide B2 and 
diastereomers thereof display potent antitumor activities with IC50 values 
ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the 
different stereoisomers, the proposed structure of amphidinolide B2 is over 
12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate 
cancer cells. These data suggest that the epoxide stereochemistry is a 
significant factor for anticancer activity.

DOI: 10.1021/jo3026077
PMCID: PMC3631602
PMID: 23406192 [Indexed for MEDLINE]


4. Org Lett. 2007 Nov 8;9(23):4713-6. doi: 10.1021/ol701999h. Epub 2007 Oct 19.

Asymmetric CuH-catalyzed hydrosilylations en route to the C-9 epimer of 
amphidinoketide iota.

Lipshutz BH(1), Lee CT, Servesko JM.

Author information:
(1)Department of Chemistry and Biochemistry, University of California, Santa 
Barbara, CA 93106, USA. lipshutz@chem.ucsb.edu

The C-9 diastereomer of amphidinoketide I has been synthesized. An asymmetric 
CuH-catalyzed hydrosilylation based on the Solvias nonracemic Josiphos-related 
ligand (R,S)-PPF-P(t-Bu)2 was successfully used to introduce each of three 
stereocenters found in the target compound.

DOI: 10.1021/ol701999h
PMID: 17949006


5. Nat Prod Res. 2006 Dec;20(14):1321-5. doi: 10.1080/14786410601101969.

9-epi-Viridiol, a novel cytotoxic furanosteroid from soil fungus Trichoderma 
virens.

Phuwapraisirisan P(1), Rangsan J, Siripong P, Tip-Pyang S.

Author information:
(1)Natural Product Research Unit, Department of Chemistry, Faculty of Science, 
Chulalongkorn University, Bangkok 10330, Thailand. preecha.p@chula.ac.th

A novel furanosteroid named 9-epi-viridiol (1), along with viridiol (2) and 
mevalonic acid (3), was isolated from Trichoderma virens. The structure of 1 was 
verified by combined spectroscopic data (COSY, HSQC, HMBC and NOESY) to be a C-9 
epimer of viridiol. 9-epi-Viridiol exhibited cytotoxicity towards HeLa and KB 
cells with IC50 values of 19 and 50 microg mL(-1), respectively.

DOI: 10.1080/14786410601101969
PMID: 17393658 [Indexed for MEDLINE]