Pumiliotoxin 251D

Pumiliotoxin 251D

Names
IUPAC name (8R,8aS)-8-methyl-6-[(2R)-2-methylhexylidene]-1,2,3,5,7,8a-hexahydroindolizine-8-ol
Other names Pumiliotoxin 251D
Identifiers
CAS Number	73376-35-9 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:35596 Y
ChemSpider	4944741 N
PubChem CID	6440480
InChI InChI=1S/C16H29NO/c1-4-5-7-13(2)10-14-11-16(3,18)15-8-6-9-17(15)12-14/h10,13,15,18H,4-9,11-12H2,1-3H3/b14-10-/t13-,15+,16+/m1/s1 N Key: OKTQTXDNHCOLHT-AJKPHIATSA-N N InChI=1/C16H29NO/c1-4-5-7-13(2)10-14-11-16(3,18)15-8-6-9-17(15)12-14/h10,13,15,18H,4-9,11-12H2,1-3H3/b14-10-/t13-,15+,16+/m1/s1 Key: OKTQTXDNHCOLHT-AJKPHIATBP
SMILES O[C@]1(CC(=C\[C@H](C)CCCC)\CN2[C@H]1CCC2)C
Properties
Chemical formula	C16H29NO
Molar mass	251.41 g·mol−1
Hazards
Main hazards	Toxic
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N  (what is YN ?)
Infobox references

Pumiliotoxin 251D is a toxic organic compound. It is found in the skin of poison frogs from the Dendrobates, Epipedobates, Minyobates, and Phyllobates genera and toads from the Melanophryniscus genus. Its name comes from the pumiliotoxin family (PTXs) and its molecular mass of 251 Daltons. When the toxin enters the bloodstream through cuts in the skin or by ingestion, it can cause hyperactivity, convulsions, cardiac arrest and ultimately death. It is especially toxic to arthropods (e.g. mosquitoes), even at low (naturally occurring) concentrations.

The chiral centers in pumiliotoxin 251D can give several stereoisomers of the compound. Only one form of the toxin is present in nature and has toxic properties.

Two enantiomers of pumiliotoxin 251D. On the left the plus enantiomer is shown which is toxic. On the right side the minus enantiomer, which is not toxic, is shown.

The side chain conformation of substituents at the C-2’ position plays an important role in the toxicity of the compound.

The synthesis of pumiliotoxin 251D is quite complex and contains multiple steps.

One of the starting materials of the synthesis include the N-Boc derivative of L-proline methyl ester (1). Then, a Wittig type of reaction followed by dehydration with thionyl chloride and pyridine results in alkene 2. When alkene 2 undergoes epoxidation with m-chloroperbenzoic acid (MCPBA), epoxide 3 is formed. This then reacts with the lithium salt of dibromoalkene (6) to afford compound 7. Deprotection of compound 7 followed by cyclization and iodination results in vinyl iodide 8. After purification, this yields the hydrochloride of pumiliotoxin (+)-251D (9).

Pumiliotoxin (-)-251D can be synthesized in a similar way with minor alterations to the overall synthesis.