 | |
 | |
| Names | |
|---|---|
| Preferred IUPAC name 5-Methylidenefuran-2(5H)-one | |
| Other names 4-Methylenebut-2-en-4-olide | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider |
|
| ECHA InfoCard | 100.003.244 |
| UNII | |
| |
| |
| Properties | |
| C5H4O2 | |
| Molar mass | 96.085 g·mol−1 |
| Appearance | Pale yellow oil |
| Boiling point | 73[2] °C (163 °F; 346 K) |
| Hazards | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 190 mg·kg−1 (mouse)[3] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Protoanemonin (sometimes calledanemonol orranunculol[4]) is atoxin whoseglycosidic precursorranunculin is found in many plants of thebuttercup family (Ranunculaceae). When the plant is wounded ormacerated,ranunculin isenzymatically broken down intoglucose and protoanemonin.[5][6] This toxin's ability to inhibit bothgram positive andgram negative bacteria is linked to the presence of a 5-memberedlactone ring with a highly reactive double bond system.[7]
 | ranunculin |
| ↓ –glucose | (maceration,enzymatically) |
| protoanemonin |
| ↓dimerization | (spontaneous) |
 | anemonin |
| ↓hydrolyzation | |
 | 4,7-dioxo-2-decenedioic acid |
Protoamenonin hasvesicant properties, which cause rashes or blistering upon contact with the skin ormucosa.[6] Ingesting large amounts of the toxin despite its bitter taste can causenausea, vomiting,dizziness,spasms, acutehepatitis,jaundice, orparalysis in animals and humans.[6][8][9][10][11]
At room temperature, protoanemonin spontaneouslydimerizes into the potentially therapeutic compoundanemonin, which can then be hydrolyzed into adicarboxylic acid.[5][12][13] As such, plants containing glycosidic precursors of protoanemonin are considered safe for humans to handle andlivestock to eat after being properly harvested and dried into hay. The hydrolization product of anemonin- anemoninic acid- is also non-toxic but lacks its potentially therapeutic antimicrobial activity, having lost the highly reactive unsaturatedlactone ring.[7] This makes anemonin of greater interest for the synthesis of therapeutic compounds.
A patent from 1955 describes a method for extracting protoanemonin from fresh plants, but the extract must be kept at nearly neutral pH and requires the addition of someradical scavenger to avoid spontaneous formation of anemonin.[12][14]Depending on the specific amount of added weak acid and storage temperature, solutions of extracted protoanemonin have been reported to be able to retain their potency for periods ranging from days to months.[12][15] Due to the variable stability of protoanemonin solutions obtained by complicated fresh plant extractions, reliable synthetic preparation has been pursued from many starting points. Methods starting from levulinic acid- widely used in the early 2000s- require tedious extraction steps and have been associated with difficult replication of results,[16] while a novel catalytic oxidation ofsilvan required extreme conditions.[17] In 2006, a paper was published detailing a convenient synthesis that proceeds through a crystal which is stable for storage at room temperature. When stirred withtriethylamine overnight, this solid affords protoanemonin with an 80% yield; Kotera and colleagues balance simplicity and efficiency well, as the overall yield of protoanemonin from this 4 step synthesis is 46%.[18]
 | 2-Deoxy-D-ribose |
| ↓ HCl, MeOH | |
| 2 | 1-O-Methyl-2-Deoxy-D-ribose |
| ↓ TolCl/pyridine | |
| 3 | |
| ↓ MCPBA/ BF3-OEt2 | |
| 4 | Crystalline solid; 58% overall yield |
| ↓ 5eq. NEt3 (stirred overnight) | 80% yield |
| Protoanemonin; 46% overall yield[18] |
The LD50 of protoanemonin in male Swiss albino mice was 190 mg/kg.
