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| Names | |
|---|---|
| Preferred IUPAC name 1,1′,6,6′,7,7′-Hexahydroxy-3,3′-dimethyl-5,5′-di(propan-2-yl)[2,2′-binaphthalene]-8,8′-dicarbaldehyde | |
| Identifiers | |
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3D model (JSmol) | |
| ChEMBL | |
| ChemSpider |
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| DrugBank | |
| ECHA InfoCard | 100.164.654 |
| KEGG |
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| UNII | |
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| Properties | |
| C30H30O8 | |
| Molar mass | 518.562 g·mol−1 |
| Appearance | Brown solid |
| Density | 1.4 g/mL |
| Melting point | 177 to 182 °C (351 to 360 °F; 450 to 455 K) (decomposes) |
| Boiling point | 707 °C (1,305 °F; 980 K) |
| Hazards | |
| GHS labelling: | |
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| Warning | |
| H351 | |
| P201,P202,P281,P308+P313,P405,P501 | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Gossypol (/ˈɡɒsəpɒl/) is anatural phenol derived from the cotton plant (genusGossypium). Gossypol is a phenolicaldehyde that permeates cells and acts as aninhibitor for severaldehydrogenaseenzymes. It is a yellowpigment. The structure exhibitsatropisomerism, with the twoenantiomers having different biochemical properties.[1]
Among other applications, it has been tested as amale oral contraceptive inChina. In addition to its putative contraceptive properties, gossypol has also long been known to possessantimalarial properties.[2]
Utilization of cotton-seed oil in the 19th century was complicated by the fact that it stained everything. In 1882-1883 James Longmore from Liverpool took several patents on separating the colorant by partialsaponification of the oil,[3][4] and in 1886 he presented his findings to the local section of theSociety of Chemical Industry.[5] He is often considered the discoverer of gossypol, even though he only isolated it in crude form.[6]
The name was coined in 1899 byLeon Marchlewski, who first purified the compound and studied some of its chemical properties.[7] W. A. Withers and F. E. Carruth first attributed the toxic properties of the cotton seed (known since the 19th c.) to gossypol in 1915,[8] and its chemical formula was established in 1927 by Earl Perry Clark (1892-1943).[9]
Gossypol is aterpenoidaldehyde which is formed metabolically throughacetate via theisoprenoid pathway.[10] Thesesquiterpene dimer undergoes a radical coupling reaction to form gossypol.[11] The biosynthesis begins whengeranyl pyrophosphate (GPP) andisopentenyl pyrophosphate (IPP) are combined to make thesesquiterpene precursorfarnesyl diphosphate (FPP). The cadinyl cation (1) is oxidized to2 by(+)-δ-cadinene synthase. The(+)-δ-cadinene (2) is involved in making the basic aromatic sesquiterpene unit, homigossypol, by oxidation, which generates the3 (8-hydroxy-δ-cadinene) with the help of (+)-δ-cadinene 8-hyroxylase. Compound3 goes through various oxidative processes to make4 (deoxyhemigossypol), which is oxidized by one electron into hemigossypol (5,6,7) and then undergoes a phenolicoxidative coupling,ortho to the phenol groups, to form gossypol (8).[12] The coupling is catalyzed by ahydrogen peroxide-dependentperoxidase enzyme, which results in the final product.[12]
A 1929 investigation inJiangxi showed correlation between lowfertility in males and use of crudecottonseed oil for cooking. The compound causing the contraceptive effect was determined to be gossypol.[13]In the 1970s, theChinese government began researching the use of gossypol as acontraceptive. Their studies involved over 10,000 subjects, and continued for over a decade. They concluded that gossypol provided reliable contraception, could be taken orally as a tablet, and did not upset men's balance of hormones.
However, gossypol also had serious flaws. The studies also discovered an abnormally high rate (0.75%) ofhypokalemia (low bloodpotassium levels) among subjects.[13][14] Hypokalemia causes symptoms offatigue, muscle weakness, and at its most extreme,paralysis. In addition, about 7% of subjects reported effects on theirdigestive systems,[13] about 12% had increased fatigue, some subjects experienced impotence or reduced libido, and 9.9% became irreversibly infertile, apparently associated with longer treatment and greater total dose of gossypol.[13] Most subjects recovered after stopping treatment and taking potassium supplements. The same study showed taking potassium supplements during gossypol treatment did not prevent hypokalemia inprimates.[14] The potassium deficiency may also be a result of the Chinese diet or genetic predisposition.[14]
In the mid-1990s, the Brazilian pharmaceutical company Hebron announced plans to market a low-dose gossypol pill called Nofertil, but the pill never came to market. Its release was indefinitely postponed due to unacceptably high rates of permanent infertility.[citation needed] 5% to 25% of the men remainedazoospermic up to a year after stopping treatment.[14]
Researchers have suggested gossypol might make a good noninvasive alternative to surgicalvasectomy.[15]
In 1986, in conjunction with the Chinese Ministry of Public Health and theRockefeller Foundation, theWorld Health Organization formalized a decision to discontinue research into gossypol as a male contraceptive drug.[16] In addition to the other side effects, the WHO researchers were concerned about gossypol's toxicity: theLD50 in primates is less than 10 times the contraceptive dose,[14] creating a smalltherapeutic window. This report effectively ended further studies of gossypol as a temporary contraceptive, but research into using it as an alternative to vasectomy continues in Austria, Brazil, Chile, China, the Dominican Republic, and Nigeria.
Food and animal agricultural industries must manage cotton-derivative product levels to avoid toxicity. For example, onlyruminantmicroflora can digest gossypol, and then only to a certain level, andcottonseed oil must be refined.Genetically engineered cotton plants that contain little gossypol in the seed may still contain the compound in the stems and leaves.[17]
Media related toGossypol at Wikimedia Commons
