amygdalin

Amygdalin
IUPAC name	[(6-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy](phenyl)acetonitrile
Identifiers
CAS number	29883-15-6
PubChem	34751
MeSH	Amygdalin
SMILES	O[C@@H]3[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]3OC[C@H]2O[C@@H](OC(C#N)c1ccccc1)[C@H](O)[C@@H](O)[C@@H]2O
Properties
Molecular formula	C20H27NO11
Molar mass	457.43 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Amygdalin (from Greek: ἀμυγδάλη amygdálē “almond”), C₂₀H₂₇NO₁₁, is a glycoside initially isolated from the seeds of the tree Prunus dulcis, also known as bitter almonds, by Pierre-Jean Robiquet^[1] and A. F. Boutron-Charlard in 1803, and subsequently investigated by Liebig and Wöhler in 1830, and others. Several other related species in the genus of Prunus, including apricot (Prunus armeniaca) and black cherry (Prunus serotina),^[2] also contain amygdalin. It was promoted as a cancer cure by Ernst T. Krebs under the name "Vitamin B17", but studies have found it to be ineffective.^[3][4][5]

Chemistry

Amygdalin is extracted from almond or apricot kernel cake by boiling ethanol; on evaporation of the solution and the addition of diethyl ether, amygdalin is precipitated as white minute crystals. Liebig and Wöhler were already able to find three decomposition products of the newly discovered amygdalin: sugar, benzaldehyde, and prussic acid (hydrogen cyanide).^[6] Later research showed that sulfuric acid decomposes it into D-glucose, benzaldehyde, and prussic acid ; while hydrochloric acid gives mandelic acid, D-glucose, and ammonia.^[7]

The decomposition induced by enzymes may occur in two ways. Maltase partially decomposes it, giving D-glucose and mandelic nitrile glucoside, C₆H₅CH(CN)O·C₆H₁₁O₅; this compound is isomeric with sambunigrin, a glucoside found by E.E. Bourquelot and Danjou in the berries of the Common Elder, Sambucus nigra. Emulsin, on the other hand, decomposes it into benzaldehyde, cyanide, and two molecules of glucose; this enzyme occurs in the bitter almond, and consequently the seeds invariably contain free cyanide and benzaldehyde. An "amorphous amygdalin" is said to occur in the cherry-laurel. Closely related to these glucosides is dhurrin, C₁₄H₁₇O₇N, isolated by W. Dunstan and T. A. Henry from the common sorghum or "great millet," Sorghum vulgare; this substance is decomposed by emulsin or hydrochloric acid into D-glucose, cyanide, and 4-hydroxybenzaldehyde.^{[citation needed]}

Natural amygdalin has the R configuration at the chiral benzyl center. Under mild basic conditions, this stereogenic center epimerizes; the S epimer is called neoamygdalin.^[8]

Laetrile

Laetrile (CAS No. 1332-94-1)

Amygdalin is sometimes confounded with laevomandelonitrile, also called laetrile for short; however, amygdalin and laetrile are different chemical compounds.^[8] Laetrile, which was patented in the United States, is a semi-synthetic molecule sharing part of the amygdalin structure, while the "laetrile" made in Mexico is usually amygdalin, the natural product obtained from crushed apricot pits, or neoamygdalin.^[9]

Though it is sometimes sold as "Vitamin B17", it is not a vitamin. Amygdalin/laetrile was claimed to be a vitamin by Ernst T. Krebs in the hope that if classified as a nutritional supplement it would escape the federal legislation regarding the marketing of drugs. He could also capitalise on the public fad for vitamins at that time.^[10]

Toxicity

Beta-glucosidase, one of the enzymes that catalyzes the release of the cyanide from amygdalin, is present in human small intestine and in a variety of common foods. This leads to an unpredictable and potentially lethal toxicity when amygdalin or laetrile is taken orally.^[10][11][12]

Cancer treatment

Amygdalin was first isolated in 1830. In 1845 it was used for cancer in Russia, and again in the 1920s in the United States, but it was considered too poisonous.^[13] In the 1950s a reportedly nontoxic, synthetic form was patented for use as a meat preservative,^[14] and later marketed as laetrile for cancer treatment.^[13]

Initial studies at Sloan-Kettering

In 1972, Memorial Sloan-Kettering Cancer Center (MSKCC) board member Benno C. Schmidt, Sr. convinced the hospital to test laetrile so that he could assure others of its ineffectiveness "with some conviction."^[15] However, the scientist in charge of the testing, Kanematsu Sugiura, found that laetrile inhibited the secondary tumors in mice, though it did not destroy the primary tumors. He repeated the experiment several times with the same results. However, three other researchers were unable to confirm Sugiura's results. While these uncontrolled results were considered too preliminary to publish, they were leaked to laetrile advocates, resulting in significant public attention.^[15]

To expand on Sugiura's results, MSKCC researchers conducted a controlled experiment in which they injected some mice with laetrile (as Sugiura had done) and others with placebo. Sugiura, who was unaware of which mice had received laetrile, performed the pathologic analysis. In this controlled, blinded follow-up of Sugiura's initial uncontrolled experiment, laetrile showed no more activity than placebo.^[15]

Subsequently, laetrile was tested on 14 tumor systems without evidence of effectiveness. Given this collection of results, MSKCC concluded that "laetrile showed no beneficial effects."^[15] Minor mistakes in the MSKCC press release were highlighted by a group of laetrile proponents led by Ralph Moss, former public affairs official of MSKCC who was fired following his appearance at a press conference accusing the hospital of covering up the benefits of laetrile.^[16] These mistakes were considered scientifically inconsequential, but Nicholas Wade in Science stated that "even the appearance of a departure from strict objectivity is unfortunate."^[15] The results from these studies were published all together.^[17]

Subsequent clinical studies and advocacy

In 1974, the American Cancer Society officially labelled laetrile as quackery, but advocates for laetrile dispute this label, asserting that financial motivations have tainted the published research.^[18] Some North American cancer patients have travelled to Mexico for treatment with the substance, allegedly under the auspices of Dr. Ernesto Contreras.^[19] One of these patients was actor Steve McQueen, who died in Mexico following surgery to remove a stomach tumour while undergoing treatment for mesothelioma.^[20] Laetrile advocates within the United States include Dean Burk Ph.D.,^[21] a former chief chemist of the National Cancer Institute's cytochemistry laboratory^[22] and national arm wrestling champion Jason Vale, who claimed that his kidney and pancreatic cancers were cured by eating apricot seeds. Vale was convicted in 2003 for, among other things, marketing laetrile.^[23] The US Food and Drug Administration continues to seek jail sentences for vendors selling laetrile for cancer treatment, calling it a "highly toxic product that has not shown any effect on treating cancer."^[24]

A 2006 systematic review by the Cochrane Collaboration concluded: "The claim that [l]aetrile has beneficial effects for cancer patients is not supported by data from controlled clinical trials. This systematic review has clearly identified the need for randomised or controlled clinical trials assessing the effectiveness of [l]aetrile or amygdalin for cancer treatment."^[25] Given the lack of evidence, laetrile has not been approved by the U.S. Food and Drug Administration.^[9] The U.S. National Institutes of Health evaluated the evidence separately and concluded that clinical trials of amgydalin showed little or no effect against cancer.^[13] For example, a 1982 trial of 178 patients found that tumor size had increased in all patients. Minimal side effects were seen except in two patients who consumed bitter almonds and suffered from cyanide poisoning.^[5]

See also

• United States v. Rutherford, 442 U.S. 544 (1979). Finding: The Federal Food, Drug, and Cosmetic Act makes no express exception for drugs used by the terminally ill and no implied exemption is necessary to attain congressional objectives or to avert an unreasonable reading of the terms "safe" and "effective" in 201 (p) (1).

References

• This article incorporates text from the article "Amygdalin" in the Encyclopædia Britannica, Eleventh Edition, a publication now in the public domain.

External links

• Laetrile/Amygdalin information from the U.S. National Cancer Institute
• Laetrile treatment for cancer, from the Cochrane Library
• Food and Drug Administration Commissioner's Decision on Laetrile