Lactone

Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (–(C=O)–O–), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (–(C=O)–O–), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the corresponding hydroxycarboxylic acids, which takes place spontaneously when the ring that is formed is five- or six-membered. Lactones with three- or four-membered rings (α-lactones and β-lactones) are very reactive, making their isolation difficult. Special methods are normally required for the laboratory synthesis of small-ring lactones as well as those that contain rings larger than six-membered. Lactones are usually named according to the precursor acid molecule (aceto = 2 carbon atoms, propio = 3, butyro = 4, valero = 5, capro = 6, etc.), with a -lactone suffix and a Greek letter prefix that specifies the number of carbon atoms in the heterocycle — that is, the distance between the relevant -OH and the -COOH groups along said backbone. The first carbon atom after the carbon in the -COOH group on the parent compound is labelled α, the second will be labeled β, and so forth. Therefore, the prefixes also indicate the size of the lactone ring: α-lactone = 3-membered ring, β-lactone = 4-membered, γ-lactone = 5-membered, etc. The other suffix used to denote a lactone is -olide, used in substance class names like butenolide, macrolide, cardenolide or bufadienolide. To obtain the preferred IUPAC names, lactones are named as heterocyclic pseudoketones by adding the suffix ‘one’, ‘dione’, ‘thione’, etc. and the appropriate multiplicative prefixes to the name of the heterocyclic parent hydride. The name lactone derives from the ring compound called lactide, which is formed from the dehydration of 2-hydroxypropanoic acid (lactic acid) CH3-CH(OH)-COOH. Lactic acid, in turn, derives its name from its original isolation from soured milk (Latin: lac, lactis). An internal dehydration within the same molecule of lactic acid would have produced alpha-propiolactone, a lactone with a 3-membered ring. Naturally occurring lactones are mainly saturated and unsaturated γ- and δ-lactones, and to a lesser extent macrocyclic lactones. The γ- and δ-lactones are intramolecular esters of the corresponding hydroxy fatty acids. They contribute to the aroma of fruits, butter, cheese, and other foods. Cyclopentadecanolide is responsible for the musklike odor of angelica root oil. Of the naturally occurring bicyclic lactones, phthalides are responsible for the odors of celery and lovage oils, and coumarin for woodruff. Lactone rings occur widely as building blocks in nature, such as in ascorbic acid, kavain, nepetalactone, gluconolactone, hormones (spironolactone, mevalonolactone), enzymes (lactonase), neurotransmitters (butyrolactone, avermectins), antibiotics (macrolides like erythromycin; amphotericin B), anticancer drugs (vernolepin, epothilones), phytoestrogens (resorcylic acid lactones, cardiac glycosides). Many methods in ester synthesis can also be applied to that of lactones. In one industrial synthesis of oxandrolone the key lactone-forming step is an organic reduction - esterification.