acid is a monocarboxylic β-hydroxy acid and natural product with the molecular formula . At room temperature, pure acid occurs as a transparent, colorless to light yellow liquid which is soluble in water. acid is a weak acid with a pKa of 4.4. Its refractive index () is 1.42. Chemical structure acid is a member of the carboxylic acid family of organic compounds. It is a structural analog of butyric acid with a<unk> l functional group and a methyl substituent located on its<unk>  carbon. By extension, other structural analogs include acid and acid. Synthesis A variety of synthetic routes to acid have been developed. The first reported chemical syntheses approached HMB by oxidation of alkene, vicinal diol, and alcohol precursors: * in 1877, Russian chemists Michael and Alexander Zaytsev reported the preparation of HMB by oxidation of 2-methylpent-4-en-2-ol with chromic acid (H2CrO4); * in 1880 and 1889, Schirokoff and Reformatsky (respectively) reported that the oxidative cleavage of the vicinal diol 4-methylpentane-1,2,4-triol with acidified potassium permanganate (KMnO4) yields HMB – this result is closest related to the first synthesis as cold dilute KMnO4 oxidises alkenes to vicinal cis-diols which hot acid KMnO4 further oxidises to carbonyl-containing compounds, and the diol intermediate is not obtained when hot acidic conditions are used for alkene oxidation. In other words, racemic 4-methylpentane-1,2,4-triol is a derivative of 2-methylpent-4-en-2-ol and β-hydroxy β-methylbutyric acid is a derivative of both; and, * in 1892, Kondakow reported the preparation of HMB by permanganate oxidation of 3-methylbutane-1,3-diol. First synthetic routes to acid Depending on the experimental conditions, cycloaddition of acetone and ketene produces either or 4,4-dimethyloxetan-2-one, both of which<unk> ze under basic conditions to yield the conjugate base of HMB. The haloform reaction provides another pathway to HMB involving the exhaustive halogenation of the methyl-ketone region of diacetone alcohol with sodium hypobromite or sodium hypochlorite; Diacetone alcohol is readily available from the aldol condensation of acetone. An organometallic approach to HMB involves the carboxylation of tert-butyl alcohol with carbon monoxide and Fenton's reagent (hydrogen peroxide and ferrous iron). Alternatively, HMB can be prepared through microbial oxidation of acid by the fungus Galactomyces reessii. Later synthetic routes to acid Detection in body fluids + HMB concentrations measured in healthy individuals Biofluid Age group Concentration Sources Mean Range Units Blood plasma Adults (18+) 4.0 0–10.0 Adults (18+) 4.0 2.0–6.0 μM Sarcoplasma Adults (21–23) 7.0 4.0–10.0 μM Breast milk Adults (18+) – 42–164 Urine Adults (18+) – 3.2–25.0 creatinine Urine Children (1–18) – 0–68 μmol/mmol creatinine The concentration of naturally produced HMB has been measured in several human body fluids using nuclear magnetic resonance spectroscopy, liquid chromatography–mass spectrometry, and gas chromatography–mass spectrometry methods. In the blood plasma and cerebrospinal fluid (CSF) of healthy adults, the average molar concentration of HMB has been measured at 4.0 micromolar (μM). The average concentration of HMB in the intramuscular fluid of healthy men of ages has been measured at 7.0 μM. In the urine of healthy individuals of any age, the excreted urinary concentration of HMB has been measured in a range of micromoles per millimole (μmol/mmol) of creatinine. In the breast milk of healthy lactating women, HMB and have been measured in ranges of μg/L and mg/L. In comparison, HMB has been detected and measured in the milk of healthy cows at a concentration of μg/L. This concentration is far too low to be an adequate dietary source of HMB for obtaining pharmacologically active concentrations of the compound in blood plasma. In a study where participants consumed 2.42 grams of pure while fasting, the average plasma HMB concentration increased from a basal level of 5.1 to 408 μM after 30 minutes. At 150 minutes post-ingestion, the average plasma HMB concentration among participants was 275 μM. Abnormal HMB concentrations in urine and blood plasma have been noted in several disease states where it may serve as a diagnostic biomarker, particularly in the case of metabolic disorders. The following table lists some of these disorders along with the associated HMB concentrations detected in urine or blood plasma. + Abnormal HMB concentrations measured in disease states Medical condition Biofluid Age group Concentration Sources Mean Range Units Biotinidase deficiency† Blood Adults (18+) 9.5 0–19.0 Biotinidase deficiency† Blood Children (1–13) 88.0 10.0–166.0 μM Biotinidase deficiency† Urine Children (1–13) 275.0 50.0–500.0 creatinine 3-Methylglutaconic aciduria (Type I)† Urine Children (1–13) 200.0 150.0–250.0 μmol/mmol creatinine Eosinophilic esophagitis Urine Children (1–13) 247.4 0–699.4 μmol/mmol creatinine Gastroesophageal reflux disease Urine Children (1–13) 119.8 5.5–234.0 μmol/mmol creatinine HMG-CoA lyase deficiency† Urine Children (1–13) 2030.0 60.0–4000.0 μmol/mmol creatinine MC-CoA carboxylase deficiency† Urine Children (1–13) 30350.0 1700.0–59000.0 μmol/mmol creatinine
Beta-Hydroxy beta-methylbutyric acid
Phenylacetic acid
Keto acid
Gamma-Amino-beta-hydroxybutyric acid
Choline
3-Indolepropionic acid
Gamma-Hydroxybutyric acid
Creatine