Prenalterol is a

cardiac stimulant A cardiac stimulant is a substance which acts as a stimulant of the heart – e.g., via positive chronotropic or inotropic action. Examples of cardiac stimulant drugs are cocaine and methamphetamine Methamphetamine (contracted from ) is a p ...

which acts as a β₁ adrenoreceptor agonist.

Synthesis

Stereospecific

Prenalterol exhibits adrenergic agonist activity in spite of an interposed oxymethylene group. The

stereospecific In chemistry, stereospecificity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one (or a subset) of the stereoisomers."Overlap Con ...

synthesis devised for this molecule relies on the fact that the side chain is very similar in

oxidation state In chemistry, the oxidation state, or oxidation number, is the hypothetical charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...

to that of a sugar. Prenalterol synthesis

Condensation of

monobenzone Monobenzone, also called 4-(Benzyloxy)phenol and monobenzyl ether of hydroquinone (MBEH) is an organic chemical in the phenol family with chemical formula C6H5CH2OC6H4OH. It is used as a topical drug for medical depigmentation. It is a colourless ...

(2) with the epoxide derived from α-D-

glucofuranose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

affords the glycosylated derivative (3). Hydrolytic removal of the

acetonide In organic chemistry, an acetonide is the functional group composed of the cyclic ketal of a diol with acetone. The more systematic name for this structure is an isopropylidene ketal. Acetonide is a common protecting group for 1,2- and 1,3- diol ...

protecting groups followed by cleavage of the sugar with

periodate Periodate is an anion composed of iodine and oxygen. It is one of a number of oxyanions of iodine and is the highest in the series, with iodine existing in oxidation state +7. Unlike other perhalogenates, such as perchlorate, it can exist in two ...

gives aldehyde (4). This is reduced to the

glycol A diol is a chemical compound containing two hydroxyl groups ( groups). An Aliphatic compound, aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. The most common ...

by means of NaBH₄ and the terminal alcohol is converted to the

mesylate In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group ...

(5). Displacement of the

leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...

with

isopropylamine Isopropylamine (monoisopropyl amine, MIPA, 2-Propylamine) is an organic compound, an amine. It is a hygroscopic colorless liquid with ammonia-like odor. It is miscible with water and flammable. It is a valuable intermediate in chemical industry. ...

followed by hydrogenolytic removal of the ''O''-benzyl ether affords the β₁-adrenergic selective adrenergic agonist prenalterol (6).

Racemic

Prepns of the racemic mixture: corresp to H. Köppe et al., (1965, 1972 both to

Boehringer Ingelheim C.H. Boehringer Sohn AG & Co. is the parent company of the Boehringer Ingelheim group, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein, Germany. As of 2018, Boehringer Ingelheim is one of the world's largest pharmaceutical ...

); corresp to A. F. Crowther, L. H. Smith, (1965, 1970 both to ICI);

References

Secondary alcohols Amines Beta1-adrenergic agonists Cardiac stimulants Inotropic agents Phenol ethers Phenols {{cardiovascular-drug-stub

Synthesis

Stereospecific

Racemic

Further reading

See also

References