Pirandamine (AY-23,713) is a

tricyclic Tricyclics are cyclic chemical compounds that contain three fused rings of atoms. Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs. They include antidepr ...

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

which acts as a

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

(SSRI). It was investigated in the 1970s as a potential

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

but clinical development was not commenced and it was never marketed. Pirandamine is

structurally A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

related to tandamine, which, in contrast, is a selective

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epinep ...

Synthesis

Pirandamine can be synthesized starting from

1-indanone 1-Indanone is the organic compound with the formula C6H4(CH2)2CO. It is one of two isomeric benzocyclopentanones, the other being 2-indanone. It is a colorless solid. 1-Indanone is a substrate for the enzyme indanol dehydrogenase. Preparation ...

.I. Jirkovsky, L. G. Humber and R. Noureldin,Eur. J. Med. Chem., 11, 571 (1976). The

Reformatsky reaction The Reformatsky reaction (sometimes transliterated as Reformatskii reaction) is an organic reaction which condenses aldehydes or ketones with α-halo esters using metallic zinc to form β-hydroxy-esters: The organozinc reagent, also called a ...

between 1-indanone (1) and

ethyl bromoacetate Ethyl bromoacetate is the chemical compound with the formula . It is the ethyl ester of bromoacetic acid and is prepared in two steps from acetic acid. It is a lachrymator and has a fruity, pungent odor. It is also a highly toxic alkylating agen ...

in the presence of zinc gives ethyl 2-(1-hydroxy-2,3-dihydroinden-1-yl)acetate (2). The reduction of the ester with ester with

lithium aluminum hydride Lithium (from , , ) is a chemical element; it has symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid element. Like all alkali metals, ...

(LiAlH₄) gives 1-(2-hydroxyethyl)-2,3-dihydroinden-1-ol (3). Acid-catalyzed

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

then leads to indene-3-ethanol (4). Acid-catalyzed

condensation Condensation is the change of the state of matter from the gas phase into the liquid phase, and is the reverse of vaporization. The word most often refers to the water cycle. It can also be defined as the change in the state of water vapor ...

with

ethyl acetoacetate The organic compound ethyl acetoacetate (EAA) is the ethyl ester of acetoacetic acid. It is a colorless liquid. It is widely used as a chemical intermediate in the production of a wide variety of compounds. Preparation At large scale, ethyl ac ...

then gives (5). The

saponification Saponification is a process of cleaving esters into carboxylate salts and Alcohol (chemistry), alcohols by the action of aqueous alkali. Typically aqueous sodium hydroxide solutions are used. It is an important type of alkaline hydrolysis. When the ...

of the ester then gives the corresponding acid. The reaction of this with

ethyl chloroformate Ethyl chloroformate is an organic compound with the chemical formula . It is the ethyl ester of chloroformic acid. It is a colorless, corrosive and highly toxic liquid. It is a reagent used in organic synthesis for the introduction of the ethyl c ...

gives a mixed anhydride, and further reaction of this with

dimethylamine Dimethylamine is an organic compound with the formula (CH3)2NH. This secondary amine is a colorless, flammable gas with an ammonia-like odor. Dimethylamine is commonly encountered commercially as a solution in water at concentrations up to around ...

then leads to the amide (6). Reduction with lithium aluminium hydride completes the synthesis of pirandamine (7).

References

{{Tricyclics Dihydropyrans

Synthesis

See also

References