Substitution of the

heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis ...

isoquinoline Isoquinoline is a heterocyclic aromatic organic compound. It is a structural isomer of quinoline. Isoquinoline and quinoline are benzopyridines, which are composed of a benzene ring fused to a pyridine ring. In a broader sense, the term isoquin ...

at the C1 position by a

benzyl group In organic chemistry, benzyl is the substituent or molecular fragment possessing the structure . Benzyl features a benzene ring () attached to a methylene group () group. Nomenclature In IUPAC nomenclature, the prefix benzyl refers to a subst ...

provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

s. The 1-benzylisoquinoline

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

can be identified within numerous compounds of pharmaceutical interest, such as

moxaverine Moxaverine has been used in therapy based on the direct vasodilatory effect of the drug, a phosphodiesterase inhibitor, and on its influence on the rheological properties of red blood cells. Moxaverine hydrochloride (Kollateral forte®, Ursapharm ...

; but most notably it is found within the structures of a wide variety of plant

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...

s, collectively referred to as benzylisoquinoline

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

s. This class is exemplified in part by the following compounds:

papaverine Papaverine (Latin ''papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of erec ...

noscapine Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae ( ...

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

apomorphine Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagon ...

berberine Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydra ...

tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or ...

Biosynthesis

(''S'')-

Norcoclaurine Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including ''Nandina domestica'' (fruit), ''Aconitum carmichaelii'' (root), ''Asarum heterotropioides'', '' Galium divaricatum'' (stem and vine), ''Annona squamosa'', ...

(

higenamine Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including '' Nandina domestica'' (fruit), ''Aconitum carmichaelii'' (root), '' Asarum heterotropioides'', '' Galium divaricatum'' (stem and vine), ''Annona squamosa'' ...

) has been identified as the central 1-benzyl-tetrahydro-isoquinoline precursor from which numerous complex biosynthetic pathways eventually emerge. These pathways collectively lead to the structurally disparate compounds comprising the broad classification of plant natural products referred to as benzylisoquinoline alkaloids (BIA), which have been comprehensively discussed by Hagel. The biosynthesis of

(S)-norcoclaurine Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including ''Nandina domestica'' (fruit), ''Aconitum carmichaelii'' (root), ''Asarum heterotropioides'', '' Galium divaricatum'' (stem and vine), ''Annona squamosa'', ...

, which is catalyzed by (''S'')-norcoclaurine synthase, is accomplished by the stereoselective condensation of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

and 4-hydroxyphenylacetaldehyde (4-HPAA); each of these compounds is prepared by multiple enzymatic transformations from

L-tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

. It is of interest to note that early studies initially identified norlaudanosoline (

tetrahydropapaveroline Tetrahydropapaveroline (norlaudanosoline) is a benzyltetrahydroisoquinoline alkaloid. It can be formed in trace amounts in the brain by a condensation reaction of dopamine and dopaldehyde (a metabolite of dopamine). It inhibits dopamine uptak ...

) as the purported central precursor for the biosynthesis of BIAs. However, more than two decades latter it was finely unequivocally established that (''S'')-norcoclaurine was the central precursor for the biosynthesis of the structurally diverse BIAs.

Examples of benzylisoquinoline alkaloids

File:Benzylisoquinoline structure in Papaverin.svg,

Papaverine Papaverine (Latin ''papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of erec ...

File:Benzylisoquinoline structure in Noscapine.svg,

Noscapine Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a benzylisoquinoline alkaloid, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family Papaveraceae ( ...

File:Benzylisoquinoline structure in Apomorphone.svg,

Apomorphine Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagon ...

''(one additional ring closure)'' File:Benzylisoquinoline structure in Morphine.svg,

Morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

''(two additional ring closures)'' File:Benzylisoquinoline structure in Berberine.svg,

Berberine Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifolium'' (Oregon grape), ''Hydra ...

''(one additional ring closure with incorporated N-methyl)'' File:Benzylisoquinoline structures in Tubocurarine.svg,

Tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or ...

''(composed of two benzylisoquinoline units)''

References

{{Reflist
Benzylisoquinoline biosynthesis by cultivated plant cells and isolated enzymes
Alkaloids

Biosynthesis

Examples of benzylisoquinoline alkaloids

See also

References