Substitution of the
heterocycle
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic organic chemistry is the branch of organic chemistry dealing with the synthesis, proper ...
isoquinoline
Isoquinoline is an individual chemical specimen - a heterocyclic aromatic organic compound - as well as the name of a family of many thousands of natural plant alkaloids, any one of which might be referred to as "an isoquinoline". It is a struc ...
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 ().
Nomenclature
In IUPAC nomenclature, the prefix benzyl refers to a substituent, ...
provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural
isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...
s. The 1-benzylisoquinoline
moiety can be identified within numerous compounds of pharmaceutical interest, such as
moxaverine; 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 s ...
s, collectively referred to as
benzylisoquinoline alkaloids. 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 ...
,
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 (p ...
,
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, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...
,
apomorphine,
berberine
Berberine is a Quaternary ammonium cation, quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of ''Berberis'', from which its name ...
,
tubocurarine
Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic benzylisoquinoline 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 relaxat ...
.
Biosynthesis
(''S'')-
Norcoclaurine (
higenamine) 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, 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 chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
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 conditionally essential amino acid with a polar side group. The word "tyrosine" is ...
.
It is of interest to note that early studies initially identified norlaudanosoline (
tetrahydropapaveroline) as the purported central precursor for the biosynthesis of BIAs.
However, more than two decades later 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 ...
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 (p ...
File:Benzylisoquinoline structure in Apomorphone.svg, Apomorphine ''(one additional ring closure)''
File:Benzylisoquinoline structure in Morphine.svg, Morphine
Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...
''(two additional ring closures)''
File:Benzylisoquinoline structure in Berberine.svg, Berberine
Berberine is a Quaternary ammonium cation, quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of ''Berberis'', from which its name ...
''(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 benzylisoquinoline 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 relaxat ...
''(composed of two benzylisoquinoline units)''
See also
*
Aminosteroid
Aminosteroids are a group of steroids with a similar structure based on an amino- substituted steroid nucleus. They are neuromuscular blocking agents, acting as competitive antagonists of the nicotinic acetylcholine receptor (nAChR), and block t ...
*
Gallamine
Gallamine triethiodide (Flaxedil) is a non-depolarising muscle relaxant. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine is a non-depolarising typ ...
*
Morphinan
Morphinan is the prototype chemical structure of a large chemical class of psychoactive drugs, consisting of opiate analgesics, cough suppressants, and dissociative hallucinogens, among others. Typical examples include compounds such as morphine, ...
*
Indole
Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...
*
Indolizidine
References
{{Reflist
Benzylisoquinoline biosynthesis by cultivated plant cells and isolated enzymes
Alkaloids