Castanospermine Biosynthesis With Enamine Intermediate on:
[Wikipedia]
[Google]
[Amazon]
Castanospermine is an indolizidine
alkaloid
Alkaloids are a class of basic
BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Th ...
first isolated from the seeds of ''Castanospermum australe
''Castanospermum australe'' (Moreton Bay chestnut or blackbean), the only species in the genus ''Castanospermum'', is a flowering plant in the family Fabaceae, native to the east coast of Australia in Queensland and New South Wales, and to the ...
''. It is a potent inhibitor
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
of some glucosidase
Glucosidases are the glycoside hydrolase enzymes categorized under the EC number 3.2.1.
Function
Alpha-glucosidases are enzymes involved in breaking down complex carbohydrates such as starch and glycogen into their monomers.
They catalyze t ...
enzymes and has antiviral activity ''in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...
'' and in mouse models.
The castanospermine derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...
celgosivir is an antiviral drug candidate currently in development for possible use in treating hepatitis C virus
The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family '' Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatoc ...
(HCV) infection.
Biosynthesis of castanospermine
L-Lys undergoes a transamination to form α-aminoadipic acid. α-aminoadipic acid undergoes a ring closure and then a reduction to form L-pipecolic acid (Figure 1). In the alternate pathway (Figure 2), L-Lys cyclizes and forms the enamine, which reduces to L-pipecolic acid. HSCoA and then malonyl-CoA react in a Claisen reaction with L-pipecolic acid to form SCoA ester which undergoes a ring closure to form 1-indolizidinone. The carbonyl on 1-indolizidinone is reduced to the hydroxyl group. The molecule is then further hydroxylated to form the final product castanospermine. Biosynthesis shown in figure:
See also
*Swainsonine
Swainsonine is an indolizidine alkaloid. It is a potent inhibitor of Golgi alpha-mannosidase II, an immunomodulator, and a potential chemotherapy drug. As a toxin in locoweed (likely its primary toxin) it also is a significant cause of economi ...
References
{{cite journal , last1=Michael , first1=Denis , last2=Hartmann , first2=Kim , last3=Bernsdorff , first3=Friederike , last4=Ajami-Rashidi , first4=Ziba , last5=Scholten , first5=Nicola , title=Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity , journal=Plant Physiology , date=May 2017, volume=174, issue=1, pages=124–153, doi=10.1104/pp.17.00222, pmid=28330936, pmc=5411157 Alkaloids Indolizidines Alkaloids found in Fabaceae Polyols Iminosugars