Castanospermine Biosynthesis With Enamine Intermediate on:
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Castanospermine is an indolizidine alkaloid first isolated from the seeds of ''
In the alternate pathway 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.
Castanospermum australe
''Castanospermum'' is a monotypic genus (i.e. a genus that contains only one species) in the legume family Fabaceae. The sole species is ''Castanospermum australe'', commonly known as Moreton Bay chestnut or black bean. It is native to rainfo ...
''. It is a potent inhibitor
Inhibitor or inhibition may refer to:
Biology
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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 the ...
enzymes and has antiviral activity ''in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
'' and in mouse models.
The castanospermine 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 ...
celgosivir is an antiviral drug candidate that as of 2009 was 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
L-Lysine undergoes a transamination to form α-aminoadipic acid. α-Aminoadipic acid undergoes a ring closure and then a reduction to form L-pipecolic acid.
In the alternate pathway 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.
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 econo ...
References
{{reflist Indolizidine alkaloids Indolizidines Alkaloids found in Fabaceae Polyols Iminosugars