Castanospermine is an

indolizidine Indolizidine is a heterocyclic chemical compound that forms the central core of the indolizidine alkaloids such as swainsonine and castanospermine. See also * Indole * Indolizine * Tryptophan * Tryptamine Tryptamine is an indolamine metabo ...

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 ...

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 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 ...

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 an ...

'' 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. F ...

celgosivir Celgosivir, in development by Migenix for the treatment of hepatitis C virus (HCV) infection, is an oral prodrug of the natural product castanospermine that inhibits alpha-glucosidase I, an enzyme that plays a critical role in viral maturation b ...

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 ( hepato ...

(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: Castanospermine biosynthesis with enamine intermediate

Castanospermine biosynthesis with enamine intermediate

Alternate pathway for the formation of pipecolic acid in the biosynthesis of castanospermine

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