Castanospermine

Castanospermine^[1]^[2]
Names
	Preferred IUPAC name (1S,6S,7R,8R,8aR)-Octahydroindolizine-1,6,7,8-tetrol
Identifiers
CAS Number	79831-76-8 [EBI];
3D model (JSmol)	Interactive image;
3DMet	B01556;
ChEBI	CHEBI:27860 ;
ChEMBL	ChEMBL311226 ;
ChemSpider	49177 ;
DrugBank	DB01816;
ECHA InfoCard	100.127.469
EC Number	616-743-4;
KEGG	C02256;
PubChem CID	54445;
UNII	Q0I3184XM7 ;
CompTox Dashboard (EPA)	DTXSID601026043 ;
	InChI InChI=1S/C8H15NO4/c10-4-1-2-9-3-5(11)7(12)8(13)6(4)9/h4-8,10-13H,1-3H2/t4-,5-,6 ,7 ,8 /m0/s1 Key: JDVVGAQPNNXQDW-TVNFTVLESA-N ; InChI=1/C8H15NO4/c10-4-1-2-9-3-5(11)7(12)8(13)6(4)9/h4-8,10-13H,1-3H2/t4-,5-,6 ,7 ,8 /m0/s1 Key: JDVVGAQPNNXQDW-TVNFTVLEBE;
	SMILES O[C@H]1CCN2[C@H]1[C@@H](O)[C@H](O)[C@@H](O)C2;
Properties
Chemical formula	C8H15NO4
Molar mass	189.209 g/mol
Appearance	White to off-white solid
Melting point	212 to 215 °C (414 to 419 °F; 485 to 488 K)
Solubility in water	Soluble
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H312, H332
Precautionary statements	P261, P264, P270, P271, P280, P301 P312, P302 P352, P304 P312, P304 P340, P312, P322, P330, P363, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Castanospermine is an indolizidine alkaloid first isolated from the seeds of Castanospermum australe.^[3] It is a potent inhibitor of some glucosidase enzymes^[4] and has antiviral activity in vitro and in mouse models.^[5]

The castanospermine derivative celgosivir is an antiviral drug candidate currently in development for possible use in treating hepatitis C virus (HCV) infection.^[6]

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.^[7]^[8]^[9]

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.^[10]

References

^ Merck Index, 11th Edition, 1902.
^ Castanospermine at Fermentek
^ Hohenschutz, Liza D.; Bell, E. Arthur; Jewess, Phillip J.; Leworthy, David P.; Pryce, Robert J.; Arnold, Edward; Clardy, Jon (1981). "Castanospermine, a 1,6,7,8-tetrahydroxyoctahydroindolizine alkaloid, from seeds of Castanospermum australe". Phytochemistry. 20 (4): 811–14. Bibcode:1981PChem..20..811H. doi:10.1016/0031-9422(81)85181-3.
^ R Saul; J J Ghidoni; R J Molyneux & A D Elbein (1985). "Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals". PNAS. 82 (1): 93–97. Bibcode:1985PNAS...82...93S. doi:10.1073/pnas.82.1.93. PMC 396977. PMID 3881759.
^ Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS (2005). "Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo". J Virol. 79 (14): 8698–706. doi:10.1128/JVI.79.14.8698-8706.2005. PMC 1168722. PMID 15994763.
^ Durantel, D. (2009). "Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection". Current Opinion in Investigational Drugs. 10 (8): 860–70. PMID 19649930.
^ Hartmann, Michael; Kim, Denis; Bernsdorff, Friederike; Ajami-Rashidi, Ziba; Scholten, Nicola; Schreiber, Stefan; Zeier, Tatyana; Schuck, Stefan; Reichel-Deland, Vanessa (2017-03-22). "Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity". Plant Physiology. 174 (1): 124–153. doi:10.1104/pp.17.00222. ISSN 0032-0889. PMC 5411157. PMID 28330936.
^ Hartman, Michael (Summer 2018). "Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity". Plant Physiology. 174 (1): 124–153. doi:10.1104/pp.17.00222. PMC 5411157. PMID 28330936.
^ Walsh, Christopher (2017). Natural Product Biosynthesis: Chemical Logic and Enzymatic Machinery. Royal Society of Chemistry. p. 270. ISBN 978-1788010764.
^ Dewick, Paul (2009). Medicinal Natural Products A Biosynthetic Approach. United Kingdom: Wiley. p. 330. ISBN 978-0-470-74167-2.

[1] Merck Index, 11th Edition, 1902.

[2] Castanospermine at Fermentek

[3] Hohenschutz, Liza D.; Bell, E. Arthur; Jewess, Phillip J.; Leworthy, David P.; Pryce, Robert J.; Arnold, Edward; Clardy, Jon (1981). "Castanospermine, a 1,6,7,8-tetrahydroxyoctahydroindolizine alkaloid, from seeds of Castanospermum australe". Phytochemistry. 20 (4): 811–14. Bibcode:1981PChem..20..811H. doi:10.1016/0031-9422(81)85181-3.

[4] R Saul; J J Ghidoni; R J Molyneux & A D Elbein (1985). "Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals". PNAS. 82 (1): 93–97. Bibcode:1985PNAS...82...93S. doi:10.1073/pnas.82.1.93. PMC 396977. PMID 3881759.

[5] Whitby K, Pierson TC, Geiss B, Lane K, Engle M, Zhou Y, Doms RW, Diamond MS (2005). "Castanospermine, a potent inhibitor of dengue virus infection in vitro and in vivo". J Virol. 79 (14): 8698–706. doi:10.1128/JVI.79.14.8698-8706.2005. PMC 1168722. PMID 15994763.

[6] Durantel, D. (2009). "Celgosivir, an alpha-glucosidase I inhibitor for the potential treatment of HCV infection". Current Opinion in Investigational Drugs. 10 (8): 860–70. PMID 19649930.

[7] Hartmann, Michael; Kim, Denis; Bernsdorff, Friederike; Ajami-Rashidi, Ziba; Scholten, Nicola; Schreiber, Stefan; Zeier, Tatyana; Schuck, Stefan; Reichel-Deland, Vanessa (2017-03-22). "Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity". Plant Physiology. 174 (1): 124–153. doi:10.1104/pp.17.00222. ISSN 0032-0889. PMC 5411157. PMID 28330936.

[8] Hartman, Michael (Summer 2018). "Biochemical Principles and Functional Aspects of Pipecolic Acid Biosynthesis in Plant Immunity". Plant Physiology. 174 (1): 124–153. doi:10.1104/pp.17.00222. PMC 5411157. PMID 28330936.

[9] Walsh, Christopher (2017). Natural Product Biosynthesis: Chemical Logic and Enzymatic Machinery. Royal Society of Chemistry. p. 270. ISBN 978-1788010764.

[10] Dewick, Paul (2009). Medicinal Natural Products A Biosynthetic Approach. United Kingdom: Wiley. p. 330. ISBN 978-0-470-74167-2.

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Biosynthesis

See also

References