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]

Biosynthesis of castanospermine - pathway 1: transamination of L-Lys

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]

Figure 2: Biosynthesis of castanospermine - pathway 2: cyclization of L-Lys to form pipecolic acid

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.

[3]

[4]

[5]

[1]

[2]

[6]

[7]

[8]

[9]

[10]

Castanospermine

Biosynthesis

See also

References