Castanospermine

Castanospermine
Names
Preferred IUPAC name
(1S,6S,7R,8R,8aR)-Octahydroindolizine-1,6,7,8-tetrol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.127.469 Edit this at Wikidata
EC Number
  • 616-743-4
KEGG
UNII
  • 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 X markN
    Key: JDVVGAQPNNXQDW-TVNFTVLESA-N X markN
  • 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
  • O[C@H]1CCN2[C@H]1[C@@H](O)[C@H](O)[C@@H](O)C2
Properties
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)
Soluble
Hazards
GHS labelling:
GHS07: Exclamation mark
Warning
H302, H312, H332
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).
X markN verify (what is checkYX markN ?)

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

The castanospermine derivative celgosivir is an antiviral drug candidate that as of 2009 was in development for possible use in treating hepatitis C virus (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.

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.

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

See also

References

  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.