Strictosidine

Strictosidine
Structure of strictosidine
Names
IUPAC name
Methyl (19S,20R)-19-(β-D-glucopyranosyloxy)-16,17,21,21a-tetradehydro-18-oxa-21a-homo-20,21-secoyohimban-16-carboxylate
Systematic IUPAC name
Methyl (4S,5R,6S)-5-ethenyl-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]methyl}-6-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-5,6-dihydro-4H-pyran-3-carboxylate
Other names
Isovincoside
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C27H34N2O9/c1-3-13-16(10-19-21-15(8-9-28-19)14-6-4-5-7-18(14)29-21)17(25(34)35-2)12-36-26(13)38-27-24(33)23(32)22(31)20(11-30)37-27/h3-7,12-13,16,19-20,22-24,26-33H,1,8-11H2,2H3/t13-,16+,19+,20-,22-,23+,24-,26+,27+/m1/s1
    Key: XBAMJZTXGWPTRM-NTXHKPOFSA-N
  • COC(=O)C1=CO[C@H]([C@@H]([C@@H]1C[C@H]2C3=C(CCN2)C4=CC=CC=C4N3)C=C)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O)O)O
Properties
C27H34N2O9
Molar mass 530.574 g·mol−1
Melting point 193-197 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Strictosidine is a natural chemical compound and is classified as a glucoalkaloid and a vinca alkaloid. It is formed by the Pictet–Spengler condensation reaction of tryptamine with secologanin, catalyzed by the enzyme strictosidine synthase. Thousands of strictosidine derivatives are sometimes referred to by the broad phrase of monoterpene indole alkaloids. Strictosidine is an intermediate in the biosynthesis of numerous pharmaceutically valuable metabolites including quinine, camptothecin, ajmalicine, serpentine, vinblastine, vincristine and mitragynine.

Biosynthetic pathways help to define the subgroups of strictosidine derivatives.

Biosynthesis and metabolism

Strictosidine is produced by the enzyme strictosidine synthase, which combines secologanin and the indole amine, tryptamine:

2D representation of the chemical structure of secologanin.
secologanin
+
 
2D representation of the chemical structure of tryptamine.
tryptamine
 
 
H2O
Rightward reaction arrow with minor product(s) to top right
 
 
 
2D representation of the chemical structure of strictosidine .
strictosidine

In Catharanthus species and other plants which produce indole alkaloids, the enzyme strictosidine beta-glucosidase then removes the glycoside unit from strictosidine by hydrolysis, to give strictosidine aglycone and D-glucose.

strictosidine
 
 
H2O
 
Rightward reaction arrow with minor substrate(s) from top left
 
 
 
2D representation of the chemical structure of Q27102207.
strictosidine aglycone
+
 
2D representation of the chemical structure of Q23905964.
D-glucose

Strictosidine aglycone is a precursor to about 2,000 other indole alkaloids, so the enzyme producing it has been called the "gatekeeper" to this diversity.

Distribution

Strictosidine is found in the following plant families:

Here especially in Rhazya stricta and Catharanthus roseus.

Recent efforts in metabolic engineering have permitted the synthesis of strictosidine by yeast (Saccharomyces cerevisiae). This was accomplished by adding 21 genes and 3 gene deletions.

Role in plant defense

The involvement of the glucoalkaloid strictosidine in the antimicrobial and antifeedant activity of Catharanthus roseus leaves showed that strictosidine and its aglycone were active against several microorganisms and the derived toxic indole alkaloids provide further defense to herbivores.

References

  1. ↑ Mizukami H, Nordlöv H, Lee SL, Scott AI (August 1979). "Purification and properties of strictosidine synthetase (an enzyme condensing tryptamine and secologanin) from Catharanthus roseus cultured cells". Biochemistry. 18 (17): 3760–3763. doi:10.1021/bi00584a018. PMID 476085.
  2. ↑ Treimer JF, Zenk MH (November 1979). "Purification and properties of strictosidine synthase, the key enzyme in indole alkaloid formation". European Journal of Biochemistry. 101 (1): 225–233. doi:10.1111/j.1432-1033.1979.tb04235.x. PMID 510306.
  3. ↑ Seigler DS (1998). Plant Secondary Metabolism. Springer. ISBN 978-0-412-01981-4.
  4. ↑ Wink M (2010). Biochemistry of Plant Secondary Metabolism. Blackwell. ISBN 978-0-8493-4085-7.
  5. ↑ Stöckigt J, Antonchick AP, Wu F, Waldmann H (September 2011). "The Pictet-Spengler reaction in nature and in organic chemistry". Angewandte Chemie. 50 (37): 8538–8564. Bibcode:2011ACIE...50.8538S. doi:10.1002/anie.201008071. PMID 21830283.
  6. ↑ Hemscheidt T, Zenk MH (February 1980). "Glucosidases involved in indole alkaloid biosynthesis of Catharanthus cell cultures". FEBS Letters. 110 (2): 187–91. Bibcode:1980FEBSL.110..187H. doi:10.1016/0014-5793(80)80069-X. PMID 6768587.
  7. ↑ Luijendijk TJ, Stevens LH, Verpoorte R (1998). "Purification and characterisation of strictosidine β-D-glucosidase from Catharanthus roseus cell suspension cultures". Plant Physiol. Biochem. 36 (6): 419–425. Bibcode:1998PlPB...36..419L. doi:10.1016/S0981-9428(98)80205-2.
  8. ↑ Barleben L, Ma X, Koepke J, Peng G, Michel H, Stöckigt J (February 2005). "Expression, purification, crystallization and preliminary X-ray analysis of strictosidine glucosidase, an enzyme initiating biosynthetic pathways to a unique diversity of indole alkaloid skeletons". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1747 (1): 89–92. doi:10.1016/j.bbapap.2004.09.026. PMID 15680242.
  9. ↑ Barleben L, Panjikar S, Ruppert M, Koepke J, StöCkigt J (2007). "Molecular Architecture of Strictosidine Glucosidase: The Gateway to the Biosynthesis of the Monoterpenoid Indole Alkaloid Family". The Plant Cell. 19 (9): 2886–2897. doi:10.1105/tpc.106.045682. PMC 2048697. PMID 17890378.
  10. 1 2 Stathaki A, Pantidi G, Thomopoulou M, Koudounas K (2024). "Β-Glucosidases in specialized metabolism: Towards a new understanding of the gatekeepers of plant chemical arsenal". Current Opinion in Plant Biology. 82 102638. doi:10.1016/j.pbi.2024.102638. PMID 39326155.
  11. ↑ Brown S, Clastre M, Courdavault V, O'Connor SE (March 2015). "De novo production of the plant-derived alkaloid strictosidine in yeast". Proceedings of the National Academy of Sciences of the United States of America. 112 (11): 3205–3210. Bibcode:2015PNAS..112.3205B. doi:10.1073/pnas.1423555112. PMC 4371906. PMID 25675512.
  12. ↑ Luijendijk TJ, van der Meijden E, Verpoorte R (August 1996). "Involvement of strictosidine as a defensive chemical in Catharanthus roseus". Journal of Chemical Ecology. 22 (8): 1355–66. doi:10.1007/BF02027718. PMID 24226242.