Chemical Papers

, Volume 72, Issue 4, pp 971–977 | Cite as

Stereoselective total synthesis of (−)-pyrenophorol

  • Dongamanti Ashok
  • Sridhar Pervaram
  • Venkata Ramana Reddy Chittireddy
  • Sreenivasulu Reddymasu
  • Naresh Kumar Vuppula
Original Paper


A simple and efficient stereoselective synthesis of macrodilactone of (−)-pyrenophorol (1) has been accomplished in 12 steps in 8.3% overall yield, from inexpensive and commercially available (S)-ethyl lactate. This convergent synthesis utilizes an oxidation–reduction protocol and cyclodimerisation under the Mitsunobu reaction conditions as key steps.

Graphical Abstract


(S)-ethyl lactate Wittig olefination Intermolecular Mitsunobu cyclization (−)-Pyrenophorol. 

Supplementary material

11696_2017_331_MOESM1_ESM.doc (2.5 mb)
Supplementary material 1 (DOC 2536 kb)


  1. Alluraiah G, Sreenivasulu R, Murthy IS, Raju RR (2014) Stereoselective total synthesis of verbalactone. Monatsh Chem 145:2019–2024. CrossRefGoogle Scholar
  2. Alluraiah G, Sreenivasulu R, Sadanandam P, Anitha K, Raju RR (2016) A concise stereoselective total synthesis of (-)-cephalosporolide D. Monatsh Chem 147:451–455. CrossRefGoogle Scholar
  3. Brimble MA, Bryant CJ (2007) Synthesis and assignment of the absolute configuration of the anti-Helicobacter pylori agents CJ-12, 954 and CJ-13, 014. Org Biomol Chem 5:2858–2866. CrossRefGoogle Scholar
  4. Chatopadyay A, Mamdapur VR (1995) (R)-2,3-O-Cyclohexylideneglyceraldehyde, a versatile intermediate for asymmetric synthesis of chiral alcohol. J Org Chem 60:585–587. CrossRefGoogle Scholar
  5. Christner C, Kullertz G, Fischer G, Zerlin M, Grabley S, Thiericke R, Taddei A, Zeeck A (1998) Albocycline- and carbomycin-type macrolides, inhibitors of human prolyl endopeptidases. J Antibiot 51:368–371CrossRefGoogle Scholar
  6. Collins I (1999) Saturated and unsaturated lactones. J Chem Soc Perkin Trans 1:1377–1396. CrossRefGoogle Scholar
  7. Dommerholdt EJ, Thijs L, Zwanenburg B (1991) Total synthesis of the macrodiolide pyrenophorol. Tetrahedron Lett 32:1499–1502. CrossRefGoogle Scholar
  8. Edukondalu P, Sreenivasulu R, Chiranjeevi B, Kumar VN, Raju RR (2015) Stereoselective total synthesis of (-)—(5S,8R,13S,16R)-pyrenophorol. Monatsh Chem 146:1309–1314. CrossRefGoogle Scholar
  9. Findlay JA, Li G, Miller JD, Womiloju TO (2003) Insect toxins from spruce endophytes. Can J Chem 81:284–292. CrossRefGoogle Scholar
  10. Gerlach H, Gertle K, Thahnann A (1977) Eine neue synthese von (±)-Pyrenophorin. Helv Chim Acta 60:2860–2865. CrossRefGoogle Scholar
  11. Ghisalberti EL, Hargreaves JR, Skelton BW, White AH (2002) Structural study of the anthelmintic macrodiolide pyrenophorol. Aust J Chem 55:233–236. CrossRefGoogle Scholar
  12. Grove JF (1971) Metabolic products of Stemphylium radicinum. Part IV. Minor products. J Chem Soc C, pp 2261–2263.
  13. Grove JF, Saeake RN, Ward G (1966) Metabolic products of Colletotrichum capsici: isolation and characterization of acetylcolletotrichin and colletodiol. J Chem Soc C, pp 230–234.
  14. Jamieson AG, Sutherland A (2007) Ether directed palladium(II)-catalyzed aza-claisen rearrangements: studies on the origin of the directing effect. Tetrahedron 63:2123–2131. CrossRefGoogle Scholar
  15. Kastanias MA, Chrysayi-Tokousbalides M (2000) Herbicidal potential of pyrenophorol isolated from a Drechslera avenae pathotype. Pest Manag Sci 56:227–232.<227:AID-PS115>3.0.CO;2-A CrossRefGoogle Scholar
  16. Kibayashi C, Machinaga N (1993) Preparation of macrodiolides via a common chiral building block. Total synthesis of (-)-pyrenophorin and (-)-pyrenophorol. Tetrahedron Lett 34:841–844. CrossRefGoogle Scholar
  17. Kind R, Zeeck A, Grabley S, Thiericke R, Zerlin M (1996) Secondary metabolites by chemical screening. 30. Helmidol, a new macrodiolide from Alternaria alternata. J Nat Prod 59:539–540. CrossRefGoogle Scholar
  18. Kis Z, Furger P, Sigg HP (1969) Isolation of pyrenophorol. Experientia 25:123–124CrossRefGoogle Scholar
  19. Krohn K, Farooq U, Flörke U, Schulz B, Draeger S, Pescitelli G, Salvadori P, Antus S, Kurtán T (2007) Secondary metabolites isolated from an endophytic Phoma sp.—absolute configuration of tetrahydropyrenophorol using the solid-state TDDFT CD methodology. Eur J Org Chem, pp 3206–3211.
  20. MacMillan J, Pryce RJ (1968) The structure of colletodiol, a macrocyclic dilactone from Colletotrichum capsici. Tetrahedron Lett 9:5497–5500. CrossRefGoogle Scholar
  21. MacMillan J, Simpson TJ (1973) Fungal products. Part V. The absolute stereochemistry of colletodiol and the structures of related metabolites of Colletotrichum capsici. J Chem Soc Perkin Trans 1:1487–1493. CrossRefGoogle Scholar
  22. Madala M, Raman B, Sastry KV, Musulla S (2016) A concise stereoselective total synthesis of verbalactone. Monatsh Chem 147:1985–1990. CrossRefGoogle Scholar
  23. Murthy IS, Sreenivasulu R, Alluraiah G, Raju RR (2014) An alternative stereoselective total synthesis of (+)-xephalosporolide D. Lett Org Chem 11:327–332. CrossRefGoogle Scholar
  24. Nozoe S, Hira K, Tsuda K, Ishibashi K, Grove JF (1965) The structure of pyrenophorin. Tetrahedron Lett 6:4675–4677. CrossRefGoogle Scholar
  25. Oh HS, Kang HY (2011) Synthesis of (-)-pyrenophorol. Bull Korean Chem Soc 32:2869–2870. CrossRefGoogle Scholar
  26. Powell J, Whalley WB (1969) The chemistry of fungi. Part LVIII. Structure of colletodiol, a metabolite of Chaetomium funicola. J Chem Soc C, pp 911–912.
  27. Pratapareddy B, Sreenivasulu R, Hatti I, Rao MVB, Raju RR (2015) A concise stereoselective total synthesis of diplodialide C. Monatsh Chem 146:1921–1926. CrossRefGoogle Scholar
  28. Pratapareddy B, Sreenivasulu R, Thota P, Hatti I, Rao MVB, Kumar VN, Raju RR (2017) Stereoselective synthesis of (-)-tetrahydropyrenophorol. Monatsh Chem 148:751–756. CrossRefGoogle Scholar
  29. Ramakrishna K, Sreenivasulu R, Vidavalur S, Reddy BJM (2016) Stereoselective total synthesis of (-)-pyrenophorin. Lett Org Chem 13:693–697. CrossRefGoogle Scholar
  30. Ramanujan VB, Sreenivasulu R, Chavali M, Kumar CNSSP (2017) Stereoselective total synthesis of decarestrictine. J Monatsh Chem. Google Scholar
  31. Ronald RC, Gurusiddaiah S (1980) Grahamimycin A” 1: a novel dilactone antibiotic from cytospora. Tetrahedron Lett 21:681–684. CrossRefGoogle Scholar
  32. Takahashi T, Miyazawa M, Tsuji J (1985) Stereoselctive reduction of a alkoxy acetylenic ketones with zinc borohydride and K-selectride. Tetrahedron Lett 26:5139–5142. CrossRefGoogle Scholar
  33. Yadav JS, Reddy UVS, Reddy BVS (2009) Stereoselective total synthesis of (-)-Pyrenophorol. Tetrahedron Lett 50:5984–5986. CrossRefGoogle Scholar
  34. Yadav JS, Reddy GM, Rao TS, Ghamdi AK (2012) Total synthesis of (-)-Pyrenophorol. Synthesis 44:783–787. CrossRefGoogle Scholar

Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2017

Authors and Affiliations

  • Dongamanti Ashok
    • 1
  • Sridhar Pervaram
    • 1
  • Venkata Ramana Reddy Chittireddy
    • 2
  • Sreenivasulu Reddymasu
    • 3
  • Naresh Kumar Vuppula
    • 4
  1. 1.Department of ChemistryOsmania UniversityHyderabadIndia
  2. 2.Department of ChemistryJawaharlal Nehru Technological UniversityHyderabadIndia
  3. 3.Department of Chemistry, University College of Engineering (Autonomous)Jawaharlal Nehru Technological UniversityKakinadaIndia
  4. 4.Department of ChemistrySri Chaitanya P.G CollegeGodavarikhaniIndia

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