Advertisement

Formal total synthesis of mandelalide A

  • V Yamini
  • K Mahender Reddy
  • A Shiva Krishna
  • J K Lakshmi
  • Subhash GhoshEmail author
Regular Article
  • 62 Downloads

Abstract

In this article the formal total synthesis of mandelalide A has been described in details. The highly convergent and flexible strategy developed for mandelalide A involved the construction of key building blocks ent-9 and 7, and their assembly to the target compound. For the synthesis and coupling of these building blocks, the Brown’s crotylation, Sharpless asymmetric dihydroxylation followed by in situ Williamson type etherification, modified Prins cyclization, Masamune-Roush olefination and Heck cyclization were employed, the latter being crucial for the highly stereoselective formation of the macrocycle of mandelalide A. Initially, Julia Kocienski olefination, ring-closing metathesis reaction were investigated for the synthesis of the aglycone of the proposed structure of the mandelalide A, and found to be unsuccessful.

Graphical Abstract

Highly convergent and flexible strategy has been developed for mandelalide A via coupling of two building blocks ent-9 and 7 through Masamune-Roush olefination followed by intramolecular Heck cyclization.

Keywords

Cytotoxic Heck cyclization natural products ring closing metathesis total synthesis 

Notes

Acknowledgements

V.Y thanks CSIR, New Delhi for the research fellowship. S.G is thankful to CSIR for funding through ORIGIN and CSIR-Young Scientist Research Grant.

Note: IICT Manuscript Communication Number IICT/Pubs/2018/319.

Supplementary material

12039_2019_1600_MOESM1_ESM.pdf (2 mb)
Supplementary material 1 (pdf 2046 KB)

References

  1. 1.
    Martins A, Vieira H, Gaspa H and Santos S 2014 Marketed marine natural products in the pharmaceutical and cosmeceutical industries: Tips for success Mar. Drugs. 12 1066CrossRefGoogle Scholar
  2. 2.
    Sikorska J, Hau A M, Anklin C, Parker-Nance S, Davies-Coleman M T, Ishmael J E and Mc Phail K L 2012 Mandelalides A–D, cytotoxic macrolides from a new Lissoclinum species of South African Tunicate J. Org. Chem. 77 6066CrossRefGoogle Scholar
  3. 3.
    Nazari M, Serrill J D, Wan X, Nguyen M H, Anklin C, Gallegos D A, Smith III A B, Ishmael J E and Mc Phail K L 2017 New mandelalides expand a macrolide series of mitochondrial inhibitors J. Med. Chem. 60 7850CrossRefGoogle Scholar
  4. 4.
    (a) Willwacher J and Fürstner A 2014 Catalysis-based total synthesis of putative mandelalide A Angew. Chem. Int. Ed. 53 4217; (b) Lei H, Yan J, Yu J, Liu Y, Wang Z, Xu Z and Ye T 2014 Total synthesis and stereochemical reassignment of mandelalide A Angew. Chem. Int. Ed. 53 1; (c) Willwacher J, Heggen H, Wirtz C, Thiel W and Fürstner A 2015 Total synthesis, stereochemical revision, and biological reassessment of mandelalide A: Chemical mimicry of intrafamily relationships Chem. Eur J. 21 1; (d) Brìtsch T M, Bucher P and Altmann K H 2015 Total Synthesis and biological assessment of mandelalide A Chem. Eur. J. 22 1292; (e) Nguyen M H, Imanishi M, Kurogi T and Smith III A B 2016 Total synthesis of (-)-mandelalide A exploiting anion relay chemistry (ARC): Identification of a type II ARC/CuCN cross-coupling protocol J. Am. Chem. Soc. 138 3675; (f) Veerasamy N, Ghosh A, Li J, Watanabe K, Serrill J D, Ishmael J E, Mc Phail K L and Carter R G 2016 Enantioselective total synthesis of mandelalide A and isomandelalide A: Discovery of a cytotoxic ring-expanded isomer J. Am. Chem. Soc. 138 770; (g) Anki Reddy P, Anki Reddy S and Sabitha G 2017 Synthetic studies toward the revised aglycone of mandelalide A Chem. Select 2 1032Google Scholar
  5. 5.
    (a) Reddy K M, Yamini V, Singarapu K K and Ghosh S 2014 Synthesis of proposed aglycone of mandelalide A Org. Lett. 16 2658; (b) Bhatt U, Christmann M, Quitschalle M, Claus E and Kalesse M 2011 The first total synthesis of (+)-ratjadone J. Org. Chem. 66 1885; (c) Jagel J and Maier M E 2009 Formal total synthesis of palmerolide A Synthesis. 2881; (d) For reviews related to the Heck reaction, see: Link J T 2002 The intramolecular Heck reaction Org. React. 60 157Google Scholar
  6. 6.
    (a) Liu P and Jacobsen E N 2001 Total synthesis of (+)-ambruticin J. Am. Chem. Soc. 123 10772; (b) Julia M and Paris J M 1973 Synthesis A l’aide De Sulfones \(\text{V}^{(+) }\)- Methode DeSynthese Generale De Doubles Liaisons Tetrahedron. Lett. 14 4833; (c) Blakemore P R, Cole W J, Kocienski P J and Morley A1998 A stereoselective synthesis of trans-1,2-disubstituted alkenes based on the condensation of aldehydes with metallated 1-phenyl-1\(H\)-tetrazol-5-yl sulfones Synlett 26; (d) KocienskiP J, Bell A and Blakemore P R 2000 1-tert-Butyl-1\(H\)-tetrazol-5-yl sulfones in the modified Julia olefination Synlett 365; (e) For a recent review on thistopic, see: Blakemore P R 2002 The modified Julia olefination: Alkene Synthesis via The condensation of metallated heteroarylalkylsulfones with carbonyl compounds J. Chem. Soc. Perkin. Trans. 1 2563Google Scholar
  7. 7.
    Gagnepain J, Moulin E and Fürstner A 2011 Gram-scale synthesis of iejimalide B Chem. Eur J. 17 6964CrossRefGoogle Scholar
  8. 8.
    Kolb H C, VanNieuwenhze M S and Sharpless K B 1994 Catalytic asymmetric dihydroxylation Chem. Rev. 94 2483CrossRefGoogle Scholar
  9. 9.
    Wagner H and Koert U 1994 A multiple five-membered-ring-selective Williamson reaction as a key step in the stereoselective construction of 2,5-linked oligo(tetrahydrofuran)s Angew. Chem. Int. Ed. 33 1873CrossRefGoogle Scholar
  10. 10.
    Nicolaou K C, Piscopio A D, Bertinato P, Chakraborty T K, Minowa N and Koide K 1995 Total synthesis of rapamycin Chem. Eur. J. 1 318CrossRefGoogle Scholar
  11. 11.
    Paquette L A and Chang S K 2005 The polyol domain of amphidinol 3. A stereoselective synthesis of the entire C(1)–C(30) sector Org. Lett. 7 3111CrossRefGoogle Scholar
  12. 12.
    Oikawa Y, Yoshioka T and Yonemitsu O 1982 Specific removal of O-methoxybenzyl protection by DDQ oxidation Tetrahedron. Lett. 23 885CrossRefGoogle Scholar
  13. 13.
    (a) Evans D A, Ennis M D and Mathre D J 1982 Asymmetric Alkylation reactions of chiral imide enolates. A practical approach to theenantio selective synthesis of .alpha.-substituted carboxylic acid derivatives J. Am. Chem. Soc. 104 1737; (b) Chakraborty T K and Suresh V R 1997 Chem. Lett. 6 565Google Scholar
  14. 14.
    Jadhav P K, Bhat K S, Perumal P T and Brown H C 1986 Chiral synthesis via organoboranes. 6. Asymmetric allylboration via chiral allyldialkylboranes. Synthesis of homoallylic alcohols with exceptionally high enantiomeric excess J. Org. Chem. 51 432CrossRefGoogle Scholar
  15. 15.
    Bahnck K B and Rychnovsky S D 2008 Formal synthesis of (–)-kendomycin featuring a Prins-cyclization to construct the macrocycle J. Am. Chem. Soc. 130 13177CrossRefGoogle Scholar
  16. 16.
    (a) Jaber J J, Mitsui K and Rychnovsky S D 2001 Stereoselectivity and regioselectivity in the segment-coupling Prins cyclization J. Org. Chem. 66 4679; (b) Rychnovsky S D and Thomas C R 2000 Synthesis of the C22–C26 tetrahydropyran segment of phorboxazole by a stereoselective prins cyclization Org. Lett. 2 1217Google Scholar
  17. 17.
    Mitsunobu O 1981 The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products Synthesis 1 1CrossRefGoogle Scholar
  18. 18.
    (a) Blanchette M A, Choy W, Davis J T, Essenfeld A P, Masamune S, Roush W R and Sakai T 1984 Horner-Wadsworth-Emmons reaction: Use of lithium chloride and amine for base-sensitive compounds Tetrahedron Lett. 25 2183; (b) Fürstner A, Nevado C, Waser M, Tremblay M, Chevrier C, Teplý F, Aïssa C, Moulin E and Müller O 2007 Total synthesis of iejimalide A-D and assessment of the remarkable actin-depolymerizing capacity of these polyene macrolides J. Am. Chem. Soc. 129 9150Google Scholar
  19. 19.
    Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M and Menche D J 2010 Stereoselective total synthesis of etnangien and etnangien methyl ester J. Org. Chem. 75 2429CrossRefGoogle Scholar
  20. 20.
    Paterson Florence G J, Gerlach K, Scott J P and Sereinig N 2001 A practical synthesis of (+)-discodermolide and analogues: fragment union by complex aldol reactions J. Am. Chem. Soc. 123 9535CrossRefGoogle Scholar
  21. 21.
    For a review of Peterson-type eliminations, see: Ager D 1990 The Peterson olefination reaction Org. React. 38 1Google Scholar
  22. 22.
    Andringa H, Heus-Kloos Y A and Brandsma L 1987 Trimethylsilylation of carbenoids generated in situ from allyl and benzyl halides J. Organomet. Chem. 336 C41CrossRefGoogle Scholar
  23. 23.
    Zhu K and Panek J S 2011 Total synthesis of (+)-SCH 351448 Org. Lett. 13 4652CrossRefGoogle Scholar
  24. 24.
    (a) Nagasawa T and Kuwahara S 2013 Formal total synthesis of lactimidomycin Org. Lett. 15 3002; (b) Stork G and ZhaoK 1989 A stereoselective synthesis of (\(Z)\)-1-iodo-1-alkenes Tetrahedron. Lett. 30 2173Google Scholar
  25. 25.
    Vintonyak V V and Maier M E 2007 Synthesis of the core structure of cruentaren A Org. Lett. 9 655CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.Organic Synthesis and Process Chemistry DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Department of Chemistry and Chemical BiologyHarvard UniversityCambridgeUSA
  3. 3.Centre for NMR and Structural ChemistryCSIR-Indian Institute of Chemical TechnologyHyderabadIndia

Personalised recommendations