Formal total synthesis of mandelalide A

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


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.


Cytotoxic Heck cyclization natural products ring closing metathesis total synthesis 



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)


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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

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