Synthesis 2013; 45(6): 785-790
DOI: 10.1055/s-0032-1318303
paper
© Georg Thieme Verlag Stuttgart · New York

An Expeditious Enantiospecific Total Synthesis of (–)-Crassalactone C

Kavirayani R. Prasad*
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India   Email: prasad@orgchem.iisc.ernet.in
,
S. Mothish Kumar
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India   Email: prasad@orgchem.iisc.ernet.in
› Author Affiliations
Further Information

Publication History

Received: 31 December 2012

Accepted after revision: 31 January 2013

Publication Date:
21 February 2013 (online)


Abstract

A concise and expeditious approach for the total synthesis of bioactive styryllactone (–)-crassalactone C is presented from tartaric acid. The main features of the synthesis include the desymmetrization of dimethylamide of tartaric acid and the effective use of cinnamoyl ester as a protecting group as well as a reactant in the ring-closing metathesis reaction.

Supporting Information

 
  • References

  • 1 Tuchinda P, Munyoo B, Pohmakotr M, Thinapong P, Sophasan S, Santisuk T, Reutrakul T. J. Nat. Prod. 2006; 69: 1728

    • For a review on the cytotoxic activity and other bioactivity of styryllactones, see:
    • 2a Mereyala HB, Joe M. Curr. Med. Chem.: Anti-Cancer Agents 2001; 1: 293
    • 2b Blàzquez MA, Bermejo A, Zafra-Polo MC, Cortes D. Phytochem. Anal. 1999; 10: 161
    • 2c de Fatima A, Modolo LV, Conegero LS, Pilli RA, Ferreira CV, Kohn LK, de Carvalho JE. Curr. Med. Chem. 2006; 13: 3371
  • 3 Popsavin V, Benedeković G, Srećo B, Popsavin M, Francuz J, Kojić V, Bogdanović G. Org. Lett. 2007; 9: 4235
    • 4a Popsavin V, Benedeković G, Srećo B, Popsavin M, Francuz J, Kojić V, Bogdanović G, Divjaković V. Tetrahedron 2009; 65: 10596
    • 4b Popsavin V, Srećo B, Benedeković G, Francuz J, Popsavin M, Kojić V, Bogdanović G. Eur. J. Med. Chem. 2010; 45: 2876
    • 4c Popsavin V, Benedeković G, Popsavin M, Kojić V, Bogdanović G. Tetrahedron Lett. 2010; 51: 3426
  • 5 Sharma GV. M, Mallesham S. Tetrahedron: Asymmetry 2010; 21: 2646
  • 7 For a general approach to the synthesis of γ-ketoamides by addition of alkyl or aryl Grignard reagents to tartaric acid derived amides see: Prasad KR, Chandrakumar A. Tetrahedron 2007; 63: 1798
  • 8 Diastereomeric ratio was determined by 1H NMR. Formation of the other diastereomers was not observed within detectable limits in 1H NMR. Formation of the major diastereomer 6 can be explained by the addition of hydride in a Felkin–Ahn/Cram open chain model as reported by Chikasita et al.: Chikashita H, Nikaya T, Uemura H, Itoh K. Bull. Chem. Soc. Jpn. 1989; 62: 2121
  • 9 Owing to the reactivity of the unsaturated amide as a Michael acceptor, it is necessary to avoid the addition of MeOH in the presence of CeCl3·7 H2O.
  • 10 Formation of the major diastereomer 15 in the reduction of 14 can be explained by a Cram chelation model. For a detailed study on the reduction of similar hydroxy ketones derived from tartaric acid see: Prasad KR, Chandrakumar A. Synthesis 2006; 2159
  • 11 Formation of crassalactone C (2) was further confirmed by the cleavage of the cinnamoyl ester to yield (–)-goniofufurone (3) in 66% yield.