Synthesis 2015; 47(09): 1303-1308
DOI: 10.1055/s-0034-1380228
paper
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Aculeatins A and B, and Formal Synthesis of Aculeatin D and 6-epi-Aculeatin D through an Asymmetric Aldol Reaction

Shuangping Huang
a  School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
,
Shipeng Chen
a  School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
,
Gaopeng Wang
a  School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
,
Jianting Zhang
a  School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
,
Linjun Tang
b  School of Life Science, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
,
Guangyan Du
c  Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, P. R. of China   Email: [email protected]
,
Xiaoji Wang*
a  School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, Jiangxi, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 02 September 2014

Accepted after revision: 23 January 2015

Publication Date:
26 February 2015 (online)


Abstract

A versatile and straightforward approach to the total synthesis of the dispirocyclic natural products aculeatins A, B, and D and 6-epi-aculeatin D was developed. The key steps involve a catalytic asymmetric aldol reaction using a titanium(IV) tetraisopropoxide/(S)-[1,1′-binaphthalene]-2,2′-diol system to form a C-2 hydroxy group, a hydroxy-directed­ reduction, and a Weinreb ketone synthesis.

Supporting Information

 
  • Reference

  • 1 These two authors contributed equally to this work.
    • 2a Greenwood BM, Bojang K, Whitty CJ. M, Targett GA. T. Lancet 2005; 365: 1487
    • 2b Guerra CA, Snow RW, Hay SI. Trends Parasitol. 2006; 22: 353
    • 3a Hyde JE. Trends Parasitol. 2005; 21: 494
    • 3b Hyde JE. FEBS J. 2007; 274: 4688
  • 4 Heilmann J, Mayr S, Brun R, Rali T, Sticher O. Helv. Chim. Acta 2000; 83: 2939
  • 5 Heilmann J, Brun R, Mayr S, Rali T, Sticher O. Phytochemistry 2001; 57: 1281
    • 6a Wong Y.-S. Chem. Commun. 2002; 686
    • 6b Baldwin JE, Adlington RM, Sham VW.-W, Márquez R, Bulger PG. Tetrahedron 2005; 61: 2353
    • 6c Falomir E, Álvarez-Bercedo P, Carda M, Marco JA. Tetrahedron Lett. 2005; 46: 8407
    • 6d Álvarez-Bercedo P, Falomir E, Carda M, Marco JA. Tetrahedron 2006; 62: 9641
    • 6e Peuchmaur M, Wong Y.-S. J. Org. Chem. 2007; 72: 5374
    • 6f Chandrasekhar S, Rambabu Ch, Shyamsunder T. Tetrahedron Lett. 2007; 48: 4683
    • 6g Ramana CV, Srinivas B. J. Org. Chem. 2008; 73: 3915
    • 6h Suresh V, Selvam JJ. P, Rajesh K, Venkateswarlu Y. Tetrahedron: Asymmetry 2008; 19: 1509
    • 6i Zhen Z.-B, Gao J, Wu Y. J. Org. Chem. 2008; 73: 7310
    • 6j Kamal A, Reddy PV, Prabhakar S, Balakrishna M. Tetrahedron: Asymmetry 2009; 20: 2861
    • 6k Malathong V, Rychnovsky SD. Org. Lett. 2009; 11: 4220
    • 6l Harbindu A, Kumar P. Synthesis 2010; 1479
    • 6m Ramana CV, Pandey SK. Tetrahedron 2010; 66: 390
    • 6n Yadav JS, Rao KV. R, Ravindar K, Reddy BV. S. Synlett 2010; 51
    • 6o Yadav JS, Thrimurtulu N, Venkatesh M, Prasad AR. Synthesis 2010; 431
    • 6p Yadav JS, Rao YG, Chandrakanth D, Ravindar K, Reddy BV. S. Helv. Chim. Acta 2010; 93: 2426
    • 6q Das B, Krishnaiah M, Sudhakar C. Bioorg. Med. Chem. Lett. 2010; 20: 2303
    • 6r Das B, Krishnaiah M, Nagendra S, Reddy CR. Lett. Org. Chem. 2011; 8: 244
    • 6s Yao HB, Song LY, Tong RB. J. Org. Chem. 2014; 73: 1498

      For examples, see:
    • 7a Soriente A, De Rosa M, Villano R, Scettri A. Tetrahedron: Asymmetry 2000; 11: 2255
    • 7b Soriente A, De Rosa M, Stanzione M, Villano R, Scettri A. Tetrahedron: Asymmetry 2001; 12: 959
    • 7c Carreira EM, Singer RA, Lee W. J. Am. Chem. Soc. 1994; 116: 8837
    • 7d Singer RA, Carreira EM. J. Am. Chem. Soc. 1995; 117: 12360
    • 7e Carreira EM, Singer RA, Lee W. J. Am. Chem. Soc. 1995; 117: 3649
  • 8 Chan TH, Brownbridge P. J. Chem. Soc., Chem. Commun. 1979; 578
  • 9 We found that a high purity of the silyl enol ether 5 was important to the enantioselectivity. Furthermore, the room temperature for the reaction should be above 20 °C or a low ee and yield will be obtained.
    • 10a Narasaka K, Pai F.-C. Tetrahedron 1984; 40: 2233
    • 10b Chen K.-M, Hardtman GE, Prasad K, Repič O, Shapiro MJ. Tetrahedron Lett. 1987; 28: 155
  • 11 Bonini C. Tetrahedron 1992; 48: 9801
  • 12 Xia Y, Jin YL, Kaur N, Choi Y, Lee K. Eur. J. Med. Chem. 2011; 46: 2386
  • 13 Evans DA, Chapman KT, Carreira EM. J. Am. Chem. Soc. 1988; 110: 3560