Synlett 2018; 29(07): 908-911
DOI: 10.1055/s-0036-1591539
letter
© Georg Thieme Verlag Stuttgart · New York

Towards the Total Synthesis of Schisandrene: Stereoselective Synthesis of the Dibenzocyclooctadiene Lignan Core

Arramshetti Venkanna
a   Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India   Email: suresh@iict.res.in
b   Gachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea
,
Borra Poornima
a   Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India   Email: suresh@iict.res.in
,
Bandi Siva
a   Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India   Email: suresh@iict.res.in
,
B. Hari Babu
c   Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur-522510, India
,
K. Suresh Babu*
a   Natural Products Laboratory, Division of Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500 007, India   Email: suresh@iict.res.in
› Author Affiliations
This work was financially supported by NaPAHA project grant CSC-0130 from the Council of Scientific and Industrial Research, New ­Delhi (India) under the CSIR-Network program. BS, BP, and AV thank UGC and CSIR for financial support.
Further Information

Publication History

Received: 21 November 2017

Accepted after revision: 15 January 2018

Publication Date:
19 February 2018 (online)


Abstract

A stereoselective synthesis of the dibenzocyclooctadiene ­lignan core of the natural product schisandrene is described. Starting from readily available gallic acid, the synthetic strategy involves Suzuki–Miyaura cross-coupling, Stille reaction, and ring-closing metathesis (RCM) in the reaction sequence. The required asymmetric center at C-7′ was established by an asymmetric reduction of a keto compound using the Corey–Bakshi–Shibata (CBS) catalyst. In our approach, the eight-membered ring was achieved by RCM for the first time.

Supporting Information

 
  • References and Notes

    • 1a Humphreys JM. Chapple C. Plant Biol. 2002; 5: 224
    • 1b Anterola AM. Jeon JH. Davin LB. Lewis NG. J. Biol. Chem. 2002; 277: 1827
    • 1c Dixon RA. Reddy MS. S. Phyto Chem. Rev. 2003; 2: 289
    • 1d Suzuki S. Umezawa T. J. Wood Sci. 2007; 53: 273
    • 2a Chen DF. Zhang SX. Kozuka M. Sun QZ. Feng J. Wang Q. Mukainaka T. Nobukuni Y. Tokuda H. Nishino H. Wang HK. Morris-Natschke SL. Lee KH. J. Nat. Prod. 2002; 65: 1242
    • 2b Yasukawa K. Ikeya Y. Mitsuhashi H. Iwasaki M. Aburada M. Nakagawa S. Takeuchi M. Takido M. Oncology 1992; 49: 68
    • 2c Huerta E. Grey N. Cancer J. Clin. 2007; 57: 72
    • 2d Cragg GM. Grothaus PG. Newman DJ. Chem. Rev. 2009; 109: 3012
    • 2e Ohtaki Y. Hida T. Hiramatsu K. Kanitani M. Ohshima T. Nomura M. Wakita H. Aburada M. Miyamoto KI. Anticancer Res. 1996; 16: 751
    • 3a Panossian A. Wikman G. J. Ethnopharmacol. 2008; 118: 183
    • 3b Hancke JL. Burgos RA. Ahumada F. Fitoterapia 1999; 70: 451
  • 4 Chang GT. Kang SK. Kim JH. Chung KH. Chang YC. Kim CH. J. Ethnopharmacol. 2005; 102: 430
    • 5a Poornima B. Anand Kumar D. Siva B. Venkanna A. Tiwari AK. Babu KS. Nat. Prod. Res. 2016; 30: 493
    • 5b Venkanna A. Siva B. Poornima B. Rao VP. R. Prasad KR. Reddy AK. Reddy GB. P. Babu KS. Rao JM. Fitoterapia 2014; 95: 102
    • 5c Poornima B. Siva B. Shankaraiah G. Venkanna A. Nayak CL. Rao V. Babu KS. Eur. J. Med. Chem. 2015; 92: 449
  • 6 Choi YW. Takamatsu S. Khan SI. Srinivas PV. Ferreira D. Zhao J. Khan IA. J. Nat. Prod. 2006; 69: 356
  • 7 Zhao Y. Hao X. Lu W. Cai J. Yu H. Sevenet T. Gueritte F. J. Nat. Prod. 2002; 65: 902
  • 8 Sreedhar E. Kumar RS. C. Reddy GV. Robinson A. Babu KS. Rao JM. Srinivas PV. Tetrahedron: Asymmetry 2009; 20: 440
  • 9 Song C. Zhao P. Hu Z. Shi S. Cui Y. Chang J. Bioorg. Med. Chem. Lett. 2010; 20: 2297
  • 10 Alam A. Takaguchi Y. Ito H. Yoshidab T. Tsuboia S. Tetra­hedron 2005; 61: 1909
  • 11 Jeon AR. Kim ME. Park JK. Shin WK. An DK. Tetra­hedron 2014; 70: 4420
  • 12 Kumar S. Peruncheralathan S. Ila H. Junjappa H. Org. Lett. 2008; 10: 965
  • 13 Schmidt RR. Frick W. Tetrahedron 1988; 44: 7163
  • 14 Fang G. Mello JV. Finney NS. Tetrahedron 2004; 60: 11075
  • 15 Barder TE. Walker SD. Martinelli JR. Buchwald SL. J. Am. Chem. Soc. 2005; 127: 4685
  • 16 Morgan BJ. Dey S. Johnson SW. Kozlowski MC. J. Am. Chem. Soc. 2009; 131: 9413
  • 17 Singidi RR. Babu TV. R. Org. Lett. 2008; 10: 3351
  • 18 Takaoka S. Takaoka N. Minoshima Y. Huang JM. Kubo M. Harada K. Hioki K. Fukuyama Y. Tetrahedron 2009; 65: 8354
  • 19 Coleman RS. Gurrala SR. Org. Lett. 2004; 6: 4025
  • 20 Coleman RS. Gurrala SR. Org. Lett. 2004; 6: 3711
  • 21 Boyer FD. Hanna I. Eur. J. Org. Chem. 2008; 4938
  • 22 Besong G. Billen D. Dager I. Kocienski P. Sliwinski E. Tai LR. Boyle T. Tetrahedron 2008; 64: 4700
  • 23 Synthetic Procedure for 18 A solution of S-(–)-2-methyl-CBS-oxazaborolidine (1 M solution in toluene, 4.9 mmol) in THF (5 mL) was treated with BH3·DMS (2.0 M solution in THF, 0.2 mL, 04.1 mmol) at 0 °C for 15 min. A solution of enone 3 (0.150 g, 4.1 mmol) in THF (8 mL) was added slowly at –78 °C, and the reaction mixture was stirred for 1 h maintaining the temperature. After the reaction was complete, saturated NH4Cl solution was added. The aqueous layer was extracted with EtOAc, the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography, eluting with 10% EtOAc/hexane to give compound 18 (0.128 g, 85%, ee 98%) as a colorless liquid: [α]D 25 –2.53 (c 4.8, CHCl3). IR (KBr): νmax= 3562, 2972, 2920, 2847, 1586, 1448, 1227, 1107, 720 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.73 (s, 1 H), 6.33 (s, 1 H), 5.93–5.84 (m, 5 H), 5.77–5.70 (m, 1 H), 4.88–4.82 (m, 1 H), 3.85 (s, 3 H), 3.83 (s, 3 H), 2.93–2.86 (m, 1 H), 2.76–2.70 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 149.7, 149.4, 140.0, 139.6, 135.5, 135.4, 134.8, 134.7, 130.0, 129.2, 121.1, 119.9, 103.5, 101.1, 100.9, 98.8, 68.9, 59.4 (2 C), 31.9 ppm. HRMS: m/z calcd for C20H20O7: 371.1052; 371.1048 [M + H]+.
    • 24a Venkanna A. Sreedhar E. Siva B. Babu KS. Prasad KR. Rao JM. Tetrahedron: Asymmetry 2013; 24: 1010
    • 24b Zhantao Y. Xiaolong X. Chun-Hua Y. Yunfeng T. Xinyi C. Lihui L. Wenwei P. Xuncheng S. Weicheng Z. Yue C. Org. Lett. 2016; 18: 5768
    • 25a Adam W. Humpf H.-U. Roschmann KJ. Saha-Möller CR. J. Org. Chem. 2001; 66: 5796
    • 25b Jacobsen EN. Zhang W. Muci AR. Ecker JR. Deng L. J. Am. Chem. Soc. 1991; 113: 7063
    • 25c Hughes DL. Smith GB. Liu J. Dezeny GC. Senanayake CH. Larsen RD. Verhoeven TR. Reider PJ. J. Org. Chem. 1997; 62: 2222
    • 25d Brandes BD. Jacobsen EN. J. Org. Chem. 1994; 59: 4378