Synlett 2014; 25(07): 1014-1018
DOI: 10.1055/s-0033-1340872
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of the Proposed Structure for Itralamide B

Xiaoji Wang*
a   School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, 330013, P. R. of China   eMail: professorwxj@163.com
,
Chanshan Lv
a   School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, 330013, P. R. of China   eMail: professorwxj@163.com
b   Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, University Town of Shenzhen, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   eMail: xuzs@pkusz.edu.cn
,
Junyang Liu
b   Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, University Town of Shenzhen, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   eMail: xuzs@pkusz.edu.cn
c   Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong   Fax: +85222641912   eMail: tao.ye@polyu.edu.hk
,
Linjun Tang
a   School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, 330013, P. R. of China   eMail: professorwxj@163.com
,
Junmin Feng
a   School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, 330013, P. R. of China   eMail: professorwxj@163.com
,
Shoubin Tang
b   Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, University Town of Shenzhen, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   eMail: xuzs@pkusz.edu.cn
,
Zhuo Wang
c   Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong   Fax: +85222641912   eMail: tao.ye@polyu.edu.hk
,
Yuqing Liu
c   Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong   Fax: +85222641912   eMail: tao.ye@polyu.edu.hk
,
Yi Meng
b   Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, University Town of Shenzhen, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   eMail: xuzs@pkusz.edu.cn
,
Tao Ye*
c   Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong   Fax: +85222641912   eMail: tao.ye@polyu.edu.hk
,
Zhengshuang Xu*
a   School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, 330013, P. R. of China   eMail: professorwxj@163.com
b   Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, University Town of Shenzhen, Xili, Nanshan District, Shenzhen, 518055, P. R. of China   eMail: xuzs@pkusz.edu.cn
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 28. Dezember 2013

Accepted after revision: 05. Februar 2014

Publikationsdatum:
14. März 2014 (online)


Abstract

A stereocontrolled total synthesis of the cyclodepsipeptide, itralamide B, has been achieved. Both R- and S-stereoisomers of the side chain were attached to the macrocyclic ring, however, the synthesized structure appears to be different from that of the marine natural product.

Supporting Information

 
  • References and Notes

  • 1 Lemmens-Gruber R, Kamyar MR, Dornetshuber R. Curr. Med. Chem. 2009; 16: 1122
  • 2 Suyama TL, Gerwick WH, McPhail KL. Bioorg. Med. Chem. 2011; 19: 6675
  • 5 Jiménez JI, Vansach T, Yoshida WY, Sakamoto B, Pörzgen P, Horgen FD. J. Nat. Prod. 2009; 72: 1573
  • 6 Bhushan R, Brückner H. Amino Acids 2004; 27: 231
  • 7 Medina RA, Goeger DE, Hills P, Mooberry SL, Huang N, Romero LI, Ortega-Barria E, Gerwick WH, McPhail KL. J. Am. Chem. Soc. 2008; 130: 6324
  • 8 Ford PW, Gustafson KR, McKee TC, Shigematsu N, Maurizi LK, Pannell LK, Williams DE, Dilip de Silva E, Lassota P, Allen TM, Van Soest R, Andersen RJ, Boyd MR. J. Am. Chem. Soc. 1999; 121: 5899
  • 9 Ridley CP, Bergquist PR, Harper MK, Faulkner DJ, Hooper JN, Haygood MG. Chem. Biol. 2005; 12: 397

    • Lyngbyabellin A was isolated from marine cyanobacterium Lyngbya majuscule, see:
    • 10a Luesch H, Yoshida WY, Moore RE, Paul VJ, Mooberry SL. J. Nat. Prod. 2000; 63: 611

    • Its structure and absolute stereochemistry were confirmed by total syntheses, see:
    • 10b Pang HW, Xu ZS, Chen ZY, Ye T. Lett. Org. Chem. 2005; 2: 699
    • 10c Yokokawa F, Sameshima H, Shioiri T. Tetrahedron Lett. 2001; 42: 4171
  • 11 Jin Y, Liu YQ, Wang Z, Kwong S, Xu ZS, Ye T. Org. Lett. 2010; 12: 1100
  • 12 All the attempts to close the macrocycle by macrolactamization met with failure. The detailed studies will be reported in due course.
  • 14 Evans DA, Wu LD, Wiener JJ. M, Johnson JS, Ripin DH. B, Tedrow JS. J. Org. Chem. 1999; 64: 6411
  • 15 Lapatsanis L, Milias G, Paraskewas S. Synthesis 1985; 513
  • 16 Rodríguez-Escrich C, Urpí F, Vilarrasa J. Org. Lett. 2008; 10: 5191
  • 17 De Luca L, Giacomelli G, Porcheddu A. Org. Lett. 2001; 3: 3041
  • 19 White KN, Konopelski JP. Org. Lett. 2005; 7: 4111
  • 21 Albericio F, Cases M, Alsina J, Triolo SA, Carpino LA, Kates SA. Tetrahedron Lett. 1997; 38: 4853
  • 23 Evans EF, Lewis NJ, Kapfer I, Macdonald G, Taylor RJ. K. Synth. Commun. 1997; 27: 1819
  • 24 Shiina I, Kubota M, Oshiumi H, Hashizume M. J. Org. Chem. 2004; 69: 1822
  • 25 Synthesis of Itralamide B (1): Compound 18 (23.0 mg, 0.03 mmol, 1.0 equiv) was dissolved in CH2Cl2 (1.0 mL) at 0 °C, and BF3·OEt2 (34 μL, 0.3 mmol, 10.0 equiv) was added dropwise to the solution at 0 °C. The reaction solution was allowed to warm to r.t. and stirred for 0.5–1.0 h (reaction monitored by TLC). The reaction was quenched by the addition of saturated NH4Cl (2 mL) and diluted with CH2Cl2 (60 mL). The organic phase was washed with saturated NH4Cl (3 × 20 mL) and brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo to afford the crude hydroxy acid. A solution of this hydroxy acid in THF–PhMe (10 mL, 1:1) was slowly added to a solution of DMAP (33 mg, 0.3 mmol, 10.0 equiv) and MNBA (47 mg, 0.14 mmol, 5.0 equiv) in PhMe (10 mL) at 0 °C. The reaction mixture was warmed to r.t., then stirred and heated to 60 °C for 2 d. The reaction mixture was diluted with EtOAc (100 mL) and washed successively with saturated NH4Cl (3 × 20 mL) and brine (2 × 20 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc) to afford (S)-itralamide B (1; 5.0 mg, 21%). (S)-Itralamide B (1): [α]D 25 –44.63 (c 0.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.45–7.12 (m, 5 H), 6.90 (d, J = 9.6 Hz, 1 H), 6.47 (d, J = 8.0 Hz, 1 H), 5.99 (d, J = 2.9 Hz, 1 H), 5.75–5.65 (m, 2 H), 5.53–5.43 (m, 1 H), 5.08 (q, J = 6.8 Hz, 1 H), 4.98 (dd, J = 7.9, 4.2 Hz, 1 H), 4.71 (dd, J = 9.4, 4.1 Hz, 1 H), 4.62 (q, J = 7.6 Hz, 1 H), 3.66 (dd, J = 15.5, 4.9 Hz, 1 H), 3.33 (d, J = 23.6 Hz, 3 H), 3.19 (d, J = 7.1 Hz, 3 H), 3.17–3.07 (m, 3 H), 3.07–2.94 (m, 3 H), 2.87 (dd, J = 15.6, 12.1 Hz, 1 H), 2.80 (d, J = 4.0 Hz, 1 H), 2.76–2.65 (m, 1 H), 2.46 (dd, J = 16.5, 7.5 Hz, 1 H), 2.28–2.21 (m, 1 H), 2.06–1.99 (m, 1 H), 1.29 (d, J = 2.0 Hz, 3 H), 1.26 (d, J = 2.8 Hz, 3 H), 1.20 (dd, J = 6.6, 3.5 Hz, 3 H), 1.08–1.01 (m, 6 H), 0.92 (dd, J = 9.4, 7.2 Hz, 6 H), 0.80 (d, J = 6.8 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 174.89, 172.84, 172.53, 170.65, 170.17, 169.90, 169.47, 137.35, 128.54, 128.34, 126.48, 78.18, 69.62, 56.92, 56.75, 54.69, 54.68, 53.98, 51.43, 40.65, 35.75, 33.92, 33.77, 32.15, 31.83, 31.12, 31.00, 30.54, 19.90, 19.63, 17.82, 17.10, 15.61, 15.35, 14.10, 13.82. HRMS (ESI): m/z [M+Na]+ calcd for C38H58Cl2N6NaO8 +: 819.3585; found: 819.3587. (R)-Itralamide B (1): [α]D 25 –42.33 (c 0.2, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.24–7.16 (m, 5 H), 6.89 (d, J = 9.1 Hz, 1 H), 6.48 (d, J = 7.8 Hz, 1 H), 6.04 (d, J = 2.9 Hz, 1 H), 5.78–5.63 (m, 1 H), 5.49 (dd, J = 6.6, 3.2 Hz, 1 H), 5.45–5.35 (m, 1 H), 5.12–5.02 (m, 1 H), 4.98 (dd, J = 7.8, 4.2 Hz, 1 H), 4.71 (dd, J = 9.3, 4.0 Hz, 1 H), 4.67–4.55 (m, 1 H), 3.66 (dd, J = 15.3, 5.1 Hz, 1 H), 3.28 (d, J = 63.9 Hz, 3 H), 3.18 (s, 3 H), 3.13 (d, J = 23.1 Hz, 3 H), 3.01 (d, J = 11.3 Hz, 3 H), 2.93 (d, J = 15.7 Hz, 1 H), 2.90–2.78 (m, 1 H), 2.78–2.67 (m, 1 H), 2.43 (dd, J = 16.7, 6.0 Hz, 1 H), 2.25 (dd, J = 11.9, 5.9 Hz, 1 H), 2.04 (d, J = 9.5 Hz, 1 H), 1.38 (dd, J = 18.4, 7.2 Hz, 3 H), 1.30 (d, J = 6.7 Hz, 3 H), 1.20 (d, J = 6.6 Hz, 3 H), 1.06 (d, J = 6.8 Hz, 6 H), 0.92 (dd, J = 11.7, 7.0 Hz, 6 H), 0.80 (d, J = 6.8 Hz, 3 H); 13C NMR (100 MHz, CDCl3): δ = 174.88, 172.83, 172.56, 170.68, 170.17, 169.85, 169.51, 137.37, 128.55, 128.34, 126.48, 78.02, 69.64, 56.88, 56.75, 54.75, 54.22, 53.99, 51.47, 40.45, 35.98, 33.97, 33.78, 32.18, 31.85, 31.12, 31.02, 30.55, 19.89, 19.63, 17.82, 17.09, 17.07, 15.60, 15.05, 13.83 ppm. HRMS (ESI): m/z [M+Na]+ for C38H58Cl2N6NaO8 +: 819.3585; found: 819.3589.
  • 26 See the Supporting Information for detailed analyses.