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A new convenient asymmetric approach to herbarumin III
Chinese Chemical Letters 18 (2007) 255–257 www.elsevier.com/locate/cclet
A new convenient asymmetric approach to herbarumin III Xue Song Chen, Shi Jun Da, Li Hong Yang, Bo Yan Xu, Zhi Xiang Xie, Ying Li * The State Key Laboratory of Applied Organic Chemistry, Institute of Organic Chemistry, Lanzhou University, Lanzhou 730000, China Received 6 November 2006
Abstract The asymmetric total synthesis of herbarumin III 3, a naturally occurred phytotoxin, along with 8-epi-herbarumin III 22, was succeeded in 12 steps from n-butyraldehyde based on Brown’s asymmetric allylation, taking modified Julia olefination and Yamaguchi’s macro-lactonization as key steps. # 2007 Ying Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Herbarumin III; Asymmetric allylation; Modified Julia olefination; Yamaguchi’s macro-lactonization
Lactone functionality is ubiquitous in bioactive compounds [1], i.e., triptolides and coumarins. Most of them contain large or small size lactone ring, and possess various important activities. However, natural lactone products with a medium ring size are rare and their syntheses are challenging. These compounds showed surprising activities in many aspects, and have been aroused wide interest of chemists and biologists in recent years [2]. Herbarumin III 3 [3] is such a bioactive compound with a 10-membered lactone ring, which was isolated [4] firstly from the mycelium and culture broth of the fungus Phoma herbarum (Sphaeropsidaceae) as a phytotoxin, along with herbarumin I 1 and II 2. Herbarumin III inhibited radical growth with 10 times higher potency than 2,4-dichlorophenoxyacetic acid [5]. The phototoxic effect of 3 is comparable to that of 1 and higher than that of 2. Herbarumin III also interacted with bovinebrain calmodulin and has the same inhibitory effect as those of herbarumin I 1 and herbarumin II 2.
The first synthesis of herbarumin III was reported [5] by Mohapatra in 2004 using D-glucose as starting material and RCM reaction as the key step. Shortly afterwards, Nanda [6] and Chattopadhyay [7] reported two new methods, respectively. The former is based on a Julia coupling reaction and a lipase catalyzed irreversible transesterification. The latter is also based on RCM protocol. Herein, we described a very convenient synthesis of herbarumin III using modified Julia olefination as key step and Brown’s asymmetric allylation to form chiral center. * Corresponding author. E-mail addresses: [email protected] (S.J. Da), [email protected] (Y. Li). 1001-8417/$ – see front matter # 2007 Ying Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.01.035
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X.S. Chen et al. / Chinese Chemical Letters 18 (2007) 255–257
Scheme 1. (a) lIpc2BAll, THF, 78 8C, then NaOH, H2O2, reflux, 70%; (b) Imidazole, TBSCl, DMF, r.t., 92%; (c) AD-mix-b, H2O-t-BuOH (1:1), 0 8C, 60%; (d) BzCl, pyridine, CH2Cl2, 0 8C, 90%; (e) MOMCl, DIPEA, THF, reflux, 93%; (f) EtMgBr, Et2O, r.t., 95%; (g) (COCl)2, DMSO, CH2Cl2, 78 8C, then Et3N, 72%.
The present synthesis of 3 was started from n-butryaldehyde 4 as shown in Scheme 1. Firstly, 4 was converted to homoallyl alcohol compound 5 by treatment with lIpc2BCH2CH CH2 prepared from BH3SMe2 and (+)-a-pinene [8]. This reaction formed the first chiral center. The second chiral center came from Sharpless’ asymmetric dihydroxylation of compound 6. Unfortunately, two diastereoisomers of 7 with 1:1 ratio formed, which cannot be separated by silica gel column chromatography. Using a bulkier silyl substitution TBDPS instead of TBS has not dissolve the problem yet (Scheme 1). Another precursor of modified Julia olefination compound 15 was prepared following the procedure as shown in Scheme 2. The stage was now set for the key modified Julia olefination, using KHMDS as the base, the reaction
Scheme 2. (a) PivCl, pyridine, CH2Cl2, 58%; (b) 1-phenyl-1H-tetrazole-5-thiol, DIAD, PPh3, THF, 0 8C–r.t., 1 h; (c) m-CPBA, NaHCO3, CH2Cl2, r.t., 83% for two steps; (d) KN(TMS)2, DME, 60 8C, then 11, 60 8C–r.t., 62%; (e) DIBAL-H, Et2O, 78 8C, 94%; (f) (i) (COCl)2, DMSO, CH2Cl2, 78 8C, then Et3N, 85%, (ii) AgNO3, NaOH, EtOH, r.t., 95%; (g) TBAF, THF, reflux, 78%; (h) 2,4,6-trichlorobenzoyl chloride, Et3N, then DMAP, toluene, reflux, 62%; (i) PPTS, t-BuOH, reflux, 93%.
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between 11 and 15 took place smoothly giving compound 16 in a yield of 62% as expected [9]. After removing Piv with DIBAl-H, oxidizing the obtained alcohol to acid and removing the TBS protecting group, compound 19 yielded. Intramolecular esterification of seco-acid 19 took place under Yamaguchi’s conditions [10] by treatment of 19 with 2,4,6-tricholrobenzoyl chloride/Et3N and DMAP afforded a mixture of 20 and 21 in a moderate yield, which were separated by silica gel column chromatography. Deprotection of compound 20 and 21 proceeded with PPTS in t-BuOH yielded herbarumin III 3 [11] and its isomer 8-epi-herbarumin III 22 [12], respectively. The data of 3 [11] are in consistent with those reported in ref. [4]. In conclusion, a new convenient asymmetric synthesis to naturally occurred product herbarumin III 3 from simple starting materials was established based on Brown’s asymmetric allylation by taking modified Julia olefination and Yamaguchi’s macro-lactonization as key steps. Acknowledgment The project was supported by the National Natural Science Foundation of China (No. 20672050). References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
[12]
H.D. Belitz, W. Grosch, Food Chemistry, Springer, Berlin, 1986 (Chapter 5). G. Rousseau, Tetrahedron 51 (1995) 2777. J.F. Rivero-Cruz, G. Garcı0 a-Aguirre, C.M. Cerda-Garcı0 a Rojas, R. Mata, Tetrahedron 56 (2000) 5337. J.F. Rivero-Cruz, M. Macı0 as, C.M. Cerda-Garcı0 a Rojas, R. Mata, J. Nat. Prod. 66 (2003) 511. (a) M.K. Gurjar, S. Karmakar, D.K. Mohapatra, Tetrahedron Lett. 45 (2004) 4525; (b) M.K. Gurjar, R. Nagaprasad, C.V. Ramana, D.K. Mohapatra, ARKIVOC (Part 3) (2005) 237. S. Nanda, Tetrahedron Lett. 46 (2005) 3661. A. Salaskar, A. Sharma, S. Chattopadhyay, Tetrahedron: Asymmetry 17 (2006) 325. P.K. Jadhav, K.S. Bhat, P. Thirumalai Perumal, H.C. Brown, J. Org. Chem. 51 (1986) 432. (a) P.R. Blakemore, W.J. Cole, P.J. Kocienshi, A. Morley, Synlett (1998) 26; (b) P.R. Blakemore, J. Chem. Soc., Perkin Trans. 1 (2002) 2563. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 52 (1979) 1989. Data of compound 3: [a]25D = +198 (c 0.1, EtOH), (lit. [a]25D = +228 (c 0.1, EtOH)); IR: 3449, 2959, 2929, 1726, 1203, 1046 cm1; 1H NMR (CDCl3, 300 MHz, d ppm): 5.59–5.64 (m, 1H), 5.34–5.44 (m, 1H), 5.10–5.21 (m, 1H), 4.42–4.47 (m, 1H), 2.37–2.42 (m, 2H), 2.24–2.29 (m, 1H), 2.02 (m, 1H), 1.98–2.02 (m, 3H), 1.77–1.85 (m, 2H), 1.49–1.76 (m, 2H), 1.32–1.42 (m, 2H), 0.87 (t, 3H, J = 7.2 Hz); 13C NMR (CDCl3, 75 MHz, d ppm): 176.9, 134.5, 124.9, 68.0, 67.8, 40.5, 37.3, 34.6, 33.6, 25.9, 18.4, 13.8; EIMS m/z 212 (1, M+), 194 (12), 169 (1), 151 (15), 143 (22), 125 (95), 113 (27), 97 (50), 70 (51), 55 (93), 41 (100); HRMS m/z 230.1747 [M + NH4+] (calcd. for C12H24NO3, 230.1751). Data of compound 22: [a]25D = 0.68 (c 0.5, EtOH); IR: 3433, 2958, 2923, 1728, 1210, 1028 cm1; 1H NMR (CDCl3, 300 MHz, d ppm): 5.57 (d, J = 7.2 Hz, 1H), 5.50–5.32 (m, 1H), 5.05–4.98 (m, 1H), 4.10–4.05 (m, 1H), 2.38–2.31 (m, 2H), 2.24–2.29 (m, 1H), 2.02 (m, 1H), 1.98–2.02 (m, 3H), 1.77–1.85 (m, 2H), 1.49–1.76 (m, 2H), 1.32–1.42 (m, 2H), 0.87 (t, 3H, J = 7.2 Hz); 13C NMR (CDCl3, 75 MHz, d ppm): 175.5, 135.9, 131.2, 72.8, 71.0, 41.6, 37.8, 34.7, 33.4, 26.1, 18.3, 13.8.
A new convenient asymmetric approach to herbarumin III Xue Song Chen, Shi Jun Da, Li Hong Yang, Bo Yan Xu, Zhi Xiang Xie, Ying Li * The State Key Laboratory of Applied Organic Chemistry, Institute of Organic Chemistry, Lanzhou University, Lanzhou 730000, China Received 6 November 2006
Abstract The asymmetric total synthesis of herbarumin III 3, a naturally occurred phytotoxin, along with 8-epi-herbarumin III 22, was succeeded in 12 steps from n-butyraldehyde based on Brown’s asymmetric allylation, taking modified Julia olefination and Yamaguchi’s macro-lactonization as key steps. # 2007 Ying Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Herbarumin III; Asymmetric allylation; Modified Julia olefination; Yamaguchi’s macro-lactonization
Lactone functionality is ubiquitous in bioactive compounds [1], i.e., triptolides and coumarins. Most of them contain large or small size lactone ring, and possess various important activities. However, natural lactone products with a medium ring size are rare and their syntheses are challenging. These compounds showed surprising activities in many aspects, and have been aroused wide interest of chemists and biologists in recent years [2]. Herbarumin III 3 [3] is such a bioactive compound with a 10-membered lactone ring, which was isolated [4] firstly from the mycelium and culture broth of the fungus Phoma herbarum (Sphaeropsidaceae) as a phytotoxin, along with herbarumin I 1 and II 2. Herbarumin III inhibited radical growth with 10 times higher potency than 2,4-dichlorophenoxyacetic acid [5]. The phototoxic effect of 3 is comparable to that of 1 and higher than that of 2. Herbarumin III also interacted with bovinebrain calmodulin and has the same inhibitory effect as those of herbarumin I 1 and herbarumin II 2.
The first synthesis of herbarumin III was reported [5] by Mohapatra in 2004 using D-glucose as starting material and RCM reaction as the key step. Shortly afterwards, Nanda [6] and Chattopadhyay [7] reported two new methods, respectively. The former is based on a Julia coupling reaction and a lipase catalyzed irreversible transesterification. The latter is also based on RCM protocol. Herein, we described a very convenient synthesis of herbarumin III using modified Julia olefination as key step and Brown’s asymmetric allylation to form chiral center. * Corresponding author. E-mail addresses: [email protected] (S.J. Da), [email protected] (Y. Li). 1001-8417/$ – see front matter # 2007 Ying Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2007.01.035
256
X.S. Chen et al. / Chinese Chemical Letters 18 (2007) 255–257
Scheme 1. (a) lIpc2BAll, THF, 78 8C, then NaOH, H2O2, reflux, 70%; (b) Imidazole, TBSCl, DMF, r.t., 92%; (c) AD-mix-b, H2O-t-BuOH (1:1), 0 8C, 60%; (d) BzCl, pyridine, CH2Cl2, 0 8C, 90%; (e) MOMCl, DIPEA, THF, reflux, 93%; (f) EtMgBr, Et2O, r.t., 95%; (g) (COCl)2, DMSO, CH2Cl2, 78 8C, then Et3N, 72%.
The present synthesis of 3 was started from n-butryaldehyde 4 as shown in Scheme 1. Firstly, 4 was converted to homoallyl alcohol compound 5 by treatment with lIpc2BCH2CH CH2 prepared from BH3SMe2 and (+)-a-pinene [8]. This reaction formed the first chiral center. The second chiral center came from Sharpless’ asymmetric dihydroxylation of compound 6. Unfortunately, two diastereoisomers of 7 with 1:1 ratio formed, which cannot be separated by silica gel column chromatography. Using a bulkier silyl substitution TBDPS instead of TBS has not dissolve the problem yet (Scheme 1). Another precursor of modified Julia olefination compound 15 was prepared following the procedure as shown in Scheme 2. The stage was now set for the key modified Julia olefination, using KHMDS as the base, the reaction
Scheme 2. (a) PivCl, pyridine, CH2Cl2, 58%; (b) 1-phenyl-1H-tetrazole-5-thiol, DIAD, PPh3, THF, 0 8C–r.t., 1 h; (c) m-CPBA, NaHCO3, CH2Cl2, r.t., 83% for two steps; (d) KN(TMS)2, DME, 60 8C, then 11, 60 8C–r.t., 62%; (e) DIBAL-H, Et2O, 78 8C, 94%; (f) (i) (COCl)2, DMSO, CH2Cl2, 78 8C, then Et3N, 85%, (ii) AgNO3, NaOH, EtOH, r.t., 95%; (g) TBAF, THF, reflux, 78%; (h) 2,4,6-trichlorobenzoyl chloride, Et3N, then DMAP, toluene, reflux, 62%; (i) PPTS, t-BuOH, reflux, 93%.
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between 11 and 15 took place smoothly giving compound 16 in a yield of 62% as expected [9]. After removing Piv with DIBAl-H, oxidizing the obtained alcohol to acid and removing the TBS protecting group, compound 19 yielded. Intramolecular esterification of seco-acid 19 took place under Yamaguchi’s conditions [10] by treatment of 19 with 2,4,6-tricholrobenzoyl chloride/Et3N and DMAP afforded a mixture of 20 and 21 in a moderate yield, which were separated by silica gel column chromatography. Deprotection of compound 20 and 21 proceeded with PPTS in t-BuOH yielded herbarumin III 3 [11] and its isomer 8-epi-herbarumin III 22 [12], respectively. The data of 3 [11] are in consistent with those reported in ref. [4]. In conclusion, a new convenient asymmetric synthesis to naturally occurred product herbarumin III 3 from simple starting materials was established based on Brown’s asymmetric allylation by taking modified Julia olefination and Yamaguchi’s macro-lactonization as key steps. Acknowledgment The project was supported by the National Natural Science Foundation of China (No. 20672050). References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
[12]
H.D. Belitz, W. Grosch, Food Chemistry, Springer, Berlin, 1986 (Chapter 5). G. Rousseau, Tetrahedron 51 (1995) 2777. J.F. Rivero-Cruz, G. Garcı0 a-Aguirre, C.M. Cerda-Garcı0 a Rojas, R. Mata, Tetrahedron 56 (2000) 5337. J.F. Rivero-Cruz, M. Macı0 as, C.M. Cerda-Garcı0 a Rojas, R. Mata, J. Nat. Prod. 66 (2003) 511. (a) M.K. Gurjar, S. Karmakar, D.K. Mohapatra, Tetrahedron Lett. 45 (2004) 4525; (b) M.K. Gurjar, R. Nagaprasad, C.V. Ramana, D.K. Mohapatra, ARKIVOC (Part 3) (2005) 237. S. Nanda, Tetrahedron Lett. 46 (2005) 3661. A. Salaskar, A. Sharma, S. Chattopadhyay, Tetrahedron: Asymmetry 17 (2006) 325. P.K. Jadhav, K.S. Bhat, P. Thirumalai Perumal, H.C. Brown, J. Org. Chem. 51 (1986) 432. (a) P.R. Blakemore, W.J. Cole, P.J. Kocienshi, A. Morley, Synlett (1998) 26; (b) P.R. Blakemore, J. Chem. Soc., Perkin Trans. 1 (2002) 2563. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 52 (1979) 1989. Data of compound 3: [a]25D = +198 (c 0.1, EtOH), (lit. [a]25D = +228 (c 0.1, EtOH)); IR: 3449, 2959, 2929, 1726, 1203, 1046 cm1; 1H NMR (CDCl3, 300 MHz, d ppm): 5.59–5.64 (m, 1H), 5.34–5.44 (m, 1H), 5.10–5.21 (m, 1H), 4.42–4.47 (m, 1H), 2.37–2.42 (m, 2H), 2.24–2.29 (m, 1H), 2.02 (m, 1H), 1.98–2.02 (m, 3H), 1.77–1.85 (m, 2H), 1.49–1.76 (m, 2H), 1.32–1.42 (m, 2H), 0.87 (t, 3H, J = 7.2 Hz); 13C NMR (CDCl3, 75 MHz, d ppm): 176.9, 134.5, 124.9, 68.0, 67.8, 40.5, 37.3, 34.6, 33.6, 25.9, 18.4, 13.8; EIMS m/z 212 (1, M+), 194 (12), 169 (1), 151 (15), 143 (22), 125 (95), 113 (27), 97 (50), 70 (51), 55 (93), 41 (100); HRMS m/z 230.1747 [M + NH4+] (calcd. for C12H24NO3, 230.1751). Data of compound 22: [a]25D = 0.68 (c 0.5, EtOH); IR: 3433, 2958, 2923, 1728, 1210, 1028 cm1; 1H NMR (CDCl3, 300 MHz, d ppm): 5.57 (d, J = 7.2 Hz, 1H), 5.50–5.32 (m, 1H), 5.05–4.98 (m, 1H), 4.10–4.05 (m, 1H), 2.38–2.31 (m, 2H), 2.24–2.29 (m, 1H), 2.02 (m, 1H), 1.98–2.02 (m, 3H), 1.77–1.85 (m, 2H), 1.49–1.76 (m, 2H), 1.32–1.42 (m, 2H), 0.87 (t, 3H, J = 7.2 Hz); 13C NMR (CDCl3, 75 MHz, d ppm): 175.5, 135.9, 131.2, 72.8, 71.0, 41.6, 37.8, 34.7, 33.4, 26.1, 18.3, 13.8.