Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2014; 25(16): 2337-2340
DOI: 10.1055/s-0034-1378562
DOI: 10.1055/s-0034-1378562
letter
Studies toward the Second-Generation Synthesis of Epolactaene: Highly Stereoselective Construction of the Epoxy-γ-Lactam Moiety
Further Information
Publication History
Received: 11 June 2014
Accepted after revision: 08 July 2014
Publication Date:
11 August 2014 (online)
![](https://www.thieme-connect.de/media/synlett/201416/lookinside/thumbnails/10.1055-s-0034-1378562-1.jpg)
Abstract
Highly stereoselective synthesis of the epoxy-γ-lactam moiety toward the second-generation total synthesis of epolactaene was achieved via an E-selective Horner–Wadsworth–Emmons reaction using our new reagent and diastereoselective epoxidation of an allyl diol with VO(acac)2 and TBHP.
-
References and Notes
- 1 Kakeya H, Takahashi I, Okada G, Isono K, Osada H. J. Antibiot. 1995; 48: 733
- 2 Kakeya H, Onozawa C, Sato M, Arai K, Osada H. J. Med. Chem. 1997; 40: 391
- 3 Mizushina Y, Kobayashi S, Kuramochi K, Nagata S, Sugawara F, Sakaguchi K. Biochem. Biophys. Res. Commun. 2000; 273: 784
- 4 Nakai J, Kawada K, Nagata S, Kuramochi K, Uchiro H, Kobayashi S, Ikekita M. Biochim. Biophys. Acta 2002; 1581: 1
- 5 Mizushina Y, Kuramochi K, Ikawa H, Kuriyama I, Shimazaki N, Takemura M, Oshige M, Yoshida H, Koiwai O, Sugawara F, Kobayashi S, Sakaguchi K. Int. J. Mol. Med. 2005; 15: 785
- 6a Kuramochi K, Yukizawa S, Ikeda S, Sunoki T, Arai S, Matsui R, Morita A, Mizushina Y, Sakaguchi K, Sugawara F, Ikekita M, Kobayashi S. Bioorg. Med. Chem. 2008; 16: 5039
- 6b Kuramochi K, Sunoki T, Tsubaki K, Mizushina Y, Sakaguchi K, Sugawara F, Ikekita M, Kobayashi S. Bioorg. Med. Chem. 2011; 19: 4162
- 7a Naruto S, Marumoto S, Kogen H. JP H11-130765, 1999 ; a patent application was filed before Patent Office on October 30, 1997 as a patent filing number of H09-297983
- 7b Marumoto S, Kogen H, Naruto S. J. Org. Chem. 1998; 63: 2068
- 7c Marumoto S, Kogen H, Naruto S. Tetrahedron 1999; 55: 7129
- 7d Marumoto S, Kogen H, Naruto S. Tetrahedron 1999; 55: 7145
- 8a Hayashi Y, Narasaka K. Chem. Lett. 1998; 313
- 8b Hayashi Y, Kanayama J, Yamaguchi J, Shoji M. J. Org. Chem. 2002; 67: 9443
- 8c Kuramochi K, Itaya H, Nagata S, Takao K, Kobayashi S. Tetrahedron Lett. 1999; 40: 7367
- 8d Kuramochi K, Itaya H, Nagata S, Takao K, Kobayashi S. Tetrahedron Lett. 1999; 40: 7371
- 8e Kuramochi K, Nagata S, Itaya H, Matsubara Y, Sunoki T, Uchiro H, Takao K, Kobayashi S. Tetrahedron 2003; 59: 9743
- 8f Tan Z, Negishi E. Org. Lett. 2006; 8: 2783
- 9 Marumoto S, Kogen H, Naruto S. Chem. Commun. 1998; 2253
- 10a Tago K, Kogen H. Org. Lett. 2000; 2: 1975
- 10b Tago K, Kogen H. Tetrahedron 2000; 56: 8825
- 10c Nakata A, Kobayashi K, Kogen H. Chem. Pharm. Bull. 2013; 61: 108
- 11 Lactone 5 is actually the enantiomer of the known intermediate in our previous synthesis of unnatural (+)-epolactaene, see ref. 7c.
- 12 Massad SK, Hawkins LD, Baker DC. J. Org. Chem. 1983; 48: 5180
- 13 TBS ether 8b was used in the next step without purification because of its instability.
- 14 The stereochemistries of the resulting E-configured double bonds were confirmed after reduction to alcohols 7a–c with DIBAL-H by the NOE correlation between the allylic methine proton and methylene protons.
- 15 Although the Bn and TBS groups had no advantage over TBDPS in the HWE reaction, the subsequent steps were carried out to confirm their influence on the stereoselectivity of the epoxidation.
- 16a Luche JL. J. Am. Chem. Soc. 1979; 101: 5848
- 16b TBDPS ether in 13c was derivatized to (R)- or (S)-MTPA ester after protection of 1,3-diol functionality as an acetonide. Since 1H NMR of each crude product did not show the signals of the other diastereomer, we confirmed no epimerization occurred during the synthesis of 13c.
- 17a Johnson MR, Kishi Y. Tetrahedron Lett. 1979; 20: 4347
- 17b Kogen H, Nishi T. J. Chem. Soc., Chem. Commun. 1987; 311
-
18 Katsuki T, Sharpless KB. J. Am. Chem. Soc. 1980; 102: 5974
- 19 Wang Z.-X, Tu Y, Frohn M, Zhang J.-R, Shi Y. J. Am. Chem. Soc. 1996; 119: 11224
- 20 Sharpless KB, Michaelson RC. J. Am. Chem. Soc. 1973; 95: 6136
- 21 The low yield is due to the deprotection of the TBS group during the reaction.
- 22 Procedure for Synthesizing Epoxide 6c (Table 1 Entry 9) To a stirred solution of allyl diol 13c (96 mg, 0.26 mmol) in CH2Cl2 (5.0 mL) was added VO(acac)2 (14 mg, 0.052 mmol) at r.t. After stirring for 10 min, TBHP (5.5 M solution in decane, 0.10 mL, 0.55 mmol) was added, and the mixture was stirred for 6 h. The reaction was quenched by addition of a sat. aq Na2S2O3 solution. The mixture was extracted with CH2Cl2 (4 × 20 mL). The combined extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane–EtOAc, 1:1) to afford epoxide 6c (97 mg, 97%) as a colorless oil. [α]25 D –9.2 (c 0.99, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.63–7.72 (m, 4 H), 7.35–7.50 (m, 6 H), 3.81 (dd, J = 12.3, 4.8 Hz, 1 H), 3.71 (dq, J = 7.8, 6.0 Hz, 1 H), 3.59 (dd, J = 12.3, 8.1 Hz, 1 H), 3.33 (dd, J = 12.3, 6.3 Hz, 1 H), 3.26 (dd, J = 12.3, 6.3 Hz, 1 H), 3.11 (d, J = 7.8 Hz, 1 H), 1.73 (dd, J = 8.1, 5.1 Hz, 1 H), 1.44 (t, J = 6.3 Hz, 1 H), 1.29 (d, J = 6.0 Hz, 3 H), 1.03 (s, 9 H). 13C NMR (100 MHz, CHCl3): δ = 135.7, 135.6, 133.6, 133.3, 130.1, 130.0, 127.8, 127.7, 66.3, 64.4, 63.9, 63.3, 61.0, 26.7, 21.6, 19.1. IR (CHCl3): 3588, 2963, 2933, 1472, 1373, 1235, 1111, 952, 822 cm–1. LRMS (FAB+): m/z = 387 [M + H]+. Anal. Calcd for C22H30O4Si·H2O: C, 65.31; H, 7.97. Found: C, 65.13; H, 7.74.
- 23 Maruyama K, Ueda M, Sasaki S, Iwata Y, Miyazawa M, Miyashita M. Tetrahedron Lett. 1998; 39: 4517
- 24 Spectral Data for 4b [α]22 D –60.4 (c 0.10, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 6.17 (br s, 1 H), 5.64 (br s, 1 H), 3.81 (m, 1 H), 3.77 (s, 3 H), 3.51 (br s, 1 H), 3.23 (br s, 3 H), 1.33 (d, J = 4.5 Hz, 3 H), 0.88 (s, 9 H), 0.08 (s, 3 H), 0.06 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.2, 165.5, 65.8, 64.7, 63.3, 61.6, 32.4, 25.7 (3 C), 21.7, 17.9, –4.7 (2 C). IR (CHCl3): 3517, 3401, 2932, 1703, 1678, 1572, 1390, 1260, 1216, 1116, 840, 746 cm–1. HRMS (FAB+): m/z calcd for C14H29O5N2Si [M + H]+: 333.1846; found: 333.1846.
Our previous works on epolactaene:
Total synthesis of epolactaene by other research groups: