Subscribe to RSS
DOI: 10.1055/s-2002-34214
Enantioselective Synthesis of 6-nor-Fluvirucinin B1
Publication History
Publication Date:
23 September 2002 (online)
Abstract
An enantioselective synthesis of the 6-nor-derivative 3 of the antiviral macrocyclic lactam fluvirucinin B1 (2) is presented. Key steps are two regioselective ring opening reactions of chiral epoxides, and a ring-closing metathesis with Grubbs’ catalyst. The choice of appropriate protective groups was essential for the success and efficiency of the synthesis.
Key words
asymmetric synthesis - epoxides - fluvirucin - natural products - metathesis
- 1
Hedge VR.Patel MG.Gullo VP.Ganguly AK.Sarre O.Puar MS.McPhail AT. J. Am. Chem. Soc. 1990, 112: 6403 - 2
Naruse N.Tsuno T.Sawada Y.Konishi M.Oki T. J. Antibiot. 1991, 44: 741 -
3a
Houri AF.Xu Z.Cogan DA.Hoveyda AH. J. Am. Chem. Soc. 1995, 117: 2944 -
3b
Xu Z.Johannes CW.Houri AF.La DS.Cogan DA.Hofilena GE.Hoveyda AH. J. Am. Chem. Soc. 1997, 119: 10302 -
4a
Trost BM.Ceschi MA.König B. Angew. Chem., Int. Ed. Engl. 1997, 36: 1486 -
4b
Martin M.Mas G.Urpi F.Vilarrasa J. Angew. Chem. Int. Ed. 1999, 38: 3086 -
4c For the synthesis of the
related aglycone fluvirucinin A1 see:
Suh Y.-G.Kim S.-A.Jung J.-K.Shin D.-Y.Min K.-H.Koo B.-A.Kim H.-S. Angew. Chem. Int. Ed. 1999, 38: 3545 - 5
Grubbs RH.Chang S. Tetrahedron 1998, 54: 4413 - 6
Evans DA.Rieger DL.Jones TK.Kaldor SW. J. Org. Chem. 1990, 55: 6260 -
7a
Vandewalle M.Van der Eycken J.Oppolzer W.Vullioud C. Tetrahedron 1986, 42: 4035 -
7b
Thom C.Kocienski P. Synthesis 1992, 582 -
8a
Oppolzer W.Poli G. Tetrahedron Lett. 1986, 27: 4717 -
8b Review articles about
Oppolzer’s chiral auxiliaries:
Oppolzer W. Tetrahedron 1987, 43: 1969 -
8c Also see:
Oppolzer W. Pure Appl. Chem. 1990, 62: 1241 - 9
Hasegawa T.Yamamoto H. Synlett 1998, 882 -
10a
Honda M.Katsuki T.Yamaguchi M. Tetrahedron Lett. 1984, 25: 3857 -
10b
Claßen A.Wershofen S.Yusufoglu A.Scharf H.-D. Liebigs Ann. Chem. 1987, 629 - 12
Fukuyama T.Laird AA.Hotchkiss LM. Tetrahedron Lett. 1985, 26: 6291 -
13a
Skrydstrup T.Bénéchie M.Khuong-Huu F. Tetrahedron Lett. 1990, 31: 7145 -
13b See also:
Alexakis A.Jachiet D. Tetrahedron 1989, 45: 6197 - 14
Cink RD.Forsyth CJ. J. Org. Chem. 1995, 60: 8122 -
15a
Debenham JS.Debenham SD.Fraser-Reid B. Bioorg. Med. Chem. 1996, 4: 1909 -
15b
Jia ZJ.Kelberlau S.Olsson L.Anilkumar G.Fraser-Reid B. Synlett 1999, 565 - 16
Davies JS.Mohammed AK. J. Chem. Soc., Perkin Trans. 1 1981, 2982 - 17
Fürstner A.Langemann K. J. Am. Chem. Soc. 1997, 119: 9130
References
The corresponding trityl ether was also examined, but gave ring opening products only in yields <10%. Similar observations with bulky protective groups have already been described. [13]
18
Ring-closing
metathesis: A solution of diene 18 (30
mg, 0.075 mmol) and Ti(i-PrO)4 (6
mg, 0.02 mmol) in 50 mL anhydrous CH2Cl2 was
refluxed under N2 for 1 hour. Then 2 mg (0.002 mmol)
benzylidene-bis(tricyclohexylphos-phine)dichlororuthenium, dissolved
in 0.5 mL CH2Cl2, was added and the mixture
was refluxed for 4 days. Purification by flash column chromatography
(silica, hexanes-ethyl acetate 5:2) gave 20 mg (72%) 19 as colorless crystals, mp 176 °C. [α]D
20 = +35.4
(CHCl3); 1H NMR (400 MHz, CDCl3) δ (ppm)
0.84 (t, J = 7.4 Hz, 3 H), 0.90
(t, J = 7.5 Hz, 3 H), 1.20-1.60
(m, 13 H), 2.00 (m, 2 H), 2.08 (m, 1 H), 2.39 (m, 1 H), 2.65 (m,
1 H), 3.21 (m, 1 H), 3.50 (m, 1 H), 3.75 (m, 1 H), 4.42 (d, J = 11.1 Hz, 1 H), 4.54 (d, J = 11.1 Hz,
1 H),
5.38 (m, 1 H), 5.42 (m, 2 H), 7.30 (m, 5 H). 13C
NMR (100 MHz, CDCl3) δ (ppm) 11.0, 12.2, 21.9,
23.4, 24.8, 25.1, 26.9, 29.7, 31.5, 35.3, 39.4, 42.5, 50.3, 72.1,
81.5, 127.4, 127.8 (2 C), 128.3 (2 C), 131.5, 131.7, 139.0, 175.0.
MS (EI, 70 eV): m/z 371 (6,
M+), 280 (100), 263 (12), 100 (12), 91 (91).
Analytical data of 3: Mp 208 °C. [α]D 20 = +50.8 (CHCl3); 1H NMR (400 MHz, CDCl3-CD3OD 1:1) δ (ppm) 0.88 (t, J = 7.5 Hz, 3 H), 0.89 (t, J = 7.1 Hz, 3 H), 1.20-1.75 (m, 22 H), 2.15 (m, 1 H), 2.71 (dt, J = 4.4 and 13.7 Hz, 1 H), 3.48 (m, 1 H), 3.65 (m, 1 H), 5.40 (s, 1 H). 13C NMR (100 MHz, CDCl3/CD3OD 1:1) δ (ppm) 10.9, 12.3, 21.7, 22.1, 26.0 (2 C), 26.3, 26.4, 27.4, 27.6, 32.4, 33.5, 39.6, 44.9, 52.9, 73.7, 178.2. MS (EI, 70 eV): m/z 283 (44, M+), 265 (51), 212 (22), 184 (30), 171 (49), 156 (26), 128 (51), 115 (43), 100 (38), 81 (29), 69 (46), 55 (100), 43 (50).