Subscribe to RSS
DOI: 10.1055/s-0031-1290529
A Diels-Alder Approach to Anthrapyran Antibiotics
Publication History
Publication Date:
24 February 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201205/lookinside/thumbnails/10.1055-s-0031-1290529-1.jpg)
Abstract
A new entry to the synthesis of anthrapyran antibiotics has been accomplished through the synthesis of a 4H-anthra[1,2-b]pyran-4,7,12-trione model. The key step features a Diels-Alder reaction between a substituted 5-vinyl-3,4-dihydro-2H-pyran and naphthoquinone as the dienophile. The resulting tetracyclic adduct is then processed towards the targeted trione in a few steps.
Key words
anthrapyran antibiotics - Diels-Alder reaction - quinones - Stille reaction - 4H-anthra[1,2-b]pyran-4,7,12-trione
- 1
Hansen MR.Hurley LH. Acc. Chem. Res. 1996, 29: 249 -
2a
Fei ZB.McDonald FE. Org. Lett. 2007, 9: 3547 -
2b
O’Keefe BM.Mans DM.Kaelin DE.Martin SF. J. Am. Chem. Soc. 2010, 132: 15528 -
3a
Hauser FM.Rhee RP. J. Am. Chem. Soc. 1979, 101: 1628 -
3b
Hauser FM.Rhee RP. J. Org. Chem. 1980, 45: 3061 -
3c
Uno H.Sakamoto K.Honda E.Fukuhara K.Ono N.Tanaka J.Sakanaka M. J. Chem. Soc., Perkin Trans. 1 2001, 229 -
3d
Krohn K.Vitz J. Eur. J. Org. Chem. 2004, 209 -
3e
Fei ZB.McDonald FE. Org. Lett. 2005, 7: 3617 -
3f
Krohn K.Vidal A.Vitz J.Westermann B.Abbas M.Green I. Tetrahedron: Asymmetry 2006, 17: 3051 -
3g
Tietze LF.Gericke KM.Singidi RR. Angew. Chem. Int. Ed. 2006, 45: 6990 -
3h
Tietze LF.Singidi RR.Gericke KM. Org. Lett. 2006, 8: 5873 -
3i
Krohn K.Tran-Thien HT.Vitz J.Vidal A. Eur. J. Org. Chem. 2007, 1905 -
3j
Tietze LF.Singidi RR.Gericke KM. Chem. Eur. J. 2007, 13: 9939 -
3k
Gattinoni S.Merlini L.Dallavalle S. Tetrahedron Lett. 2007, 48: 1049 -
3l
Wright BJD.Hartung J.Peng F.Van de Water R.Liu H.Tan Q.-H.Danishefsky SJ. J. Am. Chem. Soc. 2008, 130: 16786 -
3m
Dallavalle S.Gattinoni S.Mazzini S.Scaglioni L.Merlini L.Tinelli S.Beretta GL.Zunino F. Bioorg. Med. Chem. Lett. 2008, 18: 1484 -
3n
Elban MA.Hecht SM. J. Org. Chem. 2008, 73: 785 -
4a
Collet S.Remi J.-F.Cariou C.Laib S.Guingant A.Vu N.-Q.Dujardin G. Tetrahedron Lett. 2004, 45: 4911 -
4b
Vu N.-Q.Dujardin G.Collet S.Raiber E.-A.Guingant A.Evain M. Tetrahedron Lett. 2005, 46: 7669 -
4c
Sissouma D.Maingot L.Collet S.Guingant A. J. Org. Chem. 2006, 71: 8384 -
4d
Maingot L.Thuaud F.Sissouma D.Collet S.Guingant A.Evain M. Synlett 2008, 263 -
5a
Danishefsky SJ.Larson E.Askin D.Kato N. J. Am. Chem. Soc. 1985, 107: 1246 -
5b
Danishefsky SJ.Pearson WH.Harvey DF.Maring CJ.Springer JP. J. Am. Chem. Soc. 1985, 107: 1256 - Examples of dihydropyran-4-one iodination:
-
6a
Chemler SR.Iserloh U.Danishefsky SJ. Org. Lett. 2001, 3: 2949 -
6b
Gardiner JM.Mills R.Fessard T. Tetrahedron Lett. 2004, 45: 1215 -
6c
Leonelli F.Capuzzi M.Calcagno V.Passacantilli P.Piancatelli G. Eur. J. Org. Chem. 2005, 2671 -
7a
Luche J.-L.Gemal AL. J. Am. Chem. Soc. 1979, 101: 5848 -
7b
Danishefsky SJ.Bednarski M. Tetrahedron Lett. 1985, 26: 3411 - 8
Seyferth D.Stone FGA. J. Am. Chem. Soc. 1957, 79: 515 - 9 For a Lewis acid catalysed cycloaddition
with a related diene, see:
Huang H.-L.Liu R.-S. J. Org. Chem. 2003, 68: 805 - 11 For an analysis of substituent effects
on regioselectivities of cycloadditions to naphthoquinones, see:
Rozeboom MD.Tegmo-Larsson I.-M.Houk KN. J. Org. Chem. 1981, 46: 2338 - 13 For an example of B-ring aromatisation
via an epoxide in the field of angucyclines, see:
Krohn K.Micheel J. Tetrahedron 1998, 54: 4827 ; aromatisation of 14 could be explained by aerial oxidation of ring C followed by abstraction of a proton at C6 (or C12c) of ring B with subsequent opening of the epoxide and dehydration of the resulting alcohol - 14
Tan Z.Wang L.Wang J. Chin. Chem. Lett. 2000, 11: 753 - 15
Patonay T.Cavaleiro J.Lévai A.Silva A. Heterocycl. Commun. 1997, 3: 223
References and Notes
Procedure for
the Preparation of 3b
To a solution of (2-benzyloxymethyl-5-vinyl-3,4-dihydro-2H-pyran-4-yloxy)-tert-butyl(dimethyl)silane
(diene 6, 890 mg, 2.45 mmol) in MeCN (13 mL) was added 1,4-naphtho-quinone
(4, 465 mg, 2.94 mmol). The reaction was stirred for 24 h at r.t.
H2O (30 mL) was then added, and the aqueous layer was
extracted with CH2Cl2 (2 × 50
mL). The combined organic phases were dried (MgSO4),
filtered, and concentrated. The residue was purified by silica gel
column chromatography (Et2O-PE = 1:4)
to yield Diels-Alder adduct 3b (1.18
g, 77%) as a white solid (mp 97 ˚C). ¹H NMR
(400 MHz, CDCl3): δ = 8.07-8.02
(m, 1 H, H11), 7.95-7.89 (m, 1 H, H8),
7.65-7.59 (m, 2 H, H9 and H10), 7.34-7.18 (m,
5 H, H-Ph), 5.81 (dd, J
5-6 = 5.9
Hz, J
5-6
′ = 1.6
Hz, 1 H, H5), 4.79 (dd, J
12b-12a = 5.2
Hz, J
12b-6b = 1.2
Hz, 1 H, H12b), 4.30 (X part of an ABX system, J
XA = 4.2
Hz, J
XB = 3.7
Hz, 1 H, H4), 4.31 and 4.26 (AB system, J
AB = 12.0
Hz, 2 H, CH2Ph), 3.76 and 3.32 (AB part of an ABX system, J
AB = 11.0
Hz, J
AX = 7.6
Hz, J
BX = 4.5
Hz, 2 H, CH2O), 3.64-3.56 (m, X part of 2 ABX
systems, 1 H, H2), 3.44 (M part of an AMX system, J
12a-12b = 5.2
Hz, J
12a-6a = 5.8
Hz, 1 H, H12a), 3.37 (M part of an ABMX system, J
12a-6a = 5.8
Hz, J
6a-6 = 6.0
Hz, J
6a-6
′ = 1.2
Hz, 1 H, H6a), 3.0 and 2.13 (AB part of an ABXY system, J
AB = 18
Hz, J
6-7 = 6
Hz, J
6-6a = 1.2
Hz, J
6
′
-6a = 6.0
Hz, J
6
′
-5 = 1.6
Hz, J
6
′
-12b = 1.2
Hz, 2 H, H6 and H6
′),
1.92 and 1.66 (AB part of ABXY system, J
AB = 14.1
Hz, J
3-2 = 6.0
Hz, J
3-4 = 4.2
Hz, J
3
′
-4 = 3.7
Hz,
J
3
′
-2 = 3.7
Hz, 2 H, H3 and H3
′),
0.84 (s, 9 H, H22), 0.02 (s, 3 H, H20), -0.01
(s, 3 H, H20
′). ¹³C
NMR (75 MHz, CDCl3): δ = 197.5
and 196.44 (2 Cq, C7 and C12), 138.7 (Cq,
C16), 137.2 and 136.4 (2 Cq, C7a and C11a),
136.8 (Cq, C4a), 133.5 and 133.1 (2 CH, C9 and
C10), 128.2 (2 CH, C17 and C17
′), 127.5
(2 CH, C18 and C18
′),
127.3 (CH, C19), 126.2 and 125.7 (2 CH, C8 and
C11), 121.6 (CH, C5), 72.8 (CH, C2),
72.5 (CH2, C15), 70.8 (CH, C4),
70.7 (CH2, C13), 63.1 (CH, C12b), 51.8
(CH, C12a), 43.65 (CH, C6a), 37.4 (CH2,
C3), 25.7 (3 CH3, C22), 22.31 (CH2,
C6), 17.9 (Cq, C21), -4.6 (CH3,
C20), -5.1 (CH3, C20’).
IR (KBr): 2930, 1699, 1254, 1095, 1052 cm-¹.
MS (EI): m/z (%) = 386
(16), 370 (8), 353 (14), 327 (7), 295 (7), 265 (13), 261 (7), 133
(22) 91 (100), 73 (25). MS (CI, NH3): m/z = 536 [(M + NH4)+].
HRMS (Maldi DHB/MeCN + PEG600): m/z calcd
for C31H38O5SiNa [MNa]+:
541.2381; found: 541.2397, Δ = 2.3
ppm.
Crystal Structure
Data for 17
C31H38O6Si, M
r = 534.7,
monoclinic, P21/c, a = 11.1097 (11), b = 18.9124
(12), c = 13.8124
(15) Å, β = 106.699
(9), V = 2779.7
(5) ų, Z = 4, ρ
calcd = 1.2773
g cm-³, µ = 1.27 mm-¹, F(000) = 1144,
colourless block, 0.19 × 0.18 × 0.17 mm³,
2θ
max = 56˚, T = 120 K,
48226 reflections, 6629 unique (98% completeness), R
int = 0.096,
346 parameters, GOF = 1.54, wR2 = 0.1231, R = 0.0563
for 4795 reflections with I > 2σ(I).
CCDC 855339 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Spectroscopic
Data for Trione 1
Tan solid (mp 165 ˚C). ¹H
NMR (300 MHz, CDCl3): δ = 8.63
(d, J
6-5 = 8.3
Hz, 1 H, H6), 8.37 (d, J
5-6
= 8.3 Hz,
1 H, H5), 8.33-8.27 (m, 2 H, H8 and
H11), 7.90-7.79 (m, 2 H, H9 and H10),
7.49-7.30 (m, 5 H, H-Ph), 6.68 (s, 1 H, H3), 4.80
(s, 2 H, CH2Ph), 4.57 (d, J = 0.8
Hz, 2 H, CH2O). ¹³C NMR
(100 MHz, CDCl3): δ = 182.4
and 181.3 (2 Cq, C7 and C12), 176.6 (Cq, C4),
167,6 (Cq, C12b), 154.7 (Cq, C2), 137.9 (Cq,
C6a), 137.1 (Cq, C16), 134.9 and 134.2 (2
CH, C9 and C10), 134.3 (Cq, C11a),
132.3 (Cq, C7a), 132.1 (CH, C6), 128.8 (2
CH, C17, C17
′), 128.5
(Cq, C4a), 128.3 (CH, C19), 128.0 (2 CH, C18 and
C18
′), 127.3 and 127.2 (2 CH, C8 and
C11), 123.3 (CH, C5), 122.7 (Cq, C12a), 110.1
(CH, C3), 73.8 (CH2, C15), 67.9
(CH2, C13). IR (KBr): 1674, 1657, 1589, 1418,
1324, 1283, 1122 cm-¹. MS (EI): m/z (%) = 280
(20), 125 (27), 111 (30), 97 (47), 83 (45), 71 (59), 57 (100), 43
(69). MS (CI, NH3): m/z = 397 [(M + H)+].
ESI-HRMS: m/z calcd for C25H17O5 [MH]+:
397.1071; found: 397.1056, Δ = 3.6
ppm.