Navarro et al.
JOCArticle
reaction conditions used for the acyl-ketene generation, the
tolerance of delicate functionality during the generation of
the resorcylate units by ketene trapping, and aromatization
as well as the minimum use of protecting group manipula-
tions are especially noteworthy.
(2C), 102.2, 73.8, 73.5, 70.7, 63.0, 47.7, 43.9, 43.7, 25.4, 21.1,
20.6, 19.7, 19.6 (2C), 18.6 (3C), 18.5 (3C), 13.4 (3C); MS (CI) m/z
889 [M þ H]þ; HRMS (CI) calcd for C49H64O13Si [M þ H]þ,
889.4194, found [M þ H]þ 889.4185. Anal. Calcd for C49H64-
O13Si: C, 66.19; H, 7.26. Found: C, 66.32; H, 7.20.
(S)-1-(3,5-Dihydroxy-2-((2,4,6-trimethylbenzyloxy)carbonyl)-
phenyl)propan-2-yl 2-((S)-2-(2-((S)-2-(2,4-dihydroxy-6-((S)-2-(triiso-
propylsilyloxy)propyl)benzoyloxy)propyl)-4,6-dihydroxybenzoyloxy)-
propyl)-4,6-dihydroxybenzoate (21b): Rf 0.55 (EtOAc:hexanes
The synthesized (all S)-carboxylic acids 1a, 1b, and 1c were
compared with the authentic natural products W1278A, -B,
and -C, isolated from Ascomycete sp. LL-W1278, and the
physical properties of the natural and synthetic samples are
identical with one exception. The optical rotations of the
synthetic 1a, 1b, and 1c as well as synthetic intermediates en
route to these compounds are positive and of opposite sign to
the natural products. This is fully consistent with the natural
products being all R and not all S, which is in accord with the
absolute stereochemistry of the related natural products
15G256β (2) and 15G256ι (3).3,19 Thus W1278A, -B, and
-C have the mirror image absolute stereochemistries to those
depicted in structures 1a-c. We are currently reinvestigating
several reactions used in the degradation and stereochemical
assignment of the natural products2 and will report on these
findings in a forthcoming publication.
1:3); [R]25 þ217.1 (c 2.8 CH3COCH3); IR (film) 3360 (br),
D
1
1642, 1617, 1449, 1312, 1254 cm-1; H NMR (400 MHz, d6-
Me2CO) δ 11.88 (1H, s), 11.61 (1H, s), 11.55 (1H, s), 11.48
(1H, s), 9.10 (4H, br s), 6.82 (2H, s), 6.33-6.24 (5H, m),
6.18-6.14 (3H, m), 5.70-5.60 (1H, s), 5.59-5.51 (1H, s), 5.48
(dd, J = 12.0 Hz, 1H), 5.36 (dd, J = 12.0 Hz, 1H), 5.35-5.25
(1H, s), 4.30-2.20 (1H, s), 3.60-3.45 (2H, m), 3.33 (dd, J=13.4,
4.7 Hz, 1H), 3.16-2.95 (4H, m), 2.49 (dd, J=12.6, 9.3 Hz, 1H),
2.37 (6H, s), 2.10 (3H, s), 1.43 (d, J=6.2 Hz, 3H), 1.42 (d, J=
6.2 Hz, 3H), 1.29 (d, J=6.2 Hz, 3H), 0.91 (21H, s), 0.88 (d, J=
6.2 Hz, 3H); 13C NMR (101 MHz, d6-Me2CO) δ 172.4, 171.9,
171.4, 171.3, 167.0, 166.7, 166.6 (2C), 163.3, 163.0, 162.9 (2C),
145.5, 143.3, 143.0 (2C), 139.6, 139.1 (2C), 130.0 (2C), 129.1,
114.8, 113.8, 113.6, 113.5, 105.5, 105.4, 105.1, 104.9, 103.0 (2C),
102.8, 102.2, 73.8, 73.8, 73.5, 70.7, 62.9, 47.7, 43.9, 43.6 (2C),
25.4, 21.1, 20.7, 20.5, 19.7, 19.6 (2C), 18.6 (3C), 18.5 (3C), 13.4
(3C); MS (CI) m/z 1083 [M þ H]þ; HRMS (CI) calcd for
C59H74O17Si [M þ H]þ 1083.4789; found [M þ H]þ 1083.4774.
Anal. Calcd for C59H74O17Si: C, 65.41; H, 6.89. Found: C,
65.38; H, 6.80.
Experimental Section
General Procedure for the Polymer Chain Elongation Proce-
dure (Product 21a-c). H2SiF6 in H2O (20% w/w; 0.45 mL,
0.7 mmol) was added with stirring to ester 16 (or 21 or 21b,
1 mmol) in MeCN (20 mL) and stirring was continued for
45 min. The reaction mixture was poured into AcOEt (110 mL),
washed with H2O (3 ꢀ 15 mL), and dried (MgSO4). After rotary
evaporation, the residue was dissolved in AcOEt (25 mL) and
dioxinone 20 (561 mg, 1.15 mmol) was added. The mixture was
heated at reflux for 4 h. After rotary evaporation, the residue
was dissolved in CH2Cl2 and i-PrOH (1.5:1; 30 mL) and CsOAc
(1.14 g, 6 mmol) were added, then the mixture was stirred at
room temperature for 10 h. The solution was acidified to pH 2
with TFA (0.7 mL, 9 mmol) and stirred for an additional 5 h.
The reaction mixture was poured into AcOEt (125 mL), washed
with water (3 ꢀ 15 mL), and dried (MgSO4). Rotary evaporation
and chromatography (hexanes:EtOAc 4:1) gave resorcylate
oligomers 21a (n = 2, 55%), 21b (n = 3, 56%), or 21c (n = 4,
65%) as pale yellow oils.
(S)-1-(3,5-Dihydroxy-2-((2,4,6-trimethylbenzyloxy)carbonyl)-
phenyl)propan-2-yl 2-((S)-2-(2-((S)-2-(2-((S)-2-(2,4-dihydroxy-
6-((S)-2-(triisopropylsilyloxy)propyl)benzoyloxy)propyl)-4,6-di-
hydroxybenzoyloxy)propyl)-4,6-dihydroxybenzoyloxy)propyl)-4,
6-dihydroxybenzoate (21c): Rf 0.40 (EtOAc:hexanes 1:3); [R]25
D
þ180.1 (c 0.8 CH3COCH3); IR (film) 3358 (br), 1648, 1619,
1
1446, 1312, 1251 cm-1; H NMR (400 MHz, CD3COCD3) δ
11.93 (1H, s), 11.88 (1H, s), 11.62 (1H, s), 11.50 (2H, s), 9.13 (5H,
br s), 6.79 (2H, s), 6.32-6.23 (6H, m), 6.18-6.15 (4H, m),
5.70-5.60 (2H, s), 5.59-5.50 (1H, s), 5.48 (dd, J = 12.0 Hz,
1H), 5.37 (dd, J = 12.0 Hz, 1H), 5.35-5.25 (1H, s), 4.30-2.20
(1H, s), 3.60-3.45 (3H, m), 3.34 (dd, J = 13.3, 4.9 Hz, 1H),
3.16-2.95 (5H, m), 2.49 (dd, J=12.8, 9.3 Hz, 1H), 2.38 (6H, s),
2.10 (3H, s), 1.47 (d, J=6.2 Hz, 3H), 1.42 (d, J =6.2 Hz, 6H),
1.29 (d, J=6.2 Hz, 3H), 0.91 (21H, s), 0.89 (d, J=6.2 Hz, 3H);
13C NMR (101 MHz, d6-Me2CO) δ 172.4, 171.9, 171.5, 171.5,
171.4, 167.0, 166.8, 166.7 (2C), 166.6, 163.3, 163.1, 163.1, 163.0
(2C), 145.5, 143.3, 143.1 (2C), 139.6, 139.2, 130.0 (2C), 129.1,
114.8, 113.8, 113.6 (2C), 113.6, 105.4 (2C), 105.3, 105.1, 104.9,
102.9 (3C), 102.2 (2C), 73.9, 73.9, 73.8, 73.5, 70.8, 63.0, 47.7,
43.9, 43.6, 43.6, 43.6, 25.4, 21.1, 20.7, 20.6, 19.8, 19.6 (2C), 18.6
(3C), 18.5 (3C), 13.4 (3C); MS (CI) m/z 1277 [M þ H]þ. Anal.
Calcd for C69H84O21Si: C, 64.87; H, 6.63. Found: C, 64.91;
H, 6.57.
(S)-1-(3,5-Dihydroxy-2-((2,4,6-trimethylbenzyloxy)carbonyl)-
phenyl)propan-2-yl 2-((S)-2-(2,4-dihydroxy-6-((S)-2-(triisopropyl-
silyloxy)propyl)benzoyloxy)propyl)-4,6-dihydroxybenzoate (21a):
Rf 0.75 (EtOAc:hexanes 1:3); [R]25D þ140.7 (c 1.7 CH3COCH3);
IR (film) 3357 (br), 1647, 1619, 1449, 1312, 1256 cm-1; 1H NMR
(400 MHz, d6-Me2CO) δ 11.89 (s, 1H), 11.60 (s, 1H), 11.51
(s, 1H), 9.10 (br s, 3H), 6.87 (s, 2H), 6.32 (d, J = 2.4 Hz, 1H),
6.29-6.26 (m, 3H), 6.22 (d, J=2.4 Hz, 1H), 6.19 (d, J=2.4 Hz,
1H), 5.60-5.50 (m, 1H), 5.54 (d, J=12.0 Hz, 1H), 5.39 (d, J=
12.0 Hz, 1H), 5.39-5.30 (m, 1H), 4.31-5.22 (m, 1H), 3.56 (dd,
J=12.9, 2.9 Hz, 1H), 3.39 (dd, J=13.4, 4.9 Hz, 1H), 3.15 (dd,
J=13.4, 5.2 Hz, 1H), 3.05-2.95 (m, 2H), 2.53 (dd, J=12.9, 8.9
Hz, 1H), 2.41 (s, 6H), 2.15 (s, 3H), 1.42 (d, J=6.2 Hz, 3H), 1.31
Acknowledgment. We thank GlaxoSmithKline for the gene-
rous endowment (to A.G.M.B.), the EU for Marie-Curie
Human Mobility Intra-European Fellowships (I.N.), and the
Deutscher Akademischer Austausch Dienst for a Postdoctoral
Fellowship (C.P.).
(d, J=5.9 Hz, 3H), 0.94 (br s, 21H), 0.90 (d, J=6.2 Hz, 3H); 13
C
NMR (101 MHz, d6-Me2CO) δ 172.4, 171.8, 171.3, 167.0, 166.8,
166.6, 163.3, 162.9 (2C), 145.4, 143.3, 143.0, 139.6, 139.2 (2C),
130.0 (2C), 129.2, 114.8, 113.8, 113.6, 105.3, 105.1, 104.9, 102.9
Supporting Information Available: Experimental proce-
dures, spectroscopic data, and copies of 1H and 13C NMR
spectra for all new compounds. This material is available free
(19) The CD spectra of lactone 6 and synthetic oligomeric esters 1b and 1c
versus samples of the isolated natural oligomers W1278 support this ob-
servation; see the Supporting Information.
8142 J. Org. Chem. Vol. 74, No. 21, 2009