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Total Synthesis of Clathculins A and B natural product to have a terminal CH2dCH(CH2)2CHd

CHCtCCH2- subunit.
Rebecca C. Hoye,* Gretchen L. Anderson, Given these unique structural features as well as their
Susan G. Brown, and Erica E. Schultz inherent inseparability, we decided to prepare each of the
natural products by chemical synthesis. Our retrosynthetic
Department of Chemistry, Macalester College, 1600 approach is shown above. It was anticipated that palladium-
Grand Avenue, Saint Paul, Minnesota 55105, United States catalyzed coupling of alkyne B with the appropriate vinyl
iodide A or A0 would create a precursor for C-N bond
[email protected] formation with commercially available N,N0 -dimethylethy-
Received May 30, 2010 lenediamine (C).
The R,ω-alkynyl alcohol (B) was prepared as shown in
Scheme 1. The dianion of propargyl alcohol was generated in
THF and treated with 1-bromooctane in DMPU3 to yield
3-undecyn-1-ol (3) in 60% yield. Zipper isomerization to the
terminal alkyne B was effected in 87% yield in THF with 5.0
equiv of diaminopropane in the presence of 4.0 equiv of
n-BuLi and 4.0 equiv of t-BuOK. These conditions are
operationally simpler than the standard zipper isomerization
conditions4 and also avoid the use of noxious 1,3-diamino-
propane as the reaction solvent.
SCHEME 1. Preparation of Compound B

Clathculins A and B represent a new class of vic-diamine

alkaloids containing a PA2 unit as the basic structure. We
report the first total syntheses of 1 and 2, which confirm
the assigned structure of each. Dependence of their NMR
spectroscopic behavior as a function of protonation state
has been observed. Vinyl iodides A and A0 were prepared as shown in Scheme 2.
Following a strategy first reported by Kluge, Untch, and
Fried,5 1-iodohexyne,6 4, was reduced with diimide7 to give
(Z)-1-iodohexene, A, in 55% yield. Similarly, 5-hexyn-1-ol
Clathculins A and B were isolated from the Indo-Pacific was converted to iodide 58 and reduced with diimide to give
sponge Clathrina aff. reticulum collected in Sodwana Bay, 6. Formation of the tosylate9 7 and conversion to the selenide
South Africa.1 They were described as an unstable (and, not 8 followed by oxidation and elimination10 afforded A0 .
surprisingly, inseparable) mixture of compounds 1 and 2.1 Clathculins A and B were obtained as shown in Scheme 3.
Structures were assigned on the basis of NMR spectroscopy Sonogashira coupling11 of iodide A or A0 with B afforded the
(COSY, TOCSY, and HMBC correlations) of the mixture as enynes 9 and 10, respectively. Formation of the correspond-
well as by acetylation and reduction to the common satu- ing tosylates 11 and 12 and reaction of each with N,N0 -
rated analog. Clathculins A and B are the first reported dimethylethylenediamine afforded clathculins A (1) and B
examples of acyclic long-chain marine metabolites contain- (2), respectively.
ing a >NCH2CH2N< (PA2) moiety.2 Additionally, there
appear to be no known examples of natural substances
(3) Kaiser, A.; Marazano, C.; Maier, M. J. Org. Chem. 1999, 64, 3778–
containing the array of substituents R1R2NCH2CH2NHR3 3782.
where R1, R2, and R3 are any combination of Me and (4) Abrams, S. R.; Shaw, A. C. Organic Syntheses; Wiley & Sons: New
York, 1993; Collect. Vol. No. 8, pp 146-148.
-CH2R substituents. This contrasts with the 1,3-diamino- (5) Kluge, A. F.; Untch, K. G.; Fried, J. H. J. Am. Chem. Soc. 1972, 94,
propane (PA3) and 1,4-diaminobutane (PA4) elements com- 9256–9258.
mon to the spermidine and spermine classes of polyamines. (6) Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083–1090.
(7) Paquette, L. A.; Browne, A. R.; Chamot, E.; Blount, J. F. J. Am. Chem.
Other key structural features are the presence of an internal Soc. 1980, 102, 643–651. Pasto, D. J.; Taylor, R. L. In Organic Syntheses;
enyne moiety in a C-17 chain and the differentiating alkene Paquette, L. A., Ed.; Wiley & Sons: New York, 1991; Vol. 40, pp 91-155.
vs alkane chain termini. Clathculin A is the only known (8) Denmark, S. E.; Yang, S. M. Tetrahedron 2004, 60, 9695–9708.
(9) Kabalka, G. W.; Varma, M.; Varma, R. S. J. Org. Chem. 1986, 51,
2386–2388.
(1) Rudi, A.; Schleyer, M.; Kashman, Y. J. Nat. Prod. 2000, 63, 1434– (10) Chakraborty, T. K.; Mohan, B. K. Tetrahedron Lett. 2006, 47, 4999–
1436. 5002.
(2) Bienz, S.; Bisegger, P.; Guggisberg, A.; Hesse, M. Nat. Prod. Rep. (11) Chackalamannil, S.; Davies, R.; McPhail, A. T. Org. Lett. 2001, 3,
2005, 22, 647–658. 1427–1429.

7400 J. Org. Chem. 2010, 75, 7400–7403 Published on Web 10/11/2010 DOI: 10.1021/jo100971j
r 2010 American Chemical Society
Hoye et al.
JOC Note
1
TABLE 1. H NMR Data (300 MHz) of Clathculins A and B (1 and 2) in CDCl3

SCHEME 2. Preparation of Vinyl Iodides A and A0 SCHEME 3. Convergent Couplings Leading to 1 and 2

1
H NMR chemical shifts data for selected protons of 1 and
2 in CDCl3 (synthetic vs natural1) and in 2% TFA in CDCl3
(synthetic) are shown in Table 1. Our initial concern over us to probe the question of protonation. It has been shown
differences in chemical shifts between those reported for that chemical shifts of protons12 and carbons13 in close
natural vs those we observed for the synthetic samples led proximity to amines are dependent on degree of protonation.
To give confidence that we were observing the free-base
forms of the synthetic materials, the crude reaction pro-
(12) Rabenstein, D. L.; Sayer, T. L. Anal. Chem. 1976, 48, 1141–1146.
(13) Hague, D. N.; Moreton, A. D. J. Chem. Soc., Perkin Trans. 2 1994, ducts were chromatographed on silica gel using CMA
265–270. [chloroform/methanol/ammonia (83: 17: 0.5)] as eluent,
J. Org. Chem. Vol. 75, No. 21, 2010 7401
JOC Note Hoye et al.

and the NMR spectra were recorded in CDCl3 that had been 2.10 (ddt, J = 1.1, 7.0, 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ
stored over K2CO3. We have investigated the 1H NMR 144.6, 140.2 133.0, 129.8, 127.8, 83.1, 70.1, 33.7, 28.0, 23.6, 21.5;
spectral behavior of clathculins A and B in CDCl3 in the HRMS (ESI) calcd for C13H17IO3S [M þ Na]þ 402.9835, found
presence of 2% trifluoroacetic and 2% acetic acid-d4. Upon 402.9858.
addition of trifluoroacetic acid (2% TFA in CDCl3), full (i.e., (Z)-(6-Iodohex-5-en-1-yl)(phenyl)selane (8). With modifica-
tion of a literature procedure,15 diphenyl diselenide (4.92 g,
double) protonation of clathculins was observed, as judged
15.8 mmol, 0.6 equiv) in 200 mL of absolute ethanol was treated
by the diastereotopic nature of the methylene protons at C1 with NaBH4 (1.45 g, 38.2 mmol) in portions until the solution
and at C10 adjacent to the stereogenic nitrogen of the tertiary became colorless. The solution was cooled in an ice bath, and a
ammonium ion. The salient differences are highlighted in solution of 7 (10.03 g, 26.3 mmol, 1 equiv) in 30 mL of THF was
gray boxes. In contrast, in the presence of the weaker acetic added. The reaction was gradually warmed to room tempera-
acid, less than full protonation was observed (see the Sup- ture and stirred overnight. The reaction mixture was poured into
porting Information). The chemical shifts reported for the 500 mL of 5% Na2CO3 and 100 mL of brine and extracted with
natural sample1 fall between those we observed for the free- Et2O. The combined organic extracts were washed with brine,
base versus in the presence of either TFA or AcOH. The most dried (MgSO4), filtered, and evaporated in vacuo. Purification
reasonable explanation is that the spectral data for the by flash chromatography (hexanes) afforded a light yellow oil
(7.27 g, 20.0 mmol, 76%): IR (neat) 3069, 3014, 2929, 2853,
natural material were recorded for a sample that was slightly
1609, 1578 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.58 - 7.45
protonated. (m), 7.29 - 7.23 (m), 6.19 (dt, J = 7.3, 11.1 Hz), 6.13 (dt, J = 7.2,
Although the natural material was described as a mixture 6.3 Hz), 2.93 (t, J = 7.6 Hz), 2.15 (q, J = 7.1 Hz), 1.75 (quintet,
of two unstable compounds,1 we have not observed instabil- J = 7.2 Hz) 1.56 (quintet, J = 7.3 Hz); 13C NMR (CDCl3, 75
ity with either crude or purified synthetic samples in either MHz) δ 140.7, 132.5, 130.3, 128.9, 126.7, 82.8, 34.0, 29.4, 27.9,
the free-base or protonated forms. We do not have a good 27.6; GC-MS 366 (Mþ), 239 (base, Mþ - I).
explanation for the original observations; our samples of (Z)-1-Iodohexa-1,5-diene (A0 ). m-CPBA (478 mg, 2.31 mmol,
clathculins A and B, each in 2% TFA in CDCl3, were allowed 1.2 equiv) was added portionwise to a solution of 8 (839 mg, 2.31
mmol, 1 equiv) in 5 mL of CH2Cl2 at 0 °C. The solution was
to stand at room temperature for 3 weeks, during which time
stirred for 15 min, diluted with 10 mL of CH2Cl2, and extracted
they showed no evidence of change by 1H NMR analysis. with satd NaHCO3. The organic solution was washed with
We have achieved a convergent synthesis of the natural brine, dried (MgSO4), filtered, and evaporated in vacuo to give
enyne diamines clathculins A (1) and B (2). We have also a light yellow oil that was dissolved in 3 mL of CH2Cl2 and
shown the value of recording and reporting NMR data of added to a refluxing solution of 10 mL CCl4 and diisopropyla-
basic amine-containing compounds both as the free-base as mine (270 mg, 0.390 mL, 2.77 mmol, 1.2 equiv). After being
well as in the presence of excess acid (here 2% TFA in refluxed for 30 min, the reaction mixture was poured into 30 mL
CDCl3). of water and the aqueous layer extracted with CH2Cl2.
The combined organic extracts were washed with brine, dried
Experimental Section (MgSO4), filtered, and evaporated in vacuo to give a bright
orange oil that was purified by flash chromatography (pentane)
Undec-10-yn-1-ol (B). To a solution of 1,3-diaminopropane to yield A0 as a colorless liquid (235.0 mg, 1.13 mmol, 49%): IR
(2.40 g, 2.7 mL, 32.3 mmol, 5.0 equiv) in 10 mL of THF at 0 °C (neat) 3076, 2979, 2924, 2847, 1641, 2609, 1440 cm-1; 1H NMR
was added dropwise n-BuLi (2.48 M in hexanes, 10.5 mL, (CDCl3, 300 MHz) δ 6.23-6.14 (m, 2H), 5.82 (ddt, J = 17.1,
26.0 mmol, 4.0 equiv). The resulting mixture was stirred for 10.2, 6.4 Hz), 5.04 (ddt, J = 17.2, 1.8, 1.6 Hz), 5.00 (ddt, 10.2,
20 min, and t-BuOK (1.0 M in THF, 26.0 mL, 26.0 mmol, 4.0 1.9, 1.1 Hz), 2.28-2.13 (m, 4H); 13C NMR (CDCl3, 75 MHz)
equiv) was added dropwise. The resulting yellow solution was δ 140.5, 137.4, 115.3, 82.7, 33.9, 32.0; GC-MS 208 (Mþ), 126
warmed to room temperature, and 3 (1.08 g, 6.51 mmol, 1 equiv) (M - C3H5)þ, 81 (M - I)þ.
in 2.0 mL of THF was added dropwise via cannula. The solution (Z)-Heptadeca-12,16-dien-10-yn-1-ol (9). PdCl2(PhCN)2
was stirred for 3 h (red-brown color), poured into 100 mL of satd aq (52.0 mg, 0.136 mmol, 0.05 equiv) and CuI (52 mg, 0.272 mmol,
NH4Cl, and extracted with ether. The combined organic extracts 0.10 equiv) were combined and purged with argon. Pyrrolidine
were washed with 5% HCl, satd aq NaHCO3, and brine, dried (2 mL) was added, and after the mixture was stirred for 5 min,
(MgSO4), filtered, and evaporated in vacuo. Flash chromatography the iodide A0 (680.0 mg, 3.27 mmol, 1.2 equiv) in 1 mL of
[hexanes/ethyl acetate (8:2)] afforded B14 as a colorless liquid pyrrolidine was added followed by the addition of alkyne
(0.94 g, 5.66 mmol, 87%). B (451.5 mg, 2.72 mmol, 1.0 equiv) in 1 mL of pyrrolidine.
(Z)-6-Iodohex-5-en-1-yl 4-methylbenzenesulfonate (7). Com- The solution was stirred overnight in the dark and then poured
pound 6 (13.85 g, 61.3 mmol, 1 equiv), Et3N (17.00 mL, 122.6 into 50 mL of satd aq NH4Cl. The mixture was extracted
mmol, 2.0 equiv), and DMAP (375 mg, 3.1 mmol, 0.5 equiv) were (EtOAc), and the combined extracts were washed with water
combined in 150 mL of CH2Cl2 and cooled to 0 °C. p-Toluene- and brine, dried (MgSO4), filtered, and evaporated in vacuo.
sulfonyl chloride (17.46 g, 91.9 mmol, 1.5 equiv) was added in one Purification by flash chromatography [hexanes/ethyl acetate
portion. The solution was allowed to warm to room temperature (8:2)] gave a colorless oil (541.1 mg, 2.18 mmol, 80%): IR (neat)
and stirred overnight. Saturated aq NaHCO3 was added, and 3332, 3077, 3021, 2931, 2855, 2212, 1641, 1617, 1465 cm-1; 1H
the mixture was extracted with EtOAc. The combined extracts NMR (CDCl3, 300 MHz) δ 5.83 (ddt, J = 17.3, 10.2, 6.5 Hz), 5.82
were washed with brine, dried (MgSO4), filtered, and evaporated in (dt, J = 10.6, 7.2 Hz), 5.46 (dtt, J = 10.6, 2.2, 1.5 Hz), 5.04 (ddt,
vacuo. Purification by flash chromatography [hexanes/ethyl ace- J = 17.1, 1.9, 1.6 Hz), 4.98 (ddt, J = 10.2, 2.0, 1.3 Hz), 3.64 (t, J =
tate (8:2)] provided 7 as a yellow oil (20.48 g, 53.0 mmol, 88%): IR 6.5 Hz), 2.39 (ddt, J = 7.3, 1.5, 7.3 Hz), 2.34 (dt, J = 6.9, 2.2 Hz),
(neat) 3294, 3066, 2945, 2865, 1598 cm-1; 1H NMR (CDCl3, 300 2.16 (br dt, J = 6.5, 7.5 Hz), 1.60-1.28 (m, 14H); 13C NMR
MHz) δ 7.81 (d, J = 8.4 Hz), 7.36 (d, J = 8.1 Hz), 6.26 (dt, J = 7.3, (CDCl3, 75 MHz) δ 141.4, 138.0, 114.8, 109.8, 94.8, 77.2, 63.0, 32.9,
1.4 Hz), 6.08 (dt, J = 7.1, 7.0 Hz), 4.04 (t, J = 6.3 Hz,), 2.45 (s), 32.8, 29.5, 29.3, 29.2, 29.0, 28.8, 25.7, 19.5; HRMS (ESI) calcd for
C17H28O [M þ Na]þ 271.2032, found 271.2004.
(14) Poleschner, H.; Heydenreich, M. Magn. Reson. Chem. 1995, 33, 917–
921. (15) Clark, R. D.; Heathcock, C. H. J. Org. Chem. 1976, 41, 1396–1403.

7402 J. Org. Chem. Vol. 75, No. 21, 2010

Hoye et al.
JOC Note
(Z)-Heptadeca-12-en-10-yn-1ol (10). According to the proce- of satd aq NaHCO3. The aqueous solution was extracted with
dure for 9, iodide A (1.87 g, 8.9 mmol, 1.5 equiv) and alkyne ethyl acetate. The combined organic layers were washed with
B (986 mg, 5.94 mmol, 1.0 equiv) were added to a solution of brine, dried (Na2SO4), filtered, and evaporated in vacuo.
PdCl2(PhCN)2 and CuI (113 mg, 0.594 mmol, 0.1 equiv) in Purification by flash chromatography [CMA: chloroform/
10.0 mL of pyrrolidine. Flash chromatography of the crude methanol/ammonia (83:17:0.5)] gave two components, the less
reaction mixture gave the product (1.095 g, 4.41 mmol, 74%) as polar dialkylated diamine 13 (81.0 mg, see the Supporting Informa-
a colorless oil: IR (neat) 3333, 3020, 2928, 2856, 2215, 1617, 1465 tion for complete characterization) and clathculin A (374.6 mg, 1.18
cm-1; 1H NMR (300 MHz, CDCl3) δ 5.82 (dt, J = 10.7, 7.4 Hz), mmol, 77%). These two compounds had Rf values of 0.40 and
5.44 (dtt, J = 10.7, 2.2, 1.4 Hz), 3.63 (dt, J = 3.3, 6.4 Hz, CH2OH), 0.05 in CMA: IR (neat) 3328, 3077, 3020, 2929, 2854, 2797, 2212,
2.33 (dt, J = 2.2, 7.0 Hz), 2.29 (ddt, J = 7.4, 1.5, 7.3), 1.60-1.46 (m, 1641, 1470 cm-1; 1HNMR (CDCl3, 300 MHz) δ 5.84 (ddt,
4H), 1.44-1.25 (m, 12H), 0.90 (t, J = 7.1 Hz); 13C NMR (75 MHz, J = 17.1, 10.3, 6.5 Hz, H2CdCH), 5.83 (dt, J = 10.7, 7.2 Hz,
CDCl3) δ 142.6, 109.3, 94.4, 77.4, 63.0, 32.8, 31.0, 29.7, 29.5, 29.4, CHdCHCtC), CH2CHdCHCtC), 5.47 (dtt, J = 10.7, 2.2, 1.4
29.1, 28.84, 28.82, 25.7, 22.3, 19.5, 13.9; HRMS (ESI) Calcd for Hz, CHdCHCtC), 5.05 (ddt, J = 17.1, 1.9, 1.6 Hz, HCHdCH),
C17H30O [M þ Na]þ 273.2189, found 273.2187. 4.97 (ddt, J = 10.2, 2.1, 1.2 Hz, HCHdCH), 2.68 (t, J = 6.2,
(Z)-Heptadeca-12,16-dien-10-yn-1-yl 4-Methylbenzenesulfo- NCH2CH2N), 2.49 (t, J = 6.2, NCH2CH2N), 2.47 (s, NCH3), 2.39
nate (11). According to the procedure for 7, p-toluenesulfonyl (ddt, J = 7.3, 1.5, 7.5, CH2CHdCHCtC), 2.34 (∼t with some
chloride (564.2 mg, 2.97 mmol, 1.5 equiv), alcohol 9 (491.1 mg, evidence of nonfirst order character, J = 7.0 Hz, CH2CH2CH2N),
1.98 mmol, 1.0 equiv), Et3N (400 mg, 0.55 mL, 3.96 mmol, 2.33 (dt, J = 2.2, 7.0, CtCCH2), 2.16 (dddt, J = 6.5, 1.6, 1.2, 7.5,
2.0 equiv), and DMAP (12.2 mg, 0.10 mmol, 0.05 equiv) were CH2dCHCH2), 1.58-1.22 (m, 7 CH2); 13C NMR (75 MHz,
reacted in 5 mL of CH2Cl2. Purification of the crude reaction CDCl3) δ 141.3, 137.9, 114.7, 109.8, 94.8, 77.2, 58.1, 56.7, 49.2,
mixture by flash chromatography [hexanes/ethyl acetate (8:2)] 42.2, 36.2, 29.46, 29.44, 29.21, 29.20, 29.03, 28.78, 28.76, 27.4, 27.3,
gave 11 as a colorless oil (693.0 mg, 1.72 mmol, 87%): IR (neat) 19.4; HRMS (ESI) calcd for C21H38N2 [M þ H]þ 319.3108, found
3075, 3021, 2929, 2856, 2211, 1640, 1599, 1465 cm-1; 1H NMR 319.3111.
(CDCl3, 300 MHz) δ 7.79 (d, J = 8.3 Hz), 7.34 (d, J = 8.3 Hz), Clathculin B (2). Following the procedure for 1, tosylate
5.83 (ddt, J = 17.0, 10.2, 6.5), 5.82 (dt, J = 10.6, 7.2 Hz), 5.46 10 (536.6.mg, 1.33 mmol, 1 equiv), and N,N0 -dimethylethyl-
(dtt, J = 10.7, 2.1, 1.4 Hz), 5.04 (ddt, J = 17.1, 1.9, 1.7 Hz), 4.98 enediamine (469.9 mg, 0.57 mL, 4.0 equiv) in 5.0 mL of CH3CN
(ddt, J = 10.2, 1.9, 1.3 Hz), 4.02 (t, J = 7.3 Hz), 2.45 (s), 2.39 afforded two components upon flash chromatography
(ddt, J = 7.3, 1.5, 7.3 Hz), 2.33 (dt, J = 7.0, 2.2 Hz), 2.16 (dddt, [chloroform/methanol/ammonia (83:17:0.5), the less polar dialky-
J = 6.5, 1.5, 1.5, 2.5 Hz), 1.68-1.46 (m, 4H), 1.43-1.29 (m, lated diamine 14 (50.7 mg, see the Supporting Information for full
12H); 13C NMR (CDCl3, 75 MHz) δ 144.6, 141.4, 138.0, 133.2, characterization) and clathculin B (328.1 mg, 1.03 mmol, 78%).
129.7, 127.8, 114.8, 109.8, 94.7, 77.2, 70.6, 32.9, 29.3, 29.2, 28.8, These two compounds had Rf values of 0.40 and 0.05 in CMA: IR
28.76, 28.75, 28.73, 25.3, 21.6, 19.5; HRMS (EI) calcd for (neat) 3329, 3019, 2928, 2854, 2787, 2215, 1466 cm-1; 1H NMR
C24H34O3S [M þ Na]þ 425.2121, found 425.2120. (CDCl3, 300 MHz) δ 5.80 (dt, J = 10.7, 7.4 Hz, CH2CHd), 5.43
(Z)-Heptadeca-12-en-10-yn-1-yl 4-Methylbenzenesulfonate (12). (dtt, J = 10.7, 2.2, 1.3 Hz, CHdCHCtC), 2.66 (t, J = 6.2 Hz,
According to the procedure for 7, p-toluenesulfonyl chloride NCH2CH2N), 2.50 (t, J = 6.1 Hz, NCH2CH2N), 2.46 (s, NCH3),
(912 mg, 4.80 mmol, 1.5 equiv), alcohol 10 (794.7 mg, 3.20 mmol, 2.37-2.25 (m. 6H, 3CH2), 2.20 (s, NCH3), 1.97 (brs, 1H, NH)
1 equiv), Et3N (646 mg, 0.87 mL, 6.4 mmol, 2.0 equiv), and DMAP 1.60-1.23 (m, 9 CH2), 0.91 (t, J = 6.9 Hz, CH3); 13C NMR
(19.5 mg, 0.16 mmol, 0.05 equiv) were reacted in 10 mL of CH2Cl2. (CDCl3, 75 MHz) δ 142.5, 109.3, 94.3, 77.3, 58.1, 56.9, 49.4, 42.3,
Purification by flash chromatography [hexanes/ethyl acetate (8:2)] 36.4, 31.0, 29.7, 29.50, 29.49, 29.1 28.83, 28.82, 27.4, 27.3, 22.2, 19.5,
gave 12 as a light yellow oil (1.0885 g, 2.50 mmol, 84%): IR (neat) 13.9; HRMS (ESI) calcd for C21H40N2 [M þ H]þ 321.3264, found
3019, 2028, 2857, 2213, 1653, 1599, 1495, 1465 cm-1; 1H NMR 321.3270.
(CDCl3, 300 MHz) δ 7.78 (d, J = 8.4 Hz), 7.33 (d, J = 8.5 Hz), 5.80
(dt, J = 10.7, 8.4 Hz), 5.41 (dtt, J = 10.7, 2.2, 1.4 Hz), 4.01 (t, J = Acknowledgment. S.G.B. thanks Macalester College for a
6.5 Hz), 2.44 (s), 2.32 (dt, J = 6.8, 2.2 Hz), 2.28 (dt, J = 7.3, 1.4 Hz), summer stipend from the Violet Olson Beltmann Fund. E.E.S.
1.68 - 1.29 (m, 18H), 0.91 (t, J = 7.1 Hz); 13C NMR (CDCl3, 75 thanks the Arnold and Mabel Beckman Foundation for sup-
MHz) δ 144.6, 142.6, 133.2, 129.8, 127.8, 109.3, 94.3, 77.4, 70.6,
port in the form of a Beckman Scholarship.
31.1, 29.7, 29.2, 28.9, 28.85, 28.79, 28.78, 28.75, 25.3, 22.2, 21.6,
19.5, 14.0; HRMS (ESI) calcd for C24H36O3S [M þ Na]þ 427.2277,
found 427.2297. Supporting Information Available: General experimental
Clathculin A (1). To a solution of tosylate 11 (625.0 mg, 1.55 conditions, 1H NMR and 13C NMR spectra for all new com-
mmol, 1 equiv) in 5.0 mL of CH3CN was added N,N0 -dimethy- pounds, experimental procedures for preparation and zipper
lethylenediamine (687 mg, 0.84 mL, 7.77 mmol, 5 equiv). The isomerization of 3, and our interpretative assignments for
solution was stirred overnight, concentrated in vacuo, and selected 1H NMR spectra. This material is available free of
transferred (EtOAc) to a separatory funnel containing 30 mL charge via the Internet at http://pubs.acs.org.”

J. Org. Chem. Vol. 75, No. 21, 2010 7403