and the obtained residue was purified by silica gel column
chromatography with hexane-ethyl acetate (9:1) as the eluent.
Further purification by HPLC using acetone as the eluent yielded
2,2,3,3,11,11,12,12-octamethyl-6-tetradecyl-1,4,7,10,13-pentaoxacy-
clohexadecane (C14-DTM16C5B; 180 mg, 18.3%) as a colorless
oil. Analytical data for C14-DTM16C5B are as follows: 1H-NMR
(270 MHz, CDCl3) δ 0.87 (t, 3H, -CH3), 1.14 and 1.18 (s, 24H, 8
-CH3), 1.20-1.56 (m, 26H, -CH2-), 1.69 (m, 2H, -CH2-), 3.30-
3.74 (m, 11H, -OCH2-). Anal. Calcd for C33H66O5 (542.89): C,
73.01; H, 12.25. Found: C, 72.98; H, 12.28.
evaporation of THF, the residue was extracted twice with
chloroform. The organic solvent was then evaporated, and the
obtained residue was purified by silica gel column chromatography
with hexane-ethyl acetate (9:1) as the eluent to yield 15-octadecyl-
1,4,7,10,13-pentaoxacyclohexadecane C18-16C5; 107.9 mg, 21.6%)
as a white crystal. Analytical data for C18-16C5 are as follows:
1H-NMR (270 MHz, CDCl3) and δ 0.87 (m, 3H, -CH3), 1.25 (s,
34H, 17 -CH2), 1.82 (b, 1H, -CH-), 3.44-3.72 (m, 20H, 10
-CH2-). Anal. Calcd for C29H58O5 (486.78): C, 71.56; H, 12.01.
Found: C, 71.58; H, 12.05.
(v) C1 4 -DD1 6 C5 (6 -Tetradecyl-2 ,6 ,1 3 ,1 6 ,1 9 -pentaoxa-
pentacyclo[18 .4 .4 .4 7,12.0 1.20.0 7,12]dotriacontane). NaH (220
mg, 5.40 mmol) was added to a solution of 1 1 (513.9 mg, 1.35
mmol) in THF (10 mL) and stirred at 40 °C for 1 h. A solution of
1 7 (619.4 mg, 1.35 mmol) in 12 mL of THF was then added to
this mixture. The mixture was then stirred at 70 °C for 3 days. A
small amount of methanol (12 mL) was added to quench the
excess NaH. After evaporation of THF, the residue was extracted
three times with ethyl acetate. The solvent was then evaporated,
and the obtained residue was purified by silica gel column
chromatography with hexane-ethyl acetate (9:1) as the eluent.
Further purification by HPLC using acetone as the eluent yielded
6-tetradecyl-2,6,13,16,19-pentaoxapentacyclo[18.4.4.47,12.01,20.07,12]-
dotriacontane (C14-DD16C5; 140.1 mg, 16.0%) as a colorless oil.
Analytical data for C14-DD16C5 are as follows: 1H-NMR (270
MHz, CDCl3) δ 0.87 (t, 3H, -CH3), 1.18-2.40 (m, 60H, -CH2-),
3.10-3.92 (m, 11H, -OCH2-). Anal. Calcd for C41H74O5
(647.04): C, 76.11; H, 11.53. Found: C, 76.51; H, 11.56.
(vi) Nor1 6 C5 (8 ,1 1 ,1 4 ,1 7 ,2 0 -P entaoxaspiro[5 .1 5 ]-1 ,4 -
methano-2-heneicosene). NaH (310 mg, 7.68 mmol) was added
to a solution of 2,3-bis(hydroxymethyl)-5-norbornene (493.6 mg,
3.2 mmol) in THF (10 mL) and stirred for 1 h at room temperature.
A solution of tetraethylene glycol ditosylate (1.609 g, 3.2 mmol)
in 10 mL of THF was then added to this mixture. The mixture
was then stirred at 70 °C for 20 h. A small amount of methanol
was added to quench the excess NaH. After evaporation of THF,
the residue was extracted twice with ethyl acetate. The solvent
was then evaporated, and the obtained residue was purified by
silica gel column chromatography with hexane-ethyl acetate (1:
2) as the eluent. Further purification by HPLC using methanol
as the eluent yielded 8,11,14,17,20-pentaoxaspiro[5.15]-1,4-methano-
2-heneicosene (Nor16C5; 253.8 mg, 25.38%) as a colorless oil.
Analytical data for Nor16C5 are as follows: 1H-NMR (270 MHz,
CDCl3) δ 0.70-0.80 (m, 1H, -CH-), 1.32-1.58 (m, 3H, -CH-,
-CH2-), 2.68 and 2.79 (br, 2H, -CH2-), 3.12-3.88 (m, 20H,
-OCH2-), 6.00-6.16 (m, 2H). Anal. Calcd for C17H28O5
(312.41): C, 65.36; H, 9.03. Found: C, 65.38; H, 9.07.
(vii) C1 8 -1 6 C5 (1 5 -Octadecyl-1 ,4 ,7 ,1 0 ,1 3 -pentaoxacy-
clohexadecane). Malonic acid diethyl ester (1.60 g, 9.98 mmol)
was added to the suspension of NaH (0.390 g, 9.9 mmol) in 20
mL of ethanol. A solution of 1-bromooctadecane (3.24, 9.7 mmol)
in 30 mL of ethanol was then added, and the mixture was refluxed
at 80 °C for 14 h. After evaporation of ethanol, the residue was
extracted three times with chloroform. The organic solvent was
evaporated, and the obtained residue was purified by silica gel
column chromatography (hexane-ethyl acetate 9:1) to yield
diethyl 2-octadecylmalonate (1 8 ; 1.91 g, 47.8%). Product 1 8
(420.6 mg, 1.02 mmol) was added to a suspension of LiAlH4 (58.0
mg, 1.53 mmol) in 5 mL of THF in an ice bath and stirred for 3
h. A small amount of water (1 mL) was then added to this mixture
to quench the reaction. After evaporation of THF, the residue
was extracted twice with chloroform to yield 2-octadecyl-1,3-
butanediol (1 9 ; 220 mg, 65.7%) as a white crystal. NaH (98.6 mg,
2.47 mmol) was added to a solution of 1 9 (336.47 mg, 1.03 mmol)
and stirred at room temperature for 1 h. A solution of tetraeth-
ylene glycol ditosylate (389.78 mg, 68.7 mmol) was then added,
and the mixture was refluxed at 80 °C for 14 h. A small amount
of methanol (10 mL) was added to quench the excess NaH. After
(viii) MD-1 6 C5 (2 , 5 , 8 , 1 1 , 1 5 -P entaoxatricyclo [1 4 .4 .
4 .0 ] tetracosane). To the DMF solution of triethylene glycol
(3.13 g, 20.8 mmol) in an ice bath was added NaH (1.25 g, 31.2
mmol), and the mixture was stirred for 30 min. Benzyl bromide
(3.56 g, 20.8 mmol) was then added to the reaction mixture. The
reaction mixture was then stirred at 80 °C for 2 h. A small amount
of methanol was added to quench the excess NaH. After
evaporation of DMF, the residue was extracted twice with ethyl
acetate. The organic solvent was then evaporated, and the
obtained residue was purified by silica gel column chromatography
with hexane-ethyl acetate (9:1) as the eluent to yield 8-(benzyl-
oxy)-3,6-dioxaoctanol (2 0 ; 2.83 g, 28.3%) as a colorless oil.
NaH (0.71 g, 17.7 mmol) was added to the THF solution of
2 0 (2.83 g, 11.8 mmol) in an ice bath and stirred for 30 min. Allyl
bromide (1.71 g, 1.2 mmol) was then added slowly to this mixture.
The reaction mixture was then refluxed for 2 h, and a small
amount of methanol was added to quench the excess NaH. After
evaporation of THF, the residue was extracted twice with ethyl
acetate. The organic solvent was then evaporated, and the
obtained residue was purified by silica gel column chromatography
with hexane-ethyl acetate (1:1) as the eluent to yield 12-
(benzyloxy)-4,7,10-trioxa-1-dodecene (2 1 ; 2.52 g, 76.1%) as a
colorless oil.
To the THF suspension of NaBH4 (0.139 g, 4 mmol) and BF3
ethereal complex (0.757 g, 5.33 mmol) was added a THF solution
of 2 1 (2.52 g, 9.0 mmol), and the mixture was stirred for 2 h. A
small amount of water was then added to this mixture, followed
by of 2.1 mL of NaOH (3 M) solution and 1.51 mL of 30% H2O2
solution, and this mixture was stirred for 2 h. The reaction
mixture was then extracted with ethyl acetate and the organic
solvent evaporated. The residue was purified by silica gel column
chromatography (hexane-ethyl acetate 9:1) to yield 12-(benzy-
loxy)-4,7,10-trioxadodecanol (2 2 ; 0.86 g, 32.5%).
To the methanol solution of 2 2 (583 mg, 1.95 mmol) was
added 10% Pd-C (291 mg, 50 wt %), and the reaction mixture
was stirred at room temperature under 1 atm H2 for 3 h. After
the solid was filtered off, the mixture was evaporated to yield 3,6,9-
trioxa-1,12-dodecanediol (2 3 ; 383 mg, 94.3%) as a colorless oil.
Tosyl chloride (1.052 g, 5.52 mmol) was added to a solution of
2 3 (383 mg, 1.84 mmol) in 10 mL of pyridine and stirred for 1 h
in an ice bath. The reaction mixture was then evaporated, and
the residue was extracted three times with ethyl acetate. The
organic solvent was evaporated, and the obtained residue was
purified by silica gel column chromatography with hexane-ethyl
acetate (1:2) as the eluent to yield 3,6,9-trioxa-1,12-dodecanol
ditosylate (2 4 ; 612 mg, 64.4%) as a colorless oil. NaH (188.8 mg,
4.72 mmol) was added to a solution of cis-decalindiol (201 mg,
1.18 mmol) in THF (20 mL) and stirred for 1 h. A solution of 2 4
(612 mg, 1.18 mmol) in 7 mL of THF was then added to this
mixture and stirred at 70 °C for 24 h. A small amount of methanol
was added to quench the excess NaH. After evaporation of THF,
the residue was extracted twice with ethyl acetate. The organic
solvent was then evaporated, and the obtained residue was purified
by silica gel column chromatography (hexane-ethyl acetate 1:9)
to yield 2,5,8,11,15-pentaoxatricyclo[14.4.4.0] tetracosane (MD-
16C5; 40 mg, 10.0%) as a colorless oil. Analytical data for MD-
16C5 are as follows: 1H-NMR (270 MHz, CDCl3) δ 1.22-2.18 (m,
18H, dec-H and -CH2-), 3.30-3.88 (m, 16H, 8 -OCH2). Anal.
Analytical Chemistry, Vol. 68, No. 1, January 1, 1996 211