746
C. J. Burns et al.
(4H, m). δC (100 MHz; CDCl3) 173.3 (C(O)), 171.6 (C(O)), 76.0
(CHOC(O)), 71.4 (CHOH), 52.1 (CH3), 40.3 (SCH2), 37.5 (SCH2),
29.4 (succinyl CH2), 29.1 (succinyl CH2). m/z (EI) 266 (M+, 20%),
134 (100), 115 (65), 101 (27).
13 (117 mg, 0.15 mmol) and morpho-CDI (73 mg, 0.17 mmol) in
dichloromethane (2 mL). The solution was stirred for 20 h at room tem-
perature then water was added (25 mL) and the mixture extracted with
ethyl acetate (3 × 25 mL). The combined organic extracts were washed
with brine (50 mL), dried (Na2SO4) and filtered through a plug of sil-
ica gel. The solvent was removed in vacuo to give the crude product
as a colourless viscous oil. Purification using ethyl acetate as eluent
afforded 8 (77 mg, 57%) as a colourless viscous oil: Rf 0.48 (ethyl
acetate). Found: C 61.7, H 9.1. C53H90O15S2 requires C 61.72, H 8.80%.
νmax/cm−1 1732. δH (200 MHz; CDCl3) 7.37–7.28 (5H, m), 5.00 (1H,
ddd, J 9.8, 8.6, 3.9 Hz, H4ꢀ), 4.65 and 4.58 (2H, AB quartet), 4.27–4.21
(4H, m, C(O)OCH2 × 2), 4.15–4.08 (2H, m), 3.73–3.52 (25H, m), 3.17
(2H, dt, J 13.6, 3.7 Hz), 2.96 (2H, ddd, J 13.6, 9.7, 7.0 Hz), 2.68–2.56
(8H, m, succinyl CH2 groups), 1.69–1.00 (24H, m), 0.90–0.80 (15H,
m). δC (100 MHz; CDCl3) 172.3 (C(O)), 172.1 (PhytOC(O)), 171.1
(CHOC(O)), 137.9 (Ar quat.), 128.5 (Ar), 127.9 (Ar), 127.6 (Ar), 72.3
(CH2), 70.64 (CH2), 70.60 (CH2), 69.1 (CH2), 63.9 (CH2), 63.8 (CH2),
63.4 (CH2), 39.4 (CH2), 38.2 (SCH2), 37.5 (CH2), 37.4 (CH2), 37.3
(CH2), 35.6 (CH2), 35.5 (CH2), 32.8 (CH), 29.9 (CH), 29.19 (suc-
cinyl CH2), 29.15 (succinyl CH2), 29.09 (succinyl CH2), 28.98 (succinyl
CH2), 28.0 (CH), 24.8 (CH2), 24.5 (CH2), 24.3 (CH2), 22.7 (CH3), 22.6
(CH3), 19.74–19.45 (overlapping signals, non-terminal CH3 groups).
m/z (ESI) 1055 (M + H + Na+, 57%), 1054 (M + Na+, 100).
[( )-trans-5ꢀ-Hydroxy-1ꢀ,2ꢀ-dithian-4ꢀ-yl] [(3RS,7ꢀꢀR,11ꢀꢀR)-
3ꢀꢀ,7ꢀꢀ,11ꢀꢀ,15ꢀꢀ-tetramethylhexadecyl]-5,8,11,14,17,20,23,26-
octaoxa-4,27-dioxotriacontanedioic Acid Ester 6
4-N,N-Dimethylaminopyridine (7 mg, 55 µmol) was added to a mixture
of trans-4,5-dihydroxy-1,2-dithiane 1 (25 mg, 164 µmol), hemisucci-
nate 13 (146 mg, 182 µmol) and morpho-CDI (90 mg, 213 µmol) in a
4/1 mixture of dichloromethane/THF (2.5 mL). The solution was stirred
at room temperature for 24 h then diluted with water (25 mL). The aque-
ousphasewasextractedwithethylacetate(3 × 25 mL)andthecombined
organic extracts were washed with brine (50 mL) and dried (Na2SO4).
The solvent was removed in vacuo to give the crude product as a colour-
less viscous oil. Purification using ethyl acetate as eluent afforded 6
(73 mg, 47%) as a colourless viscous oil: Rf 0.21 (ethyl acetate). Found:
C 58.5, H 8.9. C46H84O15S2 requires C 58.70, H 8.99%. νmax/cm−1
3600–3200, 1732. δH (200 MHz; CDCl3) 4.88 (1H, ddd, J 9.9, 8.8,
4.1 Hz, H4ꢀ), 4.26–4.22 (4H, m, C(O)OCH2 × 2), 4.14–4.08 (2H, m),
3.80 (1H, ddd, J 9.7, 8.8, 4.2 Hz, H5ꢀ), 3.70–3.64 (24H, m), 3.20–2.90
(4H, m), 2.75–2.58 (8H, m, succinyl CH2 groups), 2.32 (1H, br s, OH),
1.67–1.01 (24H, m), 0.89–0.81 (15H, m). δC (50 MHz; CDCl3) 172.7
(CHOC(O)), 172.3 (C(O)), 171.6 (PhytOC(O)), 71.3 (CH), 70.5 (CH2),
69.0 (CH2), 68.9 (CH2), 64.1 (CH2), 63.8 (CH2), 63.4 (CH2), 40.4
(SCH2), 39.3 (CH2), 37.6 (SCH2), 37.3 (CH2), 37.2 (CH2), 35.5 (CH2),
35.4 (CH2), 32.7 (CH), 29.8 (CH), 29.4 (succinyl CH2), 29.3 (succinyl
CH2), 29.05 (succinyl CH2), 28.99 (succinyl CH2), 27.9 (CH), 24.8
(CH2), 24.4 (CH2), 24.3 (CH2), 22.7 (CH3), 22.6 (CH3), 19.71–19.41
(overlapping signals, non-terminal CH3 groups). m/z (MALDI) 964
(M + Na+, 100%).
[( )-trans-5ꢀ-[(4ꢀꢀꢀ-Methoxy-1ꢀꢀꢀ,4ꢀꢀꢀ-dioxo-butan-1ꢀꢀꢀ-yl)-
oxy]-1ꢀ,2ꢀ-dithian-4ꢀ-yl] [(3ꢀꢀRS,7ꢀꢀR,11ꢀꢀR)-3ꢀꢀ,7ꢀꢀ,11ꢀꢀ,15ꢀꢀ-
tetramethylhexadecyl]-5,8,11,14,17,20,23,26-octaoxa-
4,27-dioxotriacontanedioic Acid Ester 9
4-N,N-Dimethylaminopyridine (7 mg, 0.06 mmol) was added to a solu-
tion of methyl ester 12 (47 mg, 0.18 mmol), hemisuccinate 13 (170 mg,
0.21 mmol) and morpho-CDI (97 mg, 0.23 mmol) in dichloromethane
(2 mL). The solution was stirred for 21 h at room temperature then
water was added (25 mL) and the mixture extracted with ethyl acetate
(3 × 25 mL). The combined organic extracts were washed with brine
(50 mL), dried (Na2SO4), and filtered through a plug of silica gel.
The solvent was removed in vacuo to give the crude product as a
pale yellow oil. Purification using ethyl acetate as eluent afforded 9
(130 mg, 70%) as a colourless oil: Rf 0.35 (ethyl acetate). Found: C 58.1,
H 8.8. C51H90O18S2 requires C 58.04, H 8.60%. νmax/cm−1 1732. δH
(200 MHz; CDCl3) 5.12–4.98 (2H, m, H4ꢀ and H5ꢀ), 4.26–4.20 (4H,
m, C(O)OCH2 × 2), 4.15–4.06 (2H, m), 3.69 (3H, s), 3.72–3.60 (24H,
m), 3.36–3.00 (4H, m), 2.70–2.58 (12H, m, succinyl CH2 groups),
1.68–1.00 (24H, m), 0.91–0.80 (15H, m). δC (50 MHz; CDCl3) 172.6
(CH3OC(O)), 172.3 (C(O)), 172.1 (PhytOC(O)), 171.2 (CHOC(O)),
72.1 (CHOC(O)), 70.5 (CH2), 69.0 (CH2), 63.9 (CH2), 63.8 (CH2),
63.4 (CH2), 51.9 (CH3OC(O)), 39.3 (CH2), 38.3 (SCH2), 37.4 (CH2),
37.3 (CH2), 35.5 (CH2), 35.4 (CH2), 32.8 (CH), 29.8 (CH), 29.1 (suc-
cinyl CH2), 29.0 (succinyl CH2), 28.8 (succinyl CH2), 28.6 (succinyl
CH2), 28.0 (CH), 24.8 (CH2), 24.5 (CH2), 24.3 (CH2), 22.7 (CH3), 22.6
(CH3), 19.66–19.44 (overlapping signals, non-terminal CH3 groups).
m/z (ESI) 1079 (M + H + Na+, 51%), 1078 (M + Na+, 100).
[( )-trans-5ꢀ-Methoxy-1ꢀ,2ꢀ-dithian-4ꢀ-yl] [(3ꢀꢀRS,7ꢀꢀR,11ꢀꢀR)-
3ꢀꢀ,7ꢀꢀ,11ꢀꢀ,15ꢀꢀ-tetramethylhexadecyl]-5,8,11,14,17,20,23,26-
octaoxa-4,27-dioxotriacontanedioic Acid Ester 7
4-N,N-Dimethylaminopyridine (5 mg, 0.04 mmol) was added to a
solution of methoxy alcohol 10 (18.5 mg, 0.11 mmol), hemisucci-
nate 13 (99 mg, 0.12 mmol) and morpho-CDI (61 mg, 0.14 mmol) in
dichloromethane (2 mL). The solution was stirred for 30 h at room tem-
perature then diluted with water (25 mL) and the mixture extracted with
ethyl acetate (3 × 25 mL). The combined organic extracts were washed
with brine (50 mL), dried (Na2SO4), and filtered through a plug of silica
gel. The solvent was removed in vacuo to give the crude product as a
pale yellow oil. Purification using ethyl acetate as eluent gave 7 (50 mg,
47%) as a colourless viscous oil: Rf 0.33 (ethyl acetate). Found: C 59.1,
H 9.3. C47H86O15S2 requires C 59.09, H 9.07%. νmax/cm−1 1732. δH
(400 MHz; CDCl3) 4.93 (1H, ddd, J 9.7, 8.4, 3.8 Hz, H4ꢀ), 4.26–4.21
(4H, m, C(O)OCH2 × 2), 4.14–4.07 (2H, m), 3.70–3.66 (4H, m), 3.63
(20H, br s), 3.40 (3H, s), 3.35 (1H, ddd, J 9.7, 8.4, 3.6 Hz, H5ꢀ), 3.18
(2H, ddd, J 21.0, 13.5, 3.6 Hz), 2.92 (2H, dt, J 13.5, 10.0 Hz), 2.66–2.56
(8H, m, succinyl CH2 groups), 1.68–0.94 (24H, m), 0.91–0.80 (15H, m).
δC (50 MHz; CDCl3) 172.3 (C(O)), 172.1 (PhytOC(O)), 171.2 (C(O)),
79.7(SCH2CHOCH3), 73.2(SCH2CHOC(O)), 70.5(CH2), 69.0(CH2),
63.9 (CH2), 63.8 (CH2), 63.3 (CH2), 57.8 (CH3O), 39.3 (CH2), 37.7
(SCH2), 37.3 (CH2), 37.2 (CH2), 35.5 (CH2), 35.4 (CH2), 32.7 (CH),
29.8 (CH), 29.1 (succinyl CH2), 29.04 (succinyl CH2), 28.98 (succinyl
CH2), 27.9 (CH), 24.7 (CH2), 24.4 (CH2), 24.2 (CH2), 22.7 (CH3), 22.6
(CH3), 19.39–19.69 (overlapping signals, non-terminal CH3 groups).
m/z (ESI) 979 (M + H + Na+, 48%), 978 (M + Na+, 100), 973 (M +
H2O, 36).
[( )-trans-5-Hydroxy-1,2-dithian-4-yl]
[2ꢀ-(trimethylsilyl)ethyl]butanedioic Acid Ester 15
Oxalyl chloride (195 mg, 1.54 mmol) was added to a solution of
the known silyl-protected hemisuccinate[31] (305 mg, 1.40 mmol) in
dichloromethane (10 mL) followed by one drop of DMF. The solvent
was removed under reduced pressure after stirring continued for 45 min
at room temperature. Dichloromethane (10 mL) was added followed
by oxidized DTT 1 (213 mg, 1.40 mmol) and triethylamine (283 mg,
2.80 mmol). After 8 h the solution was diluted with dichloromethane
(25 mL), and the organic layer was washed with water (2 × 25 mL),
brine (25 mL), and dried (Na2SO4). The solvent was removed in vacuo
to give the crude product as a dark yellow viscous oil. Purification
using 95/5 dichloromethane/diethyl ether as eluent gave 15 (133 mg,
27%) as a colourless viscous oil: Rf 0.24 (95/5 dichloromethane/diethyl
ether. Found: C 44.5, H 6.8. C13H24O5S2Si requires C 44.29, H 6.86%.
νmax/cm−1 3500–3000, 1732. δH (200 MHz; CDCl3) 4.91 (1H, ddd,
[( )-trans-5ꢀ-Benzyloxy-1ꢀ,2ꢀ-dithian-4ꢀ-yl]-[(3ꢀꢀRS,7ꢀꢀR,11ꢀꢀR)-
3ꢀꢀ,7ꢀꢀ,11ꢀꢀ,15ꢀꢀ-tetramethylhexadecyl]-5,8,11,14,17,20,23,26-
octaoxa-4,27-dioxotriacontanedioic Acid Ester 8
4-N,N-Dimethylaminopyridine (5 mg, 0.04 mmol) was added to a
solution of benzyl alcohol 11 (32 mg, 0.13 mmol), hemisuccinate