Synthesis of ω-substituted alkanethiols and (bromomethyl)methylthiomalonates

Article abstract of DOI:10.1002/1522-2675(20010321)84:3<678::AID-HLCA678>3.0.CO;2-Y

Several multifunctional derivatives of methylthiomalonic acid (= 2-(thiocarboxy)acetic acid), i.e. 20a,b, 21, 22a,b, and 24, were prepared from thiols bearing a functionalized head group, i.e. from 9a,b, 12, and 16d,f (Schemes 4 and 5). The association constants of the two dithio podands 8b and 11 with K⁺ were determined.

Full text of DOI:10.1002/1522-2675(20010321)84:3<678::AID-HLCA678>3.0.CO;2-Y

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Helvetica Chimica Acta ± Vol. 84 (2001)
Synthesis of w-Substituted Alkanethiols and
(Bromomethyl)methylthiomalonates
by Michael J. Pfammatter, Vuk Siljegovic, Tamis Darbre*, and Reinhart Keese*
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern
Several multifunctional derivatives of methylthiomalonic acid (ˆ2-(thiocarboxy)acetic acid), i.e. 20a,b, 21,
22a,b, and 24, were prepared from thiols bearing a functionalized head group, i.e. from 9a,b, 12, and 16d,f
‡
(Schemes 4 and 5). The association constants of the two dithio podands 8b and 11 with K were determined.
Introduction. ± For development of models of the coenzyme-B12-dependent
methylmalonyl-CoA mutase, we have prepared a variety of (bromomethyl)methyl-
thiomalonates (ˆ2-(bromomethyl)-2-methyl-3-oxo-3-(alkylthio)propanoates) with
head groups for molecular recognition. These model substrates are to be used to
investigate the efficiency of the methylmalonyl-succinyl rearrangement when the
substrate and the vitamin-B12 molecule are held together by noncovalent interactions.
The concept of enhancing the rearrangement by peripheral association of appropriate
groups is based on the idea that enzymes or enzyme-coenzyme complexes must
recognize their substrates and associate with them through noncovalent bonds to
provide the orientation and proximity necessary for catalysis [1 ± 4]. Hitherto, we have
reported a hydrophobic model, where lipophilic alkane chains are used for the
association between the methylmalonyl moiety and the vitamin B12, appropriately
modified in the periphery, and two models based on association in aprotic solvents
between an A ´ T and a C ´ G base pair, respectively [5 ± 8]. Enhanced rearrangement
has been observed for the hydrophobic and the A ´ T mode [5][6]. In further persuit of
vitamin-B12-related concepts for molecular recognition between methylmalonyl sub-
strates and the catalyst, we considered the association between polyether (ꢀpodandꢁ)
units mediated by cations as well as the interaction between carbohydrate-derived
units. We report here the preparation of alkanethiols bearing a polyether moiety or a
pentahydroxyhexanoyl head group as well as the efficient synthesis of thioesters
thereof. First results for the binding constants between two polyethers with alkali
cations are reported.
Alkanethiols with Terminal Polyether and Glyconoyl Groups. ± w-Aminoalkane-
thiols are used as central building blocks, to which the head groups for molecular
recognition are attached via acylation of the amino group. The thiomalonates are
subsequently obtained from the modified alkanethiols by esterification. The homo-
loguous series of N-(w-bromoalkyl)phthalimides 3a ± f with C6 and C8 to C12 alkyl
chains were prepared from 1 and 2 in 56 ± 72% yield (Scheme 1). The original

Helvetica Chimica Acta ± Vol. 84 (2001)
679
Scheme 1
a) Na2S2O3, MeOH/H2O. b) I2. c) H2N NH2, EtOH. d) HCl.
procedure [9] was modified for the longer alkyl chains (C10 to C12) and gave the
compounds 3d ± f as low-melting, colorless solids. The (dithiodialkanediyl)bis[phtha-
limides] 4a ± f were obtained by treatment of (bromoalkyl)phthalimides 3a ± f with
Na2S2O3 and oxidation of the Bunte salts with I2 in 70 ± 80% yield. The compounds 3b ± f
show the well-known behavior of alternating melting points for homologuous series of
substituted alkanes [10][11]. The stable and easily isolated (dithiodialkanediyl)-
bis[ammonium chlorides] 5a ± f were obtained in 60 ± 80% yield by treatment of the
phthalimides 4a ± f with hydrazine followed by addition of hydrochloric acid. The
bis[ammonium chloride] 5f was also characterized as the bis-amide 6.
Treatment of the acid chloride of 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (7)
with the bis[ammonium chlorides] 5a ± c gave the desired (dithiodialkanediyl)bis[a-
mides] 8a ± c in 50% yield (Scheme 2). The synthesis of the dithio derivative 11, bearing
an ester rather than an amide function as a link between the tris(oxyethanediyl) moiety
and the thio group, was performed by reaction of 3,3'-dithiobis[propanol] (10;
obtained from 3-bromopropanol [12]) with the acid chloride of 7. The dithio
derivatives 8a,b and 11 were reduced with Zn in AcOH to the thiols 9a,b and 12 in
almost quantitative yield.
The formation of the thiols incorporating a gluconoyl moiety was achieved by the
reaction of the (dithiodialkanediyl)bis[ammonium chlorides] 5b (n ˆ 8) or 5f (n ˆ 12)
with d-glucono-1,5-lactone (13) affording the dithio derivatives 14b and 14f which were

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Helvetica Chimica Acta ± Vol. 84 (2001)
Scheme 2
a) CHCl2OMe or SO2Cl2. b) 5a ± c, Et3N. c) Zn, AcOH. d) 10, CHCl2OMe, CH2Cl2, Et3N.
Scheme 3
a) 5b (n ˆ 8) or 5f (n ˆ 12), MeOH, reflux. b) 5d (n ˆ 10), MeOH; Ac2O, pyridine. c) Ac2O, pyridine for 14f.
d) Zn, AcOH, and 15d or 15f.
insoluble in most organic solvents1) (Scheme 3). The bis-amides 14b and 14f may be
considered to be bolaamphiphiles [13]. Acetylation of 14f with Ac2O in pyridine gave
the dithio derivative 15f. Treatment of 5d with 13 afforded a crude dithio derivative,
which was not isolated but directly acetylated to 15d. Subsequent reduction of 15d and
15f with Zn gave the thiols 16d and 16f in 53 and 92% yield, respectively.
1
)
Upon heating to 150 ± 1538, compound 14f developed a smectic mesophase (probably smectic A) and
decomposed below the clearing point at T> 1958. Compound 14b decomposed at 166 ± 1688, but developed
a mesophase upon quick cooling to 155 ± 1608. We thank Prof. R. Miethchen, University of Rostock, for this
analysis.

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Thioesters. ± The tert-butyl methyl methylmalonate (17), prepared as described
[14 ± 16], afforded the bromomethyl derivative 18 by deprotonation with NaH in the
presence of DMPU (3,4,5,6-tetrahydro-1,3-dimethylpyrimidin-2(1H)-one), followed
by alkylation with methylene bromide [17] (Scheme 4). The tert-butyl ester was then
hydrolyzed by treatment with CF3COOH to give the crude monoacid 19. Due to the
propensity of acid 19 to undergo fragmentation with formation of methyl methacrylate
in the presence of base [18], the general methods to generate thioesters from acids
activated with DCC (dicyclohexylcarbodiimide), phosphorodichloridates [19], or
carbonylbis[1H-imidazoles] [20] were not effective. However, addition of the acyl
chloride, obtained from crude 19 by treatment with SOCl2 or CHCl2OMe, to the thiols
in CH2Cl2 at 08 afforded the thioesters 20a (80%), 20b (40%), 21 (65%), 22a (47%),
and 22b (56%) in moderate to good yield.
Scheme 4
a) NaH, HMPT. b) CH2Br2. c) CF3COOH. d) SOCl2 or CHCl2OMe, then RSH 9a,b, 12, 16d, or 16f, Et3N,
CH2Cl2, r.t.
By the same method, the dimethylmalonate derivative 24 and the succinate 26 were
prepared in 44 and 48% yield from 23 and 25, respectively (Scheme 5).
Scheme 5
a) CHCl2OMe, 9b, Et3N, CH2Cl2. b) CF3COOH. c) CHCl2OMe, 9b, Et3N, CH2Cl2.

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Binding of Polyethers to Alkali Cations. ± Chelation of alkali cations by the
tris(oxyethanediyl) group of 20a, 20b, and 21 and those of corresponding vitamin-B12
derivatives [21] forms the basis of the ꢀpodand modelꢁ mentioned above. To establish
basic features of the association between the substrates and the vitamin B12 derived
catalyst, both bearing a podand head group, we investigated the ability of the dithio
‡
‡
derivatives 8b and 11 to bind Na and K . The association constants were determined in
‡
D2O/CDCl3 with the picrate method [22][23]. Podand 8b binds K with Kass ˆ 3.6 ´
103 m and Na with Kass ˆ 4.2 ´ 103 m . Podand 11 binds K with Kass ˆ 1.3 ´ 103 m .
Whether the observed associations involve one or two polyether moieties was not
determined. Electron-spray MS results also suggest an association of the polyether with
1
‡
1
‡
1
‡
cations. For 21, a ESI-MS peak m/z 465.20 corresponding to the thioester [21 ‡ Li ] was
observed.
Concluding Remarks. ± For the development of further models for the coenzyme-
B12-dependent methylmalonyl mutase incorporating molecular recognition, the
(bromomethyl)thiomalonates 20a,b, 21, 24, and 25 as well as 22a,b were prepared in
an efficient way. The gluconoyl moiety of 22a,b was chosen for a potential interaction
between the polyhydroxy head groups grafted to the vitamin-B12-derived catalyst
[16][24] and the model substrates 22a,b. For the ꢀpodand modelꢁ, the substrates 20a,b
and 21 bearing a tris(oxyethanediyl) moiety were prepared. Under control of alkali
cations, the podand head groups of the substrates should interact with the
complementary polyether group attached to the vitamin-B12-derived catalyst [2].
Exploring this potential, the association of the polyethers 8b and 11 with alkali cations
was investigated using the picrate extraction method.
This work has been supported by the Bundesamt für Bildung und Wissenschaft, Bern (Project BBW No.
950606), within the European Research Program TMR (Contract No. ERBFMRXCT 960018) and the Swiss
National Science Foundation (Project No. 20-43565.95). M. J. P. thanks Prof. B. T. Golding for the discussions
and the support during his stay in the Department of Chemistry at the University of Newcastle and PD Dr. J.
Schaller for the access to the ESI-MS instrument and for technical assistance.
Experimental Part
General. The reactions were carried out with reagents and solvents of Fluka (puriss. grade). For workup,
the reaction mixture was poured onto ice-water, the aq. phase extracted with the appropriate solvent, and the
combined org. phase washed with sat. NaHCO3 soln. and brine, dried (MgSO4) and evaporated. Flash
chromatography (FC): distilled commercial-grade solvents, silica gel (30 ± 60 mm) from Baker (analyzed
reagents). TLC: Merck-F-254 precoated sheets, visualization by 5% phosphomolybdic acid hydrate/EtOH or by
UV. UV/VIS Spectra: Hewlett Packard 8451 A; lmax in nm. IR Spectra: Perkin-Elmer PE 782; CHCl3 soln. in 0.2-
mm-path NaCl cells; in cm 1. NMR Spectra: if not stated otherwise, in CDCl3 at 300 MHz (1H) and 75 MHz
(13C), Bruker AC-300 instrument; d in ppm rel. to the CDCl3 signal (d(H) 7.24, d(C) 77.00), J in Hz; 13C
multiplicities from DEPT spectra. MS: Varian MAT CH-7A, 70 eV; in m/z (%). LSI-MS: Fision Autospec-Q,
acceleration voltage 8 kV, ionization Cs (32 keV), matrix as indicated; in m/z (%). ESI-MS: Fisions Instrument
VG Platform II, positive-ion measurements (3.5 kV), negative-ion measurements (2.5 kV); in m/z (%).
Acronyms: DMF, dimethylformamide; DMPA, N,N-dimethylpyridine-4-amine; EDC, N-ethyl-N'-[3-(dimethyl-
amino)propyl]carbodiimide-hydrochloride; HMPT, hexamethylphosphoric triamide.
N-(w-Bromoalkyl)phthalimides 3a ± f. The procedure [9] was modified: A suspension of potassium
phthalimide (1; 4.76 g, 25 mmol) in DMF (25 ml) was slowly added to the 1,w-dibromoalkane 2a ± f (103 mmol)
in DMF (10 ml) under Ar. After refluxing for 4 h, the KBr formed was removed by filtration, the DMF
evaporated at 658, 50 Torr, and the residue purifid by FC (hexane/Et2O 3 :1). Recrystallization from hexane/
Et2O gave pure product.

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N-(6-Bromohexyl)phthalimide (3a) was prepared as reported [9]: Rf (hexane/Et2O 3 :1): 0.30. M.p. 558 ([9]:
578). IR (KBr): 1780vs, 1730vs, 1480s, 1440s, 1400vs, 1370vs, 1340vs, 900s, 980s. 1H-NMR: 1.40 ± 1.50 (2m, 4 H);
1.65 ± 1.75 (m, 2 H); 1.81 ± 1.91 (m, 2 H); 3.40 (t, J ˆ 7.17, 2 H); 3.68 (t, 2 H); 7.70 ± 7.74 (m, 2 H); 7.80 ± 7.99
(m, 2 H). 13C-NMR: 26.02 (t); 27.70 (t); 28.41 (t); 32.60 (t); 33.64 (t); 37.82 (t); 123.18 (d); 132.14 (s); 133.87 (d);
‡
‡
168.42 (s). MS (calc. for C14H16BrNO2, 310.19): 311 (34, [M ‡ 2] ), 310 (5), 309 (35, M (79Br)), 230 (13), 161
(64), 160 (100), 148 (13), 133 (11), 130 (17), 104 (13).
N-(8-Bromooctyl)phthalimide (3b): Yield 5.3 g (62.7%). Rf (hexane/Et2O 1:2). 0.59. M.p. 508 ([11]: 498).
IR (KBr): 1770s, 1700vs, 1465s, 1435s, 1400s, 1370s, 1065s, 1055s. 1H-NMR: 1.25 ± 1.42 (m, 8 H); 1.62 ± 170
(m, 2 H); 1.70 ± 1.89 (m, 2 H); 3.39 (t, J ˆ 7.00, 2 H); 3.68 (t, J ˆ 7.35, 2 H); 7.69 ± 7.74 (m, 2 H); 7.81 ± 7.86
(m, 2 H). 13C-NMR: 26.71 (t); 28.06 (t); 28.53 (t); 28.58 (t); 28.95 (t); 32.74 (t); 33.93 (t); 37.99 (t); 123.17 (d);
132.19 (s); 133.85 (d); 168.47 (s). MS (calc. for C16H20BrNO2, 338.25): 339 (48), 337 (50), 258 (20), 174 (15), 161
(72), 160 (100), 148 (19), 133 (15), 130 (23).
N-(9-Bromononyl)phthalimide (3c): Yield 6.65 g (75.5%). Colorless, lancet-like crystals. Rf (hexane/Et2O
1
3 :1) 0.26. M.p. 318. IR (KBr): 1772s, 1714vs, 1466s, 1438s, 1398s, 1370s, 1050s, 880s, 720s. H-NMR: 1.25 ± 1.45
(m, 10 H); 1.62 ± 1.74 (m, 2 H); 1.71 ± 1.89 (m, 2 H); 3.40 (t, J ˆ 7.00, 2 H); 3.69 (t, J ˆ 7.35, 2 H); 7.65 ± 7.74
(m, 2 H); 7.86 ± 7.90 (m, 2 H). 13C-NMR: 26.77 (t); 28.11 (t); 28.55 (t); 28.64 (t); 29.03 (t); 29.24 (t); 32.79 (t);
33.94 (t); 38.01 (t); 123.14 (d); 132.19 (s); 133.83 (d); 168.42 (s). MS: 354 (33), 353 (99), 352 (35), 351 (100), 272
(29), 175 (19), 161 (66), 160 (72), 148 (41), 130 (37), 104 (24). Anal. calc. for C17H22BrNO2 (352.27): C 57.96,
H 6.29, N 3.98; found: C 58.28, H 6.35, N 3.92.
N-(10-Bromodecyl)phthalimide (3d): Yield 5.68 g (63%). Colorless, lancet-like crystals. Rf (hexane/Et2O
3 :1) 0.29. M.p. 578 ([11]: 568). IR (KBr): 1780s, 1730vs, 1475s, 1440s, 1400vs, 1375s, 1065s, 540s. 1H-NMR: 1.21 ±
1.45 (m, 12 H); 1.60 ± 1.74 (m, 2 H); 1.76 ± 1.91 (m, 2 H); 3.40 (t, J ˆ 7.0, 2 H); 3.68 (t, J ˆ 7.35, 2 H); 7.68 ± 7.73
(m, 2 H); 7.82 ± 7.90 (m, 2 H). 13C-NMR: 26.63 (t); 28.15 (t); 28.58 (t); 28.71 (t); 29.11 (t); 29.34 (t); 32.84 (t);
34.00 (t); 38.01 (t); 123.16 (d); 132.21 (s); 133.84 (d); 168.47 (s). MS (calc. for C18H24BrNO2, 366.30): 367 (38,
‡
‡
[M ‡ 2] ), 366 (7), 365 (39, M (79Br)), 286 (10), 174 (14), 161 (70), 160 (100), 148 (20), 130 (22).
N-(11-Bromoundecyl)phthalimide (3e): Yield 16.08 g (96%). Colorless, lancet-like crystals. Rf (hexane/
Et2O 1 :1) 0.41. M.p. 488. IR (KBr): 1770s, 1720vs, 1435s, 1395vs, 1370s, 720s. H-NMR (200 MHz): 1.14 ± 1.45
1
(m, 14 H); 1.60 ± 1.74 (m, 2 H); 1.76 ± 1.90 (m, 2 H); 3.37 (t, J ˆ 6.85, 2 H); 3.64 (t, J ˆ 7.3, 2 H); 7.64 ± 7.72
(m, 2 H); 7.77 ± 7.84 (m, 2 H). 13C-NMR (50 MHz): 27.02 (t); 28.34 (t); 28.77 (t); 28.92 (t); 29.33 (t); 29.58 (t);
33.02 (t); 34.24 (t); 38.25 (t); 123.34 (d); 132.38 (s); 134.02 (d); 168.66 (s). MS: 381 (78), 379 (75), 300 (20), 175
(20), 174 (40), 161 (80), 160 (100), 148 (60), 130 (45), 105 (38), 104 (42). Anal. calc. for C19H26BrNO2 (380.32):
C 60.00, H 6.89, N 3.68; found: C 59.98, H 6.87, N 3.55.
N-(12-Bromododecyl)phthalimide (3f): Yield 5.4 g (68%). Colorless crystals. Rf (hexane/Et2O 1 :1) 0.55.
M.p. 62 ± 638. IR: 1710s, 1400s.1H-NMR: 1.21 ± 1.50 (m, overlap with 1.27 (s), 16 H); 1.68 (m, 2 H); 1.86
(m, 2 H); 3.42 (t, 2 H); 3.69 (t, 2 H); 7.68 ± 7.76 (m, 2 H). 13C-NMR: 26.85 (t); 28.18 (t); 28.50 (t); 28.76 (t); 29.17
(t); 29.40 (t); 29.44 (t); 29.48 (t); 32.85 (t); 34.03 (t); 38.08 (t); 123.14 (d); 132.21 (s); 133.82 (d); 168.46 (s). MS:
‡
395 (100), 393 (100, M (79Br), 314 (16), 202, 174 (28), 161 (70), 160 (82), 148 (37), 133 (25), 130 (27). Anal.
calc. for C20H28BrNO2 (394.35): C 60.91, H 7.16, N 3.55; found: C 61.09, H 7.09, N 3.37.
N,N'-(Dithiodialkane-w,1-diyl)bis[phthalimide] 4a ± f [9]: General Procedures. A soln. of the N-(w-
bromoalkyl)phthalimide 3a ± f (31.2 mmol) and Na2S2O3 (7.53 g, 30.3 mmol) was refluxed in MeOH/H2O 1:1
(120 ml) for 4 h. The hot soln. was treated with solid I2 (ca. 4 g) in portions until the brown color remained. After
reduction of the excess I2 with Na2S2O5, the yellow soln. was allowed to cool down and left overnight in the
refrigerator (48). The solid product was separated by decanting, purified by FC (hexane/Et2O 1:1), and
precipitated from a conc. soln. in Et2O by addition of MeOH: 4a ± f as a colorless powder.
N,N'-(Dithiodihexane-6,1-diyl)bis[phthalimide] (4a): Yield 1.98 g (55.2%). Rf (hexane/Et2O 3 :1) 0.21.
M.p. 598 ([9]: 588). IR (KBr): 1780vs, 1720vs, 1440vs, 1400vs, 1370vs, 1060s. 1H-NMR: 1.25 ± 1.40 (m, 8 H);
1.68 ± 1.73 (m, 8 H); 2.69 (t, J ˆ 7.35, 4 H); 3.69 (t, 4 H); 7.67 ± 7.75 (m, 4 H); 7.76 ± 7.84 (m, 4 H). 13C-NMR:
26.31 (t); 26.36 (t); 28.36 (t); 28.91 (t); 37.74 (t); 38.74 (t); 122.98 (d); 132.01 (s); 133.73 (d); 168.12 (s). MS (calc.
‡
for C28H32N2O4S2, 524.59): 524 (12, M ), 377 (45), 377 (45), 376 (100), 216 (60), 202, 188 (39), 175 (41), 174
(44), 161 (72), 160 (100), 149 (53), 148 (51), 133 (41), 130 (45), 105 (40), 104 (40).
N,N'-(Dithiodioctane-8,1-diyl)bis[phthalimide] (4b): Similarly, 3b (3.28 g, 5.64 mmol) gave 1.98 g (55%) of
4b. Rf (hexane/Et2O 2 :1) 0.45. M.p. 488 ([9]: 478). IR (KBr): 1775s, 1465s, 1435s, 1400s, 1360s, 1050s. 1H-NMR:
1.25 ± 1.40 (m, 16 H); 1.60 ± 1.80 (m, 8 H); 2.66 (t, J ˆ 7.35, 4 H); 3.67 (t, J ˆ 7.20, 4 H); 7.65 ± 7.75 (m, 4 H); 7.81 ±
7.88 (m, 4 H). 13C-NMR: 26.74 (t); 28.38 (t); 28.52 (t); 28.99 (t); 29.03 (t); 29.12 (t); 37.94 (t); 39.03 (t); 123.07
‡
(d); 132.14 (s); 133.79 (d); 168.29 (s). MS (calc. for C32H40N2O4S2, 580.69): 580 (4, M ), 291 (14), 258 (12), 189
(14), 160 (100), 148 (28), 133 (22), 105 (20).

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N,N'-(Dithiodinonane-9,1-diyl)bis[phthalimide] (4c): Yield 7.63 g (79%). Rf (hexane/Et2O 1:1) 0.34. M.p.
538. IR (KBr): 1775m, 1710vs, 1400s, 1360s, 790s, 720s. 1H-NMR: 1.25 ± 1.40 (m, 20 H); 1.60 ± 1.80 (m, 8 H); 2.66
(t, J ˆ 7.35, 4 H); 3.67 (t, J ˆ 7.20, 4 H); 7.65 ± 7.75 (m, 4 H); 7.81 ± 7.88 (m, 4 H). 13C-NMR: 26.87 (t); 28.55 (t);
28.61 (t); 29.19 (t); 29.50 (t); 29.24 (t); 29.53 (t); 38.08 (t); 39.19 (t); 123.15 (d); 132.19 (s); 133.62 (d); 168.47 (s).
‡
MS: 608 (94, M ), 337 (26), 305 (34), 272 (32), 160 (100), 148 (26), 130 (22). Anal. calc. for C34H44N2O4S2:
C 67.07, H 7.28, N 4.60; found: C 66.90, H 7.37, N 4.46.
N,N'-(Dithiodidecane-10,1-diyl)bis[phthalimide] (4d): Similarly, 3d (15.6 g, 42.6 mmol) gave 9.61 g
(70.9%) of 4d. Rf (hexane/Et2O 1:1) 0.19. M.p. 498. IR (KBr): 1775s, 1720vs, 1465s, 1435s, 1400vs, 1365s,
1
720vs. H-NMR: 1.20 ± 1.42 (m, 24 H); 1.60 ± 1.78 (m, 8 H); 2.69 (t, J ˆ 7.35, 4 H); 3.69 (t, J ˆ 7.35, 4 H); 7.68 ±
7.79 (m, 4 H); 7.82 ± 7.91 (m, 4 H). 13C-NMR: 26.85 (t); 28.52 (t); 28.59 (t); 29.15 (t); 29.19 (t); 29.23 (t); 29.41 (t);
38.07 (t); 39.19 (t); 123.15 (d); 132.21 (s); 133.82 (d); 168.46 (s). MS (calc. for C36H48N2O4S2, 636.80): 636 (6,
‡
M ), 319 (20), 202 (22), 174 (24), 160 (100), 148 (46), 130 (38).
N,N'-(Dithiodiundecane-11,1-diyl)bis[phthalimide] (4e): Similarly, 3e (10.94 g, 28.3 mmol) gave 14.85 g
(77.6%) of 4e. Rf (hexane/Et2O 2 :1) 0.44. M.p. 458. IR (KBr): 1770m, 1715vs, 1395s, 790vs, 720s. 1H-NMR
(200 MHz): 1.11 ± 1.45 (m, 28 H); 1.58 ± 1.72 (m, 8 H); 2.62 (t, J ˆ 7.35, 4 H); 3.69 (t, 4 H); 7.64 ± 7.72 (m, 4 H);
7.75 ± 7.82 (m, 4 H). 13C-NMR (50 MHz): 26.88 (t); 28.56 (t); 28.62 (t); 28.85 (t); 29.24 (t); 29.48 (t); 38.10 (t);
‡
39.21 (t); 123.16 (d); 132.22 (s); 133.86 (d); 168.48 (s). MS: 664 (5, M ), 626 (18), 409 (35), 333 (86), 203 (22),
‡
160 (100), 148 (66), 130 (60), 104 (50). HR-MS: 664.336670 (C38H52N2O4S2 ; calc. 664.336852).
N,N'-(Dithiodidodecane-12,1-diyl)bis[phthalimide] (4f): Yield 7.1 g (77%). Wax. Rf (hexane/Et2O 1:1). IR
(KBr): 1789m, 1722s, 1401m. 1H-NMR: 120 ± 1.42 (m, overlap with 1.20 (s), 32 H); 1.60 ± 1.80 (m, 8 H); 2.69
(t, J ˆ 7.35, 4 H); 3.69 (t, J ˆ 7.35, 4 H); 7.60 ± 7.80 (m, 4 H); 7.81 ± 7.90 (m, 4 H). 13C-NMR: 26.85 (t); 28.53 (t);
28.59 (t); 29.16 (t); 29.22 (t); 29.45 (t); 29.47 (t); 29.52 (t); 38.07 (t); 39.19 (t); 123.12 (d); 132.20 (s); 133.80 (d);
‡
168.44 (s). MS: 692 (92, [M H] ), 379 (46), 347 (100), 330 (80), 315 (98), 160 (84), 148 (55). HR-MS:
‡
692.36377 (C40H56N2O4S2 ; calc. 692.368152).
w,w'-Dithiobis[alkan-1-amine] Dihydrochlorides: General Procedure. 5a ± f [9]. The N,N'-(dithioalkane-
w,1-diyl)bis[phthalimide] (4a ± f, 9.86 mmol) was refluxed with hydrazine hydrate (30.6 mmol) in EtOH (90 ml)
for 1 h under N2. A colorless solid precipitated after complete dissolution of the starting material. The solvent
was evaporated and the residue refluxed in 1m HCl (88 ml) for 1 h. After careful removal of the solvent under
reduced pressure, the residue was dissolved in EtOH, the hydrazide filtered off, and the product precipitated
with Et2O/AcOEt 1 :1. The dithiobis[alkanamine] dihydrochloride was recrystallized from EtOH/Et2O/AcOEt
1:2 :2 (200 ml).
6,6'-Dithiobis[hexan-1-amine] Dihydrochloride (5a): M.p. 224 ± 2308 ([9]: 2358). IR (KBr): 1480s, 1440s,
1400vs, 1380s. 1H-NMR (300 MHz, CD3OD): 1.44 (m, 8 H); 1.60 ± 1.80 (m, 8 H); 2.69 (t, 4 H); 2.91 (t, 4 H). MS
(calc. for C12H30Cl2N2S2, 337.30): 298 (2), 180 (8), 165 (60), 148 (16), 133 (70), 132 (100), 116 (50), 115 (51), 100 (68).
8,8'-Dithiobis[octan-1-amine] Dihydrochloride (5b): Similarly, 4b (0.31 g, 0.53 mmol) gave, after recrystal-
lization from EtOH, 0.150 g (72%) of 5b. Colorless crystals. M.p. 2138 ([9]: 2158). IR (KBr). 1496s, 1082m.
1H-NMR (300 MHz, CD3OD): 1.27 ± 1.40 (m, 16 H); 1.55 ± 1.75 (m, 8 H); 2.67 (t, J ˆ 7.20, 4 H); 2.89 (t, J ˆ 7.60,
4 H). 13C-NMR (75 MHz, CD3OD): 27.31 (t); 28.41 (t); 29.22 (t); 29.95 (t); 29.96 (t); 30.03 (t); 39.03 (t); 40.70
‡
(t). MS (calc. for C16H38Cl2N2S2, 393.41): 393 (2, M ), 160 (78), 143 (65), 128 (100), 87 (48), 69 (48).
9,9'-Dithiobis[nonan-1-amine] Dihydrochloride (5c): Yield 3.69 g (89%). Colorless powder. M.p. 1648
1
(dec.). IR (KBr): 1500s. H-NMR (300 MHz, CD3OD): 1.30 ± 1.48 (m, 20 H); 1.60 ± 1.75 (m, 8 H); 2.67 (t, J ˆ
7.25, 4 H); 2.91 (t, J ˆ 7.60, 4 H). 13C-NMR (75 MHz, CD3OD): 27.07 (t); 28.18 (t); 29.03 (t); 29.77 (t); 29.78 (t);
29.83 (t); 29.99 (t); 39.28 (t); 40.39 (t). MS (calc. for C18H42Cl2N2S2, 421.46): 380 (20), 198 (60), 190 (26), 174
(52), 157 (64), 142 (100), 129 (16), 109 (94).
10',10'-Dithiobis[decan-1-amine] Dihydrochloride (5d): Yield 4.14 g (93%), from 4d (6.3 g, 9.89 mmol).
1
M.p. 1788 ([9]: 1808). IR (KBr): 1780, 1730, 1480, 1400, 1380, 730. H-NMR (300 MHz, CD3OD): 1.24 ± 1.40
(m, 24 H); 1.61 ± 1.75 (m, 8 H); 2.66 (t, J ˆ 7.17, 4 H); 2.90 (t, 4 H). 13C-NMR (75 MHz, CD3OD): 26.28 (t); 27.36
(t); 28.24 (t); 28.99 (t, 2 Â int.); 29.08 (t); 29.21 (t); 29.31 (t); 38.59 (t); 39.62 (t).
11,11'-Dithiobis[undecan-1-amine] Dihydrochloride (5e): Similarly, 4e (14.0 g, 22.3 mmol) gave 9.44 g
(88%) of 5e. M.p. 1748. IR (KBr): 1535m, 1434m, 1094m, 931m. 1H-NMR (200 MHz, CD3OD): 1.53 (s, 28 H);
1.61 ± 1.99 (m, 8 H); 2.86 (t, J ˆ 7.17, 4 H); 3.10 (t, 4 H). 13C-NMR (50 MHz, CD3OD): 28.48 (t); 29.59 (t); 30.43
(t); 31.24 (t); 31.51 (t); 31.58 (t); 40.72 (t); 41.80 (t). MS (calc. for C22H50Cl2N2S2, 477.57): 436 (1), 385 (2), 352
(14), 235 (62), 203 (80), 202 (100), 185 (22), 171 (24), 170 (76), 162 (44), 104 (32).
12,12'-Dithiobis[dodecan-1-amine] Dihydrochloride (5f): Similarly, 4f (6 mmol) gave 1.6 g (55%) of 5f.
M.p. >1958 (dec.). 1H-NMR (300 MHz, CD3OD): 1.20 ± 1.40 (m, overlap with 1.32 (s), 32 H); 1.55 ± 1.80
(m, 8 H); 2.67 (t, J ˆ 7.35, 4 H); 2.82 ± 2.98 (m, 4 H).

Helvetica Chimica Acta ± Vol. 84 (2001)
685
For further characterization, 5f was acetylated by treatment with Ac2O and Et3N to give N,N'-
(dithiodidodecane-12,1-diyl)bis[acetamide] (6). M.p. 103 ± 1058. IR (KBr): 1679s, 1530m, 1108m. 1H-NMR:
‡
1.2 ± 1.7 (m, 20 H); 2.0 (s, 3 H); 2.7 (t, 2 H); 3.25 (q, 2 H); 5.5 (br. s, 1 H). MS: 516 (4, M ), 258 (100), 226 (98),
‡
216 (24), 184 (28), 72 (37). HR-MS: 516.375920 (C28H56N2O2S2 ; calc. 516.378323).
N,N'-(Dithiodihexane-6,1-diyl)bis[2-[2-(2-methoxyethoxy)ethoxy]acetamide] (8a). A suspension of 5a
(900 mg, 2.67 mmol), 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (7; 1.24 g, 6.96 mmol), and dichloro(methoxy)-
methane (CHCl2OMe) [24] (2.454 g, 21.35 mmol) in CH2Cl2 (50 ml) was stirred for 3 h at r.t. under Ar. After
dropwise addition of Et3N (2 ml) and stirring overnight at r.t. under Ar, the mixture was poured on water-ice
(50 ml). The aq. layer was extracted with CH2Cl2 (3 Â 30 ml) and the combined org. phase washed with sat.
NaHCO3 soln. (3 Â 30 ml) and brine (total 90 ml); dried (Na2SO4), and evaporated. FC (CH2Cl2/MeOH 10 :1)
gave 0.76 g (48%) of 8a. Oil. Rf (CH2Cl2/MeOH 10.1) 0.48. IR (CHCl3): 1750m, 1680vs, 1550s, 1340s. 1H-NMR:
1.39 (br. s, 8 H); 1.50 ± 1.59 (m, 4 H); 1.63 ± 1.72 (m, 4 H); 2.63 (t, J ˆ 7.26, 4 H); 3.24 ± 3.31 (m, 4 H); 3.38
(s, 6 H); 3.52 ± 3.58 (m, 4 H); 3.59 ± 3.69 (m, 12 H); 3.15 (s, 4 H); 7.00 (t, 2 H). 13C-NMR: 26.46 (t); 28.06 (t);
28.96 (t); 29.39 (t); 38.76 (t); 38.72 (t); 58.88 (q); 70.06 (t); 70.19 (t); 70.37 (t); 70.90 (t); 71.76 (t); 169.74 (s). MS:
‡
584 (2, M ), 325 (8), 292 (100), 260 (28), 235 (38), 216 (46), 184 (32), 172 (24), 160 (14), 133 (12), 115 (24), 103
‡
(20). HR-MS: 584.316530 (C26H52O8N2S2 ; calc. 584.316511).
N,N'-(Dithiodioctane-8,1-diyl)bis[2-[2-(2-methoxyethoxy)ethoxy]acetamide] (8b). From 5b (4.0 g,
12.5 mmol), as described for 5a. FC (CH2Cl2/MeOH 20 :1) gave 3.68 mg (46%) of 8b. Clear oil. Rf (CH2Cl2/
MeOH 20 :1) 0.26. IR (CHCl3): 1670vs, 1540vs, 1460s, 1340s. 1H-NMR: 1.25 ± 1.45 (m, 16 H); 1.48 ± 1.58
(m, 4 H); 1.58 ± 1.66 (m, 4 H); 2.63 (t, J ˆ 7.35, 4 H); 3.18 ± 3.28 (m, 4 H); 3.38 (s, 6 H); 3.51 ± 3.53 (m, 4 H);
3.54 ± 3.64 (m, 12 H); 3.95 (s, 4 H); 7.00 (t, 2 H). 13C-NMR: 26.84 (t); 28.39 (t); 29.10 (t); 29.11 (t); 29.13 (t);
29.58 (t); 38.84 (t); 39.02 (t); 58.96 (q); 70.16 (t); 70.37 (t); 70.50 (t); 70.93 (t); 71.84 (t); 169.74 (s). MS (calc. for
‡
‡
C30H60O8N2S2, 640.83): 640 (1, M ), 353 (19), 322 (23), 321 (56), 320 (100, [M/2] ), 288 (29), 263 (37), 244 (34),
212 (28), 200 (23), 188 (27).
N,N'-(Dithiodinonane-9,1-diyl)bis[2-[2-(methoxyethoxy)ethoxy]acetamide] (8c). From 5c (0.20 g,
0.475 mmol), as described for 8a. FC (CH2Cl2/MeOH 20 :1) gave 175 mg (53%) of 8c. Colorless grease. Rf
(CH2Cl2/AcOEt 6 :5) 0.11. IR (CHCl3): 1670vs, 1540s, 1340s, 1110vs. 1H-NMR (500 MHz, CD3OD): 1.33 (br. s,
16 H); 1.38 ± 1.41 (m, 4 H); 1.51 ± 1.54 (m, 4 H); 1.67 ± 1.72 (m, 4 H); 2.67 (t, J ˆ 7.25, 4 H); 3.23 (t, J ˆ 7.20, 4 H);
3.36 (s, 6 H); 3.54 ± 3.56 (m, 4 H); 3.64 ± 3.67 (m, 12 H); 4.03 (s, 4 H). 13C-NMR (125 MHz, CD3OD): 28.24 (t);
29.71 (t); 30.49 (t); 30.52 (t); 30.62 (t); 30.81 (2t); 40.05 (t); 40.24 (t); 59.43 (q); 71.46 (t); 71.61 (t); 71.64 (t); 72.24
‡
(t); 73.19 (t); 172.84 (s). MS: 668 (18, M ), 565 (24), 535 (58), 334 (62), 277 (29), 202 (40), 133 (30), 103 (38), 89
(56), 69 (38), 59 (100). Anal. calc. for C32H64O8N2S2 (668.88): C 56.49, H 9.58, N 4.19; found: C 56.26, H 9.70,
N 4.10.
2-[2-(Methoxyethoxy)ethoxy]acetic Acid (Dithiodipropane-3,1-diyl) Ester (11). According to [25], a
mixture of 7 (4.58 g, 25.7 mmol), CHCl2OMe (3.7 g, 32.1 mmol) and ZnCl2 (0.18 g, 1.2 mmol) was stirred at r.t.
for 1 h and refluxed 1 h under N2. The excess of CHCl2OMe was evaporated, the residual acid chloride dissolved
in CH2Cl2 (10 ml) and added dropwise within 30 min to a soln. of 3,3'-dithiobis[propan-1-ol] (10; 1.8 g,
9.89 mmol) [12] and Et3N (2.5 ml) in CH2Cl2 (50 ml) at r.t. The mixture was refluxed overnight under Ar and
worked up by addition of H2O (70 ml) and extraction of the aq. phase with CH2Cl2 (3 Â 20 ml). The combined
org. phase was washed with sat. Na2CO3 soln. (3Â), 2m HCl, and brine, dried (MgSO4), and evaporated. FC
(hexane/AcOEt/MeOH 10 :10 :1) gave 2.775 g (56%) of 11. Colorless oil. Rf (CH2Cl2/AcOEt/MeOH 10 :10 :1)
0.47. IR (CHCl3): 1760vs, 1480s, 1260 ± 1200s, 1180 ± 1080vs. 1H-NMR: 1.99 ± 2.08 (m, 4 H); 2.70 (t, J ˆ 7.08, 4 H);
3.35 (s, 6 H); 3.51 ± 3.54 (m, 4 H); 3.54 ± 3.64 (3 superimposed m, 12 H); 4.14 (s, 4 H); 4.23 (t, J ˆ 6.2, 4 H).
13C-NMR: 28.11 (t); 34.81 (t); 58.99 (q); 62.93 (t); 68.58 (t); 70.51 (t); 70.62 (t); 70.91 (t); 71.87 (t); 170.36 (s).
‡
‡
MS: 502 (1, M ), 161 (22), 133 (36), 117 (43), 103 (78), 89 (58), 59 (100). HR-MS: 502.190642 (C20H38O10S2
;
calc. 502.190580).
N,N'-(Dithiodioctane-8,1-diyl)bis[d-gluconamide] (14b). The known procedure [26] was adapted: to a soln.
of 5b (1 g, 2.54 mmol) in MeOH (30 ml) d-glucono-1,5-lactone (13; 0.90 g, 5.08 mmol) was added. After
dropwise addition of Et3N (2.8 ml), a colorless precipitate appeared. The mixture was refluxed for 1 h and
filtered after cooling. The precipitate was washed with MeOH and dried for 2 h under vacuum: 0.79 g (46.2%) of
14b. M.p. 166 ± 1688. IR (KBr): 1650m, 1630s, 1550s, 1090s, 1040m. 1H-NMR (300 MHz, (D6)DMSO): 1.19 ± 1.43
(m, overlap with 1.27 (s); total 20 H); 1.57 ± 1.64 (m, 4 H); 2.65 (t, J ˆ 6.99, 4 H); 2.97 ± 3.06 (m, 4 H); 3.42, 3.52
(2m); 3.80 ± 4.00 (2m, 4 H); 4.25 ± 4.56 (4m, 8 H); 3.04 ± 3.13 (m, 2 H); 5.24 ± 5.35 (m, 2 H); 7.56 (m, 2 H).
13C-NMR: (75 MHz, (D6)DMSO): 26.28 (t); 27.74 (t); 28.52 (t); 28.56 (t); 28.65 (t); 29.10 (t); 37.03 (t); 39.93 (t);
38.21 (t); 63.30 (t); 69.79 (d); 71.73 (d); 72.45 (d); 73.63 (d); 172.3 (s). LSI-MS (matrix glycerol; calc. for

686
Helvetica Chimica Acta ± Vol. 84 (2001)
‡
C28H56N2O12S2, 676.77): 677 (9, M ), 661 (2), 553 (2), 525 (2), 499 (13), 467 (2), 369 (4), 340 (10), 321 (4), 306
(5), 277 (13), 185 (100), 162 (18), 133 (55).
N,N'-(Dithiodidodecane-12,1-diyl)bis[d-gluconamide] (14f). As described for 14b, Et3N (3 ml) was added
dropwise to a soln. of 5f (2.1 g, 4.2 mmol) and 13 (1.42 g, 8 mmol) in MeOH (80 ml). The mixture was stirred at
r.t. for 4 h under N2. The colorless precipitate was filtered off and the MeOH soln. cooled and filtered again:
1
2.0 g (61%) of 14f. White solid. M.p. 152 ± 1548 (dec.). IR (KBr): 1650s, 1650s, 1636s, 1554s, 1100s. H-NMR
(300 MHz, (D6)DMSO): 1.15 ± 1.61 (m, overlap with 1.13 (s)); 1.62 ± 1.90 (m); 2.78 (m); 2.90 ± 3.20 (m, overlap
with DMSO peak); 3.30 ± 3.80 (m, overlap with H2O peak); 3.90 ± 4.10 (m); 4.35 ± 4.75 (m); 5.35 ± 5.50 (m); 7.70
‡
(m). LSI-MS (matrix glycerol): 789.6 (21, M ), 611.5 (100), 433 (54).
N,N'-(Dithiodidecane-10,1-diyl)bis[2,3,4,5,6-penta-O-acetyl-d-gluconamide] (15d). As described for 14b
Et3N (10 ml) was added dropwise to a soln. of 5d (4 g, 8.9 mmol) and 13 (3.17 g, 17.8 mmol) in MeOH (100 ml).
After reflux for 45 min and cooling in the refrigerator overnight, the precipitate was filtered off and dried in
vacuo for 3 h. The brownish bis[gluconamide] 14d (ca. 4.6 g) was treated with pyridine (35 ml) and Ac2O
(50 ml) and stirred for 4 h at 608 under N2. The reaction was quenched by addition of ice-water (50 ml) and the
aq. phase extracted with CH2Cl2 (3 Â 30 ml). The org. phases were washed with 1m HCl, sat. brine, dried
(Na2SO4), and evaporated. FC of the residue (hexane/AcOEt 1:3) gave 6.89 g (67%) of 15d. Viscous, yellowish
oil. Rf (hexane/AcOEt 1:3) 0.33. IR (CHCl3): 1750vs, 1690m, 1530s, 1375vs, 1220vs, 1050s. 1H-NMR: 1.20 ± 1.40
(m, 24 H); 1.40 ± 1.53 (2m, 4 H); 1.54 ± 1.60 (m, 4 H); 2.04, 2.05, 2.11, 2.21 (4s, total 30 H); 2.67 (t, J ˆ 7.35, 4 H);
3.20 ± 3.28 (m, 4 H); 4.13 (dd, J ˆ 12.2, 5.5, 2 H); 4.31 (dd, J ˆ 12.2, 4.1, 2 H); 5.00 ± 5.10 (m, 2 H); 5.30 (d, J ˆ
5.33, 2 H); 5.45 (q, 2 H); 5.69 (t, J ˆ 5.15, 2 H); 6.34 (t, 1 H). 13C-NMR: 20.44 (q); 20.72 (q); 20.73 (q); 26.80 (t);
28.50 (t); 29.20 (t); 29.42 (t); 39.12 (t); 39.54 (t); 61.56 (t); 68.76 (d); 69.10 (d); 69.42 (d); 71.70 (d); 165.91 (s);
169.22 (s); 169.67 (s); 169.81 (s); 169.89 (s); 170.63 (s).
N,N'-(Dithiodidodecane-12,1-diyl)bis[2,3,4,5,6-penta-O-acetyl-d-gluconamide] (15f). A soln. of 14f (2.0 g,
2.5 mmol), pyridine (15 ml), and Ac2O (40 ml) was stirred at 608 for 2 h under N2. The mixture was poured onto
ice-water and extracted with CH2Cl2 (3Â). The org. phase was washed with 1m HCl, sat. NaCl soln., dried
(MgSO4), and evaporated: 2.87 g (94%) of 15f. Oil. Rf (AcOEt/hexane 3 :1) 0.46. 1H-NMR 1.20 ± 1.80
(m, overlap with 1.26 (s), 40 H); 2.00 ± 2.30 (m, overlap with 2.05 (s), 2.09 (s), 2.11 (s), 2.20 (s), 30 H); 2.91
(t, J ˆ 7.35, 4 H); 3.23 (m, 4 H); 4.13 (dd, J ˆ 12, 5.5, 2 H); 4.31 (dd, J ˆ 12.5, 4.0, 2 H); 4.95 ± 5.10 (m, 2 H); 5.30
(d, J ˆ 5.5, 2 H); 5.45 (m, 2 H); 5.68 (t, J ˆ 5.3, 2 H); 6.09 (m, 2 H). 13C-NMR: 20.42 (q); 20.68 (q); 20.74 (t);
26.82 (t); 28.51 (t); 29.23 (t); 29.37 (t); 29.54 (t); 39.16 (t); 39.58 (t); 61.56 (t); 68.78 (t); 69.11 (d); 69.39 (d); 71.74
(d); 166.02 (s); 169.27 (s); 169.92 (s); 170.68 (s). LSI-MS (calc. for C56H92N2O22S2, 1209.46; matrix glycerol):
‡
1209.6 (86, M ), 1149.5 (38), 863.5 (100), 636.3 (70).
Reduction of the N,N'-(Dithiodialkanediyl)bis[amides]: General Procedure. The mixture of the N,N'-
(dithiodialkanediyl)bis[amide] (1.2 mmol) and activated Zn [27] (4.3 mmol) was refluxed in AcOH (50 ml) for
18 h under Ar. Residual Zn was filtered off, sat. NaHCO3 soln. (50 ml) added, and the soln. carefully
concentrated to 40 ml. After extraction with AcOEt (3 Â , total 240 ml), the org. layer was washed with sat.
NaHCO3 soln. (3 Â , total 210 ml) and brine (total 210 ml), dried (Na2SO4) and evaporated: N-(w-
mercaptoalkyl)amide.
N-(6-Mercaptohexyl)-2-[2-(2-methoxyethoxy)ethoxy]acetamide (9a): Yield 0.401 g (57%). Rf (AcOEt/
CH2Cl2/MeOH 7:5 :1) 0.60. IR (CHCl3): 1760m, 1740s, 1670vs, 1545s, 1240s, 1100vs, 1040s. 1H-NMR: 1.24 ± 1.41
(m, 5 H); 1.42 ± 1.63 (m, 4 H); 2.46 ± 2.55 (q, 2 H); 3.2 ± 3.30 (m, 2 H); 3.37 (s, 3 H); 3.52 ± 3.59 (m, 2 H); 3.61 ±
3.71 (m, 6 H); 3.95 (s, 2 H); 7.00 (s, 1 H). 13C-NMR: 24.46 (t); 26.34 (t); 27.96 (t); 29.49 (t); 33.82 (t); 38.74 (t);
58.97 (q); 70.16 (t); 70.37 (t); 70.50 (t); 70.94 (t); 71.85 (t); 169.80 (s). MS (calc. for C13H27O4NS, 293.37): 293 (17,
‡
M ), 260 (10), 235 (20), 218 (19), 172 (20), 142 (20), 117, 115 (20), 103 (20), 89 (24). HR-MS: 293.165310
‡
(C13H27O4NS ; calc. 293.166080).
N-(8-Mercaptooctyl)-2-[2-(2-methoxyethoxy)ethoxy]acetamide (9b): From 8b (1.6 g, 2.5 mmol), 9b (1.5 g,
95%) was obtained. Rf (AcOEt/CH2Cl2/MeOH 5 :5 :1) 0.55. IR (CHCl3): 1760m, 1740s, 1670vs, 1545s, 1240s,
1250m, 1100vs, 1040s. 1H-NMR: 1.25 (br. s, 9 H); 1.43 ± 1.61 (2m, 4 H); 2.49 (q, 2 H); 3.21 ± 3.28 (m, 2 H); 3.36
(s, 3 H); 3.51 ± 3.56 (m, 2 H); 3.61 ± 3.66 (m, 6 H); 3.97 (s, 2 H); 7.07 (t, 1 H). 13C-NMR: 24.60 (t); 26.86 (t);
28.28 (t); 28.97 (t); 29.17 (t); 29.56 (t); 33.99 (t); 38.99 (t); 58.99 (q); 70.17 (t); 70.28 (t); 70.50 (t); 70.98 (t); 71.87
‡
(t); 170.24 (s). MS (calc. for C15H31O4NS, 321.42): 321 (16, M ), 288 (11), 263 (21), 212 (20), 200 (26), 188 (33),
170 (13), 103 (13), 89 (19), 87 (24), 59 (100).
3-Mercaptopropyl 2-[2-(2-Methoxyethoxy)ethoxy]acetate (12): From 11 (2.0 g, 398 mmol) 12 (1.8 g, 89%)
was obtained. 12 Colorless oil. Rf (AcOEt/CH2Cl2/MeOH 10 :10 :1) 0.51. IR (CHCl3): 1760vs, 1700m, 1460s,
1435s, 1400s, 1380s, 1360s, 1260 ± 1200s, 1180 ± 1080vs, 860s. 1H-NMR: 1.40 (t, J ˆ 8.0, 1 H); 1.90 ± 1.97 (m, 2 H);
2.58 (q, 2 H); 3.37 (s, 3 H); 3.53 ± 3.55 (m, 2 H); 3.60 ± 3.72 (3 superimposed m, 6 H); 4.15 (s, 2 H); 4.26 (t, J ˆ

Helvetica Chimica Acta ± Vol. 84 (2001)
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6.2, 2 H). 13C-NMR: 20.99 (t); 32.68 (t); 59.00 (q); 62.75 (t); 68.59 (t); 70.53 (t); 70.64 (t); 70.92 (t); 71.88 (t);
‡
‡
170.42 (s). MS: 252 (7, M ), 194 (11), 179 (21), 105 (33), 103 (60), 89 (40). HR-MS: 252.103100 (C10H20O5S ;
calc. 252.103146).
N-(10-Mercaptodecyl)-2,3,4,5,6-penta-O-acetyl-d-gluconamide (16d): From 15d (1.5 g, 1.3 mmol), 16d
(0.79 g, 53%) was obtained. Oil. Rf (hexane/AcOEt 1:1) 0.44. IR (CHCl3): 1740vs, 1370s, 1240s, 1220s, 1190s,
1040s, 1030s. 1H-NMR: 1.21 ± 1.40 (br. s, overlap with 1.34 (t); 13 H); 1.43 ± 1.66 (2m, 4 H); 2.05, 2.05, 2.10, 2.11,
2.21 (5s, 15 H); 2.48 ± 2.55 (q, 2 H); 3.17 ± 3.28 (m, 2 H); 4.13 (dd, J ˆ 12.2, 5.5, 1 H); 4.31 (dd, J ˆ 12.2, 4.0, 1 H);
5.00 ± 5.10 (m, 1 H); 5.30 (d, J ˆ 5.14, 1 H); 5.44 (q, 1 H); 5.69 (t, J ˆ 5.15, 1 H); 6.34 (t, 1 H). 13C-NMR: 20.33
(q); 20.57 (q); 20.63 (q); 24.49 (t); 26.73 (t); 28.24 (t); 29.00 (t); 29.13 (t); 29.33 (t); 29.36 (t); 33.94 (t); 39.44 (t);
39.54 (t); 61.45 (t); 68.70 (d); 69.08 (d); 69.35 (d); 71.75 (d); 165.95 (s); 169.10 (s); 169.59 (s); 169.68 (s); 169.73
(s); 170.99 (s).
N-(12-Mercaptododecyl)-2,3,4,5,6-penta-O-acetyl-d-gluconamide (16f). Yield 2.45 g (92%). Clear oil. Rf
1
(AcOEt/hexane) 0.57. H-NMR: 1.20 ± 1.70 (m, overlap with 2.06 (s), 2.12 (s), total 12 H); 2.2 (s, 3 H); 2.45 ±
2.60 (m, 2 H); 3.20 ± 3.35 (m, 1 H); 4.14 (dd, J ˆ 12.1, 5.5, 1 H); 4.32 (dd, J ˆ 12.1, 4.0, 1 H); 4.95 ± 5.10 (m, 1 H);
5.30 (d, J ˆ 5.5, 1 H); 5.45 (m, 1 H); 5.69 (m, 1 H); 6.09 (m, 1 H). 13C-NMR: 20.44 (q); 20.71 (q); 24.66 (t); 26.82
(t); 28.37 (t); 29.07 (t); 29.23 (t); 29.42 (t); 29.50 (t); 29.54 (t); 34.05 (t); 39.56 (t); 61.55 (t); 68.75 (d); 69.11 (d);
69.41 (d); 71.70 (d); 165.88 (s); 169.20 (s); 169.65 (s); 169.88 (s); 170.10 (s). LSI-MS (calc. for C28H47NO11S,
‡
‡
605.74, matrix DTT/DTE 5 :1): 647.9 (14, M ‡ H ‡ K] ), 606.9 (12, [M ‡ H] ), 587.9 (12), 546 (17), 260.2 (70),
216.2 (19), 149.1 (25).
tert-Butyl Methyl 2-(Bromomethyl)-2-methylpropanedioate (18). A soln. of 17 (37.5 g, 200 mmol) in
toluene (50 ml) was added within 20 min to a suspension of NaH (55% oil dispersion; 16 g) in toluene (300 ml)
and HMPT (50 ml). The mixture was refluxed for 2 h under N2, cooled, and directly decanted into
dibromomethane (200 g, 1.15 mol) at 808. After 3 h reflux, the mixture was stirred for 18 h at r.t. and worked up.
The aq. phase was extracted with Et2O (3Â) and the combined org. phase washed with NaCl soln., dried
(MgSO4), and evaporated. Fractional destillation yielded 42.3 g (76%) of 18. Colorless liquid. B.p. 758 ± 808/
0.2 Torr. IR (CHCl3): 1751s, 1395m, 1272m, 1166s, 1123m. 1H-NMR: 1.44 ± 1.49 (m, overlap with 1.46 (s), total
9 H); 1.53 (s, 3 H); 3.72 ± 3.77 (m, overlapped with 3.76 (s), total 5 H). 13C-NMR: 19.38 (q); 27.58 (q); 35.84 (t);
52.60 (q); 55.49 (s); 82.52 (s); 168.24 (s); 170.29 (s). MS: 265 (26), 251 (15), 225 (35), 209 (88), 181 (71), 151
(51), 101 (76), 69 (37), 57 (100), 41 (52), 29 (25).
O-Methyl S-(8-Oxo-10,13,16-trioxa-7-azaheptadecyl) 2-(Bromomethyl)-2-methylmonothiomalonate
(ˆ Methyl 2-(Bromomethyl)-2-methyl-3-oxo-3-[(8-oxo-10,13,16-trioxa-7-azaheptadecyl)thio]propanoate; 20a).
The acid chloride of methyl hydrogen 2-(bromomethyl)-2-methylpropanedioate (19) was prepared by stirring a
soln. of 18 (3 g, 10.6 mmol) in CF3COOH (25 ml) at r.t. for 3 h under Ar. The excess of CF3COOH was
evaporated, the resulting monoacid 19 dissolved in CHCl2OMe (1.6 g), and the mixture stirred 4 h at r.t. under
Ar. The excess CHCl2OMe was evaporated to give the acid chloride (2.43 g, 93%) as a colorless liquid. The
freshly prepared acid chloride (330 mg, 1.36 mmol) was dissolved in CH2Cl2 (5 ml), treated with Et3N (2 ml),
and cooled to 08. A soln. of 9a (200 mg, 0.682 mmol) in CH2Cl2 (20 ml) was slowly added during 30 min and the
mixture stirred for 4 h at r.t. After workup and extraction of the aq. layer with CH2Cl2 (3 Â , 30 ml), the
combined org. layers were washed with 2m NaHCO3 (3Â), 2m HCl (3Â), and brine, dried (NaSO4), and
evaporated. The yellow oil (2.1 g) was purified by FC (AcOEt/CH2Cl2/MeOH 5 :5 :1): 0.27 g (80%) of 20a.
Clear oil. Rf (AcOEt/CH2Cl2/MeOH 5 :5 :1) 0.56. IR (CHCl3): 1740s, 1680vs, 1540s, 1460s, 1280s, 1110vs, 970s.
1H-NMR: 1.36 (br. s, 4 H); 1.49 ± 1.56 (m, superimposed at 1.63 (s); total 7 H); 2.91 (t, J ˆ 7.26, 2 H); 3.22 ± 3.29
(q, 2 H); 3.35 (s, 3 H); 3.53 ± 3.58 (m, 2 H); 3.64 ± 3.70 (m, 6 H); 3.755 (d, JAB ˆ 10.30, superimposed at 3.775 (s),
total 4 H); 3.847 (d, JAB ˆ 10.30, 1 H); 3.98 (s, 2 H); 7.05 (t, 1 H). 13C-NMR: 20.07 (q); 26.38 (t); 28.37 (t); 29.01
(t); 29.25 (t); 29.50 (t); 36.03 (t); 38.74 (t); 53.15 (q); 59.00 (q); 61.82 (s); 70.20 (t); 70.42 (t); 70.54 (t); 70.98 (t);
‡
‡
71.89 (t); 169.70 (s); 169.93 (s); 196.72 (s). MS: 501 (2, M ), 499 (2, M ), 292 (100), 260 (20), 216 (46), 184 (21),
133, 101 (18), 100 (25). HR-MS: 499.124050 (C19H34BrO7NS; calc. 499.123936).
O-Methyl S-(10-Oxo-12,15,18-trioxa-9-azanonadecyl) 2-(Bromomethyl)-2-methylmonothiomalonate
(ˆ Methyl 2-(Bromomethyl)-2-methyl-3-oxo-3-[(10-oxo-12,15,18-trioxa-9-azanonadecyl)thio]propanoate;
20b). As described for 20a, from the acid chloride (1.5 g, 6.1 mmol) of 19 (prepared as described above) in
CH2Cl2 (15 ml), Et3N (2 ml), and 9b (1.0 g, 3.11 mmol) in CH2Cl2 (25 ml): 0.632 g (39%) of 20b. Colorless oil. Rf
(AcOEt/CH2Cl2/MeOH 5 :5 :1) 0.50. IR (CHCl3): 1740vs, 1680vs, 1110vs, 970s. 1H-NMR: 1.30 (br. s, 8 H); 1.47 ±
1.58 (m, 4 H); 1.64 (s, 3 H); 2.91 (t, J ˆ 7.25, 2 H); 3.26 (q, 2 H); 3.38 (s, 3 H); 3.51 ± 3.55 (m, 2 H); 3.62 ± 3.70
(m, 6 H); 3.74 (d, JAB ˆ 10.85, superimposed 3.743 (s), total 4 H); 3.85 (d, JAB ˆ 10.48, 1 H); 3.99 (s, 2 H); 7.01
(t, 1 H). 13C-NMR: 20.04 (q); 26.8 (t); 28.61 (t); 28.91 (t); 29.02 (t); 29.07 (t); 29.31 (t); 29.54 (t); 36.01 (t); 38.89
(t); 53.12 (q); 58.96 (q); 61.78 (s); 70.16 (t); 70.27 (t); 70.49 (t); 70.95 (t); 71.85 (t); 169.68 (s); 170.02 (s); 196.71

688
Helvetica Chimica Acta ± Vol. 84 (2001)
‡
‡
(s). MS (calc. for C21H38BrO7NS 528.45): 529 (1, M ), 527 (1, M ), 321 (24), 320 (100), 288 (38), 244 (59), 212
(25), 133 (16), 103 (16).
O-Methyl S-(5-Oxo-4,7,10,13-tetraoxatetradecyl)-2-(Bromomethyl)-2-methylmonothiomalonate (ˆ Methyl
2-(Bromomethyl)-2-methyl-3-oxo-3-[(5-oxo-4,7,10,13-tetraoxatetradecyl)thio]propanoate; 21). To the soln. of
the acid chloride, obtained from 19 as described above, 12 (1.5 g, 3.2 mmol) in CH2Cl2 (20 ml) was added
dropwise within 20 min at 08 under Ar. FC (hexane/AcOEt/MeOH 10 :10 :1) gave 21 (1.758 g, 65%). Colorless
oil. Rf (hexane/AcOEt/MeOH 10 :10 :1) 0.33. IR (CHCl3): 1750vs, 1685vs, 1460vs, 1445s, 1385s, 1260 ± 1200vs,
1180 ± 1080vs. 1H-NMR: 1.64 (s, 3 H); 1.95 (d, 2 H); 3.01 (t, J ˆ 7.17, 2 H); 3.38 (s, 3 H); 3.54 ± 3.57 (m, 2 H);
3.62 ± 3.70 (m, 4 H); 3.76 (s, superimposed at 3.71 ± 3.77 (m) and (d), total 6 H); 3.824 (d, JAB ˆ 10.29, 1 H); 4.17
(s, superimposed at 4.14 (t, J ˆ 6.25), total 4 H). 13C-NMR: 19.93 (q); 25.76 (t); 28.27 (t); 35.80 (t); 53.20 (q);
58.98 (q); 61.71 (s); 61.71 (s); 62.81 (t); 68.55 (t); 70.50 (t); 70.62 (t); 70.92 (t); 71.87 (t); 169.52 (s); 170.35 (s);
196.32 (s). MS: 283 (32), 281 (36), 219 (56), 209 (46), 207 (54), 181 (44), 179 (58), 153 (38), 143 (28), 133 (50),
‡
103 (48), 59 (100). ESI-MS (MeCN/H2O 1:1 and 2% LiClO4): 467.20 (100, [M ‡ 2 ‡ Li] ), 465.20 (90, [M ‡
‡
Li] ). Anal. calc. for C16H27BrO8S (459.30): C 41.91, H 6.07; found: C 41.84, H 5.92.
O-Methyl S-{10-[(2,3,4,5,6-Penta-O-acetyl-d-gluconoyl)amino]decyl} 2-(Bromomethyl)-2-methylmono-
thiomalonate (ˆ Methyl 2-(Bromomethyl)-2-methyl-3-oxo-3-{{10-[(2,3,4,5,6-penta-O-acetyl-d-gluconoyl)ami-
no]decyl}thio}propanoate; 22a). As described for 20a, treatment of 18 (0.30 g, 1.06 mmol) first with CF3COOH,
then with SOCl2 gave the acid chloride of 19, which was treated with Et3N (2 ml) and 16d (0.60 g, 1.04 mmol) in
toluene (6 ml). FC (AcOEt/hexane 1:1) of the viscous, yellowish oil gave the diastereomer mixture 22a
(380 mg, 47%). Clear oil. Rf (AcOEt/hexane 1:1) 0.55. IR (CHCl3): 1760s, 1740s, 1380s, 1230s. 1H-NMR: 1.25 ±
1.40 (m, 12 H); 1.40 ± 1.51 (m, 2 H); 1.53 ± 1.60 (m, 2 H); 1.64 (s, 3 H); 2.05 (s, 3 H); 2.06 (s, 3 H); 2.10 (s, 3 H);
2.11 (s, 3 H); 2.20 (s, 3 H); 2.92 (t, J ˆ 7.36, 2 H); 3.18 ± 3.27 (m, 2 H); 3.76 (d, JAB ˆ 10.47, overlap with 3.78 (s),
total 4 H); 3.88 (d, JAB ˆ 10.47, 1 H); 4.13 (dd, J ˆ 12.13, 5.53, 1 H); 4.32 (dd, J ˆ 12.13, 4.05, 1 H); 5.00 ± 5.10
(m, 1 H); 5.30 (d, J ˆ 5.15, 1 H); 5.45 (q, 1 H); 5.68 (t, J ˆ 5.15, 1 H); 6.34 (t, J ˆ 5.78, 1 H). 13C-NMR: 20.03 (q);
20.40 (q); 20.65 (q); 20.71 (q); 26.76 (t); 28.63 (t); 28.96 (t); 29.08 (t); 29.15 (t); 29.31 (t); 29.34 (t); 29.37 (t);
36.05 (t); 39.50 (t); 53.13 (q); 61.50 (t); 61.79 (s); 68.75 (d); 69.11 (d); 69.40 (d); 71.76 (d); 165.98 (s); 169.16 (s);
169.64 (s); 169.67 (s); 169.78 (s); 169.81 (s); 170.54 (s); 196.68 (s). MS (calc. for C32H50BrNO14S, 784.66): 786 (1,
‡
‡
[M ‡ 2] ), 784 (1, M (79Br)), 754 (2), 752 (2), 725 (1), 723(0.9), 682 (2), 665 (3), 623 (3), 576 (100), 558 (8),
544 (12), 534 (44), 516 (76), 484 (20), 474 (22), 424 (10), 396 (8), 347 (8), 287 (9), 272 (11), 258 (9), 242 (11),
230 (62), 198 (38), 188 (42), 184 (76), 171 (18), 157 (44), 142 (54), 129 (20), 115 (54), 103 (48).
O-Methyl S-{12-[(2,3,4,5,6-Penta-O-acetyl-d-gluconoyl)amino]dodecyl} 2-(Bromomethyl)-2-methylmono-
thiomalonate (ˆ Methyl 2-(Bromomethyl)-2-methyl-3-oxo-3-{{12-[(2,3,4,5,6-penta-O-acetyl-d-gluconoyl)ami-
no]dodecyl}thio}propanoate; 22b). The acid chloride, prepared from the acid 19 with SOCl2, was dissolved in
toluene (5 ml), cooled, and treated, as described for 22a, with Et3N and 16f (200 mg, 0.33 mmol) in toluene
(5 ml) (18 h). For workup, the aq. phase was extracted with AcOEt (2Â) and the org. phase dried (MgSO4). FC
(AcOEt/hexane 3 :1) gave 150 mg (56%) of 22b as a diastereoisomer mixture. Rf (AcOEt/hexane 3 :1) 0.56.
1H-NMR: 1.20 ± 1.80 (m, overlap with 1.24 (s) and 1.63 (s), total 23 H); 2.00 ± 2.30 (m, overlap with 2.05 (s); 2.09
(s), 211 (s), and 2.20 (s), total 18 H); 2.91 (t, 2 H); 3.23 (m, 2 H); 3.75 (d, J ˆ 10.3, overlap with 3.77 (s), total
4 H); 3.87 (d, J ˆ 10.3, 1 H); 4.12 (dd, J ˆ 12.5, 5.5, 1 H); 4.31 (dd, J ˆ 12, 4.0 H); 4.95 ± 5.10 (m, 1 H); 5.29
(d, J ˆ 5.5, 1 H); 5.44 (m, 1 H); 5.67 (m, 1 H); 6.09 (m, 1 H). 13C-NMR: 20.06 (q); 20.40 (q); 20.65 (q); 20.66
(q); 20.72 (q); 26.77 (t); 28.68 (t); 29.00 (t); 29.04 (t); 29.18 (t); 29.37 (t); 29.47 (t); 29.51 (t); 29.53 (t); 29.55 (t);
36.02 (t); 39.52 (t); 53.12 (t); 61.51 (t); 61.81 (s); 68.72 (d); 69.08 (d); 69.37 (d); 71.66 (d); 165.86 (s); 169.17 (s);
169.61 (s); 169.84 (s); 170.58 (s); 196.70 (s). LSI-MS (calc. for C34H54BrNO14S, 812.77; matrix glycerol): 812 (78,
‡
M ), 754 (79), 710 (36), 604 (38); 572 (34), 540 (100), 512 (37), 470 (33), 424 (62), 361 (92), 332 (55).
O-Methyl S-(10-Oxo-12,15,18-trioxa-9-azanonadecyl) Dimethylmonothiomalonate (ˆ Methyl 2,2-Dimeth-
yl-3-oxo-3-[(10-oxo-12,15,18-trioxa-9-azanona-decyl)thio]propanoate; 24). Methyl hydrogen dimethylmalo-
nate (23; 100 mg, 0.684 mmol) in CH2Cl2 (5 ml) was treated with CHCl2OMe (1 g, 8.7 mmol) overnight [25].
The excess chlorinating agent was removed under reduced pressure and the acid chloride dissolved in CH2Cl2
(10 ml) and added dropwise to the soln. of 9b (219 mg, 0.684 mmol) and Et3N (0.5 ml) in CH2Cl2 (20 ml) at 08.
The mixture was stirred for 20 h at r.t. and worked up. FC (CH2Cl2/MeOH 20 :1) gave 134 mg (44%) of 22b.
1
Clear oil. Rf (CH2Cl2/MeOH 20 :1) 0.29. IR (CHCl3): 1740s, 1680s, 1545s, 1470s, 1155s, 1110s, 970s. H-NMR:
1.22 ± 1.45 (m, superimposed at 1.56 (s), total 14 H); 1.48 ± 1.64 (2m, 4 H); 2.88 (t, J ˆ 7.35, 2 H); 3.23 ± 3.31 (q,
2 H); 3.38 (s, 3 H); 3.55 ± 3.58 (m, 2 H); 3.65 ± 3.70 (m, 6 H); 3.68 (s, 2 H); 3.98 (s, 2 H); 7.01 (t, 1 H). 13C-NMR:
23.07 (q); 23.09 (q), 26.76 (t); 28.60 (t); 28.88 (t); 28.89 (t); 29.03 (t); 29.13 (t); 29.50 (t); 38.78 (t); 52.54 (q);
56.96 (s); 58.88 (q); 70.11 (t); 70.31 (t); 70.43 (t); 70.88 (t); 71.79 (t); 169.71 (s); 172.85 (s); 200.04 (s). MS (calc.

Helvetica Chimica Acta ± Vol. 84 (2001)
689
‡
for C21H39O7NS, 449.50): 449 (20, M ), 418 (45), 374 (14), 320 (95), 288 (30), 244 (55), 212 (30), 129 (55), 101
(92).
O-Methyl S-(10-Oxo-12,15,18-trioxa-9-azanonadecyl) 2-Methylmonothiosuccinate (ˆ Methyl 2-Methyl-4-
oxo-4-[(10-oxo-12,15,18-trioxa-9-azanonadecyl)thio]butanoate; 26). 4-(tert-Butyl) 1-methyl 2-methylsuccinate
(25; 300 mg, 1.48 mmol) was stirred in CF3COOH (7 ml) for 4 h at r.t. and, after evaporation, treated with
CHCl2OMe (1 g, 8.7 mmol) for 12 h. The excess chlorinating agent was evaporated and the acid chloride
dissolved in CH2Cl2 (7 ml) and added dropwise to a soln. of 9b (150 mg, 0.467 mmol) and Et3N (0.5 ml) in
CH2Cl2 (10 ml) within 20 min. Workup and FC (CH2Cl2/Et2O/MeOH 8 :2 :1) gave 26 (0.10 g, 48%) as a clear oil.
HPLC (H2O/MeOH 3 :7): 79.8 mg (38%). Rf (CH2Cl2/Et2O/MeOH 8 :2 :1) 0.66. IR (CHCl3): 1740s, 1680s,
1
1545s, 1110s, 970s. H-NMR: 1.20 (d, J ˆ 6.78, 3 H); 1.30 (m, 8 H); 1.50 ± 1.64 (2m, 4 H); 2.60 ± 2.64 (m, 1 H);
2.86 (t, J ˆ 7.26, 2 H); 2.94 ± 3.07 (m, 2 H); 3.24 ± 3.30 (q, 2 H); 3.38 (s, 3 H); 3.55 ± 3.58 (m, 2 H); 3.65 ± 3.70
(m, 6 H); 3.98 (s, 2 H); 7.03 (t, 1 H). 13C-NMR: 16.62 (q); 26.68 (t); 28.53 (t); 28.71 (t); 28.81 (t); 28.96 (t); 29.31
(t); 29.42 (t); 35.83 (d); 38.71 (t); 46.68 (t); 51.76 (q); 58.81 (q); 70.04 (t); 70.24 (t); 70.37 (t); 70.81 (t); 71.72 (t);
‡
169.64 (s); 175.24 (s); 197.37 (s). MS: 449 (8, M ), 418 (16), 321 (58), 320 (68), 288 (36), 263 (26), 244 (36), 219
‡
(19), 212 (15), 188 (17), 129 (100). HR-MS: 449.244960 (C21H39O7NS ; calc. 449.247425).
REFERENCES
[1] H. Dugas, ꢀBioorganic Chemistry: A Chemical Approach to Enzyme Actionꢁ, Springer-Verlag, New York,
3rd edn., 1996.
[2] J. M. Lehn, Angew. Chem. 1990, 102, 1347; Angew. Chem., Int. Ed. 1990, 29, 1304; D. J. Cram, Angew.
Chem. 1988, 100, 1041; Angew. Chem., Int. Ed. 1988, 27, 1009.
[3] F. Mancia, N. H. Keep, A. Nakagawa, P. F. Leadlay, S. McSweeney, B. Rasmussen, P. Bösecke, O. Drat, P. R.
Evans, Structure 1996, 4, 339; N. H. Thomä, T. W. Meier, P. F. Leadlay, in ꢀVitamin B12 and B12-Proteinsꢁ,
Eds. B. Kräutler, D. Arigoni, and B. T. Golding, Wiley-VCH, Weinheim-New York, 1998.
Â
[4] J. Retey, Angew. Chem. 1990, 102, 373; Angew. Chem., Int. Ed. Engl. 1990, 29, 355.
[5] A. Wolleb, T. Darbre, V. Siljegovic, R. Keese, J. Chem. Soc., Chem. Commun. 1994, 835; T. Darbre, R.
Keese, V. Siljegovic, A. Wolleb-Gygi, Helv. Chim. Acta 1996, 79, 2100.
[6] T. Darbre, R. Keese, V. Siljegovic, J. Chem. Soc., Chem. Commun. 1996, 1561.
[7] T. Darbre, V. Siljegovic, A. Amolins, T. Otten, R. Keese, L. Abrantes, J. P. Correia, ꢀNovel Trends in
Electroorganic Synthesisꢁ, Ed. S. Torii, Springer Verlag, Tokyo, 1998, p. 395.
[8] F. Sun, T. Darbre, R. Keese, Tetrahedron 1999, 55, 9777.
[9] W. Dirscherl, F. W. Weingarten, Justus Liebigs Ann. Chem. 1951, 547, 131.
[10] H. Burrows, J. Chem. Ed. 1992, 69, 1.
[11] K. Larsson, J. Am. Oil Chem. 1966, 43, 559.
[12] B. J. Evans, J. Takahashi Doi, W. K. Musker, J. Org. Chem. 1990, 55, 2580.
[13] J.-H. Fuhrhop, P. Schmieder, J. Rosenberg, E. Boekema, J. Am. Chem. 1987, 109, 3387; J.-H. Fuhrhop, D.
Fritsch, Acc. Chem. Res. 1986, 19, 130.
[14] F. W. Nader, A. Brecht, S. Kreisz, Chem. Ber. 1986, 119, 1196.
[15] T. Mosokawa, T. Yamamaka,M. Itotani, S.-I. Murahashi, J. Org. Chem. 1995, 60, 6159.
[16] V. Siljegovic, Ph.D. Thesis, Universität Bern, 1995.
[17] H. Flohr, W. Pannhorst, J. Retey, Helv. Chim. Acta 1978, 61, 1565.
[18] Susanna Müller, Ph.D. Thesis, Universität Bern, 1988.
[19] S. Masamune, S. Kamata, J. Diakur, Y. Sugihara, G. S. Bates, Can. J. Chem. 1975, 53, 3693.
[20] H.-J. Gais, Angew. Chem. 1977, 89, 251.
[21] M. J. Pfammatter, T. Darbre, R. Keese, Helv. Chim. Acta 1998, 81, 1105.
[22] K. E. Koenig, G. M. Lein, P. Stickler, T. Kaned, D. J. Cram, J. Am. Chem. Soc. 1979, 101, 3553.
[23] C. S. Wilcox, ꢀFrontiers in Supramolecular Organic Chemistry and Photochemistryꢁ, Ed. H. J. Schneider
and H. Dürr, 1991, VCH, Weinheim.
[24] A. Wolleb-Gygi, Ph.D. Thesis, University of Bern, 1993.
[25] L. Heslinga, J. F. Arens, Rec. Trav. Chim. Pays-Bas 1957, 76, 982.
[26] H. U. Geyer, Chem. Ber. 1964, 97, 2271.
[27] R. L. Shriner, F. W. Neumann, Org. Synth. 1955, Coll. Vol. 3, 73.
Received October 30, 2000