Synthesis of homochiral acyclic mono- and bis(α-amino acid)s with oligo(oxyethylene) chains

Article abstract of DOI:10.1135/cccc20031319

Synthesis of homochiral α-amino acids 3a-3e and bis(α-amino acid)s 4a-4e via BF₃·Et₂O-catalyzed ring-opening of methyl (S)-1-[(benzyloxy)carbonyl]aziridine-2-carboxylate (7) with oligo(ethylene glycol)s and subsequent acid hydrolysis

Full text of DOI:10.1135/cccc20031319

Homochiral Acyclic Mono- and Bis(α-amino acid)s
1319
SYNTHESIS OF HOMOCHIRAL ACYCLIC MONO- AND
BIS(α-AMINO ACID)S WITH OLIGO(OXYETHYLENE) CHAINS
1
2,
Martin BĚLOHRADSKÝ , Luděk RIDVAN and Jiří ZÁVADA *
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
1
2
166 10 Prague, Czech Republic; e-mail: martinb@uochb.cas.cz, zavada@uochb.cas.cz
Received April 23, 2003
Accepted Jun e 3, 2003
Syn th esis of h om och iral α-am in o acids 3a–3e an d bis(α-am in o acid)s 4a–4e via BF3·Et2O-
catalyzed rin g-open in g of m eth yl (S)-1-[(ben zyloxy)carbon yl]aziridin e-2-carboxylate (7) with
oligo(eth ylen e glycol)s an d subsequen t acid h ydrolysis is reported.
Keyw ord s: Am in o acids; Oligo(eth ylen e glycol)s, Aziridin es; Nucleoph ilic rin g-open in g
reaction ; Podan ds; Crown eth ers.
Recen tly1,2, we h ave prepared m acrocyclic am in o acid 1 an d bis(am in o
acid) 2 , wh ich are “crown ed” at th e glycin e α-carbon with th e m eth ylen e-
oligo(oxyeth ylen e)oxym eth ylen e ch ain , an d in vestigated th eir com plex-
ation an d self-assem blin g properties. As an exten sion of th is study, we wish
to provide syn th etic access also to th e acyclic an alogues 3 an d 4 an ticipat-
in g th at th e well-kn own m etal-ion -ligatin g as well as h ydrogen -bon din g
abilities of th e in corporated straigh t-ch ain oligo(oxyeth ylen e) m oiety m ay
en dow also th e target com poun ds with som e un usual (podan d)3 properties.
As it is poin ted out elsewh ere4,5, th ere is a trem en dous level of in terest in
th e de novo design an d syn th esis of n ovel un n atural am in o acids with spe-
cific properties for th e purposes of im partin g en zym e-in h ibitory, an ti-
m etabolite an d protease resistan ce-in ducin g properties to peptides an d
th eir m im etics. As a con sequen ce, th e developm en t of versatile m eth odolo-
gies for th eir preparation in optically pure form h as em erged as a h igh ly sig-
n ifican t an d ch allen gin g en deavor. For th e h om ologous series of th e
h om och iral am in o acids (S)-3a–3e an d (S,S)-4a–4e, th is syn th etic task h as
n ow been accom plish ed.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)
doi:10.1135/cccc20031319

1320
Bělohradský, Ridvan, Závada:
RESULTS AND DISCUSSION
In con trast to th e m acrocyclic am in o acids 1 an d 2 pertain in g retro-
syn th etically to 2,2-bis(h ydroxym eth yl)glycin e 5, th e acyclic an alogues
3a–3e an d 4a–4e refer to th e 2-h ydroxym eth ylglycin e (serin e) h om ologue 6
(Sch em e 1). As th e m ost con ven ien t syn th on of 6, we h ave ch osen th e acti-
vated derivative of (S)-aziridin e-2-carboxylic acid 7, wh ich is easily accessi-
ble from th e h om och iral (S)-serin e.
n
O
COOH
NH2
H2N
O
O
O
O
O
O
NH2
OH
H2N
OH
O
O
COOH
HOOC
O
COOH
n
n
5
1
2
n
n
O
O
O
OH
OH
COOH
(S)-6
O
O
COOH
(S)-3a–3e
H2N
H2N
H2N
H2N
COOH
COOH
(S,S)-4a–4e
3, 4
a
b
c
d
n
0
1
2
3
4
e
SCHEME 1
Nucleoph ilic reactivity of aziridin e 7 h as been am ply dem on strated6–9
.
Surprisin gly en ough , th e reaction with free oligo(eth ylen e glycol)s h as n ot
been as yet reported. As we h ave n ow foun d, th e n ucleoph ilic rin g-open in g
reaction of th e aziridin e derivative proceeds sm ooth ly un der BF3·Et2O catal-
ysis, yieldin g a m ixture of th e correspon din g protected am in o acid 8a–8e
an d bis(am in o acid) 9a–9e, respectively, in proportion s depen din g on th e
stoich iom etry em ployed. A sim ple ch rom atograph ic separation followed by
acid h ydrolysis afforded th e target deprotected am in o acid 3a–3e an d
bis(am in o acid) 4a–4e (Sch em e 2). A straigh tforward access to n ovel
en an tiom erically un iform (S)-serin e an alogues is th us provided.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

Homochiral Acyclic Mono- and Bis(α-amino acid)s
1321
COOMe
N
Z
(S)-7 (Z = PhCH2OCO)
n
OH
HO
O
BF3·Et2O
n
OH
n
O
O
O
O
O
COOMe
(S)-8a–8e (Z = PhCH2OCO)
ZNH
ZNH COOMe ZNH COOMe
(S,S)-9a–9e (Z=PhCH2OCO)
3, 4, 8, 9
n
0
1
2
3
4
a
b
c
d
e
(S)-3a–3e·HCl
(S,S)-4a–4e·2HCl
SCHEME 2
EXPERIMENTAL
1H NMR spectra were m easured on a FT NMR spectrom eter Varian Un ity 200 (200 MHz,
20 °C) in CDCl3 (with TMS as in tern al stan dard) an d/or in D2O (referen ced to HDO sign al
at 4.80 ppm ). Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) in Hz.
FAB MS spectra were recorded with a ZAB-EQ VG an alytical in strum en t usin g a m ixture of
glycerol–th ioglycerol m atrix. An alytical sam ples were dried at 60 °C/5 kPa for 24 h . TLC
ch rom atograph y was perform ed on Kieselgel GF254 usin g th e Dragen dorff sprayin g reagen t.
Com m ercial oligo(eth ylen e glycol)s (Aldrich , Fluka) were distilled an d kept over m olecular
sieves 3A. Oth er reagen ts an d solven ts were purch ased from Fluka an d Aldrich an d were
used with out furth er purification . Meth yl (S)-1-[(ben zyloxy)carbon yl]aziridin e-2-carboxyl-
ate (7) was prepared by a m odification of th e earlier procedure6. Values of [α]D are given in
10–1 deg cm 2 g–1
.
Meth yl (S)-1-[(Ben zyloxy)carbon yl]aziridin e-2-carboxylate (7)
Meth yl (S)-1-tritylaziridin e-2-carboxylate6 (6.86 g, 20 m m ol) was dissolved in MeOH (20 m l)
an d CHCl3 (20 m l). Trifluoroacetic acid (28 m l, 200 m m ol) was added dropwise at 0 °C an d
th e m ixture was allowed to stan d at 0 °C for 2 h . Th e solven ts were evaporated un der re-
duced pressure an d th e residue was dissolved in CHCl3 (30 m l) an d trieth yl am in e (7 m l).
Th e resultin g m ixture was cooled to 0 °C an d a solution of ben zyl ch loroform ate (3.1 m l,
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

1322
Bělohradský, Ridvan, Závada:
22 m m ol) in CHCl3 (20 m l) was added dropwise. Th e reaction m ixture was allowed to stan d
at room tem perature for 16 h an d was th en wash ed with 10% aqueous citric acid, water, sat-
urated aqueous NaHCO3, an d brin e. Th e organ ic layer was dried (an h ydrous Na2SO4) an d
th e solven t was rem oved by evaporation . Th e pure product was obtain ed by ch rom atogra-
ph y (eth yl acetate/petroleum eth er 1:3) as oil (4.1 g, 87%). 1H NMR (CDCl3, 200 MHz): 7.35
(m , 5 H); 5.15 (s, 2 H); 3.71 (s, 3 H); 3.11 (dd, 1 H, J = 3.4 an d 5.5); 2.60 (dd, 1 H, J = 1.2
an d 3.4); 2.49 (dd, 1 H, J = 1.2 an d 5.5). [α]D –46.4 (c 1, MeOH); ref.6: [α]D –47.3 (c 0.25).
Reaction s of 7 with Oligo(eth ylen e glycol)s. Gen eral Procedure
Meth yl (S)-1-[(ben zyloxy)carbon yl]aziridin e-2-carboxylate (7; 9 m m ol) an d an appropriate
oligo(eth ylen e glycol) (6 m m ol) was dissolved in CHCl3 (4 m l) an d treated with 10% solu-
tion of BF3·Et2O in CHCl3 (2 m l). Th e m ixture was allowed to stan d at room tem perature for
20 h . After dilution with CHCl3 (30 m l), th e m ixture was sh aken with 10% NaHCO3, dried
over an h ydrous Na2SO4, an d evaporated. Th e products were separated by colum n ch rom a-
tograph y usin g th ese eluen ts: EtOAc/petroleum eth er from 1:1 to 3:1 (A), EtOAc/petroleum
eth er from 3:1 m ixture to EtOAc on ly (B), or 5% MeOH in CH2Cl2 (C).
Methyl (S)-2-{[(benzyloxy)carbonyl]amino}-6-hydroxy-4-oxahexanoate (8a; n = 0). Prepared
from 2 an d eth ylen e glycol. Isolated ch rom atograph ically usin g eluen t B; oil (0.74 g, 31%).
1H NMR (CDCl3, 200 MHz): 7.36 (m , 5 H); 5.81 (br d, 1 H, J = 8.5); 5.13 (s, 2 H); 4.53 (dt,
1 H, J = 8.5 an d 3.4); 3.92 (dd, 1 H, J = 9.8 an d 3.4); 3.77 (s, 3 H); 3.74–3.64 (m , 3 H);
3.59–3.51 (m , 2 H). FAB MS, m/z: 298 (MH+, 41), 254 (100), 164 (29). FAB HR MS: for
[C14H20NO6]+ calculated 298.1291, foun d 298.1282. [α]D –11.5 (c 1, MeOH).
Dimethyl (S,S)-2,9-bis{[(benzyloxy)carbonyl]amino}-4,7-dioxadecanedioate (9a; n = 0). Prepared
from 2 an d eth ylen e glycol. Isolated ch rom atograph ically usin g eluen t A; oil (1.29 g, 30%).
1H NMR (CDCl3, 200 MHz): 7.40–7.24 (m , 10 H); 5.80 (br d, 2 H, J = 8.5); 5.12 (s, 4 H); 4.48
(dt, 2 H, J = 8.5 an d 3.4); 3.91 (dd, 2 H, J = 9.8 an d 3.4); 3.72 (s, 6 H); 3.70–3.50 (m , 6 H).
+
FAB MS, m/z: 533 (MH+, 45), 489 (92), 399 (100). FAB HR MS: for [C26H33N2O10
533.2135, foun d 533.2144. [α]D –6.2 (c 1, MeOH).
]
calculated
Methyl (S)-2-{[(benzyloxy)carbonyl]amino}-9-hydroxy-4,7-dioxanonanoate (8b; n = 1). Prepared
from 2 an d dieth ylen e glycol. Isolated ch rom atograph ically usin g eluen t B; oil (0.70 g, 34%).
1H NMR (CDCl3, 200 MHz): 7.36 (m , 5 H); 6.03 (br d, 1 H, J = 8.6); 5.14 (s, 2 H); 4.50 (dt, 1 H,
J = 8.6 an d 3.1); 4.01 (dd, 1 H, J = 10.1 an d 3.1); 3.77 (s, 3 H); 3.76–3.56 (m , 9 H). FAB MS,
m/z: 342 (MH+, 36), 298 (100), 208 (41). FAB HR MS: for [C16H24NO7]+ calculated 342.1553,
foun d 342.1559. [α]D –7.9 (c 1, MeOH).
Dimethyl (S,S)-2,12-bis{[(benzyloxy)carbonyl]amino}-4,7,10-trioxatridecanedioate (9b; n = 1).
Prepared from 2 an d dieth ylen e glycol. Isolated ch rom atograph ically usin g eluen t A; oil
(1.4 g, 40%). 1H NMR (CDCl3, 200 MHz): 7.34 (m , 10 H); 5.88 (br d, 2 H, J = 8.6); 5.12 (s,
4 H); 4.47 (dt, 2 H, J = 8.6 an d 3.4); 3.92 (dd, 2 H, J = 9.8 an d 3.4); 3.73 (s, 6 H); 3.70–3.50
+
(m , 10 H). FAB MS, m/z: 577 (MH+, 28), 533 (100), 443 (45). FAB HR MS: for [C28H37N2O11
calculated 577.2397, foun d 577.2404. [α]D –7.9 (c 1, MeOH).
]
Methyl (S)-2-{[(benzyloxy)carbonyl]amino}-12-hydroxy-4,7,10-trioxadodecanoate (8c; n = 2).
Prepared from 2 an d trieth ylen e glycol. Isolated ch rom atograph ically usin g eluen t C; oil
(0.90 g, 39%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 5 H); 6.55 (br d, 1 H, J = 8.8); 5.13 (s,
2 H); 4.50 (dt, 1 H, J = 8.8 an d 3.4); 3.98 (dd, 1 H, J = 9.5 an d 3.4); 3.76 (s, 3 H); 3.75–3.54
(m , 13 H). FAB MS, m/z: 386 (MH+, 36), 342 (100), 252 (62). FAB HR MS: for [C18H28NO8]+
calculated 386.1815, foun d 342.1822. [α]D –5.9 (c 1, MeOH).
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Homochiral Acyclic Mono- and Bis(α-amino acid)s
1323
Dimethyl (S,S)-2,15-bis{[(benzyloxy)carbonyl]amino}-4,7,10,13-tetraoxahexadecanedioate (9c;
n = 2). Prepared from 2 an d trieth ylen e glycol. Isolated ch rom atograph ically usin g eluen t B;
oil (1.4 g, 38%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 10 H); 5.91 (br d, 2 H, J = 8.8); 5.12
(s, 4 H); 4.47 (dt, 2 H, J = 8.8 an d 3.4); 3.93 (dd, 2 H, J = 9.8 an d 3.4); 3.74 (s, 6 H); 3.73
(dd, 2 H, J = 9.8 an d 3.4); 3.75–3.50 (m , 12 H). FAB MS, m/z: 621 (MH+, 35), 577 (100), 487
+
(66). FAB HR MS: for [C30H41N2O12
MeOH).
]
calculated 621.2660, foun d 621.2669. [α]D –7.6 (c 1,
Methyl (S)-2-{[(benzyloxy)carbonyl]amino}-15-hydroxy-4,7,10,13-tetraoxapentadecanoate (8d ;
n = 3). Prepared from 2 an d tetraeth ylen e glycol. Isolated ch rom atograph ically usin g eluen t
C; oil (0.85 g, 33%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 5 H); 6.30 (br d, 1 H, J = 8.6); 5.13
(s, 2 H); 4.48 (dt, 1 H, J = 8.6 an d 3.4); 3.96 (dd, 1 H, J = 9.8 an d 3.4); 3.76 (s, 3 H);
3.76–3.52 (m , 17 H). FAB MS, m/z: 430 (MH+, 33), 386 (100), 296 (24). FAB HR MS: for
[C20H31NO9]+ calculated 430.2077, foun d 430.2082. [α]D –6.4 (c 1, MeOH).
Dimethyl (S,S)-2,18-bis{[(benzyloxy)carbonyl]amino}-4,7,10,13,16-pentaoxanonadecanedioate
(9d ; n = 3). Prepared from 2 an d tetraeth ylen e glycol. Isolated ch rom atograph ically usin g
eluen t C; oil (1.1 g, 28%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 10 H); 5.90 (br d, 2 H, J =
8.8); 5.12 (s, 4 H); 4.47 (dt, 2 H, J = 8.8 an d 3.4); 3.94 (dd, 2 H, J = 9.8 an d 3.4); 3.75 (s,
6 H); 3.71 (dd, 2 H, J = 9.8 an d 3.4); 3.78–3.63 (m , 16 H). FAB MS, m/z: 665 (MH+, 30), 621
+
(100), 531 (54). FAB HR MS: for [C32H45N2O13
]
calculated 665.2922, foun d 665.2918.
[α]D –6.3 (c 1, MeOH).
Methyl (S)-2-{[(benzyloxy)carbonyl]amino}-18-hydroxy-4,7,10,13,16-pentaoxaoctadecanoate (8e;
n = 4). Prepared from 2 an d pen taeth ylen e glycol. Isolated ch rom atograph ically usin g eluen t
C; oil (1.0 g, 35%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 5 H); 6.07 (br d, 1 H, J = 8.4); 5.13
(s, 2 H); 4.48 (dt, 1 H, J = 8.4 an d 3.6); 3.96 (dd, 1 H, J = 9.8 an d 3.6); 3.76 (s, 3 H);
3.75–3.56 (m , 21 H). FAB MS, m/z: 474 (MH+, 38), 430 (100), 252 (28). FAB HR MS: for
[C12H28NO8]+ calculated 474.2339, foun d 474.2332. [α]D –5.4 (c 1, MeOH).
Dimethyl (S,S)-2,21-bis{[(benzyloxy)carbonyl]amino}-4,7,10,13,16,19-hexaoxadocosanedioate
(9e; n = 4). Prepared from 2 an d pen taeth ylen e glycol. Isolated ch rom atograph ically usin g
eluen t C; oil (1.2 g, 28%). 1H NMR (CDCl3, 200 MHz): 7.36 (m , 10 H); 5.91 (br d, 2H, J =
8.6); 5.12 (s, 4 H); 4.47 (dt, 2 H, J = 8.6 an d 3.3); 3.95 (dd, 2 H, J = 9.6 an d 3.3); 3.75 (s,
6 H); 3.72 (dd, 2 H, J = 9.6 an d 3.3); 3.58 (m , 20 H). FAB MS, m/z: 709 (MH+, 32), 665 (100),
+
575 (62). FAB HR MS: for [C34H49N2O14
]
calculated 709.3183, foun d 709.3175. [α]D –5.5
(c 1, MeOH).
Hydrolysis of Protected Am in o Acids 8a–8e an d 9a–9e. Gen eral Procedure
An appropriate am in o acid (2 m m ol) was refluxed in aqueous 6 M HCl un der n itrogen for
16 h . After coolin g, ch arcoal was added; th e m ixture was filtered an d evaporated. Th e yields
of resultin g h ydroch lorides of 3a–3e an d dih ydroch lorides of 4a–4e were quan titative.
(S)-2-Amino-6-hydroxy-4-oxahexanoic acid hydrochloride (3a; n = 0). Obtain ed from 8a as a
h ygroscopic oil. 1H NMR (D2O, 200 MHz): 4.26 (dd, 1 H, J = 4.8 an d 3.4); 4.04 (dd, 1 H, J =
11.0 an d 4.8); 3.95 (dd, 1 H, J = 11.0 an d 3.4); 3.70 (m , 4 H). FAB MS, m/z: 150 (MH+, 100).
FAB HR MS: for [C5H12NO4]+ calculated 150.0766, foun d 150.0757.
(S,S)-2,9-Diamino-4,7-dioxadecanedioic acid dihydrochloride (4a; n = 0). Obtain ed from 9a as
a h ygroscopic glassy substan ce. 1H NMR (D2O, 200 MHz): 4.25 (dd, 2 H, J = 4.6 an d 3.4);
4.05 (dd, 2 H, J = 11.0 an d 4.6); 3.94 (dd, 2 H, J = 11.0 an d 3.4); 3.74 (m , 4 H). FAB MS, m/z:
237 (MH+, 100). FAB HR MS: for [C8H17N2O6]+ calculated 237.1087, foun d 237.1080.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

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Bělohradský, Ridvan, Závada:
(S)-2-Amino-4,7-dioxanonanoic acid hydrochloride (3b; n = 1). Obtain ed from 8b as a h ygro-
scopic oil. 1H NMR (D2O, 200 MHz): 4.23 (dd, 1 H, J = 4.9 an d 3.7); 4.04 (dd, 1 H, J = 11.0
an d 4.9); 3.95 (dd, 1 H, J = 11.0 an d 3.7); 3.78–3.62 (m , 8 H). FAB MS, m/z: 194 (MH+, 100).
FAB HR MS: for [C7H16NO5]+ calculated 194.1028, foun d 194.1033.
(S,S)-2,12-Diamino-4,7,10-trioxatridecanedioic acid dihydrochloride (4b; n = 1). Obtain ed from
9b as a h ygroscopic glassy substan ce. 1H NMR (D2O, 200 MHz): 4.26 (dd, 2 H, J = 4.6 an d
3.4); 4.05 (dd, 2 H, J = 11.0 an d 4.6); 3.94 (dd, 2 H, J = 11.0 an d 3.4); 3.82–3.64 (m , 8 H).
FAB MS, m/z: 281 (MH+, 100). FAB HR MS: for [C10H21N2O7]+ calculated 281.1349, foun d
281.1352.
(S)-2-Amino-12-hydroxy-4,7,10-trioxadodecanoic acid hydrochloride (3c; n = 2). Obtain ed from
8c as a h ygroscopic oil. 1H NMR (D2O, 200 MHz): 4.25 (dd, 1 H, J = 4.7 an d 3.4); 4.04 (dd,
1 H, J = 11.0 an d 4.7); 3.97 (dd, 1 H, J = 11.0 an d 3.4); 3.78–3.62 (m , 12 H). FAB MS, m/z:
238 (MH+, 100). FAB HR MS: for [C9H20NO6]+ calculated 238.1290, foun d 238.1299.
(S,S)-2,15-Diamino-4,7,10,13-tetraoxahexadecanedioic acid dihydrochloride (4c; n = 2). Ob-
tain ed from 9c as a h ygroscopic glassy substan ce. 1H NMR (D2O, 200 MHz): 4.24 (dd, 2 H,
J = 4.7 an d 3.4); 4.05 (dd, 2 H, J = 11.0 an d 4.7); 3.95 (dd, 2 H, J = 11.0 an d 3.4); 3.78–3.68
(m , 12 H). FAB MS, m/z: 325 (MH+, 100). FAB MS HR: for [C12H25N2O8]+ calculated
325.1611, foun d 325.1614.
(S)-2-Amino-15-hydroxy-4,7,10,13-tetraoxapentadecanoic acid hydrochloride (3d ; n = 3). Ob-
tain ed from 8d as a h ygroscopic oil. 1H NMR (D2O, 200 MHz): 4.25 (dd, 1 H, J = 4.9 an d
3.7); 4.05 (dd, 1 H, J = 11.0 an d 4.9); 3.96 (dd, 1 H, J = 11.0 an d 3.7); 3.79–3.62 (m , 16 H).
FAB MS, m/z: 282 (MH+, 100). FAB HR MS: for [C11H24NO7]+ calculated 282.1553, foun d
282.1557.
(S,S)-2,18-Diamino-4,7,10,13,16-pentaoxanonadecanedioic acid dihydrochloride (4d ; n = 3).
Obtain ed from 9d as a h ygroscopic glassy substan ce. 1H NMR (D2O, 200 MHz): 4.24 (dd,
2 H, J = 4.6 an d 3.7); 4.05 (dd, 2 H, J = 11.3 an d 4.6); 3.95 (dd, 2 H, J = 11.3 an d 3.7);
3.88–3.64 (m , 16 H). FAB MS, m/z: 369 (MH+, 100). FAB HR MS: for [C14H29N2O9]+ calcu-
lated 369.1873, foun d 369.1869.
(S)-2-Amino-18-hydroxy-4,7,10,13,16-pentaoxaoctadecanoic acid hydrochloride (3e; n = 4). Ob-
tain ed from 8e as a h ygroscopic oil. 1H NMR (D2O, 200 MHz): 4.25 (dd, 1 H, J = 4.9 an d
3.7); 4.05 (dd, 1 H, J = 11.3 an d 4.9); 3.96 (dd, 1 H, J = 11.3 an d 3.7); 3.86–3.62 (m , 20 H).
FAB MS, m/z: 326 (MH+, 100). FAB HR MS: for [C13H28NO8]+ calculated 326.1815, foun d
326.1822.
(S,S)-2,21-Diamino-4,7,10,13,16,19-hexaoxadocosanedioic acid dihydrochloride (4e; n = 4). Ob-
tain ed from 9e as a h ygroscopic glassy substan ce. 1H NMR (D2O, 200 MHz): 4.25 (dd, 2 H,
J = 4.9 an d 3.7); 4.05 (dd, 2 H, J = 11.0 an d 4.9); 3.96 (dd, 2 H, J = 11.0 an d 3.7); 3.87–3.63
+
(m , 20 H). FAB MS, m/z: 413 (MH+, 100). FAB HR MS: for [C16H33N2O10
]
calculated
413.2135, foun d 413.2142.
This work was performed within the framework of the research project K4050111. The financial
support of the Grant Agency of the Czech Republic (grants No. 203/00/0137 and No. 203/03/0087) is
warmly acknowledged.
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