A new stereocontrolled approach to a key intermediate in the synthesis of (25,3R)-capreomycidine

Article abstract of DOI:10.1135/cccc20061199

A new stereocontrolled approach to the synthesis of advanced intermediate in the synthesis of nonproteinogenic amino acid (2S,3R)-capreomycidine via the novel domino reaction has been developed.

Full text of DOI:10.1135/cccc20061199

Synthesis of (2S,3R)-Capreomycidine
1199
A NEW STEREOCONTROLLED APPROACH TO A KEY INTERMEDIATE
IN THE SYNTHESIS OF (2S,3R)-CAPREOMYCIDINE
a2
b
Miroslava MARTINKOVÁa1,*, Jozef GONDA and Martina DŽOGANOVÁ
a
Department of Organic Chemistry, Institute of Chemistry, P. J. Šafárik University,
1
2
041 67 Košice, Slovak Republic; e-mail: mmartin@kosice.upjs.sk, jgonda@kosice.upjs.sk
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
166 10 Prague 6, Czech Republic; e-mail: dzoggy@post.sk
b
Received May 31, 2006
Accepted July 10, 2006
Dedicated to Professor Antonín Holý on the occasion of his 70th birthday.
A n ew stereocon trolled approach to th e syn th esis of advan ced in term ediate in th e syn th esis
of n on protein ogen ic am in o acid (2S,3R)-capreom ycidin e via th e n ovel dom in o reaction h as
been developed.
Keyw ord s: Capreom ycidin e; Capreom ycin s; Stereoselectivity; Non protein ogen ic am in o
acids; [3,3]-Sigm atropic rearran gem en ts; Total syn th esis.
Th e syn th esis of en an tiopure n on protein ogen ic α-am in o acids is of great
im portan ce due to th eir role as ph arm aceuticals, ch iral ligan ds an d buildin g
blocks in th e syn th esis of n atural products1. Am on g recen t developm en ts in
th e preparation of such com poun ds, th e fun ction alization of readily avail-
able protein ogen ic α-am in o acids an d th eir derivatives h as becom e an
atractive m eth od.
In th is paper we dem on strate th at D-m eth ion in e can be con verted very
efficien tly in to pure (2S,3R)-2,3-diacetam ido-5-acetoxypen tan oic acid (17)
as th e im portan t in term ediate in th e stereocon trolled syn th esis of (2S,3R)-
capreom ycidin e, wh ich is a con stituen t of th e tuberculostatic cyclic peptide
an tibiotics capreom ycin s an d related tuberactin om ycin s2.
Several syn th eses of th is n on protein ogen ic am in o acid in both racem ic
an d also optically pure form h ave been reported3. Recen tly we publish ed4
prelim in ary com m un ication con cern in g a n ew stereocon tolled approach to
a key precursor for th e syn th esis of th e cyclic guan idin o am in o acid
L-capreom ycidin e via th e n ovel dom in o reaction of th e [3,3]-sigm atropic
rearran gem en t of ch iral th iocyan ates easily prepared by ch ain len gth en in g
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210
© 2006 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc20061199

1200
Martinková, Gonda, Džoganová:
startin g from th e correspon din g α-am in o acids followed by stereoselective
cyclization 5.
We n ow describe a sequen ce of th e reaction steps for th e preparation of
th e protected ch iral am in o acid 17. As th e starin g m aterial we h ave ch osen
D-m eth ion in e wh ich was con verted in to (R)-2-am in obutan o-4-lacton e
h ydroch loride6 (1). Furth erm ore, tert-butoxycarbon ylation of 1 with di-tert-
butyl dicarbon ate in trieth ylam in e, usin g CH2Cl2 as th e solven t, gave pro-
tected lacton e 2 (92%; Sch em e 1), wh ich was th en rin g-open ed usin g
NaBH4 to form N-Boc-D-h om oserin ol (3) in 92% yield. Our subsequen t
strategy con sisted in a specific protection of th e prim ary alcoh olic group in
position 4. We assum ed th at due to bulky tert-butoxycarbon yl group th e
two prim ary alcoh ol fun ction s of 3 could be differen tiated easily. But treat-
m en t of 3 with TBDMSCl/pyridin e gave a m ixture of th ree products (two
m on osilylated regioisom ers an d on e double-protected derivative). A sim ilar
situation h as been observed em ployin g tert-butyldiph en ylsilyl ch loride7.
NHBoc
OH
R
BocN
O
(iii)
(ii)
(v)
O
OH
O
OR
4, R = H
1, R = NH2.HCl
2, R = NHBoc
3
(iv)
(i)
5, R = Bn
BnO
NHBoc
OH
BnO
NHBoc
BnO
NHBoc
(vi)
(vii)
R
COOCH3
6
1, R = OH
7
(viii)
2, R = SCN
(i) Boc2O, NEt3; (ii) NaBH4, THF; (iii) acetone, DMP; (iv) BnBr, NaH; (v) Amberlite, CH3OH/H2O;
(vi) IBX, DMSO/Ph3PCH=COOCH3; (vii) DIBAH, CH2Cl2; (viii) MsCl, NEt3/KSCN, MeCN
SCHEME 1
Th erefore we decided for th e form ation of th e oxazolidin e rin g wh ich
was ach ieved un der m ild con dition s with 2,2-dim eth oxypropan e (DMP)
in aceton e at room tem perature with BF3·OEt2 as a catalyst, yieldin g
aceton ide 4 in 83% yield. Th e ben zylation of 4 was carried out with Bn Br
an d NaH in THF to afford 4-O-ben zyl derivative 5 (87%; Sch em e 1). Hydro-
lysis of th e aceton ide usin g Am berlite IR120 H+ in CH3OH/H2O gave suit-
ably protected alcoh ol 6 (89%) wh ich was subsequen tly oxidized with
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

Synthesis of (2S,3R)-Capreomycidine
1201
o-iodoxyben zoic acid8 (IBX) in DMSO to yield correspon din g aldeh yde. Th e
aldeh yde was used directly in th e olefin ation un der Wittig con dition s
(Ph 3P=CHCOOCH3) givin g (E)-ester 7 in 80% overall yield, th e ester was
subjected to reduction with diisobutylalum in ium h ydride to yield allylic al-
coh ol 8 (80%). Th e required th iocyan ate 9 was easily prepared by th e two-
step process of m esylation of alcoh ol 8 followed by displacem en t usin g
KSCN in CH3CN in 64% overall yield. Th erm al rearan gem en t of th io-
cyan ate 9 (Sch em e 1) proceeded upon h eatin g at 80 °C in dry xylen e in th e
presen ce of catalytic am oun t of 2-h ydroxypyridin e to afford (4R,5R)-10 as
th e on ly isolatable product in 85% yield. Th e observed stereoch em istry of
cyclic th iourea 10 is in agreem en t with previous work5. Th e trans product
10 is form ed by in tram olecular am in o addition to syn-isoth iocyan ate
(Sch em e 2) wh ich was in th e reaction m ixture togeth er with anti derivative
with out selelectivity (syn/anti ≈ 50:50) as sh own by NMR an alysis of th e
crude reactiom m ixture after h eatin g at 80 °C for 35 m in wh en th e rear-
ran gem en t was com plete. Th ese diastereoisom ers, h owever, could n ot be
BnO
NHBoc
BnO
NHBoc
(i)
(ii)
9
HN
S
NH
NCS
11a,b
(i)
S
O
R
R
N
AcO
NHAc
N
NH
NH
(vi)
(v)
(iii)
NHAc
15
OBn
OBn
10, R = Boc
13, R = H
12, R = Boc
14, R = H
(iv)
(iv)
AcO
NHAc
CHO
AcO
NHAc
COOH
(vii)
NHAc
16
NHAc
17
(i) xylene, 80 oC, 2-hydroxypyridine; (ii) (aminomethyl)cyclopropane, Et2O; (iii) MNO, CH3CN;
(iv) CF3COOH/H2O 95:5; (v) 6 HCl, N2, heating, then pyridine, Ac2O; (vi) NaIO4, RuCl3,
CCl4/CH3CN/H2O 1:1:1; (vii) NaClO2, CH3CN/t-BuOH/2-methylbut-2-ene 4:4:1
M
SCHEME 2
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1202
Martinková, Gonda, Džoganová:
easily separated by ch rom atograph y, th erefore th ey were con verted in to th e
th ioureas 11a an d 11b easily differen tiable by th e reaction with (am in o-
m eth yl)cyclopropan e (Sch em e 2). Our approach to th e build-up of ch iral
am in o acid 17 was based on h ydrolysis of cyclic th iourea 10. Treatm en t of
10 with 6 M HCl resulted in n o reaction . Un protected cyclic th iourea 13
was isolated from th e reaction m ixture as a m ajor product. Rem oval of th e
tert-butoxycarbon yl protectin g group from 10 with TFA/H2O provided th e
sam e th iourea 13 (80%). We th erefore proceeded with cyclic urea 12, wh ich
was prepared from 10 by th e use of m esityln itrile oxide9 (MNO) in aceton i-
trile in 86% yield an d fully ch aracterized in th e form of th e un protected cy-
clic urea 14 (87%; Sch em e 2). Th e cyclic urea 12 was con verted in to th e
pure suitably protected diam in o acid 17 in two reaction steps. First, 12 was
subjected to reaction with 6 M HCl an d th en th e acetylation of dih ydro-
ch loride with acetic an h ydride in pyridin e gave fully protected acetate 15
in 76% overall yield. Surprisin gly, durin g th e h ydrolysis (6 M HCl, reflux)
th e ben zyl protectin g group was rem oved. Th e oxidation of 15 was accom -
plish ed with a catalytic am oun t of ruth en ium (III) ch loride an d NaIO4 in
CCl4/CH3CN/H2O (1:1:1) to give aldeh yde 16 in stead of correspon din g
acid10. With out purification (th is product was used im m ediately in th e n ext
step due to in stability of α-am in o aldeh ydes), th e crude 16 was selectively
oxidized to protected diam in o acid 17 by treatm en t with sodium ch lorite/
2-m eth ylbut-2-en e in 73% yield after flash ch rom atograph y (Sch em e 2).
A stereocon trolled syn th esis of ch iral n on -racem ic advan ced in ter-
m ediate 17 in th e syn th esis of n on protein ogen ic am in o acid (2S,3R)-
capreom ycidin e h as been reported em ploin g D-m eth ion in e as a reactan t. It
was foun d th at th e n ovel dom in o reaction 4,5 is a useful strategy for th e
preparation of diastereom erically pure (4R,5R)-4-vin yltetrah ydroim idazole-
2-th ion e 10.
EXPERIMENTAL
Th e m eltin g poin ts were determ in ed on th e Kofler block an d are un corrected. Optical rota-
tion s were m easured with a P3002 Krüss polarim eter in ch loroform an d H2O an d reported as
25
follows: [α]D (c in g/100 m l solven t). NMR spectra were recorded at room tem perature on a
FT NMR spectrom eter Varian Mercury Plus 400 (1H at 400.13 MHz an d 13C at 100.6 MHz),
on a FT NMR spectrom eter Bruker AMX 360 (1H at 360.13 MHz an d 13C at 90.55), on a FT
NMR spectrom eter Bruker Avan ce 500 (1H at 500.13 MHz an d 13C at 125.7 MHz) an d on a
FT NMR spectrom eter Varian Un ity-500 (1H at 499.8 MHz an d 13C at 125.7 MHz). Ch em ical
sh ifts (δ, ppm ) are referen ced eith er to tetram eth ylsilan e as in tern al stan dard for 1H or to
th e solven t sign al (13C NMR, δ(CDCl3) 77.0). 13C NMR m ultiplicities were determ in ed usin g
a DEPT pulse sequen ce. Couplin g con stan ts (J) are given in Hz. IR spectra (waven um bers in
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

Synthesis of (2S,3R)-Capreomycidine
1203
cm –1) were recorded on a Perkin –Elm er 599 IR spectrom eter in CHCl3. Th e reaction course
was routin ely m on itored by TLC (Merck 60 F254) an d th e products were visualized by UV
ligh t absorption at 254 n m or by sprayin g with Mo reagen t or KMn O4 reagen t. All reaction s
were perform ed un der an atm osph ere of n itrogen wh en an h ydrous solven ts were used.
Colum n ch rom atograph y was carried out in glass colum n s usin g silica gel Kieselgel (0.035–
0.070 m m ).
(R)-2-Am in obutan o-4-lacton e Hydroch loride (1)
13C NMR (90 MHz, D2O): 31.0 (C-3′); 52.7 (C-2′); 71.6 (C-4′); 178.7 (C=O). Th e procedure,
m .p. an d [α]D were con sisten t with th ose reported6. 13C NMR spectroscopic data h ave n ot
previously been reported6.
(R)-2-[(tert-Butoxycarbon yl)am in o]butan o-4-lacton e (2)
To a suspen sion of (R)-2-am in obutan o-4-lacton e h ydroch loride (1; 4.60 g, 33.5 m m ol) in dry
CH2Cl2 (42 m l) were added Et3N (4.60 m l, 33.5 m m ol) an d (Boc)2O (7.30 g, 33.5 m m ol).
After stirrin g at room tem perature for 12 h , th e reaction m ixture was wash ed with 1
M
aqueous KHSO4 (40 m l), 1 M aqueous NaHCO3 (40 m l), brin e (20 m l) an d dried (Na2SO4).
Evaporation of th e solven t at reduced pressure an d ch rom atograph y of th e residue (dich loro-
m eth an e–m eth an ol, 95:5) afforded 6.20 g (92%) of com poun d 2 as a wh ite solid, m .p.
25
21
115–118 °C (dich lorom eth an e–m eth an ol), [α]D –13.6 (c 0.23, CHCl3). (Ref.11 gives [α]D
–9.9 (c 1.3, CHCl3) but 13C NMR data were n ot correct in th is literature; in ref.12 1H an d 13C
NMR data are publish ed but with out [α]D). For C9H15NO4 (201.2) calculated: 53.72% C,
7.51% H, 6.96% N; foun d: 53.51% C, 7.30% H, 6.72% N. 1H NMR (400 MHz, CDCl3): 1.46 s,
9 H (3 × CH3); 2.20 m , 1 H (H-3′); 2.76 m , 1 H (H-3′); 4.25 ddd, 1 H, J(4′,4′) = 9.3, J(4′,3′) =
5.9, J(4′,3′) = 2.1 (H-4′); 4.36 m , 1 H (H-2′); 4.45 m , 1 H (H-4); 5.09 s, 1 H (NH). 13C NMR
(100 MHz, CDCl3): 28.1 (3 × CH3); 31.0 (C-3′); 49.9 (C-2′); 65.5 (C-4′); 80.3 ((CH3)3C); 155.3
(C=O); 175.2 (C-1′).
(R)-2-[(tert-Butoxycarbon yl)am in o]butan e-1,4-diol (3)
To a solution of lacton e 2 (6.10 g, 30.3 m m ol) in dry THF (74 m l) was added NaBH4 (2.47 g,
60.6 m m ol). Th e reaction m ixture was refluxed for 1 h , cooled an d quen ch ed with m eth an ol
(3 m l). Th e m ixture was poured in to saturated aqueous NaHCO3 (40 m l), th e product was
extracted with eth yl acetate (3 × 40 m l). Th e com bin ed organ ic layers were dried (Na2SO4)
an d con cen trated at reduced pressure. Th e residue was ch rom atograph ed on silica gel (cyclo-
h exan e–eth yl acetate, 1:2) an d afforded 5.75 g (92%) of diol 3 as a wh ite solid, m .p. 64–68 °C,
25
25
[α]D +9.9 (c 0.95, CHCl3). (Ref.13 gives [α]D +30.8 (c 0.4, MeOH), Aldrich h an dbook
20
for (S)-isom er [α]D –8 (c 1, CHCl3); refs12,14 do n ot report [α]D). For C9H19NO4 (205.3) cal-
culated: 52.67% C, 9.33% H, 6.82% N; foun d: 52.81% C, 9.29% H, 6.65% N. 1H NMR
(400 MHz, CDCl3, D2O): 1.45 s, 9 H (3 × CH3); 1.61 m , 1 H (H-3′); 1.81 m , 1 H (H-3′);
3.59–3.72 m , 4 H (H-1′, H-4′); 3.80 m , 1 H (H-2′). 13C NMR (100 MHz, CDCl3): 28.4 (3 ×
CH3); 34.8 (C-3′); 49.5 (C-2′); 58.7 (C-4′); 65.1 (C-1′); 80.0 ((CH3)3C); 157.1 (C=O).
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

1204
Martinková, Gonda, Džoganová:
tert-Butyl (4R)-4-(2-Hydroxyeth yl)-2,2-dim eth yl-1,3-oxazolidin e-3-carboxylate (4)
Diol 3 (5.70 g, 27.80 m m ol) was dissolved in a m ixture of aceton e (100 m l) an d 2,2-di-
m eth oxypropan e (30 m l) to wh ich BF3·OEt2 (0.20 m l) was added. Th e resultin g solution was
stirred at room tem perature for 1 h (TLC sh owed n o startin g 3). Th e solven t was rem oved
un der reduced pressure, residual oil taken up in CH2Cl2 (100 m l) an d th e resultin g solution
was wash ed with a m ixture of saturated aqueous NaHCO3 an d H2O (60 m l, 1:1), th en brin e
(60 m l), dried (Na2SO4) an d th e solven t was evaporated. Ch rom atograph y of th e residue
(cycloh exan e–eth yl acetate, 2:1) gave 5.63 g (83%) of com poun d 4 as a wh ite solid, m .p.
25
74–76 °C, [α]D
+13.4 (c 1.8, CHCl3). For C12H23NO4 (245.3) calculated: 58.75% C,
9.45% H, 5.71% N; foun d: 58.83% C, 9.34% H, 5.82% N. 1H NMR (500 MHz, CDCl3): 1.49 s,
12 H (4 × CH3); 1.53 s, 3 H (CH3); 1.71 m , 1 H (H-3′); 1.82 m , 1 H (H-3′); 3.53 m , 1 H (H-4′);
3.62 m , 1 H (H-2′); 3.68 d, 1 H, J = 8.7 (OH); 3.99 m 2 H (H-1′); 4.21 m , 1 H (H-4′).
13C NMR (100 MHz, CDCl3, 50 °C): 24.4 (CH3); 27.8 (CH3); 28.4 (3 × CH3); 37.7 (C-3′); 54.1
(C-2′); 58.7 (C-4′); 68.3 (C-1′); 80.9 ((CH3)3C); 93.7 (OCN); 153.8 (C=O). 1H NMR spectro-
scopic data were con sisten t with th ose reported in refs14b,15
ously been reported in refs14b,15
.
13C NMR data h ave n ot previ-
.
tert-Butyl (4R)-4-[2-(Ben zyloxy)eth yl]-2,2-dim eth yl-1,3-oxazolidin e-3-carboxylate (5)
To a solution of alcoh ol 4 (4.20 g, 17.12 m m ol) in dry THF (34 m l) at 0 °C was added NaH
(1.37 g, 34.32 m m ol, 60% dispersion in m in eral oil, freed of oil with an h ydrous THF). Th e
reaction was stirred at 0 °C for 20 m in an d th en Bn Br (3.10 m l, 25.68 m m ol) was added at
th e sam e tem perature. Th e m ixture was allowed to warm to room tem perature an d stirred
for 12 h an d th en partition ed between CH2Cl2 (50 m l) an d ice water (50 m l). Th e aqueous
ph ase was extracted with an oth er portion of CH2Cl2 (50 m l). Th e com bin ed organ ic ph ases
were dried (Na2SO4) an d th e solven t evaporated un der reduced pressure. Th e ch rom atogra-
ph y of residue on silica gel (cycloh exan e–eth yl acetate, 9:1) afforded 5.00 g (87%) of com -
25
poun d 5 as a colorless oil, [α]D +16 (c 0.24 CHCl3). For C19H29NO4 (335.5) calculated:
68.03% C, 8.71% H, 4.18% N; foun d: 68.14% C, 8.61% H, 4.27% N. 1H NMR (400 MHz,
CDCl3): 1.47 s, 12 H (4 × CH3); 1.57 s, 3 H (CH3); 1.85 m , 1 H (H-3′); 2.06 m , 1 H (H-3′);
3.53 s, 2 H (H-4′); 3.93 m , 3 H (H-1′, H-2′); 4.47 d, 1 H, J = 12.4 (CH2Ph ); 4.51 d, 1 H, J =
12.4 (CH2Ph ); 7.26–7.34 m , 5 H (Ph ). 13C NMR (100 MHz, CDCl3): 24.6 (CH3); 27.6 (CH3);
28.5 (3 × CH3); 33.8 (C-3′); 56.3 (C-2′); 67.4 (C-1′); 68.0 (C-4′); 72.9 (CH2Ph ); 80.0 ((CH3)3C);
93.5 (OCN); 127.5 (3 × C-arom .); 128.3 (2 × C-arom .); 138.4 (C-arom .); 152.2 (C=O).
tert-Butyl N-[(1R)-3-(Ben zyloxy)-1-(h ydroxym eth yl)propyl]carbam ate (6)
To a solution of 5 (4.90 g, 14.61 m m ol) in m eth an ol–H2O (9:1, 62 m l) was added Am berlite
IR-120 H+ (18.57 g). Th e m ixture was stirred at room tem perature overn igh t, filtered an d th e
solid was wash ed with m eth an ol. Evaporation of th e solven t from th e com bin ed filtrates
gave an oil wh ich was purified by ch rom atograph y on silica gel (cycloh exan e–eth yl acetate,
25
3:1) to afford 3.85 g (89%) of th e alcoh ol 6 as a colorless oil, [α]D +15 (c 0.23, CHCl3). For
C
16H25NO4 (295.4) calculated: 65.06% C, 8.53% H, 4.74% N; foun d: 64.83% C, 8.59% H,
4.62% N. 1H NMR (400 MHz, CDCl3): 1.44 s, 9 H (3 × CH3); 1.77–1.94 m , 2 H (H-3′);
3.25 bs, 1 H (OH); 3.57–3.62 m , 4 H (H-1′, H-4′); 3.76 m , 1 H (H-2′); 4.46 d, 1 H, J = 12.3
(CH2Ph ); 4.49 d, 1 H, J = 12.3 (CH2Ph ); 5.23 bs, 1 H (NH); 7.24–7.37 m , 5 H (Ph ). 13C NMR
(100 MHz, CDCl3): 28.5 (3 × CH3); 31.5 (C-3′); 51.3 (C-2′); 65.7 (C-4′ or C-1′); 67.3 (C-4′ or
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

Synthesis of (2S,3R)-Capreomycidine
1205
C-1′); 73.4 (CH2Ph ); 79.5 ((CH3)3C); 127.9 (3 × C-arom .); 128.6 (2 × C-arom .); 137.8
(C-arom .); 156.4 (C=O).
Meth yl (2E,4R)-6-(Ben zyloxy)-4-[(tert-butoxycarbon yl)am in o]h ex-2-en oate (7)
To a solution of 6 (3.80 g, 12.86 m m ol) in DMSO (29 m l) was added IBX (4.00 g, 14.15 m m ol).
Th e reaction m ixture was stirred at room tem perature for 5 h . Ice water (90 m l) was added
an d th e precipitate was filtered off. Th e filtrate was extracted with CH2Cl2 (2 × 90 m l). Th e
com bin ed organ ic ph ases were dried (Na2SO4) an d th e solven t was rem oved un der reduced
pressure. To th e aldeh yde dissolved in CH2Cl2 (34 m l), [(m eth oxycarbon yl)m eth yliden e]tri-
ph en ylph osph oran e (5.16 g, 15.43 m m ol) was added. Th e reaction m ixture was stirred at
room tem perature overn igh t. Th e solven t was rem oved at reduced pressure an d th e residue
was ch rom atograph ed on silica gel (cycloh exan e–eth yl acetate, 5:1) to give 3.60 g (80%) of
25
ester 7 as a colorless oil, [α]D
+53 (c 0.09, CHCl3). For C19H27NO5 (349.4) calculated:
65.31% C, 7.79% H, 4.01% N; foun d: 65.14% C, 7.63% H, 4.14% N. 1H NMR (400 MHz,
CDCl3): 1.44 s, 9 H (3 × CH3); 1.79 m , 1 H (H-5′); 1.99 m , 1 H (H-5′); 3.55 m , 2 H (H-6′);
3.72 s, 3 H (CH3O); 4.48 m , 2 H (CH2Ph ); 4.49 m , 1 H (H-4′); 5.37 d, 1 H, J = 6.6 (NH);
5.93 dd, 1 H, J(3′,2′) = 15.7, J(4′,2′) = 1.7 (H-2′); 6.87 dd, 1 H, J(3′,2′) = 15.7, J(4′,3′) = 4.9
(H-3′); 7.27–7.37 m , 5 H (Ph ). 13C NMR (100 MHz, CDCl3): 28.4 (3 × CH3); 33.6 (C-5′); 50.2
(C-4′); 51.6 (CH3O); 67.0 (C-6′); 73.3 (CH2Ph ); 79.5 ((CH3)3C); 120.6 (C-2′); 127.7 (2 ×
C-arom .); 127.8 (C-arom .); 128.5 (2 × C-arom .); 137.8 (C-arom .); 148.5 (C-3′); 155.2 (C=O);
166.7 (C=O).
tert-Butyl N-{(1R,2E)-1-[2-(Ben zyloxy)eth yl]-4-h ydroxybut-2-en -1-yl}carbam ate (8)
To a solution of ester 7 (3.50 g, 10.02 m m ol) in dry CH2Cl2 (47 m l) was added BF3·OEt2
(0.19 m l) at –10 °C. Th en diisobutylalum in ium h ydride (30.15 m l, 1.2 M toluen e solution )
was dropped in to cooled solution , th e resultin g m ixture was stirred at –10 °C for 1 h an d
th en quen ch ed with m eth an ol (7.5 m l). Th e m ixture was allowed to warm to room tem pera-
ture an d poured in to 30% aqueous KNa tartarate (157 m l). After stirrin g for 30 m in , th e
product was extracted with CH2Cl2 (3 × 70 m l). Th e com bin ed organ ic layers were dried
(Na2SO4) an d th e solven t evaporated un der reduced pressure. Ch rom atograph y of th e resi-
due (cycloh exan e–eth yl acetate, 1:1) afforded 2.58 g (80%) of allylic alcoh ol 8 as a colorless
25
oil, [α]D
+61 (c 0.18, CHCl3). For C18H27NO4 (321.4) calculated: 67.26% C, 8.47% H,
4.36% N; foun d: 67.01% C, 8.22% H, 4.48% N. 1H NMR (400 MHz, CDCl3): 1.44 s, 9 H (3 ×
CH3); 1.74 m , 1 H (H-5′); 1.91 m , 1 H (H-5′); 3.50–3.61 m , 3 H (H-6′, OH); 4.07 dd, 1 H,
J(1′,1′) = 12.0, J(2′,1′) = 5.3 (H-1′); 4.09 dd, 1 H, J(1′,1′) = 12.0, J(2′,1′) = 5.0 (H-1′); 4.28 m ,
1 H (H-4′); 4.48 s, 2 H (CH2Ph ); 5.20 bs, 1 H (NH); 5.61 dd, 1 H, J(3′,2′) = 15.4, J(4′,3′) = 5.1
(H-3′); 5.74 ddd, 1 H, J(3′,2′) = 15.4, J(2′,1′) = 5.3, J(2′,1′) = 5.0 (H-2′); 7.28–7.37 m , 5 H (Ph ).
13C NMR (100 MHz, CDCl3): 28.4 (3 × CH3); 34.6 (C-5′); 50.3 (C-4′); 62.9 (C-1′); 67.2 (C-6′);
73.2 (CH2Ph ); 79.2 ((CH3)3C); 127.7 (3 × C-arom .); 128.4 (2 × C-arom .); 129.6 (C-2′); 131.8
(C-3′); 138.1 (C-arom .); 155.5 (C=O).
tert-Butyl N-{(1R,2E)-1-[2-(Ben zyloxy)eth yl]-4-th iocyan atobut-2-en -1-yl}carbam ate (9)
To a solution of alcoh ol 8 (2.00 g, 6.22 m m ol) in dry CH2Cl2 (21.70 m l) were added Et3N
(1.30 m l, 9.33 m m ol) an d CH3SO2Cl (0.58 m l, 7.46 m m ol) at 0 °C. Th e reaction m ixture was
stirred at 0 °C for 15 m in an d th en at room tem perature for 2 h . Th e solven t was evaporated
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

1206
Martinková, Gonda, Džoganová:
un der reduced pressure. Th e residue was diluted with dieth yl eth er (40 m l) an d th e solid was
rem oved by filtration . Th e solven t was evaporated to afford th e crude m esylate wh ich was
used in th e subsequen t reaction directly with out furth er purification .
Th e crude m esylate was dissolved in CH3CN (22 m l) KSCN (0.90 g, 9.33 m m ol) was
added. After stirrin g at room tem perature for 1 h , th e solven t was evaporated. Th e residue
was diluted with dieth yl eth er (45 m l) an d th e solid was rem oved by filtration . Evaporation
of th e solven t at reduced pressure an d ch rom atograph y of th e residue (cycloh exan e–eth yl
25
acetate, 5:1) afforded 1.44 g (64%) of th iocyan ate 9 as a colorless oil, [α]D +208 (c 0.15,
CHCl3). For C19H26N2O3S (362.5) calculated: 62.96% C, 7.23% H, 7.73% N, 8.85% S; foun d:
63.06% C, 7.38% H, 7.89% N, 8.59% S. 1H NMR (400 MHz, CDCl3): 1.44 s, 9 H (3 × CH3);
1.79 m , 1 H (H-5′); 1.95 m , 1 H (H-5′); 3.47–3.67 m , 4 H (H-1′, H-6′); 4.35 m , 1 H (H-4′);
4.47 d, 1 H, J = 11.8 (CH2Ph ); 4.51 d, 1 H, J = 11.8 (CH2Ph ); 5.35 bs, 1 H (NH); 5.64–5.76 m ,
2 H (H-2′, H-3′); 7.26–7.34 m , 5 H (Ph ). 13C NMR (100 MHz, CDCl3): 28.3 (3 × CH3); 34.0
(C-5′); 35.7 (C-1′); 50.2 (C-4′); 66.9 (C-6′); 73.1 (CH2Ph ); 79.2 ((CH3)3C); 111.8 (SCN); 122.7
(C-2′); 127.6 (2 × C-arom .); 127.7 (C-arom .); 128.3 (2 × C-arom .); 138.0 (C-3′); 138.1
(C-arom .); 155.2 (C=O).
tert-Butyl (4R,5R)-4-[2-(Ben zyloxy)eth yl]-2-th ioxo-5-vin ylim idazolidin e-1-carboxylate (10)
To a solution of th iocyan ate 9 (1.35 g, 3.72 m m ol) in dry xylen e (32 m l) was added
2-h ydroxypyridin e (35.4 m g, 0.372 m m ol). Th e reaction m ixture was h eated at 80 °C for 5 h
un der n itrogen atm osph ere. Th e solven t was evaporated at reduced pressure, th e ch rom atog-
raph y of residue on silica gel (cycloh exan e–eth yl acetate, 5:1) gave 1.15 g (85%) of im id-
25
azolidin e 10 as a colorless oil, [α]D
+52 (c 0.26, CHCl3). For C19H26N2O3S (362.5)
calculated: 62.96% C, 7.23% H, 7.73% N, 8.85% S; foun d: 63.06% C, H, 7.38% H, 7.89% N,
8.59% S. IR (CHCl3): 1470 (C=S); 1740 (C=O); 3450 (NH). 1H NMR (400 MHz, CDCl3):
1.52 s, 9 H (3 × CH3); 1.98–2.07 m , 1 H (H-8′); 2.09–2.16 m , 1 H (H-8′); 3.55 ddd, 1 H,
J(9′,9′) = 10.6, J(9′,8′) = 6.0, J(9′,8′) = 4.6 (H-9′); 3.60 ddd, 1 H, J(9′,9′) = 10.6, J(9′,8′) = 5.6,
J(9′,8′) = 4.1 (H-9′); 4.10 dd, 1 H, J(6′,5′) = 6.6, J(5′,4′) = 5.4 (H-5′); 4.25 ddd, 1 H, J(8′,4′) =
9.0, J(5′,4′) = 5.4, J(8′,4′) = 2.7 (H-4′); 4.46 d, 1 H, J = 11.8 (CH2Ph ); 4.50 d, 1 H, J = 11.8
(CH2Ph ); 5.17 dd, 1 H, J(7′cis,6′) = 10.2, J(7′cis,7′trans) = 0.7 (H-7′cis); 5.21 dd, 1 H,
J(7′trans,6′) = 17.0, J(7′cis,7′trans) = 0.7 (H-7′trans); 5.77 ddd, 1 H, J(7′trans,6′) = 17.0,
J(7′cis,6′) = 10.2, J(6′,5′) = 6.6 (H-6′); 7.27–7.36 m , 5 H (Ph ); 7.56 s, 1 H (NH). 13C NMR
(100 MHz, CDCl3): 28.1 (3 × CH3); 33.2 (C-8′); 60.5 (C-5′); 64.5 (C-4′); 66.5 (C-9′); 73.4
(CH2Ph ); 83.6 ((CH3)3C); 117.6 (C-7′); 127.8 (3 × C-arom .); 128.5 (2 × C-arom .); 135.6 (C-6′);
137.9 (C-arom .); 150.0 (C=O); 180.2 (C=S).
rel tert-Butyl {(3R,4S)-1-(Ben zyloxy)-4-[3-(cyclopropylm eth yl)th ioureido]h ex-5-en -3-yl}-
carbam ate (11a) an d tert-Butyl {(3R,4R)-1-(Ben zyloxy)-4-[3-(cyclopropylm eth yl)-
th ioureido]h ex-5-en -3-yl}carbam ate (11b)
A solution of th iocyan ate 9 (0.25 g, 0.69 m m ol) in dry xylen e (6 m l) was h eated at 80 °C for
35 m in un der n itrogen atm osph ere. Th e solven t was evaporated, th e crude residue was dis-
solved in dieth yl eth er (5 m l) an d (am in om eth yl)cyclopropan e (0.07 m l, 0.76 m m ol) was
added. Th e reaction m ixture was stirred at room tem perature for 1.5 h , th en con cen trated
un der reduced pressure. Purification of th e residue by flash ch rom atograph y (cycloh exan e–
eth yl acetate, 7:1) afforded th ioureas 11a (0.10 g, 33.4%) an d 11b (0.15 g, 50.1%).
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

Synthesis of (2S,3R)-Capreomycidine
1207
25
11b : Colorless oil, [α]D
+197 (c 0.13, CHCl3). For C23H35N3O3S (433.6) calculated:
63.71% C, 8.14% H, 9.69% N, 7.39% S; foun d: 63.52% C, 8.21% H, 9.48% N, 7.54% S.
1H NMR (500 MHz, CDCl3): 0.25 m , 2 H (CH2cycloprop); 0.54 m , 2 H (CH2cycloprop); 1.06 m ,
1 H (CHcycloprop); 1.44 s, 9 H (3 × CH3); 1.70 1 H, m (H-2′); 1.98 m , 1 H (H-2′); 3.30 m , 2 H
(CH2N); 3.57 m , 1 H (H-1′); 3.60 m , 1 H (H-4′); 3.62 m , 1 H (H-1′); 3.76 m , 1 H (H-3′);
4.49 d, 1 H, J = 11.7 (Ph CH2O); 4.52 d, 1 H, J = 11.7 (Ph CH2O); 5.27 bd, 1 H J(6′cis,5′) =
10.6 (H-6′cis); 5.30 bd, 1 H, J(6′trans,5′) = 17.0 (H-6′trans); 5.74 ddd, 1 H, J(6′trans,5′) = 17.0,
J(6′cis,5′) = 10.6, J(5′,4′) = 6.3 (H-5′). 13C NMR (125.7 MHz, CDCl3): 3.6 (2 × CH2cycloprop);
10.0 (CHcycloprop); 28.3 (3 × CH3); 29.7 (C-2′); 31.8 (CH2NH); 52.9 (C-3′); 67.7 (C-1′); 73.4
(Ph CH2); 80.1 ((CH3)3C); 118.0 (C-6′); 127.7 (3 × C-arom .); 128.4 (2 × C-arom ); 128.5 (C-5′);
137.8 (C-arom .); 157.3 (C=O); 180.9 (C=S).
25
11a : Colorless oil, [α]D
+28 (c 0.18, CHCl3). For C23H35N3O3S (433.6) calculated:
63.71% C, 8.14% H, 9.69% N, 7.39% S; foun d: 63.56% C, 8.23% H, 9.52% N, 7.44% S.
1H NMR (500 MHz, CDCl3): 0.22 m , 2 H (CH2cycloprop); 0.54 m , 2 H (CH2cycloprop); 1.02 m ,
1 H (CHcycloprop); 1.44 s, 9 H (3 × CH3); 1.78 m , 1 H (H-2′); 1.92 m , 1 H (H-2′); 3.18 m , 2 H
(CH2N); 3.57 m , 1 H (H-1′); 3.62 m , 1 H (H-1′); 3.74 m , 1 H (H-4′); 3.93 m , 1 H (H-3′);
4.48 d, 1 H, J = 11.6 (Ph CH2O); 4.51 d, 1 H, J = 11.6 (Ph CH2O); 5.28 bd, 1 H, J(6′trans,5′) =
16.8 (H6′trans); 5.31 bd, 1 H, J(6′cis,5′) = 10.5 (H6′cis); 5.75 ddd, 1 H, J(6′trans,5′) = 16.8,
J(6′cis,5′) = 10.5, J(5′,4′) = 5.9 (H-5′). 13C NMR (125.7 MHz, CDCl3): 3.6 (2 × CH2cycloprop);
10.0 (CHcycloprop); 28.3 (3 × CH3); 29.7 (C-2′); 32.0 (CH2NH); 53.8 (C-3′); 67.5 (C-1′); 73.4
(CH2Ph ); 80.1 ((CH3)3C); 118.0 (C-6′); 127.8 (3 × C-arom ); 128.5 (2 × C-arom .); 133.4 (C-5′);
137.8 (C-arom .); 157.1 (C=O); 180.9 (C=S).
tert-Butyl (4R,5R)-4-[2-(Ben zyloxy)eth yl]-2-oxo-5-vin ylim idazolidin e-1-carboxylate (12)
To a solution of 10 (0.67 g, 1.85 m m ol) in CH3CN (19 m l) was added m esityln itrile oxide
(MNO) (0.158 g, 0.98 m m ol). Th e reaction m ixture was stirred at room tem perature for 15 m in ,
CH3CN was evaporated un der reduced pressure. Th e ch rom atograph y of residue on silica gel
25
(cycloh exan e–eth yl acetate, 3:1) gave 0.55 g (86%) of 12 as a colorless oil, [α]D
+105
(c 0.16, CHCl3). For C19H26N2O4 (346.4) calculated: 65.87% C, 7.57% H, 8.09% N; foun d:
65.98% C, 7.36% H, 7.94% N. 13C NMR (90 MHz, CDCl3): 28.0 (3 × CH3); 33.3 (C-8′); 55.9
(C-5′); 59.6 (C-4′); 66.4 (C-9′); 73.1 (CH2Ph ); 82.4 ((CH3)3C); 116.3 (C-7′); 127.5 (2 ×
C-arom .); 127.6 (C-arom .); 128.3 (2 × C-arom .); 137.0 (C-6′); 137.9 (C-arom .); 150.1 (C=O);
155.6 (C=O).
(4R,5R)-4-[2-(Ben zyloxy)eth yl]-5-vin ylim idazolidin e-2-th ion e (13)
Im idazolidin e 10 (0.15 g, 0.414 m m ol) was dissolved in a m ixture of CF3COOH an d H2O
(95:5, 5 m l). Th e reaction m ixture was stirred at room tem perature for 30 m in an d th en con -
cen trated un der reduced pressure. Th e residue was diluted with dieth yl eth er (10 m l) an d
wash ed with saturated aqueous NaHCO3 (5 m l). Th e organ ic ph ase was dried (Na2SO4), th e
solven t was evaporated an d th e resultin g crude product was purified by flash ch rom atogra-
ph y on silica gel (cycloh exan e–eth yl acetate, 1:1) to provide 0.087 g (80%) of 13 as a wh ite
25
solid, m .p. 69–70 °C, [α]D
+51 (c 0.86, CHCl3). For C14H18N2OS (262.4) calculated:
64.09% C, 6.92% H, 10.68% N, 12.22% S; foun d: 64.28% C, 6.76% H, 10.74% N, 12.01% S.
1H NMR (400 MHz, CDCl3): 1.81 m , 1 H (H-8′); 1.95 m , 1 H (H-8′); 3.52 m , 1 H (H-9′);
3.58 m , 1 H (H-9′); 3.78 ddd 1 H, J(5′,4′) = 8.1, J(8′,4′) = 5.1, J(8′,4′) = 3.6 (H-4′); 4.08 dd,
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

1208
Martinková, Gonda, Džoganová:
1 H, J(5′,4′) = 8.1, J(6′,5′) = 7.7 (H-5′); 4.49 d, 1 H, J = 12.2 (CH2Ph ); 4.52 d, 1 H, J = 12.2
(CH2Ph ); 5.23 d, 1 H, J(7′cis,6′) = 10.1 (H-7′cis); 5.28 d, 1 H, J(7′trans,6′) = 17.5 (H-7′trans);
5.81 ddd, 1 H, J(7′trans,6′) = 17.5, J(7′cis,6′) = 10.1, J(6′,5′) = 7.7 (H-6′); 6.01 bs, 1 H (NH);
6.50 bs, 1 H (NH); 7.29–7.39 m , 5 H (Ph ). 13C NMR (100 MHz, CDCl3): 33.7 (C-8′); 62.9
(C-5′); 66.4 (C-4′); 67.5 (C-9′); 73.4 (CH2Ph ); 119.1 (C-7′); 127.8 (2 × C-arom .); 128.0
(C-arom .); 128.6 (2 × C-arom .); 135.2, 137.6 (C-arom .); 183.2 (C=S).
(4R,5R)-4-[2-(Ben zyloxy)eth yl]-5-vin ylim idazolidin -2-on e (14)
Com poun d 12 (0.10 g, 0.289 m m ol) was dissolved in a m ixture of CF3COOH an d H2O (95:5,
3.50 m l). Th e reaction m ixture was stirred at room tem perature for 20 m in an d th en
con cen trated un der reduced pressure. Th e residue was diluted with dieth yl eth er (7 m l) an d
wash ed with saturated aqueous NaHCO3 (3.50 m l). Th e organ ic ph ase was dried (Na2SO4),
th e solven t was evaporated an d th e resultin g crude product purified by flash ch rom atogra-
ph y on silica gel (cycloh exan e–eth yl acetate, 1:2) to provide 0.062 g (87%) of 13 as a wh ite
25
solid, m .p. 76–78 °C, [α]D
+29.4 (c 0.15, CHCl3). For C14H18N2O2 (246.3) calculated:
68.27% C, 7.37% H, 11.37% N; foun d: 68.43% C, 7.56% H, 11.14% N. 1H NMR (400 MHz,
CDCl3): 1.85 m , 2 H (H-8′); 3.56 m , 3 H (H-4′, H-9′); 3.85 dd, 1 H, J(5′,4′) = 7.3, J(6′,5′) = 7.3
(H-5′); 4.47 d, 1 H, J = 12.7 (CH2Ph ); 4.50 d, 1 H, J = 12.7 (CH2Ph ); 5.09 bs, 1 H (NH);
5.16 dd, 1 H, J(7′cis,6′) = 10.1, J(7′cis,7′trans) = 0.9 (H-7′cis); 5.24 dd, 1 H, J(7′trans,6′) = 17.1,
J(7′cis,7′trans) = 0.9 (H-7′trans); 5.25 bs, 1 H (NH); 5.82 ddd, 1 H, J(7′trans,6′) = 17.1,
J(7′cis,6′) = 10.1, J(6′,5′) = 7.3 (H-6′); 7.24–7.36 m , 5 H (Ph ). 13C NMR (100 MHz, CDCl3):
34.3 (C-8′); 57.9 (C-5′); 62.1 (C-4′); 67.8 (C-9′); 73.3 (CH2Ph ); 117.6 (C-7′); 127.7 (2 ×
C-arom .); 127.8 (C-arom .); 128.5 (2 × C-arom .); 137.0 (C-6′); 137.9 (C-arom .); 162.6 (C=O).
(3R,4R)-3,4-Diacetam idoh ex-5-en -1-yl Acetate (15)
Com poun d 12 (0.41 g, 1.183 m m ol) was dissolved in 6 M HCl (20 m l) an d th e solution was
h eated un der reflux for 6 h in n itrogen atm osph ere. Th e solven t was rem oved un der
reduced pressure, th e resultin g solid was diluted with pyridin e (2 m l) an d Ac2O (0.9 m l, 9.54
m m ol) was added. Th e reaction m ixture was stirred at room tem perature overn igh t, th e
solven t was evaporated an d th e residue ch rom atograph ed on silica gel (dich lorom eth an e–
25
m eth an ol, 95:5) to give 0.23 g (76%) of 15 as a wh ite solid, m .p. 101–102 °C, [α]D +30.3
(c 0.165, CHCl3). For C12H20N2O4 (256.3) calculated: 56.24% C, 7.87% H, 10.93% N; foun d:
56.40% C, 7.56% H, 11.04% N. 1H NMR (400 MHz, CDCl3): 1.98 s, 3 H (CH3); 1.99 s, 3 H
(CH3); 2.05 s, 3 H (CH3); 1.74 m , 1 H (H-2′); 2.02 m , 1 H (H-2′); 4.03 m , 1 H (H-3′); 4.13 m ,
2 H (H-1′); 4.41 ddd, 1 H, J(4′,NH) = 8.4, J(4′,3′) = 7.6, J(5′,4′) = 7.0 (H-4′); 5.24 dd, 1 H,
J(6′cis,5′) = 10.1, J(6′cis,6′trans) = 0.5 (H-6′cis); 5.29 dd, 1 H, J(6′trans,5′) = 17.1, J(6′cis,6′trans) =
0.5 (H-6′trans); 5.76 ddd, 1 H, J(6′trans,5′) = 17.1, J(6′cis,5′) = 10.1, J(5′,4′) = 7.0 (H-5′);
6.77 d, 1 H, J(3′,NH) = 8.9 (NH); 6.93 d, 1 H, J(4′,NH) = 8.4 (NH). 13C NMR (100 MHz,
CDCl3): 20.9 (CH3); 23.0 (CH3); 23.1 (CH3); 30.5 (C-2′); 50.2 (C-3′); 56.4 (C-4′); 61.2 (C-1′);
118.1 (C-6′); 134.9 (C-5′); 170.4 (C=O); 171.0 (C=O); 171.5 (C=O).
(2S,3R)-2,3-Diacetam ido-5-acetoxypen tan oic Acid (17)
To a suspen sion of 15 (0.10 g, 0.39 m m ol) in CCl4–MeCN–H2O (1:1:1, 15 m l) were added
NaIO4 (0.42 g, 2.10 m m ol) an d RuCl3·H2O (1 m g). Th e reaction m ixture was stirred at room
tem perature for 3 h , an d th e solid was rem oved by filtration . After evaporation of th e sol-
Collect. Czech. Chem. Commun. 2006, Vol. 71, No. 8, pp. 1199–1210

Synthesis of (2S,3R)-Capreomycidine
1209
ven t un der reduce pressure, th e crude aldeh yde 16 (9.59 ppm for HCO, 197.8 ppm for C=O)
was used in th e subsequen t reaction with out purification .
A solution of NaClO2 (162 m g, 1.79 m m ol, 80 wt.%) an d NaH2PO4·2H2O (205 m g,
1.31 m m ol) in 1 m l of water was added dropwise to a solution of aldeh yde 16 (50 m g,
0.194 m m ol) in aceton itrile–tert-butyl alcoh ol–2-m eth ylbut-2-en e (4:4:1, 4 m l) at 0 °C over
5 m in an d th e resultin g solution was stirred at th e sam e tem perature for 1 h . Th en th e reac-
tion m ixture was poured in to brin e (1 m l) an d extracted with eth yl acetate (2 × 10 m l). Th e
com bin ed organ ic layers were dried (Na2SO4) an d con cen trated un der reduced pressure. Th e
residue was ch rom atograph ed on silica gel (dich lorom eth an e–m eth an ol, 3:1) affordin g
25
39 m g (73%) of acid 17 as a colorless oil, [α]D +36 (c 0.21, H2O). For C11H18N2O6 (274.3)
calculated: 48.17% C, 6.62% H, 10.21% N; foun d: 48.32% C, 6.34% H, 10.38% N. 1H NMR
(400 MHz, D2O): 1.71–1.80 m , 2 H (H-4′); 1.98 s, 3 H (CH3); 2.04 s, 3 H (CH3); 2.07 s, 3 H
(CH3); 4.10 m , 2 H (H-5′); 4.27 m , 1 H (H-2′); 4.34 m , 1 H (H-3′). 13C NMR (400 MHz, D2O):
23.1 (CH3); 24.7 (2 × CH3); 32.6 (C-4′); 51.3 (C-3′); 57.1 (C-2′); 60.9 (C-5′); 169.3 (C=O);
170.9 (C=O; 171.6 (2 × C=O).
This work was supported by the Grant Agency (projects 1/0446/03 and 1/2472/05) of the Ministry
of Education, Slovak Republic. NMR experiments were supported by the Ministry of Education, Slovak
Rebublic (project 200280203/2003).
REFERENCES
1. a) Williams R. M.: Synthesis of Optically Active α-Amino Acids. Pergamon, Oxford 1989;
b) Calmes M., Daunis J.: Amino Acids 1999, 16, 215.
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