Stereoselective total synthesis of protected sulfamisterin and its analogues

Article abstract of DOI:10.2478/s11696-013-0392-y

The stereoselective synthesis of sulfamisterin I and its unnatural analogues II and V in their protected form was achieved through a common strategy. The Wittig reaction of aldehydes VIII and IX with the C₁₄ hydrophobic side-chain X served as the key C-C connecting transformation. Subsequent functional group inter-conversions in the coupling products XI and XX completed the total synthesis.

Full text of DOI:10.2478/s11696-013-0392-y

Chemical Papers 67 (10) 1317–1329 (2013)
DOI: 10.2478/s11696-013-0392-y
ORIGINAL PAPER
Stereoselective total synthesis of protected sulfamisterin
and its analogues
Jana Špaková Raschmanová, Miroslava Martinková*, Jozef Gonda,
Alena Uhríková
Department of Organic Chemistry, Institute of Chemical Sciences, P. J. Šafárik University,
Moyzesova 11, 040 01 Košice, Slovakia
Received 26 October 2012; Revised 18 January 2013; Accepted 29 January 2013
The stereoselective synthesis of sulfamisterin I and its unnatural analogues II and V in their
protected form was achieved through a common strategy. The Wittig reaction of aldehydes VIII
and IX with the C14 hydrophobic side-chain X served as the key C—C connecting transformation.
Subsequent functional group inter-conversions in the coupling products XI and XX completed the
total synthesis.
c
ꢀ 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: sulfamisterin, total synthesis, stereoselective, α-substituted α-amino acid, Wittig re-
action, serine palmitoyltransferase
Introduction
no essential role in the biological activity (Sato et
al., 2005; Yamaji-Hasegawa et al., 2005). Although
I and also its analogues II, III, and IV have an in-
teresting β-hydroxy-α-substituted serine motif (Kang
et al., 2005; Ohfune & Shinada, 2005; Byun et al.,
2006) and exhibit remarkable bioactivity, only one to-
tal synthesis of I and its structurally-related deriva-
tives has been reported to date (Sato et al., 2005).
Prompted by these facts, and pursuing our interest
in the construction of structures containing a densely
functionalised quaternary centre (Gonda et al., 2006;
Martinková et al., 2006, 2008, 2010, 2012a, 2012b), we
focused on the synthesis of I and its desulphated con-
geners II and V (Sato et al., 2005) in their protected
form.
(+)-Sulfamisterin I, (2S,3R)-2-amino-(2-hydroxy-
methyl)-12-oxo-3-(sulphooxy)octadecanoic acid
(Fig. 1), is a new, natural, antifungal product that has
been isolated from the culture broths of Pycnidiella
sp. AB5366 (Sato et al., 2005; Yamaji-Hasegawa et al.,
2005). This compound is reported to be responsible for
both in vivo and in vitro inhibitory activity (Sato et
al., 2005; Yamaji-Hasegawa et al., 2005) towards ser-
ine palmitoyltransferase (Hanada, 2003), an enzyme
playing a crucial role in the sphingolipid biosynthesis.
The structure-elucidation study (Sato et al., 2005;
see also references herein) revealed that I is an un-
usual α-substituted α-amino acid derivative possess-
—
ing a C18 straight carbon chain with the C O group
—
at C-12, two stereogenic centres which are (2S,3R)-
configured and C-3 alcohol function bearing a sul-
phate moiety. The inhibitory profile of I and related
compounds depends on the stereochemistry at the C-2
quaternary centre and the 2S configuration is essential
for high activity (Sato et al., 2005; Yamaji-Hasegawa
et al., 2005). On the other hand, the stereochemistry
of the 3-hydroxy group as well as its sulphation plays
Experimental
All commercial reagents were used with the high-
est available purity from Aldrich, Fluka, Merck or
Acros Organics, without further purification. Solvents
were dried and purified prior to use following standard
procedures. Kieselgel 60 (0.040–0.063 mm, Merck)
was used for flash column chromatography. Solvents
*Corresponding author, e-mail: miroslava.martinkova@upjs.sk

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J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
Fig. 1. Sulfamisterin (I) and its analogues.
for flash chromatography (hexane, EtOAc, CH3OH,
CH2Cl2) were distilled prior to use. Thin layer chro-
matography was performed using Merck silica gel 60
F254 analytical plates; detection was performed with
either ultraviolet light (254 nm) or spraying with a
solution of phosphomolybdic acid, a basic potassium
permanganate solution, or a solution of concentrated
H2SO4, with subsequent heating. 1H and 13C NMR
spectra were recorded in CDCl3 and CD3OD on a Var-
(5S,6S)-8,8-Dimethyl-2-oxo-3,7,9-trioxa-1-
azaspiro[4.5]decane-6-carbaldehyde (IX)
Using the procedure described for the prepara-
tion of VIII, alcohol VII (0.15 g, 0.69 mmol) and
IBX (0.29 g, 1.04 mmol), after purification by flash
chromatography on silica gel (EtOAc), afforded crys-
talline aldehyde IX (0.14 g, 94 %); [α]2D5 = –72.1◦ (c
= 4.2 g L−1, CHCl3).
1
ian Mercury Plus 400 FT NMR (400.13 MHz for H,
100.6 MHz for 13C) or on a Varian Premium Com-
pact 600 (599.87 MHz for 1H, 150.84 MHz for 13C)
spectrometer using TMS as internal reference. For the
assignment of signals, homonuclear COSY and het-
eronuclear 2D correlated (HSQC, HMBC) techniques
were used. Optical rotations, [α]D (c in grams per
1000 mL, solvent), were measured on a P-2000 Jasco
polarimeter. Melting points were recorded on a Kofler
hot block and are uncorrected. All reactions were per-
formed under an atmosphere of nitrogen, unless noted
otherwise.
(5R,6R)-6-[(1ꢀZ)-8ꢀ-(2ꢀꢀ-Hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-
2ꢀꢀ-yl)oct-1ꢀ-en-1ꢀ-yl]-8,8-dimethyl-3,7,9-trioxa-
1-azaspiro[4.5]decan-2-one ((Z)-XI) and
(5R,6R)-6-[(1ꢀE)-8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-
2ꢀꢀ-yl)oct-1ꢀ-en-1ꢀ-yl]-8,8-dimethyl-3,7,9-trioxa-
1-azaspiro[4.5]decan-2-one ((E)-XI)
n-BuLi (2.43 mL of 1.6 M solution in hexane)
was added to a solution of 1,1,1,3,3,3-hexamethyldisil-
azane (0.83 mL, 3.89 mmol) in dry THF (4.1 mL)
at ambient temperature. The solution of lithium
bis(trimethylsilyl)azanide (LHMDS) thus generated
was treated with the known phosphonium salt X
(2.66 g, 4.45 mmol), and the resulting dark mixture
was stirred at ambient temperature for 5 min. A so-
lution of aldehyde VIII (0.30 g, 1.39 mmol) in dry
THF (4.1 mL) was then added drop-wise, and the re-
action mixture was stirred at ambient temperature for
30 min. Following complete conversion of the starting
material (TLC), the mixture was poured into a satu-
rated aqueous NH4Cl solution (30 mL) and extracted
with EtOAc (3 × 25 mL). The combined organic lay-
ers were dried with Na2SO4, the solvent was evapo-
rated, and the residue was chromatographed on silica
gel (hexane/EtOAc, ϕr = 1 : 1) to afford 0.51 g (81 %)
of a mixture of isomers XI as a colourless oil. A small
amount of the mixture of olefins XI was separated by
(5R,6S)-8,8-Dimethyl-2-oxo-3,7,9-trioxa-1-
azaspiro[4.5]decane-6-carbaldehyde (VIII)
2-Iodoxybenzoic acid (IBX) (0.62 g, 2.21 mmol)
was added to a solution of alcohol VI (0.32 g,
1.47 mmol) in CH3CN (7.6 mL) and the resulting
mixture was heated to reflux for 15 min. Once the
starting material was completely consumed (TLC),
the reaction was stopped and allowed to cool to am-
bient temperature. The insoluble materials were re-
moved by filtration, the solvent was evaporated under
reduced pressure, and the residue was purified by flash
chromatography on silica gel (EtOAc) to afford 0.30 g
(94 %) of aldehyde VIII as white amorphous solids,
[α]2D0 = +39.7◦ (c = 3.2 g L−1, CHCl3).

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
1319
column chromatography on silica gel (hexane/EtOAc,
ϕr = 1 : 1) to afford only (Z)-XI in pure form as a
colourless oil; [α]2D5 = –23.2◦ (c = 8.6 g L−1, CHCl3).
mixture at the same temperature. After stirring at
–78◦C for 3 h, the mixture was allowed to warm to
0◦C then Et3N (2.60 mL) and a saturated aqueous
NaHCO3 solution (21 mL) were added successively.
The aqueous phase was extracted with further por-
tions of CH2Cl2 (2 × 15 mL). The combined or-
ganic layers were dried with Na2SO4, stripped of sol-
vent and the residue was passed through a small pad
of silica gel (hexane/EtOAc, ϕr = 7 : 1) to afford
crude aldehyde (0.45 g, 97 %) that was immediately
used in the subsequent reaction without NMR analy-
sis.
A solution of NaClO2 (0.74 g, 8.18 mmol) and
NaH2PO4 · 2H2O (0.92 g, 5.90 mmol) in water (4.1
mL) was added to the solution of crude aldehyde
(0.45 g, 0.85 mmol) in a mixture of CH3CN/tert-
butanol/2-metylbut-2-ene (ϕr = 4 : 4 : 1, 18 mL) at
0◦C. After stirring at 0◦C for 30 min, the solvent was
removed under reduced pressure, and the residue was
chromatographed on silica gel (hexane/EtOAc, ϕr =
1 : 2) to afford 0.46 g (99 %) of acid XV as a colourless
oil; [α]2D5 = +50.0◦ (c = 1.6 g L−1, CH3OH).
(5R,6R)-6-[8ꢀ-(2ꢀꢀ-Hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-
2ꢀꢀ-yl)octyl]-8,8-dimethyl-3,7,9-trioxa-1-
azaspiro[4.5]decan-2-one (XII)
20 % Pd(OH)2/C (37 mg) was added to a solu-
tion of olefins XI (0.49 g, 1.08 mmol) in dry EtOH
(11.7 mL). The resulting mixture was stirred at am-
bient temperature for 1 h in an atmosphere of H2 and
then filtered through a short pad of Celite. Evapora-
tion of the solvent under reduced pressure followed by
column chromatography of the crude product on sil-
ica gel (hexane/EtOAc, ϕr = 1 : 1) afforded 0.46 g
(94 %) of XII as a colourless oil; [α]2D5 = +15.6◦ (c =
3.4 g L−1, CHCl3).
(5R,6R)-tert-Butyl 6-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-
dioxolan-2ꢀꢀ-yl)octyl]-8,8-dimethyl-2-oxo-3,7,9-
trioxa-1-azaspiro[4.5]decane-1-carboxylate
(XIII)
(2S,3R)-2-Acetamido-3-acetoxy-2-(acetoxy-
methyl)-12-oxooctadecanoic acid (XVI)
Di-tert-butyl bicarbonate (Boc2O) (0.43 g,
1.97 mmol) and 4-dimethylaminopyridine (DMAP)
(0.12 g, 0.98 mmol) were successively added to a so-
lution of XII (0.45 g, 0.99 mmol) in dry CH3CN
(1.9 mL). After stirring at ambient temperature for
15 min, the solvent was removed under reduced pres-
sure, and the residue was purified by flash chromatog-
raphy on silica gel (hexane/EtOAc, ϕr = 5 : 1) to
afford 0.54 g (99 %) of XIII as a colourless oil; [α]D25
= +20.0◦ (c = 2.8 g L−1, CHCl3).
A mixture of TFA/H2O (ϕr = 2 : 1, 3.5 mL)
was added to a solution of XV (52 mg, 0.10 mmol)
in THF (1.2 mL) and then stirred and heated at
50◦C for 3.5 h. Following complete consumption of
the starting material (1H NMR monitoring), the re-
action was stopped, the mixture was allowed to cool
to ambient temperature and the solvent was evapo-
rated. The crude product was immediately dissolved
in pyridine (1.8 mL), treated with Ac2O (1.76 mL,
18.6 mmol) and stirred at ambient temperature for
1 h, then poured into a saturated aqueous NaCl solu-
tion (5.6 mL) and extracted with EtOAc (5 × 10 mL).
The combined organic layers were dried with Na2SO4,
the solvent was removed under reduced pressure and
the residue was purified by flash chromatography on
silica gel (CH2Cl2/CH3OH, ϕr = 6 : 1) to afford 36 mg
(78 %) of XVI as a colourless oil; [α]2D5 = +35.1◦ (c =
6.4 g L−1, CH3OH).
tert-Butyl {(4R,5S)-4-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-
dioxolan-2ꢀꢀ-yl)octyl]-5-(hydroxymethyl)-2,2-
dimethyl-1,3-dioxan-5-yl}carbamate (XIV)
Cs2CO3 (0.09 g, 0.28 mmol) was added to a solu-
tion of XIII (0.53 g, 0.95 mmol) in CH3OH (14.2 mL).
After stirring at ambient temperature for 1.5 h, the re-
action mixture was concentrated under reduced pres-
sure, and the residue was subjected to flash chro-
matography on silica gel (hexane/EtOAc, ϕr = 3 : 1)
to afford 0.47 g (93 %) of XIV as a colourless oil; [α]D25
= +26.5◦ (c = 9.2 g L−1, CHCl3).
(4R,5S)-Benzyl 5-[(tert-butoxycarbonyl)
amino]-4-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-
2ꢀꢀ-yl)octyl]-2,2-dimethyl-1,3-dioxane-5-
carboxylate (XVII)
(4R,5S)-5-[(tert-Butoxycarbonyl)amino]-4-
[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-2ꢀꢀ-yl)octyl]-2,2-
dimethyl-1,3-dioxane-5-carboxylic acid (XV)
K2CO3 (28 mg, 0.20 mmol) and benzyl bromide
(BnBr) (36 µL, 0.30 mmol) were successively added
to a solution of XV (0.11 g, 0.20 mmol) in dry DMF
(1 mL). The mixture was stirred at ambient tem-
perature for 30 min, then poured into water (5 mL)
and extracted with Et2O (3 × 10 mL). The com-
bined organic layers were dried with Na2SO4, the
solvent was evaporated and the residue purified by
(COCl)2 (0.13 mL, 1.51 mmol) in CH2Cl2
(1.56 mL) was added to a solution of DMSO (0.21 mL,
2.96 mmol) in dry CH2Cl2 (1.56 mL) pre-cooled to –
78◦C and the resulting mixture was stirred at –78◦C
for 1 h. A solution of alcohol XIV (0.47 g, 0.89 mmol)
in CH2Cl2 (3.65 mL) was added drop-wise to this

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J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
flash chromatography on silica gel (hexane/EtOAc,
(2S,3R)-2-Amino-12-oxo-3-(sulphooxy)-2-
ϕr = 7 : 1) to afford 0.11 g (85 %) of XVII as
[(trityloxy)methyl]octadecanoic acid (XXI)
a colourless oil; [α]2D0 = +43.6◦ (c = 4.2 g L−1
,
CHCl3).
Using the same procedure as for the preparation
of XII, compound XX (91 mg, 0.10 mmol) was hy-
drogenated with 20 % Pd(OH)2/C (32 mg) for 22 h
to afford, after flash chromatography on silica gel
(CH2Cl2/CH3OH, ϕr = 7 : 1), 62 mg (90 %) of XXI as
white crystals; [α]2D2 = –1.7◦ (c = 5.8 g L−1, CH3OH).
(2S,3R)-Benzyl 2-{[(benzyloxy)carbonyl]
amino}-3-hydroxy-2-(hydroxymethyl)-12-
oxooctadecanoate (XVIII)
A solution of XVII (0.10 g, 0.16 mmol) in a mix-
ture of TFA/H2O (ϕr = 10 : 3, 0.78 mL) was stirred
at ambient temperature for 1 h. Next, the solvents
were evaporated under reduced pressure, the residue
was dissolved in THF (1.9 mL) and treated with a
saturated aqueous solution of NaHCO3 (1.9 mL). Af-
ter stirring at ambient temperature for 15 min, benzyl
chloroformate (CBzCl) (14 µL, 0.24 mmol) was added
and stirring continued at the same temperature for 30
min. The mixture was diluted with CH2Cl2 (10 mL),
the organic layer was separated and the aqueous layer
extracted with CH2Cl2 (2 × 10 mL). The combined
organic layers were dried with Na2SO4, the solvent
was evaporated, and the residue chromatographed on
silica gel (hexane/EtOAc, ϕr = 3 : 1) to afford 83 mg
(90 %) of XVIII as a colourless oil; [α]2D0 = +19.1◦ (c
= 1.6 g L−1, CHCl3).
(5S,6R)-6-[8ꢀ-(2ꢀꢀ-Hexyl-1ꢀꢀ,3ꢀꢀ-dioxolan-
2ꢀꢀ-yl)octyl]-8,8-dimethyl-3,7,9-trioxa-1-
azaspiro[4.5]decan-2-one (XXIII)
Using the procedure as for the preparation of XI,
compound IX (0.14 g, 0.65 mmol) was converted to
an inseparable mixture of olefins XX (0.17 g, 58 %,
colourless oil, hexane/EtOAc, ϕr = 1 : 1).
Using the procedure as for the preparation of XII,
the corresponding mixture of alkenes XX (0.16 g,
0.35 mmol) was hydrogenated with 20 % Pd(OH)2/C
(12 mg) for 2 h to afford, after flash chromatogra-
phy on silica gel (hexane/EtOAc, ϕr = 1 : 1), 155 mg
(97 %) of XXIII as a colourless oil; [α]2D5 = +28.5◦ (c
= 3.2 g L−1, CHCl3).
(5S,6R)-tert-Butyl 6-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-
dioxolan-2ꢀꢀ-yl)octyl]-8,8-dimethyl-2-oxo-3,7,9-
trioxa-1-azaspiro[4.5]decane-1-carboxylate
(XXIV)
(2S,3R)-Benzyl 2-{[(benzyloxy)carbonyl]
amino}-3-hydroxy-12-oxo-2-[(trityloxy)methyl]
octadecanoate (XIX)
Triphenylmethyl chloride (TrCl) (0.39 g, 1.40
mmol) and DMAP (69 mg, 0.56 mmol) were succes-
sively added to a solution of XVIII (82 mg, 0.14 mmol)
in dry pyridine (1.35 mL). After stirring and heating
at 60◦C for 30 h, the reaction mixture was allowed
to cool to ambient temperature, poured into water
(8 mL), and extracted with Et2O (3 × 15 mL). The
combined organic layers were dried with Na2SO4, the
solvent was evaporated, and the residue was purified
by flash chromatography on silica gel (hexane/EtOAc,
ϕr = 7 : 1) to afford 91 mg (78 %) of XIX as a colour-
less oil; [α]2D1 = +31.3◦ (c = 4.8 g L−1, CHCl3).
Using the procedure as for the preparation of XIII,
compound XXIII (65 mg, 0.14 mmol) was converted
to XXIV (72 mg, 91 %, colourless oil, hexane/EtOAc,
ϕr = 5 : 1); [α]2D5 = +14.7◦ (c = 3.8 g L−1, CHCl3).
tert-Butyl {(4R,5R)-4-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀꢀ-
dioxolan-2ꢀꢀ-yl)octyl]-5-(hydroxymethyl)-2,2-
dimethyl-1,3-dioxan-5-yl}carbamate (XXV)
Using the procedure as for the preparation of XIV,
compound XXIV (72 mg, 0.13 mmol) and Cs2CO3
(13 mg, 0.04 mmol) afforded, after flash chromatogra-
phy on silica gel (hexane/EtOAc, ϕr = 3 : 1), 60 mg
(88 %) of XXV as a colourless oil; [α]2D0 = –16.6◦ (c =
3.2 g L−1, CHCl3).
(2S,3R)-Benzyl 2-{[(benzyloxy)carbonyl]
amino}-12-oxo-3-(sulphooxy)-2-
[(trityloxy)methyl]octadecanoate (XX)
(4R,5R)-5-[(tert-Butoxycarbonyl)amino]-
4-[8ꢀ-(2ꢀꢀ-hexyl-1ꢀꢀ,3ꢀ’-dioxolan-2ꢀꢀ-yl)octyl]-
2,2-dimethyl-1,3-dioxane-5-carboxylic acid
(XXVI)
Sulphur trioxide pyridine complex (0.18 g, 1.13
mmol) was added to a stirred solution of XIX (91 mg,
0.11 mmol) in dry pyridine (3.4 mL). After heating
at 80◦C for 30 min, the reaction mixture was al-
lowed to cool to ambient temperature, co-evaporated
three times with toluene and the residue was chro-
Using the procedure as for the preparation of XV,
compound XXV (59 mg, 0.11 mmol) was converted to
carboxylic acid XXVI (60 mg, 99 %, colourless oil, hex-
matographed on silica gel (CH2Cl2/CH3OH, ϕr
=
15 : 1) to afford 95 mg (95 %) of XX as a colourless
ane/EtOAc, ϕr = 1 : 2); [α]2D0 = +8.9◦ (c = 3.2 g L−1
,
oil; [α]2D1 = +16.4◦ (c = 5.2 g L−1, CHCl3).
CHCl3).

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
1321
(2R,3R)-2-Acetamido-3-acetoxy-2-
(acetoxymethyl)-12-oxooctadecanoic acid
(XXVII)
p-TsOH (74 mg, 0.39 mmol) in three portions at 10
min intervals and the mixture was stirred at ambient
temperature for 24 h. The acid was then neutralised
with Et3N (37.0 µL), the solvent was removed under
reduced pressure and the residue was purified by flash
chromatography on silica gel (hexane/EtOAc, ϕr =
1 : 2) to afford 51 mg (81 %) of XXXI as a colourless
oil; [α]2D5 = +21.3◦ (c = 2.2 g L−1, CHCl3).
Using the procedure as for the preparation of XVI,
compound XXVI (60 mg, 0.11 mmol) was converted
to XXVII (35 mg, 66 %, colourless oil, EtOAc/AcOH,
ϕr = 50 : 1); [α]2D5 = +4.6◦ (c = 6.0 g L−1, CHCl3).
(S)-4-[(R)-1ꢀ-Hydroxy-10ꢀ-oxohexadecyl]-4-
(hydroxymethyl)oxazolidin-2-one (XXVIII)
(S)-4-[(R)-1ꢀ-(Benzoyloxy)-10ꢀ-oxohexadecyl]-
2-oxooxazolidine-4-carboxylic acid (XXXII)
A solution of XXIII (86 mg, 0.19 mmol) in a mix-
ture of AcOH/H2O (ϕr = 7 : 3, 18.6 mL) was stirred
and heated at 80◦C for 6 h and then at 40◦C for 12.5 h.
The solvent was removed under reduced pressure, and
the residue was subjected to flash chromatography on
silica gel (EtOAc) to afford 65 mg (92 %) of crystalline
XXVIII; [α]2D5 = +11.9◦ (c = 3.0 g L−1, CHCl3).
IBX (42 mg, 0.15 mmol) was added to a solution
of XXXI (48 mg, 0.10 mmol) in CH3CN (2 mL) and
the mixture was heated to reflux for 45 min. Next, the
mixture was allowed to cool to ambient temperature,
the solids were removed by filtation, and the solvent
was removed under reduced pressure. The aldehyde
thus obtained (47 mg, 98 %) was used immediately in
the subsequent reaction without further purification.
A solution of NaClO2 (86 mg, 0.95 mmol) and
NaH2PO4 · 2H2O (0.11 g, 0.71 mmol) in water (0.47
mL) was added drop-wise to the solution of crude alde-
hyde (47 mg, 0.10 mmol) in a mixture of CH3CN/tert-
butanol/2-metylbut-2-ene (ϕr = 4 : 4 : 1 , 2.1 mL) at
0◦C and the mixture was stirred at 0◦C for 15 min and
then at ambient temperature for 45 min. Evaporation
of the solvent and purification of the residue by chro-
matography on silica gel (CH2Cl2/CH3OH, ϕr = 8 : 1)
afforded 46 mg (94 %) of carboxylic acid XXXII as a
colourless oil; [α]2D5 = +47.5◦ (c = 1.4 g L−1, CHCl3).
(S)-4-[(R)-1ꢀ-Hydroxy-10ꢀ-oxohexadecyl]-4-
[(trityloxy)methyl]oxazolidin-2-one (XXIX)
TrCl (0.22 g, 0.79 mmol) and DMAP (39 mg,
0.32 mmol) were added successively to a solution of
XXVIII (60 mg, 0.16 mmol) in dry pyridine (1.6 mL)
and the mixture was stirred and heated at 60◦C for
23 h. The mixture was allowed to cool to ambient
temperature, poured into water (5 mL), and extracted
with Et2O (3 × 10 mL). The combined organic lay-
ers were dried with Na2SO4, the solvent was evap-
orated under reduced pressure, and the residue was
chromatographed on silica gel (hexane/EtOAc, ϕr =
2 : 1) to afford 90 mg (91 %) of XXIX as a colourless
oil; [α]2D5 = +27.5◦ (c = 4.0 g L−1, CHCl3).
Transformation of XXXII into XVI
NaOH (10 mass % aqueous solution, 3.2 mL) was
added to a solution of XXXII (45 mg, 0.09 mmol)
in CH3OH (3.2 mL) at ambient temperature; the
mixture was stirred and heated at 80◦C for 2 h,
cooled to ambient temperature and neutralised with
10 mass % aqueous HCl solution. The solids were
removed by filtration and the solvent was evap-
orated. The crude product was immediately dis-
solved in pyridine (1.7 mL), followed by the ad-
dition of Ac2O (1.68 mL, 17.8 mmol). The reac-
tion mixture was stirred at ambient temperature for
1 h, poured into a saturated aqueous NaCl solution
(5.3 mL), and extracted with EtOAc (5 × 10 mL).
The combined organic layers were dried with Na2SO4,
the solvent was evaporated under reduced pres-
sure, and the residue chromatographed on silica gel
(CH2Cl2/CH3OH, ϕr = 6 : 1) to afford 34 mg (77 %)
of XVI.
(R)-10-Oxo-1-{(S)-2ꢀ-oxo-4ꢀ-[(trityloxy)
methyl]oxazolidin-4ꢀ-yl}hexadecyl benzoate
(XXX)
Benzoyl chloride (BzCl) (0.10 mL, 0.86 mmol) and
DMAP (1.71 mg, 14.0 µmol) were added successively
to a solution of XXIX (86 mg, 0.14 mmol) in dry pyri-
dine (1.4 mL). The reaction mixture was stirred at
ambient temperature for 4 h, then poured into water
(5 mL), and extracted with Et2O (3 × 10 mL). The
combined organic phases were dried with Na2SO4, the
solvents were removed under reduced pressure, and
the residue was subjected to flash chromatography on
silica gel (hexane/EtOAc, ϕr = 4 : 1) to afford 97 mg
(96 %) of XXX as a colourless oil; [α]2D5 = –1.8◦ (c =
4.8 g L−1, CHCl3).
(R)-1-[(S)-4ꢀ-(Hydroxymethyl)-2ꢀ-oxooxazo-
lidin-4ꢀ-yl]-10-oxohexadecyl benzoate (XXXI)
Results and discussion
The oxazolidinones VI and VII obtained using a
previous approach (Martinková et al., 2012a) are effec-
tively capable of further transformation to the desired
To a solution of XXX (95 mg, 0.13 mmol) in
CH2Cl2/CH3OH (ϕr = 2 : 1, 1.65 mL) was added

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J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
nal molecules XVI, XXI, and XXVII would be con-
structed from the highly functionalised fragments, the
derivatives VI and/or VII referred to above (Mar-
tinková, et al., 2012a) and the hydrophobic C14 coun-
terpart X (Payette & Just, 1981; Sano et al., 1995).
The known phosphonium salt X was prepared on a
multigram scale, applying combined modifications of
protocols from the literature (Payette & Just, 1981;
Sano et al., 1995; Shioiri et al., 1998). The isothio-
cyanates A and B derived from D-xylose (Martinková,
et al., 2012a) with a defined configuration on both the
stereogenic centres were chosen as the starting mate-
rial to afford VI and VII, respectively.
Transformation of VI to α-substituted α-
amino acids XVI and XXI
Synthesis of sulfamisterin I and its desulphated
analogue II in their protected forms (see amino
acids XXI and XVI, respectively) commenced with
the branched aminopolyol VI, prepared in a larger
amount (more than 5 g) together with its congener,
diastereoisomer VII (Martinková et al., 2012a). Its
oxidation with IBX (More & Finney, 2002; Satam
et al., 2010) in CH3CN afforded the stable aldehyde
VIII with a 94 % yield (Fig. 3). Wittig olefination of
VIII with non-stabilised ylide derived from the known
phosphonium salt X (Payette & Just, 1981; Sano et
al., 1995) employing LHMDS (freshly prepared from
n-BuLi and NH(SiMe3)2) (Azuma et al., 2000) as the
Fig. 2. Retrosynthetic pathway.
target molecules, following the strategy illustrated in
Fig. 2.
Retrosynthetically, the carbon backbone of the fi-
Fig. 3. Synthesis of XVI. Reagents and conditions: i) IBX, CH3CN, reflux, 94 %; ii) LHMDS, X, THF, r.t., 81 %; iii) H2,
Pd(OH)2/C, EtOH, r.t., 94 %; iv) Boc2O, CH3CN, DMAP, a.rt., 99 %; v) Cs2CO3, CH3OH, r.t., 93 %; vi) DMSO,
(COCl)2, Et3N, –78 ◦C, 97 %, then NaClO2, CH3CN/tert-BuOH/2-methylbut-2-ene, 0◦C, 99 %; vii) TFA/H2O/THF,
50◦C, then Ac2O, pyridine, r.t., 78 % (after two steps).

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
1323
Fig. 4. Synthesis of XXI. Reagents and conditions: i) BnBr, K2CO3, DMF, r.t., 85 %; ii) TFA/H2O, r.t., then CBzCl, aqueous
NaHCO3, THF, r.t., 90 % (after two steps); iii) TrCl, pyridine, DMAP, 60◦C, 78 %; iv) sulphur trioxide pyridine complex,
pyridine, 80◦C, 95 %; v) H2, Pd(OH)2/C, CH3OH, r.t., 90 %.
base, resulted in the formation of a barely separable
of NaHCO3, resulted in the formation of the known
mixture of olefins XI (Z/E ≈ 3 : 1 ratio, determined
CBz-derivative XVIII (Sato et al., 2005) with a yield
of 90 %. The H NMR spectrum of XVIII exhibited
1
1
by H NMR) with a 81 % yield. A small amount of
the mixture of diastereomeric olefins XI was separated
using silica gel chromatography to yield only (Z)-XI
small differences from Chida’s product (Sato et al.,
2005), probably due to its measurement at 400 MHz
(see Experimental). Its 13C NMR data were in full ac-
cord with those reported in the literature (Sato et al.,
—
in pure form. The geometry of the C C bond was
—
confirmed on the basis of the vinyl proton coupling
constant value (Jcis = 11.6 Hz). Hydrogenation of XI
in the presence of Pd(OH)2/C in EtOH afforded the
saturated derivative XII (94 %, Fig. 3).
2005), but the value of the specific rotation ([α]D20
=
+19.1◦, c = 1.6 g L−1, CHCl3) was distinct from the
published value (Sato et al., 2005; [α]2D3 = +4.9◦, c
= 14.1 g L−1, CHCl3). The primary hydroxyl group
present in XVIII was selectively protected as the triph-
enylmethyl ether XIX using trityl chloride (TrCl) in
pyridine at 60◦C. The remaining alcohol function in
XIX was then treated with the sulphur trioxide pyri-
dine complex (Liav & Goren, 1984; Sanders et al.,
1997) in pyridine at 80◦C to afford compound XX
with a yield of 95 % (Fig. 4). Unfortunately, the final
catalytic hydrogenation using Pd(OH)2/C as a cata-
lyst removed only the Cbz and benzyl groups to af-
ford compound XXI (90 %) as the protected form of
I (Fig. 4). The addition of further portions of the cat-
alyst proved ineffective and led to the generation of
unidentified decomposition products. Substitution of
the tert-butyldimethylsilyl group for trityl was assayed
but its deprotection with tetra-n-butylammonium flu-
oride (TBAF) was accompanied by desulphatation.
Once the coupling product XII was achieved, it was
possible to explore its modification into the desired
α-substituted α-amino acids XVI and XXI, utilising
the stereoselective functional group transformations.
First, protection of the carbamate nitrogen atom in
XII with a Boc group by treatment with Boc2O and
DMAP in CH3CN (Hansen et al., 1995) provided XIII
with excellent yield (99 %, Fig. 3). Selective cleavage
of the cyclic carbamate moiety in XIII was achieved
with catalytic amounts of Cs2CO3 (Mita et al., 2007)
in CH3OH, affording the corresponding compound
XIV with 93 % yield. Swern oxidation of the primary
hydroxyl group in XIV followed by NaClO2 treatment
afforded the carboxylic acid XV (Fig. 3). The simulta-
neous removal of all protecting groups in XV by acid
hydrolysis (TFA/H2O) and the subsequent acetylation
with Ac2O in pyridine afforded derivative XVI (78 %,
Fig. 3) as the protected form of II.
Having secured an appropriate route to II, the next
task was to modify the corresponding amino acid XV
into sulfamisterin I. The reaction of XV with benzyl
bromide in dry DMF and in the presence of K2CO3
produced ester XVII with a yield of 85 % (Fig. 4).
Its acid hydrolysis (TFA/H2O), followed by treatment
with benzyl chloroformate (CBzCl) in the presence
Modification of VII into amino acids XVI and
XXVII
In a parallel fashion, diastereoisomer VII (Mar-
tinková et al., 2012a) was converted to (2R,3R)-
configured analogue XXVII in eight reaction steps and
with an overall yield of 27 % (Fig. 5). First, IBX-

1324
J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
Fig. 5. Synthesis of XXVII. Reagents and conditions: i) IBX, CH3CN, reflux, 94 %; ii) LHMDS, X, THF, r.t., 58 %; iii) H2,
Pd(OH)2/C, EtOH, r.t., 97 %; iv) Boc2O, CH3CN, DMAP, r.t., 91 %; v) Cs2CO3, CH3OH, rt, 88 %; vi) DMSO, (COCl)2,
Et3N, –78◦C, 99 %, then NaClO2, CH3CN/tert-BuOH/2-methylbut-2-ene, 0◦C, 99 %; vii) TFA/H2O/THF, 50◦C, then
Ac2O, pyridine, r.t., 66 % (two steps).
Fig. 6. Synthesis of XVI. Reagents and conditions: i) AcOH/H2O, 80◦C to 40◦C, 92 %; ii) TrCl, DMAP, pyridine, 60◦C, 91 %; iii)
BzCl, pyridine, DMAP, r.t., 96 %; iv) p-TsOH, CH3OH/CH2Cl2, r.t., 81 %; v) IBX, CH3CN, reflux, 98 %, then NaClO2,
CH3CN/tert-BuOH/2-methylbut-2-ene, 0◦C, 94 %; vi) 10 mass % aqueous NaOH, CH3OH, 80◦C, then Ac2O, pyridine,
r.t., 77 % (two steps).
mediated oxidation of VII afforded the correspond-
ing crystalline aldehyde IX (94 %, Fig. 5). Its cou-
pling reaction with an ylide derived from the known
X (Payette & Just, 1981; Sano et al., 1995) afforded
an inseparable mixture of alkenes XXII (Z/E ≈ 3 : 1
ratio, determined by 1H NMR). Unlike the coupling of

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
Table 1. Characterisation data of the newly prepared compounds
1325
wi(calc.)/%
wi(found)/%
Yield
M.p.
Compound
Formula
Mr
C
H
N
%
94
94
◦C
–
VIII
IX
C9H13NO5
C9H13NO5
215.20
215.20
50.23
50.20
50.23
50.29
66.19
6.09
6.15
6.09
6.02
9.55
6.51
6.45
6.51
6.58
3.09
148–150
XIa
C25H43NO6
C25H43NO6
453.61
453.61
81
–
–
–
(Z )-XI
66.19
66.15
65.90
65.95
64.84
64.88
65.75
65.72
64.06
64.00
61.83
61.81
68.22
68.26
69.95
69.89
77.06
77.01
70.25
70.31
66.93
66.85
66.19
9.55
9.59
9.95
9.93
9.61
9.63
10.46
10.45
9.82
9.85
8.93
8.95
9.38
9.31
8.46
8.49
7.69
7.75
7.01
7.05
7.54
7.59
9.53
3.09
3.05
3.07
3.09
2.52
2.59
2.64
2.67
2.58
2.63
2.88
2.95
2.21
2.26
2.40
2.36
1.70
1.66
1.55
1.51
2.05
2.01
3.09
XII
XIII
XIV
XV
C25H45NO6
C30H53NO8
C29H55NO7
C29H53NO8
C25H43NO8
C36H59NO8
C34H49NO7
C53H63NO7
455.63
555.74
529.75
543.73
485.61
633.86
583.76
826.07
906.13
681.88
94
99
93
99
78
85
90
78
95
90
–
–
–
–
XVI
XVII
XVIII
XIX
XX
–
–
–
–
–
C53H63NO10
S
XXI
C38H51NO8S
142–144
XXIIa
XXIII
C25H43NO6
C25H45NO6
453.61
455.63
58
97
–
–
65.90
65.93
64.84
64.80
65.75
65.79
64.06
64.08
61.83
61.87
64.66
64.69
76.31
76.29
76.96
76.92
68.18
68.22
66.24
66.27
9.95
9.98
9.61
9.65
10.46
10.43
9.82
9.80
8.93
8.90
10.04
10.00
8.37
8.42
7.72
7.75
8.69
8.65
8.03
8.00
3.07
3.05
2.52
2.49
2.64
2.61
2.58
2.55
2.88
2.85
3.77
3.73
2.28
2.33
1.95
1.91
2.94
2.91
2.86
2.90
XXIV
XXV
C30H53NO8
C29H55NO7
C29H53NO8
C25H43NO8
C20H37NO5
C39H51NO5
C46H55NO6
C27H41NO6
C27H39NO7
555.74
529.75
543.73
485.61
371.51
613.83
717.93
475.62
489.60
91
88
99
66
92
91
96
81
94
–
–
XXVI
XXVII
XXVIII
XXIX
XXX
–
–
69–70
–
–
–
–
XXXI
XXXII
a) Elemental analysis of compound (a mixture of geometric isomers) was not performed.
VIII with X, the lower yield (58 %) for this step was
most probably due to the formation of some minor
unidentified products. Hydrogenation of XXII with
Pd(OH)2/C in EtOH afforded the saturated prod-
uct XXIII with a yield of 97 % (Fig. 5). Protection
of the carbamate nitrogen of XXIII using the condi-
tions as described for the preparation of XIV success-
fully provided XXIV (91 %), of which the base treat-
ment (Cs2CO3, CH3OH) resulted in the formation
of the corresponding derivative XXV with a yield of
88 %. Step-wise oxidation of the primary alcohol XXV
(DMSO, oxalyl chloride followed by NaClO2) afforded

1326
J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
Table 2. Spectral data of the newly prepared compounds
Compound
Spectral data
VIII
IX
1H NMR (400 MHz, CDCl3), δ: 1.48 (s, 3H, CH3), 1.53 (s, 3H, CH3), 3.71 (d, 1H, J10,10 = 11.7 Hz, H-10), 4.04 (d,
1H, J10,10 = 11.7 Hz, H-10), 4.34 (d, 1H, J4,4 = 9.8 Hz, H-4), 4.42 (s, 1H, H-6), 4.48 (d, 1H, J4,4 = 9.8 Hz, H-4),
—
7.10 (br s, 1H, NH), 9.72 (s, 1H, CH O)
—
13C NMR (100 MHz, CDCl3), δ: 18.7 (CH3), 28.3 (CH3), 55.6 (C-5), 67.4 (C-10), 70.9 (C-4), 76.6 (C-6), 100.0
—
(C-8), 159.3 (C-2), 199.4 (CH O)
—
1H NMR (400 MHz, CDCl3), δ: 1.50 (s, 3H, CH3), 1.55 (s, 3H, CH3), 3.78 (d, 1H, J10,10 = 12.0 Hz, H-10), 3.89 (d,
1H, J10,10 = 12.0 Hz, H-10), 3.93 (d, 1H, J4,4 = 9.4 Hz, H-4), 4.14 (s, 1H, H-6), 4.62 (d, 1H, J4,4 = 9.4 Hz, H-4),
—
6.63 (br s, 1H, NH), 9.56 (s, 1H, CH O)
—
13C NMR (100 MHz, CDCl3), δ: 18.7 (CH3), 28.4 (CH3), 56.0 (C-5), 66.7 (C-4), 67.6 (C-10), 76.4 (C-6), 100.0
—
(C-8), 157.8 (C-2), 200.7 (CH O)
—
(Z )-XI 1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 7.0 Hz, CH3), 1.25–1.37 (m, 16H, 8 × CH2), 1.38 (s, 3H, CH3), 1.52
(s, 3H, CH3), 1.57–1.61 (m, 4H, 2 × CH2), 1.99–2.08 (m, 1H, H-3ꢀ), 2.11–2.20 (m, 1H, H-3ꢀ), 3.74 (d, 1H, J10,10
=
11.5 Hz, H-10), 3.93 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 3.95 (d, 1H, J10,10 = 11.5 Hz, H-10), 4.28 (d, 1H, J4,4 = 9.5 Hz,
H-4), 4.61–4.65 (m, 2H, H-4, H-6), 5.39 (ddt, 1H, J2 ,1ꢀ = 11.6 Hz, J6,1ꢀ = 8.1 Hz, J3ꢀ,1ꢀ = 1.6 Hz, J3ꢀ,1ꢀ = 1.6 Hz,
ꢀ
H-1ꢀ), 5.78 (dddd, 1H, J2 ,1 ꢀ = 6.3 Hz, J6,2ꢀ = 0.9 Hz, H-2ꢀ), 6.82 (br s, 1H, NH)
ꢀ =11.6 Hz, J3ꢀ,2ꢀ = 8.5 Hz, J3ꢀ,2
ꢀ
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 18.5 (CH3), 22.6 (CH2), 23.7 (CH2), 23.8 (CH2), 28.3 (C-3ꢀ), 28.9
(CH3), 29.1 (CH2), 29.2 (CH2), 29.6 (2 × CH2), 31.8 (CH2), 37.1 (2 × CH2), 56.5 (C-5), 64.8 (C-4ꢀꢀ, C-5ꢀꢀ), 67.8
(C-10), 69.7 (C-6), 70.1 (C-4), 99.2 (C-8), 111.8 (C-2ꢀꢀ), 122.2 (C-1ꢀ), 138.8 (C-2ꢀ), 159.6 (C-2)
XII
1H NMR (400 MHz, CDCl3), δ: 0.87 (t, 3H, J = 6.9 Hz, CH3), 1.24–1.36 (br s, 22H, 11 × CH2), 1.36 (s, 3H, CH3),
1.44 (s, 3H, CH3), 1.57–1.61 (m, 4H, 2 × CH2), 3.71 (d, 1H, J10,10 = 11.5 Hz, H-10), 3.72–3.75 (m, 1H, H-6), 3.85
(d, 1H, J10,10 = 11.5 Hz, H-10), 3.93 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 4.28 (d, 1H, J4,4 = 9.5 Hz, H-4), 4.55 (d, 1H,
J4,4 = 9.5 Hz, H-4), 6.34 (br s, 1H, NH)
13C NMR (100 MHz, CDCl3), δ: 14.1 (CH3), 18.5 (CH3), 22.6 (CH2), 23.8 (2 × CH2), 25.6 (CH2), 28.0 (CH2),
28.8 (CH3), 29.3 (CH2), 29.4 (2 × CH2), 29.6 (CH2), 29.8 (CH2), 31.8 (CH2), 37.1 (2 × CH2), 56.3 (C-5), 64.8
(C-4ꢀꢀ, C-5ꢀꢀ), 68.0 (C-10), 70.0 (C-4), 73.8 (C-6), 99.3 (C-8), 111.9 (C-2ꢀꢀ), 159.4 (C-2)
XIII
1H NMR (400 MHz, CDCl3), δ: 0.87 (t, 3H, J = 6.8 Hz, CH3), 1.22–1.34 (br s, 20H, 10 × CH2), 1.36 (s, 3H, CH3),
1.39–1.44 (m, 2H, CH2), 1.53 (s, 3H, CH3), 1.55–1.61 (m, 13H, 3 × CH3, 2 × CH2), 3.62 (d, 1H, J10,10 = 10.9 Hz,
H-10), 3.92 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 4.25 (d, 1H, J4,4 = 9.6 Hz, H-4), 4.49 (d, 1H, J4,4 = 9.6 Hz, H-4), 4.59–4.63
(m, 2H, H-6, H-10)
13C NMR (100 MHz, CDCl3), δ: 14.1 (CH3), 19.0 (CH3), 22.6 (CH2), 23.8 (2 × CH2), 25.3 (CH2), 28.0 (3 × CH3,
CH2), 28.8 (CH3), 29.2 (CH2), 29.3 (CH2), 29.5 (CH2), 29.6 (CH2), 29.8 (CH2), 31.8 (CH2), 37.1 (2 × CH2), 60.0
ꢀꢀ
ꢀꢀ
ꢀꢀ
—
(C-5), 64.8 (C-4 , C-5 ), 65.4 (C-10), 67.3 (C-4), 70.4 (C-6), 84.5 (Cq), 99.6 (C-8), 111.8 (C-2 ), 149.2 (C O),
—
159.4 (C-2)
XIV
1H NMR (400 MHz, CD3OD), δ: 0.88 (t, 3H, J = 6.6 Hz, CH3), 1.22–1.31 (m, 20H, 10 × CH2), 1.31 (s, 3H, CH3),
1.42 (s, 9H, 3 × CH3), 1.49 (s, 3H, CH3), 1.51–1.58 (m, 6H, 3 × CH2), 3.58 (d, 1H, JH,H = 11.4 Hz, CH2OH), 3.80
(d, 1H, J6,6 = 11.1 Hz, H-6), 3.88 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 3.97 (d, 1H, JH,H = 11.4 Hz, CH2OH), 4.15 (d, 1H,
J6,6 = 11.1 Hz, H-6), 4.50–4.53 (m, 1H, H-4), 6.01 (br s, 1H, NH)
13C NMR (100 MHz, CD3OD), δ: 14.6 (CH3), 19.9 (CH3), 23.7 (CH2), 25.0 (2 × CH2), 27.4 (CH2), 28.8 (3 × CH3),
29.3 (CH3), 29.5 (CH2), 30.4 (CH2), 30.6 (CH2), 30.7 (CH2), 30.8 (CH2), 31.0 (CH2), 33.1 (CH2), 38.1 (2 × CH2),
56.2 (C-5), 60.5 (CH2OH), 62.4 (C-6), 65.9 (C-4ꢀꢀ, C-5ꢀꢀ), 72.7 (C-4), 80.4 (Cq), 100.1 (C-2), 113.0 (C-2ꢀꢀ), 157.2
—
(C O)
—
XV
1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.9 Hz, CH3), 1.24–1.36 (m, 22H, 11 × CH2), 1.43 (s, 9H, 3 × CH3),
1.51 (s, 3H, CH3), 1.56–1.62 (m, 4H, 2 × CH2), 1.70 (s, 3H, CH3), 3.75 (d, 1H, J6,6 = 11.9 Hz, H-6), 3.92 (s, 4H,
2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 4.85 (d, 1H, J6,6 = 11.9 Hz, H-6), 4.93–4.95 (m, 1H, H-4), 5.71 (br s, 1H, NH) 13C NMR
(100 MHz, CDCl3), δ 14.1 (CH3), 18.9 (CH3), 22.6 (CH2), 23.8 (2 × CH2), 25.3 (CH2), 28.2 (3 × CH3), 29.0 (CH3),
29.3 (CH2), 29.4 (CH2), 29.6 (2 × CH2), 29.8 (2 × CH2), 31.8 (CH2), 37.1 (2 × CH2), 57.1 (C-5), 62.0 (C-6), 64.8
ꢀꢀ
ꢀꢀ
ꢀꢀ
—
(C-4 , C-5 ), 69.7 (C-4), 80.3 (Cq), 100.7 (C-2), 111.8 (C-2 ), 153.6 (C O), 171.3 (COOH)
—
XVI
1H NMR (400 MHz, CD3OD), δ: 0.85 (t, 3H, J = 6.8 Hz, CH3), 1.23 (m, 16H, 8 × CH2), 1.43–1.53 (m, 4H,
2 × CH2), 1.54–1.60 (m, 1H, CH2), 1.71–1.78 (m, 1H, CH2), 1.93 (s, 3H, CH3CO), 1.95 (s, 3H, CH3CO), 2.01 (s,
3H, CH3CO), 2.38 (t, 4H, J = 7.3 Hz, 2 × CH2), 4.45 (d, 1H, JH,H = 11.3 Hz, CH2O), 4.64 (d, 1H, JH,H = 11.3 Hz,
CH2O), 5.40 (dd, 1H, J4,3 = 10.7 Hz, J4,3 = 1.6 Hz, H-3)
13C NMR (100 MHz, CD3OD), δ: 14.4 (CH3), 20.8 (CH3CO), 20.9 (CH3CO), 23.1 (CH3CO), 23.6 (CH2), 24.9
(2 × CH2), 27.3 (CH2), 30.0 (CH2), 30.3 (CH2), 30.5 (3 × CH2), 31.2 (CH2), 32.8 (CH2), 43.5 (CH2), 43.5 (CH2),
—
—
—
—
—
63.3 (CH2O), 65.9 (C-2), 73.6 (C-3), 172.2 (C O), 172.4 (C O), 172.9 (C O), 173.5 (COOH), 214.3 (C-12)
—
XVII
1H NMR (400 MHz, CD3OD), δ: 0.91 (t, 3H, J = 6.8 Hz, CH3), 1.24–1.41 (m, 37H, 11 × CH2, 5 × CH3), 1.57–1.64
(m, 4H, 2 × CH2), 3.77–3.79 (m, 1H, H-4), 3.90–3.95 (m, 5H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ, H-6), 4.51 (d, 1H, J6,6 = 11.8 Hz,
H-6), 5.15 (s, 2H, CH2Ph), 7.31–7.42 (m, 5H, Ph)
13C NMR (100 MHz, CD3OD), δ: 14.5 (CH3), 22.3 (CH3), 23.7 (CH2), 24.9 (2 × CH2), 25.9 (CH3), 27.3 (CH2),
28.8 (3 × CH3), 30.5 (2 × CH2), 30.7 (CH2), 30.8 (CH2), 31.0 (CH2), 31.3 (CH2), 33.0 (CH2), 38.1 (2 × CH2),
63.4 (C-5), 65.9 (C-4ꢀꢀ, C-5ꢀꢀ), 66.2 (C-6), 68.0 (CH2Ph), 73.8 (C-4), 80.7 (Cq), 101.5 (C-2), 113.0 (C-2ꢀꢀ), 129.2
—
(CHPh), 129.5 (2 × CHPh), 129.6 (2 × CHPh), 137.2 (C ), 157.1 (C=O), 171.8 (C O)
—
i

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
1327
Table 2. (continued)
Compound
Spectral data
XVIII
XIX
XX
1H NMR (400 MHz, CDCl3), δ: 0.87 (t, 3H, J = 7.0 Hz, CH3), 1.22–1.40 (m, 17H, 8 × CH2 and 1H of CH2),
1.50–1.59 (m, 5H, 2 × CH2 and 1H of CH2), 2.35–2.39 (m, 4H, 2 × CH2), 3.08 (br s, 1H, OH), 3.67 (br s, 1H, OH),
3.95–4.07 (m, 3H, CH2OH, H-3), 5.10 (br s, 2H, CH2Ph), 5.17–5.25 (m, 2H, CH2Ph), 5.89 (br s, 1H, NH), 7.31–7.36
(m, 10H, Ph)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.5 (CH2), 23.8 (2 × CH2), 25.9 (CH2), 28.9 (CH2), 29.1 (CH2),
29.2 (4 × CH2), 31.6 (CH2), 42.7 (CH2), 42.8 (CH2), 64.2 (CH2OH), 67.3 (CH2Ph), 67.6 (CH2Ph), 69.0 (C-2), 74.0
(C-3), 128.1 (CHPh), 128.2 (2 × CHPh), 128.3 (CHPh), 128.4 (CHPh), 128.6 (5 × CHPh), 135.3 (Ci), 135.9 (Ci),
—
—
—
157.0 (C O), 170.9 (C O), 211.8 (C-12)
—
1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.9 Hz, CH3), 1.00–1.61 (m, 22H, 11 × CH2), 2.34–2.39 (m, 4H,
2 × CH2), 3.32 (d, 1H, JH,H = 9.4 Hz, CH2O), 3.67–3.75 (m, 1H, H-3), 3.93 (d, 1H, JH,H = 9.4 Hz, CH2O), 4.18
(d, 1H, J3,OH =11.4 Hz, OH), 5.08–5.15 (m, 2H, CH2Ph), 5.19 (d, 1H, JH,H = 12.2 Hz, CH2Ph), 5.24 (d, 1H, JH,H
= 12.2 Hz, CH2Ph), 5.81 (br s, 1H, NH), 7.21–7.41 (m, 25H, Ph)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 23.5 (CH2), 23.8 (2 × CH2), 25.9 (CH2), 28.9 (CH2), 29.2 (CH2),
29.3 (4 × CH2), 31.6 (CH2), 42.8 (2 × CH2), 64.2 (CH2O), 67.1 (CH2Ph), 67.5 (CH2Ph), 67.7 (C-2), 74.0 (C-3),
87.4 (CPh3), 127.3 (3 × CHPh), 127.9 (2 × CHPh), 128.0 (6 × CHPh), 128.1 (CHPh), 128.3 (4 × CHPh), 128.4
—
—
—
(6 × CHPh), 128.5 (3 × CHPh), 135.4 (C ), 136.2 (C ), 142.9 (3 × C ), 156.5 (C O), 170.4 (C O), 211.6 (C-12)
—
i
i
i
1H NMR (400 MHz, CD3OD), δ: 0.88 (t, 3H, J = 6.9 Hz, CH3), 0.95–1.35 (m, 16H, 8 × CH2), 1.40–1.56 (m, 6H,
3 × CH2), 2.37–2.43 (m, 4H, 2 × CH2), 3.60 (d, 1H, JH,H = 9.7 Hz, CH2O), 3.74 (d, 1H, JH,H = 9.7 Hz, CH2O),
4.71–4.73 (m, 1H, H-3), 5.00–5.13 (m, 4H, 2 × CH2Ph), 7.15–7.35 (m, 18H, Ph), 7.41–7.47 (m, 7H, Ph)
13C NMR (100 MHz, CD3OD), δ: 14.4 (CH3), 23.6 (CH2), 24.9 (CH2), 25.0 (CH2), 26.6 (CH2), 30.0 (CH2), 30.2
(CH2), 30.3 (2 × CH2), 30.4 (CH2), 32.2 (CH2), 32.8 (CH2), 43.5 (2 × CH2), 62.6 (CH2O), 67.1 (C-2), 67.4
(CH2Ph), 68.4 (CH2Ph), 81.9 (C-3), 88.1 (CPh3), 127.9 (3 × CHPh), 128.7 (6 × CHPh), 128.9 (CHPh), 129.3
—
—
(CHPh), 129.5 (6 × CHPh), 129.6 (CHPh), 130.2 (7 × CHPh), 136.9 (C ), 138.3 (C ), 145.3 (3 × C ), 156.9 (C O),
i
i
i
—
171.8 (C O), 214.4 (C-12)
—
XXI
1H NMR (400 MHz, CD3OD), δ: 0.87 (t, 3H, J = 6.7 Hz, CH3), 1.15–1.37 (m, 18H, 9 × CH2), 1.46–1.57 (m, 4H,
2 × CH2), 2.39–2.43 (m, 4H, 2 × CH2), 3.35 (d, 1H, JH,H = 9.3 Hz, CH2O), 3.76 (d, 1H, JH,H = 9.3 Hz, CH2O),
4.71 (m, 1H, H-3), 7.21–7.35 (m, 9H, Ph), 7.43–7.51 (m, 6H, Ph)
13C NMR (100 MHz, CD3OD), δ: 14.4 (CH3), 23.6 (CH2), 24.9 (2 × CH2), 27.0 (CH2), 30.0 (CH2), 30.3 (2 × CH2),
30.4 (CH2), 30.5 (CH2), 32.0 (CH2), 32.8 (CH2), 43.5 (2 × CH2), 64.0 (CH2O), 68.7 (C-2), 81.2 (C-3), 89.0 (CPh3),
128.4 (3 × CHPh), 129.0 (6 × CHPh), 130.2 (6 × CHPh), 144.5 (3 × Ci), 173.7 (COOH), 214.4 (C-12)
XXIII
1H NMR (400 MHz, CDCl3), δ: 0.87 (t, 3H, J = 6.9 Hz, CH3), 1.28 (m, 20H, 10 × CH2), 1.42 (s, 3H, CH3), 1.44
(s, 3H, CH3), 1.47–1.55 (m, 2H, CH2), 1.57–1.61 (m, 4H, 2 × CH2), 3.65–3.67 (m, 1H, H-6), 3.74 (d, 1H, J10,10
= 11.8 Hz, H-10), 3.82 (d, 1H, J4,4 = 9.3 Hz, H-4), 3.84 (d, 1H, J10,10 = 11.8 Hz, H-10), 3.93 (s, 4H, 2 × H-4ꢀꢀ,
2 × H-5ꢀꢀ), 4.03 (d, 1H, J4,4 = 9.3 Hz, H-4), 6.14 (br s, 1H, NH)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 18.6 (CH3), 22.5 (CH2), 23.7 (2 × CH2), 25.3 (CH2), 28.2 (CH2),
28.8 (CH3), 29.3 (CH2), 29.4 (2 × CH2), 29.5 (CH2), 29.8 (CH2), 31.8 (CH2), 37.0 (2 × CH2), 57.0 (C-5), 64.8
(C-4ꢀꢀ, C-5ꢀꢀ), 67.8 (C-4), 67.8 (C-10), 73.9 (C-6), 99.4 (C-8), 111.8 (C-2ꢀꢀ), 158.1 (C-2)
XXIV
1H NMR (400 MHz, CDCl3), δ: 0.84 (t, 3H, J = 6.9 Hz, CH3), 1.25 (m, 22H, 11 × CH2), 1.28 (s, 3H, CH3), 1.41
(s, 3H, CH3), 1.54 (m, 13H, 3 × CH3, 2 × CH2), 3.45 (m, 1H, H-6), 3.49 (d, 1H, J10,10 = 11.1 Hz, H-10), 3.78 (d,
1H, J4,4 = 9.1 Hz, H-4), 3.90 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 4.26 (d, 1H, J10,10 = 11.1 Hz, H-10), 4.35 (d, 1H, J4,4
= 9.1 Hz, H-4)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.5 (CH2), 22.9 (CH3), 23.7 (2 × CH2), 24.2 (CH3), 26.2 (CH2), 27.4
(CH2), 28.0 (3 × CH3), 29.3 (2 × CH2), 29.4 (CH2), 29.5 (CH2), 29.8 (CH2), 31.7 (CH2), 37.0 (2 × CH2), 61.9
ꢀꢀ
ꢀꢀ
ꢀꢀ
—
(C-10), 64.8 (C-4 , C-5 ), 65.3 (C-5), 69.7 (C-4), 72.9 (C-6), 84.4 (Cq), 101.6 (C-8), 111.7 (C-2 ), 149.5 (C O),
—
152.7 (C-2)
XXV
1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.8 Hz, CH3), 1.24–1.40 (m, 25H, 11 × CH2, CH3), 1.43 (s, 3H,
CH3), 1.46 (s, 9H, 3 × CH3), 1.56–1.60 (m, 4H, 2 × CH2), 3.43 (t, 1H, JH,H = 11.6 Hz, JH,OH = 11.6 Hz, CH2OH),
3.64–3.68 (m, 1H, H-4), 3.77 (d, 1H, J6,6 = 12.3 Hz, H-6), 3.93 (s, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 3.94–3.97 (m, 1H,
CH2OH), 4.00 (d, 1H, J6,6 = 12.3 Hz, H-6), 4.81 (m, 1H, OH), 5.37 (br s, 1H, NH)
13C NMR (100 MHz, CDCl3), δ: 14.1 (CH3), 18.5 (CH3), 22.5 (CH2), 23.8 (2 × CH2), 25.4 (CH2), 28.3 (3 × CH3),
28.6 (CH3), 29.3 (2 × CH2), 29.4 (CH2), 29.5 (2 × CH2), 29.8 (CH2), 31.8 (CH2), 37.1 (2 × CH2), 55.6 (C-5), 64.8
ꢀꢀ
ꢀꢀ
ꢀꢀ
—
(C-4 , C-5 , CH2OH), 64.9 (C-6), 74.6 (C-4), 80.2 (Cq), 98.8 (C-2), 111.8 (C-2 ), 157.2 (C O)
—
XXVI
1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.9 Hz, CH3), 1.24–1.37 (m, 22H, 11 × CH2), 1.43 (s, 3H, CH3),
1.45 (s, 3H, CH3), 1.47 (s, 9H, 3 × CH3), 1.56–1.63 (m, 4H, 2 × CH2), 3.94 (m, 4H, 2 × H-4ꢀꢀ, 2 × H-5ꢀꢀ), 4.12 (m,
1H, H-4), 4.21 (br s, 2H, 2 × H-6), 5.27 (br s, 1H, NH)
13C NMR (100 MHz, CDCl3), δ: 14.1 (CH3), 18.6 (CH3), 22.6 (CH2), 23.6 (CH2), 23.7 (CH2), 25.4 (CH2), 28.2
(3 × CH3), 28.9 (CH2), 29.1 (CH3), 29.3 (CH2), 29.5 (2 × CH2), 29.6 (2 × CH2), 31.8 (CH2), 37.0 (CH2), 37.1
ꢀꢀ
ꢀꢀ
ꢀꢀ
—
—
(CH2), 60.0 (C-5), 63.8 (C-6), 64.8 (C-4 , C-5 ), 73.1 (C-4), 81.0 (Cq), 99.3 (C-2), 112.0 (C-2 ), 156.5 (C O),
172.2 (COOH)

1328
J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
Table 2. (continued)
Compound
Spectral data
XXVII 1H NMR (400 MHz, CD3OD), δ: 0.83 (t, 3H, J = 6.9 Hz, CH3), 1.22 (m, 18H, 9 × CH2), 1.42–1.52 (m, 4H,
2 × CH2), 1.91 (s, 3H, CH3CO), 1.92 (s, 3H, CH3CO), 1.99 (s, 3H, CH3CO), 2.37 (t, 4H, J = 7.3 Hz, 2 × CH2),
4.51 (d, 1H, JH,H = 10.7 Hz, CH2O), 4.65 (d, 1H, JH,H = 10.7 Hz, CH2O), 5.45–5.50 (m, 1H, H-3)
13C NMR (100 MHz, CD3OD), δ: 14.4 (CH3), 20.7 (CH3CO), 21.0 (CH3CO), 23.3 (CH3CO), 23.6 (CH2), 24.9
(2 × CH2), 27.0 (CH2), 30.0 (CH2), 30.3 (2 × CH2), 30.4 (2 × CH2), 31.0 (CH2), 32.8 (CH2), 43.5 (2 × CH2),
—
—
—
—
64.6 (CH2O), 65.2 (C-2), 75.0 (C-3), 172.1 (C O), 172.6 (C O), 172.9 (C O), 173.2 (COOH), 214.4 (C-12)
—
—
XXVIII 1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.8 Hz, CH3), 1.27 (m, 17H, 8 × CH2 and 1H of CH2), 1.50–1.60
(m, 5H, 2 × CH2 and 1H of CH2), 2.39 (t, 4H, J = 7.4 Hz, 2 × CH2), 3.62–3.72 (m, 3H, CH2OH, H-1ꢀ), 3.99 (br
s, 1H, OH), 4.22 (d, 1H, J5,5 = 8.7 Hz, H-5), 4.31 (d, 1H, J5,5 = 8.7 Hz, H-5), 4.39 (br s, 1H, OH), 6.93 (br s, 1H,
NH)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.5 (CH2), 23.8 (2 × CH2), 26.0 (CH2), 28.9 (CH2), 29.2 (CH2), 29.3
(2 × CH2), 29.4 (CH2), 30.6 (CH2), 31.6 (CH2), 42.7 (CH2), 42.8 (CH2), 64.2 (CH2OH), 65.9 (C-4), 68.8 (C-5),
72.4 (C-1ꢀ), 161.0 (C-2), 212.1 (C-10ꢀ)
XXIX
1H NMR (400 MHz, CDCl3), δ: 0.88 (t, 3H, J = 6.9 Hz, CH3), 1.13–1.32 (m, 17H, 8 × CH2 and 1H of CH2),
1.51–1.58 (m, 5H, 2 × CH2 and 1H of CH2), 2.38 (t, 4H, J = 7.3 Hz, 2 × CH2), 2.47 (br s, 1H, OH), 3.22 (d, 1H,
JH,H = 9.5 Hz, CH2O), 3.39 (d, 1H, JH,H = 9.5 Hz, CH2O), 3.74–3.79 (m, 1H, H-1ꢀ), 4.00 (d, 1H, J5,5 = 8.9 Hz,
H-5), 4.28 (d, 1H, J5,5 = 8.9 Hz, H-5), 5.83 (br s, 1H, NH), 7.22–7.33 (m, 9H, Ph), 7.38–7.42 (m, 6H, Ph)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.5 (CH2), 23.8 (2 × CH2), 26.0 (CH2), 28.9 (CH2), 29.1 (CH2),
29.3 (2 × CH2), 29.7 (CH2), 30.2 (CH2), 31.6 (CH2), 42.7 (CH2), 42.8 (CH2), 64.0 (C-4), 65.5 (CH2O), 69.1 (C-5),
72.8 (C-1ꢀ), 87.2 (CPh3), 127.4 (3 × CHPh), 128.1 (6 × CHPh), 128.5 (6 × CHPh), 142.9 (3 × Ci), 159.4 (C-2),
211.8 (C-10ꢀ)
XXX
1H NMR (400 MHz, CDCl3), δ: 0.86 (t, 3H, J = 7.0 Hz, CH3), 1.15–1.22 (m, 8H, 4 × CH2), 1.23–1.40 (m, 9H,
4 × CH2 and 1H of CH2), 1.41–1.58 (m, 5H, 2 × CH2 and 1H of CH2), 2.32–2.38 (m, 4H, 2 × CH2), 3.21 (d, 1H,
JH,H = 9.5 Hz, CH2O), 3.41 (d, 1H, JH,H = 9.5 Hz, CH2O), 3.99 (d, 1H, J5 ,5 ꢀ ꢀ
ꢀ = 8.9 Hz, H-5ꢀ), 4.36 (d, 1H, J5 ,5
ꢀ
= 8.9 Hz, H-5ꢀ), 5.55 (d, 1H, J2,1 = 10.4 Hz, J2,1 = 2.2 Hz, H-1), 6.41 (br s, 1H, NH), 7.20–7.29 (m, 9H, Ph),
7.39–7.47 (m, 8H, Ph), 7.55–7.60 (m, 1H, Ph), 7.94–7.98 (m, 2H, Ph)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.4 (CH2), 23.7 (CH2), 23.8 (CH2), 25.7 (CH2), 28.9 (2 × CH2),
29.1 (2 × CH2), 29.2 (2 × CH2), 31.6 (CH2), 42.7 (CH2), 42.8 (CH2), 63.7 (C-4ꢀ), 65.2 (CH2O), 68.8 (C-5ꢀ), 74.0
(C-1), 87.2 (CPh3), 127.3 (3 × CHPh), 128.0 (6 × CHPh), 128.3 (Ci), 128.5 (8 × CHPh), 129.7 (2 × CHPh), 133.3
ꢀ
—
(CHPh), 142.8 (3 × C ), 159.1 (C-2 ), 166.1 (C O), 211.7 (C-10)
—
i
XXXI
1H NMR (400 MHz, CDCl3), δ: 0.87 (t, 3H, J = 6.8 Hz, CH3), 1.19–1.39 (m, 16H, 8 × CH2), 1.48–1.57 (m, 4H,
2 × CH2), 1.63–1.75 (m, 2H, CH2), 2.36 (m, 4H, 2 × CH2), 3.34 (br s, 1H, OH), 3.64 (d, 1H, JH,H = 11.9 Hz,
CH2OH), 3.68 (d, 1H, JH,H = 11.9 Hz, CH2OH), 4.32 (d, 1H, J5 ,5 ꢀ ꢀ = 9.0 Hz,
ꢀ = 9.0 Hz, H-5ꢀ), 4.39 (d, 1H, J5 ,5
ꢀ
H-5ꢀ), 5.38 (d, 1H, J2,1 = 9.9 Hz, J2,1 = 3.1 Hz, H-1), 6.30 (br s, 1H, NH), 7.44–7.47 (m, 2H, Ph), 7.58–7.62 (m,
1H, Ph), 8.03–8.05 (m, 2H, Ph)
13C NMR (100 MHz, CDCl3), δ: 14.0 (CH3), 22.5 (CH2), 23.7 (CH2), 23.8 (CH2), 25.6 (CH2), 28.7 (CH2), 28.9
(CH2), 29.1 (3 × CH2), 29.2 (CH2), 31.6 (CH2), 42.7 (CH2), 42.8 (CH2), 64.4 (C-4ꢀ), 64.4 (CH2OH), 68.9 (C-5ꢀ),
74.2 (C-1), 128.6 (2 × CHPh), 129.0 (Ci), 129.8 (2 × CHPh), 133.7 (CHPh), 159.5 (C-2ꢀ), 166.8 (C=O), 211.8 (C-10)
XXXII 1hH NMR (400 MHz, CD3OD), δ: 0.87 (t, 3H, J = 7.0 Hz, CH3), 1.18–1.37 (m, 16H, 8 × CH2), 1.44–1.54 (m, 4H,
2 × CH2), 1.65–1.72 (m, 2H, CH2), 2.35–2.40 (m, 4H, 2 × CH2), 4.53 (d, 1H, J5,5 = 9.2 Hz, H-5), 4.69 (d, 1H, J5,5
= 9.2 Hz, H-5), 5.57–5.60 (m, 1H, H-1ꢀ), 7.44–7.48 (m, 2H, Ph), 7.57–7.61 (m, 1H, Ph), 8.03–8.05 (m, 2H, Ph)
13C NMR (100 MHz, CD3OD), δ: 14.0 (CH3), 23.6 (CH2), 24.9 (2 × CH2), 26.9 (CH2), 30.0 (CH2), 30.2 (2 × CH2),
30.3 (3 × CH2), 32.8 (CH2), 43.5 (2 × CH2), 69.2 (C-4), 69.8 (C-5), 76.6 (C-1ꢀ), 129.7 (2 × CHPh), 130.9 (2 × CHPh),
ꢀ
—
131.0 (Ci), 134.5 (CHPh), 161.0 (C-2), 167.4 (C O), 175.1 (COOH), 214.3 (C-10 )
—
product XXVI in the quantitative yield (Fig. 5). Us-
ing the same reaction sequence as for the preparation
of XVI, compound XXVI was then transformed into
the triacetyl derivative XXVII (Fig. 5).
the hydroxymethyl side chain. Thus, removal of the
acid-labile protecting groups in XXIII (AcOH/H2O,
Fig. 6) provided diol XXVIII (92 %). The primary
hydroxyl group in XXVIII was selectively protected
as triphenylmethyl ether XXIX with a yield of 91 %
using TrCl and DMAP in dry pyridine. The reac-
tion of XXIX with BzCl in pyridine in the presence
of a catalytic amount of DMAP resulted in the for-
mation of benzoate ester XXX (96 %, Fig. 6). Its
detritylation was achieved under mild conditions (p-
TsOH, CH3OH/CH2Cl2), and the alcohol XXXI thus
obtained (81 %, Fig. 6) was oxidised using a two-
step protocol to afford the corresponding acid XXXII
with a yield of 94 %. The final saponification with 10
Having established the synthetic pathway to
XXVII, the next step was to utilise the common
intermediate XXIII (Fig. 5) for the construction of
(2S,3R)-configured amino acid XVI (prepared from
diastereomeric XI, see Fig. 3). In this context, it was
necessary to modify the quaternary stereogenic cen-
tre in XXIII so that the hydroxymethyl moiety of the
1,3-O-isopropylidene ring in XXIII ultimately formed
the carboxylic acid group of XVI and the masked pri-
mary alcohol in the oxazolidinone fragment became

J. Špaková Raschmanová et al./Chemical Papers 67 (10) 1317–1329 (2013)
1329
mass % aqueous NaOH in CH3OH followed by acety-
lation (Ac2O, pyridine) produced the corresponding
triacetyl derivative of II with a yield of 77 %.
Martinková, M., Gonda, J., Raschmanová, J., & Uhríková, A.
(2008). Stereoselective synthesis of both enantiomers of α-
(hydroxymethyl)glutamic acid. Tetrahedron: Asymmetry, 19,
1879–1885. DOI: 10.1016/j.tetasy.2008.08.003.
Martinková, M., Gonda, J., Špaková Raschmanová, J., Slanin-
ková, M., & Kuchár, J. (2010). Total synthesis of a protected
form of sphingofungin E using the [3,3]-sigmatropic rear-
rangement of an allylic thiocyanate as the key reaction. Car-
bohydrate Research, 345, 2427–2437. DOI: 10.1016/j.carres.
2010.09.016.
Martinková, M., Gonda, J., Uhríková, A., Špaková Raschma-
nová, J., & Kuchár, J. (2012a). An efficient synthesis of the
polar part of sulfamisterin and its analogs. Carbohydrate Re-
search, 352, 23–36. DOI: 10.1016/j.carres.2012.02.019.
Martinková, M., Gonda, J., Špaková Raschmanová, J., Kuchár,
J., & Kožíšek, J. (2012b). A stereoselective synthesis of an
α-substituted α-amino acid as a substructure for the con-
struction of myriocin. Tetrahedron: Asymmetry, 23, 536–546.
DOI: 10.1016/j.tetasy.2012.04.012.
Conclusions
In summary, the following total syntheses were
achieved: XXI (12 steps with 32 % overall yield from
VI), XVI (8 steps with 49 % overall yield from VI
or in 9 steps with 25 % overall yield from VII ) and
XXVII (8 steps with 27 % overall yield from VII ), as
the protected forms of the naturally occurring sulfam-
isterin I and its unnatural analogues II and V, respec-
tively. The coupling of two polar fragments VIII and
IX with the aliphatic tail substrate X was achieved by
a Wittig olefination to establish the complete carbon
framework of the above target compounds. It is worth
noting that these syntheses effectively utilised all of
the functional groups of the starting oxazolidinones
VI and VII.
Mita, T., Fukuda, N., Roca, F. X., Kanai, M., & Shibasaki, M.
(2007). Second generation catalytic asymmetric synthesis of
Tamiflu: Allylic substitution route. Organic Letters, 9, 259–
262. DOI: 10.1021/ol062663c.
More, J. D.,
& Finney, N. S. (2002). A simple and ad-
vantageous protocol for the oxidation of alcohols with o-
iodoxybenzoic acid (IBX). Organic Letters, 4, 3001–3003.
DOI: 10.1021/ol026427n.
Ohfune, Y., & Shinada, T. (2005). Enatio- and diastereos-
elective construction of α,α-disubstituted α-amino acids
for the synthesis of biologically active compounds. Euro-
pean Journal of Organic Chemistry, 2005, 5127–5143. DOI:
10.1002/ejoc.200500434.
Acknowledgements. This work was financially supported
by the Grant Agency of the Ministry of Education, Slovakia
(grants nos. 1/0568/12 and 1/0433/11). We wish to thank Dr.
Mária Vilková (P. J. Šafárik University, Košice) for her assis-
tance in NMR measurements.
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