Synthesis of heteroanellated pyranosides starting from methyl 4,6-O-benzylidene-2,3-dideoxy-α-D-erythrohexopyranosid-2- ylidenemalononitrile

Article abstract of DOI:10.1080/07328300500495852

The hexopyranosid-2-ylidenemalononitrile 1 reacted with phenyl isothiocyanate in the presence of triethylamine to furnish (2R,4aR,6S,10bS)-8- amino-4a,6,10,10b-tetrahydro-6-methoxy-2-phenyl-10-phenylimino-4H- thiopyrano[3′,4′:4,5]py rano[3,2-d][1,3] dioxi

Full text of DOI:10.1080/07328300500495852

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Synthesis of Heteroanellated
Pyranosides Starting from Methyl
4,6‐O‐benzylidene‐2,3‐dideoxy‐α‐d‐erythro‐hexopyranosid‐2‐yl
Holger Schulz , Holger Feist & Klaus Peseke
To cite this article: Holger Schulz , Holger Feist & Klaus Peseke (2006)
Synthesis of Heteroanellated Pyranosides Starting from Methyl
4,6‐O‐benzylidene‐2,3‐dideoxy‐α‐d‐erythro‐hexopyranosid‐2‐ylidenemalononitrile,
Journal of Carbohydrate Chemistry, 25:1, 43-51, DOI: 10.1080/07328300500495852
To link to this article: http://dx.doi.org/10.1080/07328300500495852
Published online: 21 Aug 2006.
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Date: 01 January 2016, At: 06:02

Journal of Carbohydrate Chemistry, 25:43–51, 2006
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300500495852
Synthesis of
Heteroanellated
Pyranosides Starting from
Methyl 4,6-O-benzylidene-
2,3-dideoxy-a-D-erythro -
hexopyranosid-2-
ylidenemalononitrile
Holger Schulz, Holger Feist, and Klaus Peseke
¨
Institut fu¨r Chemie, Universitat Rostock, Rostock, Germany
The hexopyranosid-2-ylidenemalononitrile 1 reacted with phenyl isothiocyanate in the
presence of triethylamine to furnish (2R,4aR,6S,10bS)-8-amino-4a,6,10,10b-tetrahy-
dro-6-methoxy-2-phenyl-10-phenylimino-4H-thiopyrano[30,40:4,5]py
rano[3,2-d][1,3]
dioxine-7-carbonitrile (2). Starting from 1, cyclization with sulphur and diethyl-
amine yielded (2R,4aR,6S,9bR)-8-amino-4,4a,6,9b-tetrahydro-6-methoxy-2-phenylthieno
[20,30:4,5]pyrano[3,2-d][1,3]dioxine-7-carbonitrile (3), which could be transformed into
the corresponding aminomethylenamino derivative 4 by treatment with triethyl ortho-
formate and ammonia. Intramolecular cyclization of 4 to yield (2R,4aR,6S,11bR)-
4,4a,6,11b-tetrahydro-6-methoxy-2-phenyl[1,3]dioxino[400,500:50,60]pyrano[30,40:4,5]thieno
[2,3-d]pyrimidin-7-amine (5) was achieved by using NaH as base. (2R,4aR,6S,9bS)-8-
Amino-4a,6,9,9b-tetrahydro-6-methoxy-9-(4-methylphenyl-sulfonyl)-2-phenyl-4H-[1,3]-
dioxino[40,50:5,6]pyrano[4,3-b]pyrrole-7-carbonitrile (6) was prepared by treatment of
compound 1 with tosylazide and triethylamine.
Keywords Hexopyranosidylidenemalononitrile, Heteroanellated pyranosides, Anel-
lated heterocycles, Nucleoside analogs
Received November 22, 2004; accepted January 17, 2005.
¨
Address correspondence to Klaus Peseke, Institut fu¨r Chemie, Universitat Rostock,
D-18051, Rostock, Germany. E-mail: klaus.peseke@uni-rostock.de
43

H. Schulz et al.
44
INTRODUCTION
The development of new methods for the synthesis of anellated monosaccharide
derivatives has attracted a current interest in the organic synthesis because of
the biologic importance that some compounds of this class have shown. The
activities include main topics like remarkable anticancer,[1–3] enzyme inhibi-
tory,[4–6] and anti-inflammatory effects[7] as well as actions as spruce budworm
antifeedants[8] or as neuronal differentiation agents.[9] Continuing our studies
about heterocyclic anellated monosaccharides,[10–14] herein we want to
describe the synthesis of thieno and pyrrolo anellated pyranosides, respectively.
RESULTS AND DISCUSSION
The branched-chain pyranoside 1 can be synthesized in seven steps starting
from D-glucose. The final reaction step of this synthetic sequence consisted of
a Knoevenagel reaction of the corresponding hexopyranosid-2-ulose with mal-
ononitrile.[15] Caused by the strong electron-withdrawing effect of the neigh-
boring dicyanomethylene group, the high CH acidity of H-3 in compound 1
could be used for the reaction with phenyl isothiocyanate in the presence of tri-
ethylamine at room temperature. After introductory attack of the carbanion
arising from 1 at phenyl isothiocyanate, a nitrile cyclization occurred to
furnish the (2R,4aR,6S,10bS)-8-amino-4a,6,10,10b-tetrahydro-6-methoxy-2-
phenyl-10-phenylimino-4H-thiopyrano[30,40:4,5]pyrano[3,2-d][1,3]dioxine-7-
carbonitrile (2) in 62% yield (Sch. 1). In the 13C NMR spectrum the compound 2
showed in contrast to the starting material 1 only one nitrile group. The gen-
1
erated amino group appeared in H NMR (d ¼ 5.27) and also in IR (n ¼ 3439,
3314, 3198 cm21). Due to the absence of a strong downfield shifted thioamide
signal in 13C NMR, the alternatively imaginable Dimroth rearrangement
product could be excluded. These results are in concordance with the literature.
Such reactions performed at room temperature preferably led to the formation
of the thiopyran ring, while the corresponding dihydropyridinethiones were
formed as a major product at higher temperatures.[16]
Recently, based on literature procedures,[17,18] we were able to synthesize
thiophene C-nucleoside analogs by treatment of monosaccharide derivatives
chain elongated through a 3,3-dicyanoprop-2-enyl group with elementary
sulphur and triethylamine in DMF.[19] A comparably functionalization
present in compound 1 should allow to prepare thieno anellated pyranoside.
The reaction of 1 with sulphur and diethylamine in methanol instead of
DMF as solvent afforded the (2R,4aR,6S,9bR)-8-amino-4,4a,6,9b-tetrahydro-
6-methoxy-2-phenylthieno[20,30:4,5]pyrano[3,2-d][1,3]dioxine-7-carbonitrile (3)
in 69% yield (Sch. 1). The successful anellation by this nitrile cyclization was
1
proved mainly by the detectable new amino group in the H NMR spectrum
(d ¼ 6.57) and in the IR spectrum (n ¼ 3356, 3300, 3196 cm21).

Heteroanellated Pyranosides
45
Scheme 1: (i) PhNCS, Et3N, DMF, 62%; (ii) S8, Et2NH, MeOH, 69%; (iii) CH(OEt)3 82%; (iv) NaH,
DMF, 71%.
The a-aminonitrile structure element in the thiophene ring of 3 should
allow a further cyclization. In contrast to earlier examinations,[19] the
reaction of compound 3 with triethyl orthoformate/ammonia under reflux
gave not directly the desired (2R,4aR,6S,11bR)-4,4a,6,11b-tetrahydro-6-
methoxy-2-phenyl[1,3]dioxino[400,500:50,60]pyrano[30,40:4,5]thieno[2,3-d]pyrimidin-
7-amine (5) but the open-chain (2R,4aR,6S,9bR)-8-(aminomethylenamino)-6-
methoxy-4,4a,6,9b-tetrahydro-2-phenylthieno[20,30:4,5]pyrano[3,2-d][1,3]dioxine-
7-carbonitrile (4). Nitrile cyclization could be achieved only after treating
compound 4 with sodium hydride in DMF at room temperature, yielding 5 in
71% yield. In accordance with the structure, no signal for a nitrile group was
visible in the 13C NMR and in the IR spectrum of compound 5. The amino
1
group appeared in the H NMR spectrum (d ¼ 6.88) and in the IR spectrum
(n ¼ 3486 and 3284 cm21). Together with all other analytical data structure 5
was substantiated without any doubt also by the 13C NMR shifts, which
1
were determined using H, 13C correlation and COLOC experiments.

H. Schulz et al.
A further interesting, but not expected, anellation of compound 1 was
46
observed in the reaction with tosylazide providing the (2R,4aR,6S,9bS)-8-
amino-4a,6,9,9b-tetrahydro-6-methoxy-9-(4-methylphenylsulfonyl)-2-phenyl-
4H-[1,3]dioxino[40,50:5,6]pyrano[4,3-b]pyrrole-7-carbonitrile (6) in 39% yield.
Following the established reaction mechanism for the transformation of
carbonyl compounds with tosyl azide as 1,3-dipolar cycloaddition,[20] we
would like to postulate as first intermediate the triazoline I (Sch. 2). Then,
nitrogen could split off to create the aziridine II, which undergoes a rearrange-
ment to yield compound 6. In conformity with the values of the elemental
1
analysis, three nitrogen atoms were present in the molecule. The H NMR,
13C NMR, and IR data proved the existence of two phenyl rings only one
cyano group, are an amine function.
In summary, hexopyranosid-2-ylidenemalononitrile 1 represents a suitable
starting material to synthesize pyranosides fused with different types of
heterocycles.
EXPERIMENTAL
General Methods
TLC was carried out on silica gel 60 GF254 (Merck, layer thickness 0.2 mm)
with detection by UV light (l ¼ 254 nm) and/or by charring with 10% sulphuric
acid in methanol. Silica gel 60 (0,063–0,200 mm) (Merck) was used for column
chromatography with the solvent systems specified. Melting points were deter-
mined by using a Boetius melting point apparatus and are corrected. IR spectra
were recorded with a Nicolet 205 FT-IR spectrometer. Specific rotations were
determined with a Polar LmP (IBZ Messtechnik) or with a Gyromat HP
1
(Dr. Kernchen GmbH). H NMR (250.13 MHz and 300.13 MHz, respectively)
Scheme 2: (i) TsN3, Et3N, MeCN, 39%.

Heteroanellated Pyranosides
47
and 13C NMR (62.9 MHz and 75.5 MHz, respectively) spectra were recorded on
Bruker instruments AC 250 and ARX 300, with CDCl3, [D6]-DMSO or
[D6]-acetone as solvent. Calibration of spectra was carried out on solvent
signals CDCl3: d (1H) ¼ 7.25, d (13C) ¼ 77.0; [D6]-DMSO: d (1H) ¼ 2.50, d
1
(13C) ¼ 39.7; [D6]-acetone: d (1H) ¼ 2.04, d (13C) ¼ 29.7. The H and 13C NMR
1
1
1
signals were assigned by DEPT, two-dimensional H, H correlation, H, 13C
correlation, and/or COLOC experiments. The mass spectra were recorded on
an AMD 402/3 spectrometer (AMD Intectra GmbH). Elemental analysis
were performed on a Leco CHNS-932 instrument. The solvents and liquid
reagents were purified and dried according to recommended procedures.
(2R,4aR,6S,10bS)-8-Amino-4a,6,10,10b-tetrahydro-6-methoxy-2-phenyl-
10-phenylimino-4H-thiopyrano[30,40:4,5]pyrano[3,2-d][1,3]dioxine-7-c
arbonitrile (2). A solution of 1 (312 mg, 1.0 mmol), phenyl isothiocyanate
(0.12 mL, 1.0 mmol), and triethylamine (0.140 mL, 1.0 mmol) in anhydrous
DMF (15 mL) was stirred for 5 h at rt. Then, the reaction mixture was poured
into ice water (70 mL) and extracted with dichloromethane (3 ꢀ 20 mL). The
combined extracts were washed with water (3 ꢀ 20 mL), dried (Na2SO4), and
concentrated to leave a syrup. The raw product was chromatographed on a
column of silica gel with 3:1 toluene/ethyl acetate to give, after recrystalliza-
tion from diethyl ether/heptane, 2 (227 mg, 62%) as yellow crystals;
mp . 2008C (decomposition); [a]2D2 þ2738 (c 1.0, CHCl3); Rf 0.37 (toluene/
ethyl acetate 4:1); IR (KBr): n 3439, 3314, 3198 (NH2), 2201 (CN), 1607, 1586
1
(C55C) cm21; H NMR (250 MHz, CDCl3): d 3.60 (s, 3H, OMe), 3.93 (t, 1H,
J4 ,4 10.1 Hz, J4 ,4a 10.1 Hz, H-40), 4.16–4.27 (m, 1H, H-4a), 4.39 (dd, 1H,
0
00
0
J4 ,4a 4.4 Hz, H-400), 4.71 (d, 1H, J10b,4a 9.0 Hz, H-10b), 5.18 (s, 1H, H-6), 5.27
00
(s, 2H, NH2), 5.72 (s, 1H, H-2), 6.80 (d, 2H, o-NPh), 7.15 (t, 1H, p-NPh),
7.26–7.51 (m, 7H, m-NPh, Ph); 13C NMR (75 MHz, CDCl3): d 56.6 (OMe),
64.4 (C-4a), 69.0 (C-4), 74.7 (C-10b), 77.1 (C-7), 97.5 (C-6), 101.3 (C-2), 115.4
(CN), 118.8 (C-10a), 119.2, 124.8, 125.9, 128.0, 128.6, 129.7, 137.6 (Ph, NPh),
139.7 (C-6a), 146.9, 149.8, 160.3 (NPh, C-8, C-10); MS (EI, 70 eV): m/z (%)
447 (11) [M]þ, 149 (100).
Anal. Calcd for C24H21N3O4 S: C, 64.41; H, 4.73; N, 9.38; S, 7.16. Found: C,
64.43; H, 4.67; N, 9.40; S, 6.94.
(2R,4aR,6S,9bR)-8-Amino-4,4a,6,9b-tetrahydro-6-methoxy-2-phenylthi
eno[20,30:4,5]pyrano[3,2-d][1,3]dioxine-7-carbonitrile (3). Diethylamine
(0.11 mL, 1.1 mmol) was added to a suspension of 1 (312 mg, 1.0 mmol) and
elementary sulphur (35 mg, 1.1 mmol) in anhydrous methanol (30 mL). The
mixture was stirred for 2 h at 458C, then filtrated and evaporated in vacuo.
After purification by column chromatography (toluene/acetone 4:1) and recrys-
tallization from dichloromethane/heptane, 3 (238 mg, 69%) was obtained as
colorless needles; mp 207–2098C; [a]2D2 þ18.68 (c 1.0, CHCl3); Rf 0.39
(toluene/acetone 4:1); IR (KBr): n 3356, 3300, 3196 (NH2), 2226 (CN), 1518

H. Schulz et al.
48
(C55C) cm21; 1H NMR (250 MHz, [D6]-acetone): d 3.53 (s, 3H, OMe), 3.91–4.09
(m, 2H, J4 ,4a 8.8 Hz, H-40, H-4a), 4.29 (dd, 1H J4 ,4 8.8 Hz, J4 ,4a 3.4 Hz, H-400),
4.72 (d, 1H, J4a,9b 8.2 Hz, H-9b), 5.33 (s, 1H, H-6), 5.80 (s, 1H, H-2), 6.57 (s, 2H,
NH2), 7.30–7.54 (m, 5H, Ph); 13C NMR (63 MHz, [D6]-acetone): d 56.5 (OMe),
66.8 (C-4a), 69.5 (C-4), 76.0 (C-9b), 84.7 (C-7), 96.9 (C-6), 102.5 (C-2), 114.6
(CN), 120.5 (C-6a), 127.3, 128.9, 129.8, 133.7, (Ph), 138.7 (C-9a), 165.2 (C-8);
MS (CI, isobutane): m/z (%) 345 (100) [M þ H]þ.
0
0
00
00
Anal. Calcd for C17H16N2O4 S: C, 59.29; H, 4.68; N, 8.13; S, 9.31. Found: C,
59.81; H, 4.74; N, 7.98; S, 9.07.
(2R,4aR,6S,9bR)-8-(Aminomethylenamino)-4,4a,6,9b-tetrahydro-6-met
hoxy-2-phenylthieno[20,30:4,5]pyrano[3,2-d][1,3]dioxine-7-carbonitrile
(4). A solution of 3 (300 mg, 0.87 mmol) in triethyl orthoformate (10 mL) was
heated for 2 h under reflux. Then the reaction mixture was concentrated
under reduced pressure yielding a solid, which was dissolved in a saturated
ethanolic solution of ammonia (15 mL) and stirred over night at rt. Evaporation
in vacuo supplied a light yellow solid, which after treatment with charcoal in
acetone was pure enough for the preparation of compound 5. Column chrom-
atography (toluene/acetone 2:1) furnished analytically pure 4 (305 mg, 82%)
as colorless crystals; mp 262–2658C; [a]2D2 280.58 (c 1.0, DMF); Rf 0.45
(toluene/acetone 2:1); IR (KBr): n 3400, 3143 (NH2), 2215 (CN), 1694 (C55C)
cm21 1H NMR (250 MHz, [D6]-DMSO): d 3.46 (s, 3H, OMe), 3.81–4.03
;
(m, 2H, J4 ,4a 9.6 Hz, H-40, H-4a), 4.27 (dd, 1H, J4 ,4 9.5 Hz, J4 ,4a 3.7 Hz,
H-400), 4.79 (d, 1H, J4a,9b 8.4 Hz, H-9b), 5.43 (s, 1H, H-6), 5.82 (s, 1H, H-2),
7.34–7.48 (m, 5H, Ph), 7.73 (s, 1H, NHH), 7.84 (t, 1H, CHNH2), 8.10 (d, 1H,
NHH); 13C NMR (63 MHz, [D6]-DMSO): d 56.2 (OMe), 65.7 (C-4a), 68.2 (C-4),
74.4 (C-9b), 93.4 (C-7), 95.5 (C-6), 101.1 (C-2), 114.8 (CN), 124.4 (C-6a),
126.5, 128.3, 129.3, 132.7, (Ph), 137.4 (C-9a), 155.7 (CHNH2), 168.2 (C-8); MS
(70 eV): m/z (%) 371 (100) [M]þ.
0
0
00
00
Anal. Calcd for C18H17N3O4 S: C, 58.21; H, 4.61; N, 11.31; S, 8.63. Found: C,
58.00; H, 4.69; N, 11.07; S, 8.35.
(2R,4aR,6S,11bR)-4,4a,6,11b-Tetrahydro-6-methoxy-2-phenyl-[1,3]diox-
ino[400,500:50,60]pyrano[30,40:4,5]thieno[2,3-d]pyrimidin-7-amine (5).
A
solution of 4 (300 mg, 0.81 mmol) in anhydrous DMF (10 mL) was treated
under stirring with NaH (35 mg, 0.9 mmol, 60%) for 1 h at room temperature.
After addition of ice water the mixture was extracted with dichloromethane
(3 ꢀ 30 mL). The combined organic layers were washed with water
(2 ꢀ 30 mL), dried (Na2SO4), and evaporated. Purification by column chrom-
atography (toluene/acetone 2:1) and recrystallization from methanol yielded
5 (264 mg, 71%) as colorless needles; mp 259–2628C; [a]2D2 þ1828 (c 1.0,
DMF); Rf 0.35 (toluene-acetone 2:1); IR (KBr): n 3486, 3284 (NH2), 1637
(C55C) cm21
;
1H NMR (250 MHz, [D6]-DMSO): d 3.57 (s, 3H, OMe),
3.91–4.09 (m, 2H, J4 ,4a 10.4 Hz, H-40, H-4a), 4.40 (dd, 1H, J4 ,4 9.2 Hz, J4 ,4a
0
0
00
00

Heteroanellated Pyranosides
49
3.7 Hz, H-400), 5.01 (d, 1H, J4a,11b 7.6 Hz, H-11b), 5.93 (s, 1H, H-2), 6.00 (s, 1H,
H-6), 6.88 (s, 2H, NH2), 7.38–7.52 (m, 5H, Ph), 8.23 (s, 1H, H-9); 13C NMR
(63 MHz, [D6]-DMSO): d 54.8 (OMe), 64.7 (C-4a), 68.2 (C-4), 74.4 (C-11b),
94.9 (C-6), 101.3 (C-2), 112.9 (C-6b), 126.5 (Ph), 126.8 (C-6a), 128.4, 129.3
(Ph), 133.1 (C-11a), 137.3 (Ph), 154.1 (C-9), 158.3 (C-7), 166.9 (C-10a); MS
(CI, isobutane): m/z (%) 372 (40) [M þ H]þ, 107 (100).
Anal. Calcd for C18H17N3O4 S: C, 58.21; H, 4.61; N, 11.31; S, 8.63. Found: C,
57.90; H, 4.69; N, 11.24; S, 8.74.
(2R,4aR,6S,9bS)-8-Amino-4a,6,9,9b-tetrahydro-6-methoxy-9-(4-methyl-
phenyl-sulfonyl)-2-phenyl-4H-[1,3]dioxino[40,50:5,6]pyrano[4,3-b]pyrro
le-7-carbonitrile (6). Triethylamine (0.09 mL, 0.65 mmol) was added at –208C
to a solution of 1 (200 mg, 0.64 mmol) and tosylazide (128 mg, 0.65 mmol) in
acetonitrile (20 mL). Within 2 h the stirred mixture was allowed to warm up
to þ108C and then poured into ice water (60 mL). After extraction with dichlor-
omethane (3 ꢀ 20 mL) the combined organic layers were washed with water
(3 ꢀ 20 mL), dried (Na2SO4), and concentrated to leave a syrup, which was
purified by column chromatography (toluene/ethyl acetate 3:1). Recrystalliza-
tion from dichloromethane/hexane furnished 6 (120 mg, 39%) as colorless
crystals; mp . 1508C (decomposition); [a]2D1 þ 26.98 (c 1.0, CHCl3); Rf 0.55
(toluene/ethyl acetate 4:1); IR (KBr): n 3453, 3365 (NH2), 2216 (CN) cm21
;
1H NMR (250 MHz, CDCl3): d 2.44 (s, 3H, Me), 3.50 (s, 3H, OMe), 3.91 (t, 1H,
J4 ,4 10.1 Hz, H-40), 4.05–4.16 (m, 1H, J4 ,4a 10.1 Hz, H-4a), 4.31 (dd, 1H,
0
00
0
J4 ,4a 4.4 Hz, H-400), 4.68 (d, 1H, J4a,9b 8.9 Hz, H-9b), 5.29 (s, 2H, NH2), 5.58
00
(s, 1H, H-6), 5.70 (s, 1H, H-2), 7.29–7.91 (m, 9H, Ph, p-MeC6H4SO2); 13C
NMR (75 MHz, [D6]-acetone): d 21.6 (Me), 60.0 (OMe), 65.4 (C-4a), 69.4 (C-4),
72.1 (C-7), 74.8 (C-9b), 95.8 (C-6), 102.0 (C-2), 114.5 (CN), 120.3 (C-6a),
123.0, 127.0, 128.6, 128.7, 129.4, 130.9, 135.5 (Ph, p-MeC6H4SO2), 138.8
(C-9a), 147.5 (p-MeC6H4SO2), 150.5 (C-8); (CI, isobutane): m/z (%) 482 (3)
[M þ H]þ, 107 (100).
Anal. Calcd for C24H23N3O6S: C, 59.86; H, 4.81; N, 8.73; S, 6.66. Found: C,
59.84; H, 5.03; N, 8.69; S, 6.87.
ACKNOWLEDGEMENTS
The authors would like to thank the Deutsche Forschungsgemeinschaft, the
¨
¨
Fonds der Chemischen Industrie, and Dr. Otto Rohm Gedachtnisstiftung,
Darmstadt, for financial support.
REFERENCES
[1] Stamos, D.P.; Chen, S.S.; Kishi, Y. New synthetic route to the C.14–C.18 segment
of halichondrins. J. Org. Chem. 1997, 62, 7552–7553.

H. Schulz et al.
50
[2] Tietze, L.F.; Keim, H. Synthesis of a novel stable GM3-lactone analog as hapten for
a possible immunization against cancer. Angew. Chem. Int. Ed. Engl. 1997, 36,
1615–1617.
[3] Robeson, D.J.; Gray, G.R.; Strobel, G.A. Production of the phytotoxins radicinin
and radicinol by Alternaria chrysanthemi. Phytochemistry 1982, 21, 2359–2362.
[4] Knapp, S.; Yang, C.; Haimowitz, T. Addition of trialkylaluminium reagents to gly-
conolactones. Synthesis of 1-C-methyl GlcNAc oxazoline and thiazoline. Tetrahe-
dron Lett. 2002, 43, 7101–7104.
[5] Zhang, H.-X.; Peng, X.; Zhou, W.-S. Novel asymmetric total synthesis of the natural
(þ)-6-epicastanospermine. Tetrahedron 2003, 59, 2015–2020.
[6] Cardona, F.; Faggi, E.; Liguori, M.C.; Goti, A. Total syntheses of hyacinthacine A2
and 7-deoxycasuarine by cycloaddition to a carbohydrate derived nitrone. Tetrahe-
dron Lett. 2003, 44, 2315–2318.
[7] Takeda, Y.; Morimoto, Y.; Matsumoto, T.; Honda, G.; Tabata, M.; Fujita, T.;
Otsuka, H.; Sezik, E.; Yesilada, E. Nepetanudoside, an iridoide glucoside with an
unusual stereostructure from Nepeta nuda ssp Albiflora. J. Nat. Prod. 1995, 58,
1217–1221.
[8] Mohammad-Ali, A.K.; Chan, T.H.; Thomas, A.W.; Jewett, B.; Strunz, G.M. Spruce
budworm (Choristaneura fumiferana) antifeedants 4. Synthesis of specionin and
biological studies. Can. J. Chem. 1994, 72, 2137–2143.
[9] Kikuchi, H.; Saito, Y.; Komiya, J.; Takaya, Y.; Honma, S.; Nakahata, N.; Ito, A.;
Oshima, Y. Furanodictine A and B: amino sugar analogues produced by cellular
slime mold Dictyostelium discoideum showing neuronal differentiation activity.
J. Org. Chem. 2001, 66, 6982–6987.
[10] Peseke, K.; Feist, H.; Cuny, E. Syntheses of branched-chain sugars with push-pull
functionality. Carbohydr. Res. 1992, 230, 319–325.
[11] Peseke, K.; Thiele, G.; Michalik, M. A new approach to C-branched monosacchar-
ides by the stereoselective hydrodesulphurization of methyl 4,6-O-benzylidene-3-
[bis (methylthio)methylene]-3-deoxy-a-D-erythro-hexopyranosid-2-ulose. Liebigs
Ann. 1995, 1633–1636.
[12] Kuhla, B.; Peseke, K.; Thiele, G. An approach to C-branched and heterocyclic anel-
lated pyranosides by reaction of a-D-erythro-hexopyranosid-2-ulose with orthofor-
mic acid derivatives. J. Prakt. Chem. 2000, 342, 240–244.
[13] Peseke, K.; Thiele, G.; Michalik, M.; Powell, D.R. Anellation rections of pyranose
derivatives. Liebigs Ann. 1997, 1019–1022.
[14] Thiele, G.; Feist, H.; Peseke, K. Synthesis of pyrano and pyrido anellated
pyranosides as precursors for nucleoside analogues. J. Carbohydr. Chem. in
preparation.
[15] Peseke, K.; Feist, H.; Hanefeld, W.; Kopf, J.; Schulz, H. Branched-chain sugars as
push-pull butadienes. J. Carbohydr. Chem. 1995, 14, 317–325.
[16] Bogdanowicz-Szwed, K. The Knoevenagel reaction of malononitrile with some
cyclic b-ketocarbothionic acid anilides. Synthesis of cycloalkenopyridines and
cycloalkenothiopyrans. Monatsh. Chem. 1982, 113, 583–592.
[17] Gewald, K.; Kleinert, M.; Thiele, B.; Hentschel, M. Zur basenkatalysierten
Reaktion von methylenaktiven Nitrilen mit Schwefel. J. Prakt. Chem. 1972, 314,
303–314.

Heteroanellated Pyranosides
51
[18] Unverferth, K. Wirkstoffe durch Gewald-Reaktionen. Pharmazie 1990, 45,
545–548.
[19] Garcia, I.; Feist, H.; Cao, R.; Michalik, M.; Peseke, K. Synthesis of (2,3,4,6-tetra-O-
acetyl-a-D-glycopyranosy)thiophene derivatives as new C-nucleoside analogues.
J. Carbohydr. Chem. 2001, 20, 681–687.
[20] Regitz, M. Reaktionen von aktiven Methylenverbindungen mit Aziden. VI. Neue
Synthese fu¨r a-Diazocarbonylverbindungen. Chem. Ber. 1965, 98, 1210–1224.