C-glycosyl amino-substituted hydro- and benzoquinones: Synthesis and preliminary biological evaluation

PAPER

3473

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones: Synthesis and

Preliminary Biological Evaluation

C-Glycosyl

A

mino

u

-Substituted

n

H

ydro- and Benzo

Z

quinones hi Zhang,^a,bKaïss Aouadi,^aGuo-Rong Chen,^bJean-Pierre Praly*^a

a

Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), CNRS, UMR5246, Université Lyon 1, CPE Lyon, bâtiment

308, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France

Fax +33(4)72448349; E-mail: jean-pierre.praly@univ-lyon1.fr

Laboratory of Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology (ECUST),

130 Meilong Road, POB 257, 200237 Shanghai, P. R. of China

b

Received 20 June 2007; revised 18 July 2007

creasing interest, as regard to their synthesis³and because

of bioactivities^2,4anticipated for such glycomimics, based

on possible interactions with sugar-processing enzymes

and on their resistance to both acid-, and enzyme-cata-

Abstract: Reaction of C-b-D-glycopyranosyl-1,4-dimethoxyben-

zenes with acetyl nitrate afforded 2-(b-D-glycopyranosyl)-1,4-

dimethoxy-5-nitrobenzenes in high yields. These were converted

smoothly (reduction to amines, N-acylation, oxidation, and reduc-

tion) into the corresponding C-glycosyl-hydro(benzo)quinone de- lyzed hydrolysis.⁵

rivatives, with different amide-based substituents at C-5. Reduction

of the nitro compounds to amines proceeded smoothly by catalytic

hydrogen transfer with HCO₂NH₄.

Our interest in this field stems from earlier studies devot-

ed to the synthesis of 5-thio-b-D-xylopyranosides⁶and C-

5-thio-b-D-xylopyranosyl compounds⁷as orally active

venous antithrombotics. C-5-Thio-b-D-xylopyranosyl de-

rivatives of phenol, resorcinol, phloroglucinol were ob-

tained by aromatic electrophilic substitution, or by O →

C-glycoside rearrangement, showing the reactivity of

electron-rich aryls, in agreement with studies aiming at

preparing C-glycosyl flavonoids,^8,9or D-glycosyl deriva-

tives (furanose¹⁰or pyranose¹¹type) of dimethylhydro-

quinone. By such a coupling and subsequent oxidation

and reduction, Kalvoda first obtained various glycofura-

Key words: glycosides, electrophilic aromatic substitution, hydro-

gen transfer, reduction, amines, amides

Even though C-glycosyl flavonoids constitute a specific

class of natural products,¹carbohydrates directly bound to

an aromatic moiety through a C–C bond are rare, as com-

pared to common sugars. However, glycosyl arenes (also

termed C-aryl glycosides)²are currently attracting in-

OMe

R²

OAc

O

R¹

AcO

+

OAc

R³

OAc

OH

OMe

OH

O

OH

HO

OH

O

OH

HO

OH

O

OH

O

OH

O

HO

3

C-glycosyl tocopherols^13,15

OH

O

new glucose-based

inhibitors of glycogen

phosphorylase^13,14

this work

OR

OAc

O

R = Me, H

X

AcO

X = NO₂, NH₂

amide substituents

OAc

Scheme 1 Recent synthetic developments with 2-C-b-D-glycopyranosyl-1,4-dimethoxybenzenes

SYNTHESIS 2007, No. 22, pp 3473–3488

x

x.

x

.

2

0

7

Advanced online publication: 29.10.2007

DOI: 10.1055/s-2007-990856; Art ID: Z14907SS

3474

Y. Z. Zhang et al.

PAPER

nosyl-hydro(1,4-benzo)quinones,¹⁰a class of simple com- herein report on the synthesis of 2-glycosyl-1,4-

pounds with only few synthetic¹²representatives.

dimethoxy-5-nitrobenzenes. After reduction, they gave

access to a library of sugar-based amide-linked aromatics,

which have been tested against A375 human melanoma

cell lines.

Because glycosyl-hydro(benzo)quinones correspond to a

stable scaffold amenable to various functionalizations or

modifications, resulting in possible bioactivities,^12bthe

synthesis of glycopyranosyl derivatives was carried out, Because of the lability of acetyl protecting groups, nitra-

using 1,4-dimethoxybenzene, and its 2,3-, and 2,6-dimethyl tion of 2-(2,3,4,6-tetra-O-acetyl-b-D-glycopyranosyl)-

derivatives.¹³While enzymatic and crystallographic stud- 1,4-dimethoxybenzenes (1,2)^13,14was envisaged under

ies showed that the glucosyl-hydro(benzo)quinones were mild conditions and in particular with acyl nitrates,¹⁶be-

weak inhibitors of glycogen phosphorylase (GP) due to cause such nitrating agents are accessible by simple meth-

binding at the active site,¹⁴the o- and m-dimethyl ana- ods avoiding harsh acidic conditions.¹⁷Acetyl nitrate [ca.

logues opened the first access to C-glycosyl-toco- 2.1 equiv prepared in situ in anhyd MeCN from NH₄NO₃

pherols,¹³as unprecedented antioxidants.¹⁵This (2.4 equiv) and AcCl (2.1 equiv)] was found effective to

encouraged us to further investigate the potential of such achieve the regioselective nitration of 1 and 2 within 2

glycosyl-arenes, in particular by electrophilic substitution hours, to afford 3 and 5 in 81% and 75% yield, respective-

(halogenation, formylation, nitration; Scheme 1). We ly (Scheme 2). The substrates were reactive enough for

OMe

R²

R¹R²

1 OAc

OAc

O

R¹

H

D-Glc

AcO

2 H

OAc D-Gal

OAc

a

OMe

4

OMe

R²

OAc

O

OAc

O

X

NH₂

R¹

3

2

R¹

AcO

5

b

6

1

AcO

OAc

OMe

D-Gal

OMe

O

D-Glc

X

D-Glc 7

D-Gal 8

NO₂

Cl

3

4

5

6

OMe

R²

H

N

H

N

OAc

O

OAc

O

R

R¹

e

RCOCl

c

AcO

O

AcO

OAc

OMe

O

13a–l,n

9a–n D-Glc

10f D-Gal

d

f

OMe

OH

R²

H

N

H

N

OH

O

OAc

O

R

R¹

HO

AcO

O

OH

OAc

OMe

R¹R²

11f OH

12f

14a–l,n

H

D-Glc

H

OH D-Gal

R = a: vinyl; b: (E)-styryl; c: p-tolyl; d: 4-methoxyphenyl; e: 3,5-dimethoxyphenyl;

f: 4-nitrophenyl; g: 4-biphenyl; h: 1-naphthyl; i: 2-naphthyl; j: 2-furyl; k: 2-thienyl;

l: 3-pyridyl; m: 2-(pyridinyl-6-formate ethyl ester)

n:

OR¹

O

H

N

O

β-D-Glcp

OR¹

¹= Me (9n), H (14n)

O

R

13n

Scheme 2 Reagents and conditions: (a) NH₄NO₃, AcCl, MeCN, 0 °C to r.t., 2 h; (b) Na₂S₂O₄(H₂O–MeOH) or HCO₂NH₄(MeOH), 10%

Pd/C, r.t.; (c) RCOCl, pyridine, CH₂Cl_2;(d) BaO, MeOH; (e) CAN, MeCN–H₂O; (f) Na₂S₂O₄, CHCl₃/H₂O.

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3475

the nitration to proceed with limited amounts of an haz- In order to prepare the corresponding amino derivatives,

ardous reagent (caution: AcONO₂may explode upon reduction of compounds 3 and 5 was attempted in the

heating).¹⁸The grade of NH₄NO₃appeared to be critical presence of Raney nickel in EtOH,²²but not surprisingly

since limited drying led to incomplete nitration of 1, while this led to deacetylation and other unwanted transforma-

extensive drying in the presence of P₂O₅favored dinitra- tions. Other reductive conditions applicable to nitro com-

tion (see experimental section). Minor side-products, to pounds were not tried because of limited efficiency

be fully described in a forthcoming paper, were separated (NaBH₄) or possible side reactions (LiAlH₄, NH₂NH₂),

by column chromatography and identified as chlorinated but catalytic hydrogen transfer was considered. Sodium

regioisomers (see Scheme 2 for numbering). Not surpris- dithionite/hydrosulfite (Na₂S₂O₄),²³currently used in our

ingly, the C-5 chloro isomers were more abundant [4 (5- group for reducing glycosyl benzoquinones 13^13,14was

Cl): 11%, 6 (5-Cl): 13%] as compared to the C-6 ana- envisaged, although it usually requires heating under ba-

logues (D-Glc: 3%, D-Gal: 2%). Regarding their forma- sic conditions. Compound 3 was reduced within 13 min-

+

tion, we assumed that, because NO₂ions or acetyl nitrate utes in the presence of Na₂S₂O₄and Pd/C 10% in H₂O–

are oxidizing agents,¹⁹chloride anions, still present in the MeOH to afford 7 in 60% yield, together with a polar by-

–

+

medium even after filtration of precipitated NH₄Cl (see product. Another experiment with HCO₂NH₄as the hy-

experimental) may undergo oxidation, thus forming reac- drogen donor in MeOH with Pd/C 10% afforded within 75

tive species (e.g., chlorine atom, chloronium ion) capable minutes 7 as the sole product in 82% yield. Use of a com-

of aromatic substitution with activated substrates. This is bination of Na₂S₂O₄and HCO₂NH₄with Pd/C in H₂O–

reminiscent of reported halogenations, occurring together MeOH led within 15 minutes to 7 in 54% yield, in addi-

with nitration,^20aor favored by the electrophilic fluorina- tion to a polar by-product, assumed to be a salt of 7.

tion agent Selectfluor,^20bor dimethyldioxirane.^20cWhile

To the best of our knowledge, catalytic hydrogen transfer

more complete removal of precipitated NH₄Cl appeared

with Na₂S₂O₄has not been reported previously,²⁴al-

difficult, few attempts to minimize chlorination by reduc-

though nitroarenes have been reduced with Na₂S₂O₄in

ing the quantity of AcCl (NH₄NO₃/AcCl ratio changed

aqueous or biphasic medium in the presence of an electron

from 2.4/2.1 to 2.7/1.8) were not encouraging, since the

transfer catalyst.²⁵Interestingly, a bacterial cellulose with

reaction was slower (3.5 h) while the chloro isomers were

a palladium deposit was recently shown to catalyze the

again detected. Probably, use of silver nitrate would allow

generation of hydrogen when incubated with sodium

a more efficient elimination of chloride anions, as insolu-

dithionite.²⁶

ble silver chloride. Moreover, attempts to achieve nitrosa-

tion or nitration of glycosyl hydroquinone failed, mainly

Compounds 7,8 were acylated in high yields with 13 acyl

chlorides to afford 9a–n and 10f (D-Gal) which display

due to oxidation to glycosyl-benzoquinone under the con-

various substituents bound by a fairly stable amide link-

ditions applied (NaNO₂/AcCl, NH₄NO₃/AcCl in varying

age (Scheme 3). 2,6-Bis(chloroformyl)pyridine (0.53

amounts ~1.1 equiv, 1.5 equiv, 2.1 equiv, CAN–

equiv) was used to prepare compounds 9n (87%) and 9m

(6%, an ethyl ester formed most probably during extrac-

NaHCO₃).²¹

H

R³

NH₂

N

OMe

H

N

H

OAc

O

OAc

O

N

RCOCl

b

AcO

O

OAc

a

OMe

15

9f

16 R³= (E)-styryl,

17 R³= 2-thienyl

18 R³= 3-pyridyl

13f

14f

a

NH₂

O

OH

H

OAc

O

H

N

OAc

O

N

air

c

AcO

O

OAc

O

OAc

OH

20

19

Scheme 3 Reagents and conditions: (a) Na₂S₂O₄(H₂O–MeOH) or HCO₂NH₄(MeOH), 10% Pd/C, r.t.; (b) acyl chloride, pyridine, CH₂Cl₂;

(c) oxidation by air.

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

3476

Y. Z. Zhang et al.

PAPER

mass spectra were recorded in the positive mode (unless stated oth-

erwise) using a Thermo Finnigan Mat 95 XL spectrometer. MS

(ESI) mass spectra were recorded in the positive mode using a Ther-

mo Finnigan LCQ spectrometer. Optical rotations were measured

using a PerkinElmer polarimeter. Elemental analyses were per-

formed at the Service Central d’Analyses du CNRS (Vernaison,

France).

tion with CH₂Cl₂containing EtOH as stabilizer). Com-

pounds 9f and 10f were deacetylated cleanly by BaO in

anhydrous MeOH²⁷at 0–4 °C to afford 11f and 12f. Mean-

while 9a–l and 9n were oxidized to the benzoquinone an-

alogues 13a–l and 13n with ceric ammonium nitrate

(CAN) in aqueous acetonitrile solution in good to excel-

lent yields.^13,14Then hydroquinone analogues 14a–l and

14n were obtained upon reduction with Na₂S₂O₄in good

to excellent yields.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-nitrobenzene (3)

A mixture of NH₄NO₃(previously dried under vacuum for 2–3

days) (175 mg, 2.18 mmol, 2.4 equiv) and AcCl (140 mL, 1.97

mmol, 2.1 equiv) in anhyd MeCN (5 mL) was stirred at 0 °C for 40

min. Due to the limited solubility of NH₄Cl, a precipitate appeared

meanwhile in the turbid solution. After removal of the insoluble ma-

terials by filtration, 1,4-dimethoxy-2-(2,3,4,6-tetra-O-acetyl-b-D-

glucopyranosyl)benzene (1; 450 mg, 0.96 mmol) was added to the

filtrate obtained. Upon stirring at r.t. for 2 h, TLC showed that com-

pound 1 was converted into three compounds (R_f= 0.53, 0.49, 0.40,

PE–EtOAc, 1:1). The more polar spot was easily visible under day-

light. H₂O (10 mL) was added to the mixture, which was extracted

with CH₂Cl₂(3 × 15 mL). The extracts were combined and washed

with brine (15 mL), H₂O (15 mL), dried (MgSO₄), and evaporated.

The residue was purified by chromatography (PE–EtOAc, 3:1) on

silica gel to afford successively the C-6 chlorinated compound (13

mg, 3%), its C-5 isomer (53 mg, 11%) (found to be identical to an-

alytical samples obtained by other routes), and the nitro compound

3 (400 mg, 81%).

Further work (Scheme 3) demonstrated the efficiency and

the mildness of the reduction of nitro compounds by cata-

lytic hydrogen transfer. For example, 9f was reduced to

afford 15 in high yield (86%) which was then converted

by acylation into 16–18. Interestingly, upon treatment

with Na₂S₂O₄, benzoquinone 13f was reduced as men-

tioned before to hydroquinone 14f, without modification

of the nitro group. However, the aniline derivative 19 was

formed upon reduction with Na₂S₂O₄, HCO₂NH₄, 10%

Pd/C in H₂O–MeOH. This compound proved to be highly

sensitive to oxidation, since it was converted during work-

up and chromatography into the benzoquinone 20 (71%),

probably because of air oxidation. The smooth and selec-

tive reduction of both polyfunctional nitro compounds 9f

and 14f to the corresponding anilines showed again the in-

terest of catalytic hydrogen transfer conditions.

Other experiments suggested that the content of H₂O in NH₄NO₃

was critical as regard to the nitration outcome. An assay similarly

carried out with 1 (20 mg), NH₄NO₃(previously dried under vacu-

um for 1 day, 2.4 equiv) and AcCl (2.1 equiv) led, after 5 days, to

incomplete conversion of 1, with formation of 3 and chloro isomers

(TLC). Use of NH₄NO₃(7.2 equiv) dried for 24 h in the presence of

P₂O₅and AcCl (6.3 equiv) resulted in complete conversion of 1 af-

ter 40 min and afforded 3 (39%), the chloro isomer 4 (6.5%), and a

5,6-dichloro product (23%) (MS, NOE 1D). If the nitration was car-

ried out with NH₄NO₃dried for one week under vacuum in the pres-

ence of P₂O₅, 1 was not completely transformed but a dinitro

compound (MS) was found predominantly among the products. At-

tempted nitration of 1 (60 mg) in MeCN at r.t. with NH₄NO₃, dried

for one week under vacuum in the presence of P₂O₅(2.0, 2.4 and 3.0

equiv) and trifluoroacetic anhydride¹⁷(6 equiv) led, even after 3–4

days, to partial conversion of 1 (ca 60%) and formation of separable

dinitro isomers (MS). They were identified by NMR spectroscopy

based on NOE 1D as the 3,6-dinitro (minor isomer) and the 5,6-

dinitro (major isomer) derivatives.

While assays showed no inhibition of GP by deacetylated

compound 11f, the antitumor activities in vitro of some of

the compounds synthesized were evaluated by MTT tetra-

zolium dye assay²⁸against A375 cell line (human melano-

ma cell), on consideration of structural similarities

(benzoquinone, amido moieties) with anticancer agents as

anthracyclines or naphthalimides.²⁹Each compound was

tested at five different concentrations to determine IC₅₀

(m/mL) required to inhibit cell growth by 50%. The results

revealed that compounds derived from 1,4-dimethoxy-

benzene had low activities, as 17, 18 were found to be in-

active, while 10f and 16 had IC₅₀= 260, 160 mg/mL

respectively. The benzoquinones tested have IC₅₀(mg/mL)

values as follows: 13b: 74; 13c: 110; 13e: 57; 13f: 20;

13g: 23; 13i: 40 (mean value for 2 assays); 13l: 146; 13n:

no activity. The hydroquinones tested showed the follow-

ing IC₅₀(mg/mL): 14b: 20; 14c: 87; 14g: 107.

Yellow-green solid; mp 142.5–143 °C (CH₂Cl₂–PE); R_f= 0.40

(PE–EtOAc, 1:1); [a]_D¹⁸–25.0 (c 0.75 CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 7.38 (s, 1 H, Ar), 7.17 (s, 1 H,

Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.25 (t, J_2,3= 9.6 Hz, 1 H, H-

2), 5.23 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.97 (d, J_1,2= 9.9 Hz, 1 H, H-1),

4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.14 (dd, J_5,6¢= 2.1

Hz, 1 H, H-6¢), 3.94 (s, 3 H, OCH₃), 3.87 (s, 3 H, OCH₃), 3.86 (ddd,

1 H, H-5), 2.07, 2.06, 2.01, 1.82 (4 s, 12 H, OCOCH₃).

¹³C NMR (75 MHz, CDCl₃): d = 171.0, 170.6, 170.0, 169.5 (4 C=O,

acetyl), 150.8 (COMe), 148.0 (COMe), 139.5 (C_q, Ar), 131.9 (C_q,

Ar), 114.5 (CH_Ar), 108.4 (CH_Ar), 76.8, 74.5, 73.1, 72.4, 69.0 (C-1/

C-5), 62.7 (C-6), 57.5 (OCH₃), 56.8 (OCH₃), 21.2, 21.0, 21.0, 20.8

(4 CH₃, acetyl).

CH₂Cl₂was washed three times with H₂O, dried (CaCl₂), and dis-

tilled over CaH₂before use. Other organic solvents were distilled.

Petroleum ether (PE) used had bp 45–60 °C. TLC was carried out

on aluminum sheets coated with silica gel 60 F₂₅₄(Merck, Darm-

stadt, Germany). TLC plates were inspected under 254 and 312 nm

UV light (except for 9m and 9n, all compounds in the 1,4-

dimethoxyhydroquinone, 1,4-benzoquinone series were visible on

TLC plates as either red-violet spots/312 nm UV light or black

spots/254 nm UV light), and/or developed by treatment with a mix-

ture of 5% H₂SO₄in EtOH followed by heating. Silica gel column

chromatography was performed with Geduran^®silica gel Si 60 (40–

1

63 mm) purchased from Merck. H and ¹³C NMR spectra were re-

MS (ESI+): m/z (%) = 513.8 (10, [M + H]⁺), 536.0 (15, [M + Na]⁺),

corded at 23 °C using Bruker AC200, DRX300 or DRX500 spec-

trometers with the residual solvent as the internal standard. In the ¹H

NMR spectra, the coupling constants for pyranosyl rings have been

assigned and listed without duplication. NMR solvents were pur-

chased from Euriso-Top (Saint Aubin, France). HRMS (LSIMS)

1048.6 (100, [2 M + Na]⁺).

HRMS (LSIMS): m/z [M + Na]⁺calcd for C₂₂H₂₇NO₁₃+ Na:

536.1380; found: 536.1385.

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3477

2-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-1,4-

dimethoxy-5-nitrobenzene (5)

¹³C NMR (50.3 MHz, CDCl₃): d = 170.8, 170.4, 169.7, 169.3 (4

C=O, acetyl), 152.5 (COMe), 141.5 (COMe), 137.7 (C_q, Ar),

113.0 (C_q, Ar), 110.4 (CH_Ar), 99.6 (CH_Ar), 76.0, 74.9, 73.7, 71.6,

69.0 (C-1/C-5), 62.6 (C-6), 56.6 (OCH₃), 56.1 (OCH₃), 20.8, 20.7,

20.7, 20.5 (4 CH₃, acetyl).

Treatment of 2 (350 mg, 0.75 mmol), according to the above proce-

dure for the synthesis of 3, afforded 5 (288 mg, 75%), as well as mi-

nor products chlorinated at C-6 (10 mg, 3%) and at C-5 (51 mg,

13%) [R_f= 0.55, 0.52 (PE–EtOAc, 1:1)]; yellow-green crystals

(PE–CH₂Cl₂–Et₂O); mp 156–157 °C; R_f= 0.41 (PE–EtOAc, 1:1);

[a]_D¹⁷–10.2 (c 0.9, CH₂Cl₂).

¹H NMR (300 MHz, CDCl₃): d = 7.40 (s, 1 H, Ar), 7.23 (s, 1 H, Ar),

5.54 (br d, J_3,4= 3.3 Hz, 1 H, H-4), 5.43 (t, J_2,3= 9.9 Hz, 1 H, H-2),

5.24 (dd, 1 H, H-3), 4.96 (d, J_1,2= 9.9 Hz, 1 H, H-1), 4.18–4.08 (m,

3 H, H-5, H-6, H-6¢), 3.97 (s, 3 H, OCH₃), 3.87 (s, 3 H, OCH₃), 2.22,

2.04, 2.00, 1.84 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 170.8, 170.6, 170.5, 169.6 (4

C=O, acetyl), 150.8 (COMe), 148.1 (COMe), 139.5, 132.3 (2 C_q,

Ar), 114.8 (CH_Ar), 108.4 (CH_Ar), 75.4 (C-5), 73.6 (C-1), 72.5 (C-3),

69.7 (C-2), 68.1 (C-4), 62.0 (C-6), 57.6 (OCH₃), 56.9 (OCH₃), 21.2,

21.1, 21.0, 20.9 (4 CH₃, acetyl).

MS (EI, 70 eV): m/z (%) = 290 (100), 483 (85, [M]⁺).

MS (ESI+): m/z (%) = 483.9 (100, [M + H]⁺), 966.5 (40, [2 M +

H]⁺).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₂₂H₂₉NO₁₁: 483.1741;

found: 483.1735.

The other polar compound formed with Na₂S₂O₄as the hydrogen

donor was poorly soluble in CHCl₃, but was soluble in DMSO and

MeOH; R_f= 0 (PE–EtOAc, 1:1); R_f= 0.26 (MeOH–EtOAc, 1:6);

[a]_D²¹–12.8 (c 0.75, MeOH). NMR data as for 7.

MS (ESI+): m/z (%) = 484.0 (95, [M + H]⁺), 506.1 (100, [M +

Na]⁺), 586.1 (10, [M¢ + H]⁺), 608.2 (52, [M¢ + Na]⁺), 966.6 (30, [2

M + H]⁺), 989.0 (35, [2 M + Na]⁺), 1091.0 (72, [M + M¢ + Na]⁺),

1193.1 (75, [2 M¢ + Na]⁺).

MS (ESI+): m/z (%) = 514 (13, [M + H]⁺), 531 (33, [M + NH₄]⁺),

536 (15, [M + Na]⁺), 1048 (100, [2 M + Na]⁺).

4-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-2,5-di-

methoxyaniline (8)

Treatment of 5 (205 mg, 0.4 mmol) with HCO₂NH₄according to the

previous procedure, afforded 8 (158 mg, 82%) as a pale-yellow syr-

up; [a]_D²⁹–0.9 (c 0.8, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 6.82 (s, 1 H, Ar), 6.28 (s, 1 H,

Ar), 5.55–5.48 (m, 2 H, H-2, H-4), 5.19 (dd, J = 3.3, 9.9 Hz, 1 H, H-

3), 4.85 (d, J_1,2= 9.9 Hz, 1 H, H-1), 4.20–4.03 (m, 3 H, H-5, H-6_,H-

6¢), 3.93–3.82 (br s, 2 H, NH₂, exch. D₂O), 3.82 (s, 3 H, OCH₃), 3.74

(s, 3 H, OCH₃), 2.20, 2.01, 1.98, 1.79 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 170.8, 170.8, 170.5, 169.7 (4

C=O, acetyl), 152.9, 141.7, 138.2, 113.4 (4 C_q, Ar ), 111.1, 99.8

(CH_Ar), 74.9 (C-5), 74.5 (C-1), 73.1(C-3), 69.3, 68.4 (C-2 and C-4),

62.1 (C-6), 56.9 (OCH₃), 56.5 (OCH₃), 21.2, 21.1, 21.0, 20.9 (4

CH₃, acetyl).

Anal. Calcd for C₂₂H₂₇NO₁₃: C, 51.46; H, 5.30; N, 2.73; O, 40.51.

Found: C, 51.13; H, 5.35; N, 2.70; O, 41.18.

4-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-2,5-dimethoxy-

aniline (7)

Reduction with Na₂S₂O₄as the Hydrogen Donor: Compound 3 (20

mg, 0.038 mmol) was dissolved in MeOH (1 mL). Na₂S₂O₄(160

mg, 0.92 mmol), H₂O (0.15 mL) and 10% Pd/C (ca 5 mg) were add-

ed to the above solution contained in a well-stoppered flask filled

with argon. After 13 min, TLC showed completion of the reduc-

tion, the starting material [R_f= 0.40 (PE–EtOAc, 1:1)] being

changed into two new polar compounds [R_f= 0.28 and 0 (PE–

EtOAc, 1:1)]. The mixture was filtered through a Celite pad and the

filtrate was extracted with CHCl₃(3 × 10 mL). The extracts were

combined, washed with brine (10 mL), dried (MgSO₄), and concen-

trated. The residue was purified by chromatography (PE–EtOAc,

1:1) on silica gel to afford compound 7 (11 mg, 60%).

MS (ESI+): m/z (%) = 483.9 (100, [M + H]⁺), 966.5 (40, [2 M +

H]⁺).

Reduction with HCO₂NH₄as the Hydrogen Donor: Compound 3

(22 mg, 0.042 mmol) was dissolved in MeOH (1.5 mL). HCO₂NH₄

(40 mg, 0.63 mmol) and 10% Pd/C (ca 5 mg) were added to the

above solution contained in a well-stoppered flask filled with argon.

After 75 min, TLC showed completion of the reduction. The mix-

ture was filtered through a Celite pad and the filtrate was concen-

trated under vacuum. The residue was purified by chromatography

(PE–EtOAc, 1:1) on silica gel to afford compound 7 (17 mg, 82%).

MS (EI, 70 eV): m/z (%) = 483 (85, [M]⁺).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₂₂H₂₉NO₁₁: 483.1741;

found: 483.1740.

Acylation of 7 and 8 to 9a–n and 10f; General Procedure A

4-C-Glycosyl-2,5-dimethoxyaniline 7 or 8 (1 equiv) was dissolved

in anhyd CH₂Cl₂(3 mL), and anhyd pyridine (20.3 mL, 1.2 equiv)

was added. Acyl chloride (0.218 mmol, 1.05 equiv) was then added.

After the above mixture had been stirred at r.t. for ~2 h, TLC

showed the complete conversion of the starting material into a new

more mobile compound. Then the mixture was concentrated under

vacuum and purified using PE–EtOAc (1:1) as eluent to yield the

desired compound.

Reduction with Na₂S₂O₄/HCO₂NH₄as the Hydrogen Donor: Com-

pound 3 (20 mg, 0.038 mmol) was dissolved in MeOH (1 mL).

Na₂S₂O₄(85% tech.) (160 mg, 0.92 mmol, ca. 20 equiv), H₂O (0.2

mL), HCO₂NH₄(40 mg, 0.63 mmol) and 10% Pd/C (5 mg) were

added to the above solution and stirred at r.t. under argon. After 15

min, TLC showed that the starting material changed into new polar

compounds (R_f= 0.28 and 0). The mixture was filtered through a

Celite pad and the filtrate was extracted with CHCl₃(3 × 10 mL).

The extracts were combined, washed with brine (10 mL), dried

(MgSO₄), and concentrated. The residue was purified by chroma-

tography (PE–EtOAc, 1:1) on silica gel to afford 7 (10 mg, 54%);

pale-yellow oil; [a]_D²⁹–16.7 (c 1, CHCl₃).

¹H NMR (300.13 MHz, CDCl₃): d = 6.75 (s, 1 H, Ar), 6.27 (s, 1 H,

Ar), 5.34 (t, J_3,4= 9.0 Hz, 1 H, H-3), 5.22 (t, J_2,3= 9.9 Hz, 1 H, H-

2), 5.20 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.85 (d, J_1,2= 9.3 Hz, 1 H, H-1),

4.25 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.10 (dd, J_5,6¢= 2.1

Hz, 1 H, H-6¢), 3.82 (s, 3 H, OCH₃), 3.76 (s, 3 H, OCH₃), 4.10–3.75

(overlapping signals, 3 H, H-5 and NH₂, exch. D₂O), 2.05, 2.03,

1.99, 1.77 (4 s, 12 H, OCOCH₃).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(acrylamido)benzene (9a)

Treatment of 7 (100 mg) according to procedure A afforded 9a (104

mg, 94%) as a colorless syrup; R_f= 0.37 (PE–EtOAc, 1:1);

[a]_D²¹+0.6 (c 1.0, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.27 (s, 1 H, Ar), 8.01 (s, 1 H,

CONH), 6.92 (s, 1 H, Ar), 6.43 (dd, J = 1.2 Hz, J_trans= 16.8 Hz, 1

H_alkene), 6.31 (dd, J_cis= 9.6 Hz, J_trans= 16.8 Hz, 1 H_alkene), 5.77 (dd,

J = 1.5, 9.9 Hz, 1 H_alkene), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.28 (t,

J_2,3= 9.6 Hz, 1 H, H-2), 5.22 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.99 (d,

J_1,2= 9.9 Hz, 1 H, H-1), 4.29 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H,

H-6), 4.13 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.87 (s, 3 H, OCH₃), 3.87–

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3478

Y. Z. Zhang et al.

PAPER

3.83 (hidden, 1 H, H-5), 3.83 (s, 3 H, OCH₃), 2.07, 2.06, 2.01, 1.79

(4 s, 12 H, OCOCH₃).

¹H NMR (300.13 MHz, CDCl₃): d = 8.58 (s, 1 H, CONH), 8.33 (s,

1 H, Ar), 7.85 (d, J = 8.7 Hz, 2 H, Ar), 6.99 (d, J = 8.7 Hz, 2 H, Ar),

6.95 (s, 1 H, Ar), 5.39 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.6

Hz, 1 H, H-2), 5.24 (t, J_4,5= 9.6 Hz, 1 H, H-4), 5.01 (d, J_1,2= 9.6 Hz,

1 H, H-1), 4.30 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.15

(dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.92 (s, 3 H, OCH₃), 3.90–3.83 (hid-

den, 1 H, H-5), 3.87 (s, 3 H, OCH₃), 3.86 (s, 3 H, OCH₃), 2.08, 2.07,

2.02, 1.81 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.6, 170.0, 169.7 (4

C=O, acetyl), 163.8 (CONH), 151.9, 142.3 (2 C_q, Ar), 131.7

(CH_alkene), 129.0 (C_q, Ar), 128.26 (CH_2alkene), 119.0 (C_q, Ar), 109.7,

104.1 (2 CH_Ar), 76.5 (C-5), 74.8 (C-3), 73.3 (C-1), 72.4 (C-2), 69.2

(C-4), 63.1 (C-6), 56.7, 56.6 (2 OCH₃), 21.2, 21.1, 21.1, 20.8 (4

CH₃, acetyl).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.0, 170.1, 169.7 (4

C=O, acetyl), 165.3 (CONH), 162.9, 152.1, 142.5, 129.5 (4 C_q, Ar),

129.3 (2 CH_Ar), 127.5, 118.7 (2 C_q, Ar), 114.4 (2 CH_Ar), 109.8,

103.9 (2 CH_Ar), 76.5 (C-5), 74.9 (C-3), 73.4 (C-1), 72.4 (C-2), 69.3

(C-4), 63.1 (C-6), 56.8, 56.7, 55.8 (3 OCH₃), 21.2, 21.1, 21.1, 20.8

(4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 618 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₀H₃₆NO₁₃:

MS (CI, isobutane): m/z (%) = 538 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₅H₃₂NO₁₂:

538.1924; found: 538.1925.

(E)-2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-di-

methoxy-5-(cinnamamido)benzene (9b)

Treatment of 7 (119 mg) according to procedure A afforded 9b (151

mg, 93%); pale yellow green syrup; R_f= 0.36 (PE–EtOAc, 1:1);

[a]_D¹⁷–13.7 (c 0.9, CH₂Cl₂).

618.2187; found: 618.2187.

¹H NMR (300.13 MHz, CDCl₃): d = 8.33 (s, 1 H, Ar), 8.09 (s, 1 H,

CONH), 7.73 (d, J = 15.6 Hz, 1 H_alkene), 7.55 (m, 2 H, Ar), 7.38 (m,

3 H, Ar), 6.94 (s, 1 H, Ar), 6.62 (d, J = 15.6 Hz, 1 H_alkene), 5.39 (t,

J_3,4= 9.3 Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.0 Hz, 1 H, H-2), 5.24 (t,

J_4,5= 9.3 Hz, 1 H, H-4), 5.00 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.29 (dd,

J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (dd, J_5,6¢= 1.5 Hz, 1 H,

H-6¢), 3.89 (s, 3 H, OCH₃), 3.89–3.84 (hidden, 1 H, H-5), 3.84 (s, 3

H, OCH₃), 2.06, 2.06, 2.01, 1.80 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.6, 170.1, 169.7 (4

C=O, acetyl), 164.4 (CONH), 152.0 (C_q, Ar), 142.7 (C_alkene), 142.4

(C_q, Ar), 135.0 (C_q, Ar), 130.4, 129.4, 129.3, 129.3, 128.4, 128.4 (6

CH_Ar), 121.4 (C_alkene), 118.9 (C_q, Ar), 109.8, 104.2 (2 CH_Ar), 76.5

(C-5), 74.9 (C-3), 73.4 (C-1), 72.4 (C-2), 69.2 (C-4), 62.9 (C-6),

56.7, 56.6 (2 OCH₃), 21.2, 21.0, 21.0, 20.8 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(3,5-dimethoxybenzamido)benzene (9e)

Treatment of 7 (102 mg) according to procedure A afforded 9e (122

mg, 89%); white crystals; mp 181–182 °C; R_f= 0.36 (PE–EtOAc,

1:1); [a]_D²¹–12.8 (c 0.8, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.58 (s, 1 H, CONH), 8.31 (s,

1 H, Ar), 7.00 (m, 2 H, Ar), 6.96 (s, 1 H, Ar), 6.63 (t, J = 2.1 Hz, 1

H, Ar), 5.39 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.6 Hz, 1 H,

H-2), 5.24 (t, J_4,5= 9.3 Hz, 1 H, H-4), 5.01 (d, J_1,2= 9.6 Hz, 1 H, H-

1), 4.30 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (dd,

J

_5,6¢= 1.5 Hz, 1 H, H-6¢), 3.91 (s, 3 H, OCH₃), 3.91–3.85 (hidden, 1

H, H-5), 3.87 (s, 3 H, OCH₃), 3.85 (s, 6 H, OCH₃), 2.08, 2.07, 2.02,

1.81 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.6, 170.0, 169.7 (4

C=O, acetyl), 165.5 (CONH), 161.4, 161.4, 152.0, 142.6, 137.5,

129.2, 119.1 (7 C_q, Ar), 109.8, 105.4, 105.4, 104.2, 104.0 (5 CH_Ar),

76.5 (C-5), 74.9 (C-3), 73.4 (C-1), 72.4 (C-2), 69.3 (C-4), 63.1 (C-

6), 56.7, 56.7, 56.0, 56.0 (4 OCH₃), 21.2, 21.0, 21.0, 20.8 (4 CH₃,

acetyl).

MS (CI, isobutane): m/z (%) = 614 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₁H₃₆NO₁₂:

614.2237; found: 614.2240.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-methylbenzamido)benzene (9c)

Treatment of 7 (111 mg) according to procedure A afforded 9c (129

mg, 93%); colorless syrup; R_f= 0.39 (EtOAc–PE, 1:1); [a]_D²³–14.0

(c 1.0, CH₂Cl₂).

MS (CI, isobutane): m/z (%) = 647.9 (48, [M + H]⁺), 670.1 (5, [M +

Na]⁺), 1294.7 (100, [2 M + H]⁺), 1316.7 [2 M + Na]⁺.

Anal. Calcd for C₃₁H₃₇NO₁₄: C, 57.49; H, 5.76; N, 2.16; O, 34.59.

Found: C, 56.82; H, 5.74; N, 1.96; O, 35.35.

¹H NMR (300.13 MHz, CDCl₃): d = 8.60 (s, 1 H, CONH), 8.32 (s,

1 H, Ar), 7.76 (d, J = 8.1 Hz, 2 H, Ar), 7.29 (d, J = 8.1 Hz, 2 H, Ar),

6.83 (s, 1 H, Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.28 (t, J_2,3= 9.9

Hz, 1 H, H-2), 5.22 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.99 (d, J_1,2= 9.6 Hz,

1 H, H-1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.13

(dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.90 (s, 3 H, OCH₃), 3.90–3.85 (hid-

den, 1 H, H-5), 3.85 (s, 3 H, OCH₃), 2.41 (s, 3 H, ArCH₃), 2.06,

2.05, 2.00, 1.79 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.1, 169.8 (4

C=O, acetyl), 165.8 (CONH), 152.1, 142.9, 142.6, 132.5 (4 C_q, Ar),

129.9 (2 CH_Ar), 129.5 (C_q, Ar), 127.4 (2 CH_Ar), 118.8 (C_q, Ar),

109.8 (CH_Ar), 103.9 (CH_Ar), 76.5, 74.9, 73.4, 72.4, 69.3 (C-1/C-5),

62.9 (C-6), 56.8, 56.8 (2 OCH₃), 21.9, 21.2, 21.1, 21.1, 20.9 (5 CH₃,

ArCH₃and 4 acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-nitrobenzamido)benzene (9f)

Treatment of 7 (94 mg) according to procedure A afforded 9f (118

mg, 96%); yellow-green crystals; mp 98–99 °C (CH₂Cl₂–PE–

Et₂O); R_f= 0.42 (PE–EtOAc, 1:1); [a]_D²¹–15.3 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.63 (s, 1 H, CONH), 8.34 (d,

J = 8.7 Hz, 2 H, Ar), 8.25 (s, 1 H, Ar), 8.02 (d, J = 8.7 Hz, 2 H, Ar),

6.97 (s, 1 H, Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.27 (t, J_2,3= 9.6

Hz, 1 H, H-2), 5.22 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.99 (d, J_1,2= 9.6 Hz,

1 H, H-1), 4.28 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.14

(dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.92 (s, 3 H, OCH₃), 3.87 (dq, 1 H, H-

5), 3.86 (s, 3 H, OCH₃), 2.07, 2.05, 2.00, 1.79 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.7, 170.1, 169.7 (4

C=O, acetyl), 163.6 (CONH), 152.0, 150.2, 142.7, 140.8 (4 C_q, Ar),

128.6 (2 CH_Ar), 128.6 (C_q, Ar), 124.5 (2 CH_Ar), 121.1 (C_q, Ar),

110.0 (CH_Ar), 104.1 (CH_Ar), 76.6, 74.8, 73.4, 72.5, 69.3 (C-1/C-5),

63.1 (C-6), 56.8, 56.8 (2 OCH₃), 21.2, 21.1, 21.1, 20.9 (4 CH₃,

acetyl).

MS (CI, isobutane): m/z (%) = 602 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₀H₃₆NO₁₂:

602.2237; found: 602.2239.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-methoxybenzamido)benzene (9d)

Treatment of 7 (85 mg) according to procedure A afforded 9d (103

mg, 95%) as a pale yellow syrup; R_f= 0.34 (PE–EtOAc, 1:1);

[a]_D¹⁷–16.7 (c 1.0, CH₂Cl₂).

MS (CI, isobutane): m/z (%) = 633 (10, [M + H]⁺).

MS (ESI–): m/z (%) = 631.2 (41, [M – H]^–), 666.8 (100, [M + Cl]^–),

668.8 (100, [M + Cl]^–).

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C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3479

HRMS (CI, isobutane): [M + H]⁺calcd for C₂₉H₃₃N₂O₁₄: 633.1932;

found: 633.1933.

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.1, 169.8 (4

C=O, acetyl), 165.9 (CONH), 152.1, 142.7, 135.3, 133.1, 132.6 (5

C_q, Ar), 129.5 (CH_Ar), 129.4 (C_q, Ar), 129.2 (CH_Ar), 128.4, 128.2,

128.1, 127.4, 123.8 (5 CH_Ar), 119.1 (C_q, Ar), 109.9 (CH_Ar), 104.1

(CH_Ar), 76.6, 74.9, 73.4, 72.5, 69.3 (C-1/C-5), 62.9 (C-6), 56.8, 56.8

(2 OCH₃), 21.2, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 638 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₃H₃₆NO₁₄:

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-biphenylcarboxamido)benzene (9g)

Treatment of 7 (114 mg) according to procedure A, afforded 9g

(148 mg, 95%); R_f= 0.42 (PE–EtOAc, 1:1); [a]_D¹⁷–20.3 (c 0.9,

CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.69 (s, 1 H, CONH), 8.36 (s,

1 H, Ar), 7.95 (d, J = 8.4 Hz, 2 H, Ar), 7.71 (d, J = 8.1 Hz, 2 H, Ar),

7.62 (d, J = 8.4 Hz, 2 H, Ar), 7.44 (m, 3 H, Ar), 6.98 (s, 1 H, Ar),

5.40 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.32 (t, J_2,3= 9.6 Hz, 1 H, H-2), 5.25

(t, J_4,5= 9.9 Hz, 1 H, H-4), 5.03 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.31

(dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.16 (dd, J_5,6¢= 2.1 Hz,

1 H, H-6¢), 3.92 (s, 3 H, OCH₃), 3.92–3.88 (hidden, 1 H, H-5), 3.88

(s, 3 H, OCH₃), 2.07, 2.06, 2.02, 1.82 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.7, 170.1, 169.7 (4

C=O, acetyl), 165.4 (CONH), 152.1, 152.1, 145.1, 142.6, 140.2,

133.9 (6 C_q, Ar), 129.4, 129.4, 128.5, 128.0, 128.0, 127.9, 127.9,

127.6, 127.6 (9 CH_Ar), 119.1 (C_q, Ar), 109.9, 104.0 (2 CH_Ar), 76.5

(C-5), 74.9 (C-3), 73.5 (C-1), 72.5 (C-2), 69.3 (C-4), 63.1 (C-6),

56.8, 56.8 (2 OCH₃), 21.2, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

638.2237; found: 638.2237.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(2-furylcarboxamido)benzene (9j)

Treatment of 7 (81 mg) according to procedure A afforded 9j (94

23

mg, 97%); pale yellow syrup; R_f= 0.29 (PE–EtOAc, 1:1); [a]_D

–13.8 (c 1.05, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.82 (s, 1 H, CONH), 8.28 (s,

1 H, Ar), 7.55 (br s, 1 H_furyl), 7.22 (d, J = 4.2 Hz, 1 H_furyl), 6.95 (s, 1

H, Ar), 6.56 (q, J_m= 1.8 Hz, J_o= 3.0 Hz, 1 H_furyl), 5.38 (t, J_3,4= 9.3

Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.6 Hz, 1 H, H-2), 5.24 (t, J_4,5= 9.3 Hz,

1 H, H-4), 5.00 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.29 (dd, J_5,6= 4.8 Hz,

J

_6,6¢= 12.3 Hz, 1 H, H-6), 4.15 (dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.93

(s, 3 H, OCH₃), 3.89 (dq, 1 H, H-5), 3.86 (s, 3 H, OCH₃), 2.08, 2.07,

2.01, 1.80 (4 s, 12 H, OCOCH₃).

MS (CI, isobutane): m/z (%) = 664 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₅H₃₈NO₁₂:

664.2394; found: 664.23910.

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.7, 170.1, 169.7 (4

C=O, acetyl), 156.5 (CONH), 152.0, 148.3 (2 C_q, Ar), 144.9 (CH_Ar),

142.6, 128.8, 119.1 (3 C_q, Ar), 115.6, 113.0, 109.9, 104.0 (4 CH_Ar),

76.5 (C-5), 74.9 (C-3), 73.5 (C-1), 72.4 (C-2), 69.2 (C-4), 62.9 (C-

6), 56.8, 56.7 (2 OCH₃), 21.2, 21.1, 21.1, 20.8 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(1-naphthamido)benzene (9h)

Treatment of 7 (111 mg) according to procedure A afforded 9h (148

MS (CI, isobutane): m/z (%) = 578 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₇H₃₂NO₁₃:

mg, 95%); colorless syrup; [a]_D²³–8.4 (c 1.05, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.41 (br d, J = 4.2 Hz, 3 H,

CONH and 2 Ar), 7.98 (d, J = 8.1 Hz, 1 H, Ar), 7.91 (d, J = 6.9 Hz,

1 H, Ar), 7.75 (d, J = 6.9 Hz, 1 H, Ar), 7.55 (m, 3 H, Ar), 6.95 (s, 1

H, Ar), 5.40 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.31 (t, J_2,3= 9.9 Hz, 1 H,

H-2), 5.24 (t, J_4,5= 9.9 Hz, 1 H, H-4), 5,03 (d, J_1,2= 9.6 Hz, 1 H, H-

1), 4.30 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.15 (br d, J =

12.3 Hz, 1 H, H-6¢), 3.91 (s, 3 H, OCH₃), 3.91–3.83 (hidden, 1 H,

H-5), 3.83 (s, 3 H, OCH₃), 2.07, 2.07, 2.02, 1.84 (4 s, 12 H,

OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.1, 169.8 (4

C=O, acetyl), 167.9 (CONH), 152.1, 142.6, 134.9, 134.2 (4 C_q, Ar),

131.6 (CH_Ar), 130.5, 129.5 (2 C_q, Ar), 128.8, 127.8, 127.0, 125.7,

125.7, 125.2 (6 CH_Ar), 119.3 (C_q, Ar), 109.8, 104.1 (2 CH_Ar), 76.5

(C-5), 75.0 (C-3), 73.4 (C-1), 72.5 (C-2), 69.3 (C-4), 63.0 (C-6),

56.9, 56.6 (2 OCH₃), 21.2, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

578.1874; found: 578.1874.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(2-thienylcarboxamido)benzene (9k)

Treatment of 7 (52 mg) according to procedure A afforded 9k (61

mg, 96%); pale yellow syrup; R_f= 0.41 (PE–EtOAc, 1:1); [a]_D

–12.6 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.47 (s, 1 H, CONH), 8.23 (s,

1 H, Ar), 7.59 (dd, J_o= 3.9 Hz, J_m= 0.9 Hz, 1 H_thienyl), 7.54 (dd,

J_o= 4.8 Hz, J_m= 0.9 Hz, 1 H_thienyl), 7.11 (dd, J_o= 3.9 Hz, J_o= 4.8

Hz, 1 H_thienyl), 6.93 (s, 1 H, Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.27

(t, J_2,3= 9.6 Hz, 1 H, H-2), 5.22 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.98 (d,

J_1,2= 9.6 Hz, 1 H, H-1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H,

H-6), 4.14 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.90 (s, 3 H, OCH₃), 3.85

(dq, 1 H, H-5), 3.83 (s, 3 H, OCH₃), 2.06, 2.05, 2.00, 1.78 (4 s, 12

H, OCOCH₃).

21

MS (CI, isobutane): m/z (%) = 638 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₃H₃₆NO₁₂:

638.2237; found: 638.2237.

¹³C NMR (75.5 MHz, CDCl₃): d = 170.8, 170.3, 169.7, 169.3 (4

C=O, acetyl), 159.8 (CONH), 151.7, 142.0, 139.6 (3 C_q, Ar), 131.1

(CH_Ar), 128.7 (C_q, Ar), 128.2, 127.9 (2 CH_Ar), 118.7 (C_q, Ar), 109.5,

103.6 (2 CH_Ar), 76.2, 74.5, 73.1, 72.1, 68.9 (C-1/C-5), 63.0 (C-6),

56.5, 56.4 (2 OCH₃), 20.9, 20.7, 20.7, 20.5 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(2-naphthamido)benzene (9i)

Treatment of 7 (92 mg) according to procedure A afforded 9i (120

mg, 99%); colorless syrup; R_f= 0.42 (PE–EtOAc, 1:1); [a]_D²¹–19.5

(c 0.7, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.78 (s, 1 H, CONH), 8.40 (s,

1 H, Ar), 8.39 (s, 1 H, Ar), 7.93 (m, 4 H, Ar), 7.58 (m, 2 H, Ar), 6.97

(s, 1 H, Ar), 5.39 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.31 (t, J_2,3= 9.3 Hz, 1

H, H-2), 5.25 (t, J_4,5= 9.3 Hz, 1 H, H-4), 5.02 (d, J_1,2= 9.6 Hz, 1 H,

H-1), 4.30 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.15 (dd,

MS (CI, isobutane): m/z (%) = 594 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₇H₃₂NO₁₂S:

594.1645; found: 594.1647.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-nicotinamidobenzene (9l)

Treatment of 7 (85 mg) according to procedure A (note: 2.2 equiv

of pyridine was added) afforded 9l (61 mg, 91%); pale yellow syr-

up; R_f= 0.21 (PE–EtOAc, 1:2); [a]_D¹⁷–8.9 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 9.13 (br s, 1 H_py), 8.79 (d,

J = 3.9 Hz, 1 H, Ar), 8.65 (s, 1 H, CONH), 8.28 (s, 1 H, Ar), 8.21

(dt, J = 7.8, 1.8, 1.8 Hz, 1 H_py), 7.47 (dd, J = 7.8, 4.8 Hz, 1 H_py),

J_5,6¢= 1.2 Hz, 1 H, H-6¢), 3.94 (s, 3 H, OCH₃), 3.94–3.89 (hidden, 1

H, H-5), 3.89 (s, 3 H, OCH₃), 2.08, 2.07, 2.01, 1.81 (4 s, 12 H,

OCOCH₃).

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

3480

Y. Z. Zhang et al.

PAPER

6.98 (s, 1 H, Ar), 5.40 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.3

Hz, 1 H, H-2), 5.25 (t, J_4,5= 9.6 Hz, 1 H, H-4), 5.02 (d, J_1,2= 9.9 Hz,

1 H, H-1), 4.30 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.16

(dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.93 (s, 3 H, OCH₃), 3.93–3.87 (hid-

den, 1 H, H-5), 3.87 (s, 3 H, OCH₃), 2.08, 2.07, 2.02, 1.81 (4 s, 12

H, OCOCH₃).

110.5 (2 CH_Ar), 104.1 (2 CH_Ar), 76.6 (2 C-5), 74.9 (2 C-3), 73.4 (2

C-1), 72.4 (2 C-2), 69.2 (2 C-4), 68.2 (2 C-6), 57.1, 56.8 (4 OCH₃),

21.2, 21.1, 21.1, 20.9 (8 CH₃, acetyl).

MS (ESI+): m/z (%) = 1120.3 (95, [M + Na]⁺), 1098.1 (100, [M +

H]⁺).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.0, 170.6, 170.0, 169.7 (4

C=O, acetyl), 163.8 (CONH), 153.0 (CH_py), 152.0 (C_q, Ar), 148.4

(CH_py), 142.6 (C_q, Ar), 135.4 (CH_py), 131.0, 128.8 (2 C_q, Ar), 124.1

(CH_py), 119.7 (C_q, Ar), 109.9, 104.1 (2 CH_Ar), 76.5 (C-5), 74.8 (C-

3), 73.4 (C-1), 72.4 (C-2), 68.2 (C-4), 62.9 (C-6), 56.8, 56.7 (2

OCH₃), 21.2, 21.0, 21.0, 20.8 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 589 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₈H₃₃N₂O₁₂:

2-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-1,4-

dimethoxy-5-(4-nitrobenzamido)benzene (10f)

Treatment of 8 (157 mg) according to procedure A afforded 10f

(205 mg, 99%); yellow-green crystals; mp 84–85 °C (CH₂Cl₂–PE–

Et₂O); R_f= 0.40 (PE–EtOAc, 1:1); [a]_D²¹–1.2 (c 0.93, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.68 (s, 1 H, CONH), 8.34 (d,

J = 9.0 Hz, 2 H, Ar), 8.26 (s, 1 H, Ar), 8.04 (d, J = 9.0 Hz, 2 H, Ar),

7.06 (s, 1 H, Ar), 5.56 (d, J_3,4= 3.3 Hz, 1 H, H-4), 5.48 (t, J_2,3= 9.9

Hz, 1 H, H-2), 5.26 (dd, 1 H, H-3), 5.00 (d, J_1,2= 9.6 Hz, 1 H, H-1),

4.23–4.11 (m, 3 H, H-5, H-6, H-6¢), 3.97 (s, 3 H, OCH₃), 3.88 (s, 3

H, OCH₃), 2.24, 2.04, 2.00, 1.84 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.8, 170.6, 170.4, 169.8 (4

C=O, acetyl), 163.5 (CONH), 151.9, 150.1, 142.6, 140.7 (4 C_q, Ar),

128.6 (2 CH_Ar), 128.5 (C_q, Ar), 124.4 (2 CH_Ar), 120.5 (C_q, Ar),

110.3 (CH_Ar), 104.1 (CH_Ar), 75.1 (C-5), 73.9 (C-1), 72.7 (C-3), 69.8

(C-2), 68.3 (C-4), 62.1 (C-6), 56.8 (2 OCH₃), 21.1, 21.0, 21.0, 20.9

(4 CH₃, acetyl).

589.2033; found: 589.2031.

N-Carbonyl-(6-ethoxycarbonyl-2-pyridyl)-4-(2,3,4,6-tetra-O-

acetyl-b-D-glucopyranosyl)-2,5-dimethoxyaniline (9m) and 2,6-

[Bis-2,5-dimethoxy-4-(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-

syl)anilino-N-carbonyl]pyridine (9n)

Treatment of 7 (102 mg) according to procedure A (note: 0.53 equiv

of pyridine-2,6-dicarbonyl chloride was added) afforded 9m (8 mg,

6%) and 9n (101 mg, 87%).

MS (ESI+): m/z (%) = 632.8 (100, [M + H]⁺), 655.1 (8, [M + Na]⁺),

9m

710.5 (15, [M + H + DMSO]⁺), 1286.6 (97, [2 M + Na]⁺).

Yellow-green syrup; R_f= 0.55 (PE–EtOAc, 1:1, UV 312 nm or-

ange, 254 nm black).

MS (ESI–): m/z (%) = 631.2 (45, [M – H]^–), 666.7 (100, [M + Cl]^–).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₉H₃₃N₂O₁₄:

¹H NMR (300.13 MHz, CDCl₃): d = 10.75 (s, 1 H, CONH), 8.43

(dd, J_m= 1.2 Hz, J_o= 7.8 Hz, 1 H, pyridine H-3¢ or H-5¢), 8.37 (s, 1

H, Ar), 8.29 (dd, J = 1.2, 7.8 Hz, 1 H, pyridine H-3¢ or H-5¢), 8.06

(t, J = 7.8 Hz, 1 H, H-4¢), 6.97 (s, 1 H, Ar), 5.39 (t, J_3,4= 9.3 Hz, 1

H, H-3), 5.32 (t, J_2,3= 9.3 Hz, 1 H, H-2), 5.25 (t, J_4,5= 9.6 Hz, 1 H,

H-4), 5.01 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.51 (q, J = 7.0, 2 H, OCH₂),

4.30 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.16 (dd, J_5,6¢= 2.1

Hz, 1 H, H-6¢), 3.98 (s, 3 H, OCH₃), 3.89 (m, 1 H, H-5), 3.89 (s, 3

H, OCH₃), 2.09, 2.07, 2.01, 1.79 (4 s, 12 H, OCOCH₃), 1.52 (t, J =

7.0 Hz, 3 H, CH₃CH₂).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.1, 169.7 (4

C=O, acetyl), 164.8 (CO₂Et), 161.8 (CONH), 152.1, 150.4, 147.3,

143.4 (4 C_q, Ar), 139.3 (CH, pyridine, C-4¢), 127.8, 125.5 (CH, py-

ridine, C-3¢ and C-5¢), 119.3 (C_q, Ar), 110.2 (CH_Ar), 103.9 (CH_Ar),

76.5 (C-5), 74.9 (C-3), 73.6 (C-1), 72.4 (C-2), 69.3 (C-4), 62.9 (C-

6), 56.9, 56.8 (2 OCH₃), 21.2, 21.1, 21.1, 20.8 (4 CH₃, acetyl), 14.7

(CH₃CH₂O).

633.1932; found: 633.1929.

2-(b-D-Glucopyranosyl)-1,4-dimethoxy-5-(4-nitrobenzami-

do)benzene (11f)

Compound 9f (59 mg, 0.187 mmol) was dissolved in anhyd MeOH

(5 mL) and cooled in an ice-water mixture. After the addition of

Ba(OMe)₂solution [1.25 mL of 0.02 M/L of Ba(OMe)₂, prepared

by dissolving BaO (153 mg) in anhyd MeOH (50 mL)], the mixture

was allowed to stand, with occasional shaking, in the refrigerator

for 20 h. TLC showed that the starting material 9f (R_f= 0.92,

MeOH–CH₂Cl₂, 1:5) had completely changed into a more polar

compound 11f (R_f= 0.45 (MeOH–CH₂Cl₂, 1:5). BaO was removed

by stirring with a slight excess of Dowex 50wX2 (H⁺) ion-exchange

resin. The solution was filtered and evaporated to a syrup under re-

duced pressure and purified using 12:1 MeOH–CH₂Cl₂as eluent to

yield pure 11f (42 mg, 97%); orange-red solid; mp 202–204 °C;

[a]_D²¹–10.6 (c 0.62, DMSO).

¹H NMR (300.13 MHz, DMSO-d₆): d = 9.88 (s, 1 H, CONH), 8.36

(d, J = 8.7 Hz, 2 H, Ar), 8.18 (d, J = 8.7 Hz, 2 H, Ar), 7.45 (s, 1 H,

Ar), 7.02 (s, 1 H, Ar), 4.97 (d, J = 4.2 Hz, 1 H, OH exch. D₂O), 4.93

(d, J = 4.2 Hz, 1 H, OH exch. D₂O), 4.71 (d, J = 5.4 Hz, 1 H, OH

exch. D₂O), 4.50 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.45 (t, J = 5.7 Hz, 1

H, OH exch. D₂O), 3.80 (s, 3 H, OCH₃), 3.73 (s, 3 H, OCH₃), 3.68

(m, 1 H, H-6), 3.48–3.40 (m, 2 H, H-2 and H-6¢), 3.30 (m, 1 H, H-

5), 3.21 (br s, 2 H, H-3 and H-4).

MS (CI, isobutane): m/z (%) = 661 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₁H₃₇N₂O₁₄:

661.2245; found: 661.2248.

9n

Yellow-green syrup; [a]_D¹⁷–72.7 (c 1.0, CH₂Cl₂); R_f= 0.34 (PE–

EtOAc, 1:1, UV 312 nm orange, 254 nm black).

¹H NMR (300.13 MHz, CDCl₃): d = 10.37 (s, 2 H, CONH), 8.48 (d,

J = 7.8 Hz, 2 H_py), 8.38 (s, 2 H, Ar), 8.17 (t, J = 7.8 Hz, 1 H_py), 7.06

(s, 2 H, Ar), 5.41 (t, J_3,4= 9.0 Hz, 2 H, H-3), 5.33 (t, J_2,3= 9.6 Hz, 2

H, H-2), 5.27 (t, J_4,5= 9.3 Hz, 2 H, H-4), 5.05 (d, J_1,2= 9.6 Hz, 2 H,

H-1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 2 H, H-6), 4.14 (dd,

¹³C NMR (75.5 MHz, DMSO-d₆): d = 151.2, 149.1, 145.8, 140.1

(CONH and 3 C_q, Ar), 129.1, 129.1 (2 CH_Ar), 126.1, 125.9 (2 C_q,

Ar), 123.5, 123.5 (2 CH_Ar), 114.1 (C_q, Ar), 111.6, 109.0 (2 CH_Ar),

81.5 (C-3 or C-4), 78.5 (C-5), 74.1 (C-1), 73.6 (C-2), 70.4 (C-4 or

C-3), 61.4 (C-6), 56.6, 52.2 (2 OCH₃).

MS (ESI+): m/z (%) = 950.8 (100, [2 M + Na]⁺).

HRMS (ESI+): m/z [M + Na]⁺calcd for C₂₁H₂₄N₂O₁₀+ Na:

J

_5,6¢= 1.8 Hz, 2 H, H-6¢), 3.95 (s, 6 H, 2 OCH₃), 3.87 (hidden, 2 H,

H-5), 3.92 (s, 6 H, 2 OCH₃), 2.11, 2.08, 2.03, 1.82 (4 s, 24 H,

OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.1, 170.7, 170.0, 169.7 (8

C=O, acetyl), 161.5 (2 CONH), 152.1, 149.5, 143.4 (6 C_q, Ar),

140.0 (CH_Ar), 128.7 (2 C_q, Ar), 125.7 (2 CH_Ar), 119.8 (2 C_q, Ar),

487.1329; found: 487.1331.

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3481

2-(b-D-Galactopyranosyl)-1,4-dimethoxy-5-(4-nitrobenzami-

do)benzene (12f)

Treatment of 10f (88 mg) according to the above procedure afford-

ed 12f (61 mg, 94); orange-red solid; mp 214–216 °C; R_f= 0.44

(MeOH–CH₂Cl₂, 1:5); [a]_D²¹–2.6 (c 0.53, DMSO).

(E)-2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(cinnam-

amido)-1,4-benzoquinone (13b)

Treatment of compound 9b (148 mg) according to procedure B af-

forded 13b (134 mg, 95%) as a orange-red solid; mp 194–196 °C;

R_f= 0.63 (PE–EtOAc, 1:1); [a]_D¹⁷–26.7 (c 1.1, CH₂Cl₂).

¹H NMR (300.13 MHz, DMSO-d₆): d = 9.90 (s, 1 H, CONH), 8.36

(d, J = 8.7 Hz, 2 H, Ar), 8.19 (d, J = 8.7 Hz, 2 H, Ar), 7.44 (s, 1 H,

Ar), 7.10 (s, 1 H, Ar), 4.73 (br s, 1 H, OH exch. D₂O), 4.58 (br s, 2

H, OH exch. D₂O), 4.46 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.37 (br s, 1 H,

OH exch. D₂O), 3.80 (s, 3 H, OCH₃), 3.80–3.73 (hidden, 2 H, H-2

and H-3), 3.73 (s, 3 H, OCH₃), 3.51–3.41 (m, 4 H, H-4, H-5, H-6,

H-6¢).

¹³C NMR (75.5 MHz, DMSO-d₆): d = 163.6 (CONH), 151.1, 149.1,

145.8 (3 C_q, Ar), 129.5, 129.5 (2 CH_Ar), 126.3, 126.0 (2 C_q, Ar),

123.5, 123.5 (2 CH_Ar), 114.1 (C_q, Ar), 111.8, 108.9 (2 CH_Ar), 79.8,

75.1, 74.4 (C-1), 70.6, 69.0 (C-2 to C-5), 60.8 (C-6), 56.5, 52.2 (2

OCH₃).

¹H NMR (300.13 MHz, CDCl₃): d = 8.34 (s, 1 H, CONH), 7.76 (d,

J = 15.6 Hz, 1 H_alkene) 7.69 (s, 1 H, Ar), 7.58 (m, 2 H, Ar), 7.42 (m,

3 H, Ar), 6.93 (s, 1 H, Ar), 6.69 (d, J = 15.6 Hz, 1 H_alkene), 5.39 (t,

J_3,4= 9.3 Hz, 1 H, H-3), 5.16 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.94 (t,

J_2,3= 9.3 Hz, 1 H, H-2), 4.74 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.27 (dd,

J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.16 (dd, J_5,6¢= 1.8 Hz, 1 H,

H-6¢), 3.83 (dq, 1 H, H-5), 2.10, 2.06, 2.01, 1.92 (4 s, 12 H,

OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.4, 183.0 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 165.1

(CONH), 146.4 (C_q, Ar), 145.2 (CH_alkene), 139.0, 134.4 (2 C_q, Ar),

131.2, 130.7, 129.4, 129.4, 128.7, 128.7 (6 CH_Ar), 119.8 (CH_alkene),

114.8 (CH_Ar), 76.5 (C-5), 74.9 (C-3), 73.2 (C-2), 71.9 (C-1), 68.7

(C-4), 62.5 (C-6), 21.2, 21.0, 21.0, 20.9 (4 CH₃, acetyl).

MS (ESI+): m/z (%) = 950.8 (100, [2 M + Na]⁺).

HRMS (ESI+): m/z [M + Na]⁺calcd for C₂₁H₂₄N₂O₁₀+ Na:

MS (CI, isobutane): m/z (%) = 586 (100, [phenol + H]⁺), 584 (45,

487.1329; found: 487.1330.

[M + H]⁺).

Oxidation of 9a–9l and 9n to 13a–13l and 13n; General Proce-

dure B

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₉H₃₀NO₁₂:

584.1768; found: 584.1767.

The C-glycosyl amido benzene (1 equiv) dissolved in MeCN (2

mL) was reacted with ceric ammonium nitrate (400 mg, 0.73 mmol,

4 equiv) dissolved in H₂O (5 mL) at r.t. After ~2 h, TLC (PE–

EtOAc, 1:1 or similar) showed that the starting material had been

consumed, to afford a more mobile compound. H₂O (10 mL) was

poured into the mixture which was extracted with CH₂Cl₂(3 × 15

mL). The extracts were combined and washed with brine (15 mL),

H₂O (15 mL), dried (MgSO₄), and concentrated. The residue was

chromatographed (PE–EtOAc, 3:2 or similar) on silica gel. Concen-

tration of the homogeneous fractions led to the desired benzoqui-

none.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-methyl-

benzamido)-1,4-benzoquinone (13c)

Treatment of compound 9c (85 mg) according to procedure B af-

forded 13c (74 mg, 91%); yellow-green crystals; mp 103–104 °C

(CH₂Cl₂–PE–Et₂O); R_f= 0.52 (EtOAc–PE, 1:1); [a]_D¹⁷–21.0 (c 0.6,

CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.82 (s, 1 H, CONH), 7.78 (d,

J = 8.1 Hz, 2 H, Ar), 7.72 (s, 1 H, Ar), 7.33 (d, J = 8.1 Hz, 2 H, Ar),

6.96 (s, 1 H, Ar), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.14 (t, J_4,5= 9.6

Hz, 1 H, H-4), 4.94 (t, J_2,3= 9.6 Hz, 1 H, H-2), 4.74 (d, J_1,2= 9.6 Hz,

1 H, H-1), 4.26 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.15

(dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.82 (dq, 1 H, H-5), 2.45 (s, 3 H,

CH₃), 2.10, 2.06, 2.01, 1.92 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.5, 183.2 (2 C=O, benzo-

quinone), 171.1, 170.4, 170.4, 170.0 (4 C=O, acetyl), 166.1

(CONH), 146.5, 144.4, 138.9 (3 C_q, Ar), 130.7 (CH_Ar), 130.6 (C_q,

Ar), 130.2, 127.8 (4 CH_Ar), 114.5 (CH_Ar), 76.6 (C-5), 73.9 (C-3),

73.2 (C-2), 72.1 (C-1), 68.7 (C-4), 62.4 (C-6), 22.1 (ArCH₃), 21.2,

21.0, 21.0, 20.9 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(acrylamido)-

1,4-benzoquinone (13a)

Treatment of compound 9a (98 mg) according to procedure B af-

forded 13a (62 mg, 67%) as a yellow-green syrup; R_f= 0.44 (PE–

EtOAc, 1:1); [a]_D¹⁹–19.0 (c 1.0, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.21 (s, 1 H, CONH), 7.64 (s,

1 H, Ar), 6.93 (s, 1 H, Ar), 6.47 (d, J = 16.2 Hz, 1 H_alkene), 6.32 (dd,

J = 16.2, 10.2 Hz, 1 H_alkene), 5.90 (d, J = 10.2, 16.2 Hz, 1 H_alkene),

5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.14 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.93

(t, J_2,3= 9.3 Hz, 1 H, H-2), 4.72 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.26

(dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (dd, J_5,6¢= 2.1 Hz,

1 H, H-6¢), 3.82 (dq, 1 H, H-5), 2.10, 2.06, 2.01, 1.91 (4 s, 12 H,

OCOCH₃).

MS (CI, isobutane): m/z (%) = 572 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₈H₃₀NO₁₂:

572.1768; found: 572.17675.

¹³C NMR (75.5 MHz, CDCl₃): d = 186.4, 182.9 (2 C=O, benzo-

quinone), 171.0, 170.3, 170.3, 170.0 (4 C=O, acetyl), 164.6

(CONH), 146.4, 138.7 (2 C_q, Ar), 130.7 (CH_2alkene), 130.7 (CH_alkene),

115.1, 104.6 (2 CH_Ar), 76.6 (C-5), 73.9 (C-3), 73.2 (C-2), 72.0 (C-

1), 68.7 (C-4), 62.5 (C-6), 21.1, 21.0, 21.0, 20.9 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-methoxy-

benzamido)-1,4-benzoquinone (13d)

Treatment of compound 9d (100 mg) according to procedure B af-

forded 13d (81 mg, 85%); yellow crystals; mp 141–142 °C

(CH₂Cl₂–PE–Et₂O); R_f= 0.48 (EtOAc–PE, 1:1); [a]_D²³–20.5 (c

0.88, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.78 (s, 1 H, CONH), 7.85 (d,

J = 8.7 Hz, 2 H, Ar), 7.69 (s, 1 H, Ar), 7.00 (d, J = 8.7 Hz, 2 H, Ar),

6.96 (s, 1 H, Ar), 5.39 (t, J_3,4= 9.6 Hz, 1 H, H-3), 5.15 (t, J_4,5= 9.9

Hz, 1 H, H-4), 4.95 (t, J_2,3= 9.3 Hz, 1 H, H-2), 4.75 (d, J_1,2= 9.9 Hz,

1 H, H-1), 4.28 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15

(dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.89 (s, 3 H, OCH₃), 3.84 (dq, 1 H, H-

5), 2.11, 2.06, 2.02, 1.92 (4 s, 12 H, OCOCH₃).

MS (CI, isobutane): m/z (%) = 510 (100, [phenol + H]⁺), 508 (20,

[M + H]⁺).

MS (ESI+): m/z (%) = 1036.6 (100, [2 M + Na]⁺), 530.1 (55, [M +

Na]⁺), 507.9 (40, [M + H]⁺).

HRMS (ESI+): m/z [M + Na]⁺calcd for C₂₃H₂₅NO₁₂+ Na:

530.1274; found: 530.12761.

¹³C NMR (75.5 MHz, CDCl₃): d = 186.5, 183.2 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 165.6

(CONH), 163.8, 146.5, 138.9 (3 C_q, Ar), 130.6 129.8, 129.8 (3

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

3482

Y. Z. Zhang et al.

PAPER

CH_Ar), 125.6 (C_q, Ar), 114.7, 114.7, 114.3 (CH_Ar), 76.6 (C-5), 73.9

(C-3), 73.2 (C-2), 72.0 (C-1), 68.7 (C-4), 62.4 (C-6), 56.0 (OCH₃),

21.2, 21.0, 21.0, 20.9 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 590 (100, [phenol + H]⁺).

¹H NMR (300.13 MHz, CDCl₃): d = 8.89 (s, 1 H, CONH), 7.94 (d,

J = 8.1 Hz, 2 H, Ar), 7.73 (d, J = 8.4 Hz, 3 H, Ar), 7.73 (s, 1 H, Ar),

7.44 (m, 3 H, Ar), 6.99 (s, 1 H, Ar), 5.40 (t, J_3,4= 9.3 Hz, 1 H, H-3),

5.16 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.96 (t, J_2,3= 9.3 Hz, 1 H, H-2), 4.75

(d, J_1,2= 9.6 Hz, 1 H, H-1), 4.26 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1

H, H-6), 4.16 (dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.84 (dq, 1 H, H-5),

2.11, 2.06, 2.02, 1.93 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.5, 183.1 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.4, 170.0 (4 C=O, acetyl), 165.9

(CONH), 146.6, 146.2, 139.8, 138.8, 131.9 (5 C_q, Ar), 130.7, 129.5,

129.5, 128.9, 128.3, 128.3, 128.0, 128.0, 127.7, 127.7, 114.7 (11

CH_Ar), 76.6 (C-5), 73.9 (C-3), 73.2 (C-2), 72.1 (C-1), 68.7 (C-4),

62.5 (C-6), 21.2, 21.0, 21.0, 21.0 (4 CH₃, acetyl).

MS (ESI+): m/z (%) = 588.0 (20, [M + H]⁺), 610.1 (25, [M + Na]⁺),

1196.6 (100, [2 M + Na]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₂₈H₃₀NO₁₃: 588.1717;

found: 588.1718.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(3,5-di-

methoxybenzamido)-1,4-benzoquinone (13e)

Treatment of compound 9e (105 mg) according to procedure B af-

forded 13e (97 mg, 97%) as yellow-green crystals; mp 207–208 °C

(CH₂Cl₂–PE–Et₂O); R_f= 0.40 (EtOAc–PE, 1:1); [a]_D¹⁹–16.2 (c

0.82, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.77 (s, 1 H, CONH), 7.68 (s,

1 H, Ar), 6.96 (m, 3 H, Ar), 6.66 (t, J = 2.1, 2.1 Hz, 1 H, Ar), 5.39

(t, J_3,4= 9.3 Hz, 1 H, H-3), 5.15 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.91 (t,

J_2,3= 9.6 Hz, 1 H, H-2), 4.74 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.26 (dd,

J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (dd, J_5,6¢= 1.8 Hz, 1 H,

H-6¢), 3.91–3.82 (m, 1 H, H-5), 3.86 (s, 6 H, OCH₃), 2.10, 2.06,

2.01, 1.92 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.4, 183.0 (2 C=O, benzo-

quinone), 171.0, 170.3, 170.3, 169.9 (4 C=O, acetyl), 166.0

(CONH), 161.6, 161.6, 146.5, 138.7, 135.5 (5 C_q, Ar), 130.7, 114.8,

105.6, 105.6, 105.3 (5 CH_Ar), 76.6 (C-5), 73.9 (C-3), 73.2 (C-2),

72.1 (C-1), 68.7 (C-4), 62.4 (C-6), 56.1, 56.1 (2 OCH₃), 21.1, 21.0,

21.0, 20.9 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 636 (100, [phenol + H]⁺), 634 (60,

[M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₃H₃₂N₁O₁₄:

634.1924; found: 634.19245.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(1-naphthami-

do)-1,4-benzoquinone (13h)

Treatment of compound 9h (43 mg) according to procedure B af-

forded 13h (36 mg, 88%); yellow-green syrup; R_f= 0.54 (PE–

EtOAc, 1:1); [a]_D²³–18.9 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.65 (s, 1 H, CONH), 8.36 (dd,

J_o= 7.5 Hz, J_m= 1.5 Hz, 1 H, Ar), 8.04 (d, J = 8.4 Hz, 1 H, Ar), 7.93

(dd, J_o= 7.5 Hz, J_m= 1.5 Hz, 1 H, Ar), 7.83 (s, 1 H, Ar), 7.76 (dd,

J = 0.9 Hz, 7.2 Hz, 1 H, Ar), 7.65–7.52 (m, 3 H, Ar), 6.96 (d, J = 0.9

Hz, 1 H, Ar), 5.40 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.15 (t, J_4,5= 9.9 Hz,

1 H, H-4), 4.96 (t, J_2,3= 9.6 Hz, 1 H, H-2), 4.75 (dd, J_1,2= 9.6 Hz,

J = 0.9 Hz, 1 H, H-1), 4.28 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H,

H-6), 4.15 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.83 (dq, 1 H, H-5), 2.10,

2.06, 2.02, 1.96 (4 s, 12 H, OCOCH₃).

MS (ESI+): m/z (%) = 1256.7 (100, [2 M + Na]⁺), 1234.5 (45, [2 M

+ H]⁺), 617.9 (100, [M + H]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₂₉H₃₂NO₁₄: 618.1823;

¹³C NMR (75.5 MHz, CDCl₃): d = 186.6, 182.9 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.4, 170.0 (4 C=O, acetyl), 168.3

(CONH), 146.5, 138.9, 134.2 (3 C_q, Ar), 133.0 (CH_Ar), 132.5 (C_q,

Ar), 130.7 (CH_Ar), 130.4 (C_q, Ar), 129.0, 128.4, 127.3, 126.3, 125.3,

125.0, 115.0 (7 CH_Ar), 76.6 (C-5), 73.9 (C-3), 73.2 (C-2), 72.1 (C-

1), 68.7 (C-4), 62.5 (C-6), 21.2, 21.0, 21.0, 21.0 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 610 (50), 608 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₁H₃₀N₁O₁₂:

found: 618.18234.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-nitrobenz-

amido)-1,4-benzoquinone (13f)

Treatment of compound 9f (81 mg) according to procedure B af-

forded 13f (72 mg, 93%) as yellow-green crystals; mp 111–113 °C

(CH₂Cl₂–PE– Et₂O); R_f= 0.48 (PE–EtOAc, 1:1); [a]_D¹⁹–26.8 (c

1.11, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.86 (s, 1 H, CONH), 8.37 (d,

J = 8.7 Hz, 2 H, Ar), 8.05 (d, J = 8.7 Hz, 2 H, Ar), 7.69 (s, 1 H, Ar),

6.98 (s, 1 H, Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.12 (t, J_4,5= 9.6

Hz, 1 H, H-4), 4.91 (t, J_2,3= 9.3 Hz, 1 H, H-2), 4.71 (d, J_1,2= 9.6 Hz,

1 H, H-1), 4.26 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.14

(dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.82 (dq, 1 H, H-5), 2.08, 2.04, 2.00,

1.90 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.3, 182.8 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 164.2

(CONH), 150.8, 146.9, 138.7, 138.3 (4 C_q, Ar), 130.6 (CH_Ar), 129.0

(2 CH_Ar), 124.7 (2 CH_Ar), 115.6 (CH_Ar), 76.7 (C-5), 73.8 (C-3), 73.3

(C-2), 72.1 (C-1), 68.7 (C-4), 62.5 (C-6), 21.2, 21.0, 21.0, 20.9 (4

CH₃, acetyl).

608.1768; found: 608.1767.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-naphthami-

do)-1,4-benzoquinone (13i)

Treatment of compound 9i (56 mg) according to procedure B af-

forded 13i (46 mg, 86%); yellow-green crystals; mp 165–166 °C

(CH₂Cl₂–PE–Et₂O); R_f= 0.54 (PE–EtOAc, 1:1); [a]_D²³–28.3 (c 0.8,

CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 9.01 (s, 1 H, CONH), 8.41 (s,

1 H, Ar), 7.95 (m, 4 H, Ar), 7.78 (s, 1 H, Ar), 7.63 (m, 2 H, Ar), 7.00

(s, 1 H, Ar), 5.39 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.15 (t, J_4,5= 9.6 Hz, 1

H, H-4), 4.96 (t, J_2,3= 9.6 Hz, 1 H, H-2), 4.76 (d, J_1,2= 9.6 Hz, 1 H,

H-1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.16 (dd,

MS (CI, isobutane): m/z (%) = 603 (55, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₇H₂₇N₂O₁₄:

J

_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.84 (dq, 1 H, H-5), 2.11, 2.06, 2.02, 1.93

(4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.5, 183.2 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 166.3

(CONH), 146.6, 138.9, 135.8, 132.9 (4 C_q, Ar), 130.7 (CH_Ar), 130.6

(C_q, Ar), 129.7, 129.6, 129.1, 128.8, 128.3, 127.7, 123.6, 114.8 (8

CH_Ar), 76.7 (C-5), 74.0 (C-3), 73.2 (C-2), 72.1 (C-1), 68.7 (C-4),

62.5 (C-6), 21.2, 21.0, 21.0, 20.9 (4 CH₃, acetyl).

603.1462; found: 603.1463.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-biphenyl-

carboxamido)-1,4-benzoquinone (13g)

Treatment of compound 9g (146 mg) according to procedure B af-

forded 13g (131 mg, 94%) as yellow crystals; mp 199–200 °C

(CH₂Cl₂–PE–Et₂O); R_f= 0.48 (PE–EtOAc, 1:1); [a]_D¹⁹–26.2 (c 1.0,

CH₂Cl₂).

MS (ESI+): m/z (%) = 1236.6 (75, [2 M + Na]⁺), 607.9 (100, [M +

H]⁺).

Synthesis 2007, No. 22, 3473–3488 © Thieme Stuttgart · New York

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3483

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-furyl-

carboxamido)-1,4-benzoquinone (13j)

Treatment of compound 9j (62 mg) according to procedure B af-

forded 13j (52 mg, 89%); golden-yellow needles; mp 89–91 °C

(CH₂Cl₂–PE– Et₂O); R_f= 0.42 (PE–EtOAc, 1:1); [a]_D²³–21.7 (c

0.78, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.98 (s, 1 H, CONH), 7.65 (s,

1 H_quinone), 7.61 (dd, J_o= 1.8 Hz, J_m= 0.6 Hz, 1 H_furyl), 7.31 (dd,

J_m= 0.6 Hz, J_o= 3.6 Hz, 1 H_furyl), 6.96 (d, J = 0.9 Hz, 1 H_quinone),

6.61 (dd, J_o= 1.8 Hz, J_o= 3.6 Hz, 1 H_furyl), 5.38 (t, J_3,4= 9.3 Hz, 1

H, H-3), 5.14 (t, J_4,5= 10.2 Hz, 1 H, H-4), 4.94 (t, J_2,3= 9.6 Hz, 1 H,

H-2), 4.73 (dd, J_1,2= 9.6, 0.9 Hz, 1 H, H-1), 4.27 (dd, J_5,6= 5.1 Hz,

(CH_py), 130.3 (CH_Ar), 128.9 (C_{q py}), 124.8 (CH_py), 115.1 (CH_Ar),

76.3 (C-5), 73.5 (C-3), 72.9 (C-2), 71.7 (C-1), 68.3 (C-4), 62.1 (C-

6), 20.8, 20.6, 20.6, 20.5 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 561 (100, [phenol + H]⁺).

MS (ESI+): m/z (%) = 1116.7 (80, [2 M + H]⁺), 559.0 (100, [M +

H]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₂₆H₂₇N₂O₁₂: 559.1564;

found: 559.15591.

2,6-Bis[2-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-1,4-ben-

zoquinone-5-amino-N-carbonyl]pyridine (13n)

Treatment of compound 9n (98 mg) according to procedure B (note:

8 equiv CAN was added) afforded 13n (76 mg, 80%); golden yel-

low crystals; mp 202–204 °C (CH₂Cl₂–Et₂O–PE); R_f= 0.55 (PE–

EtOAc, 1:2); [a]_D¹⁹–40.7 (c 0.8, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 10.53 (s, 2 H, CONH), 8.52 (d,

J = 7.5 Hz, 2 H_py), 8.24 (t, J = 7.2 Hz, 1 H_py), 7.78 (s, 2 H, Ar), 7.14

(s, 2 H, Ar), 5.41 (t, J_3,4= 9.3 Hz, 2 H, H-3), 5.17 (t, J_4,5= 9.3 Hz, 2

H, H-4), 4.95 (t, J_2,3= 9.0 Hz, 2 H, H-2), 4.76 (d, J_1,2= 9.3 Hz, 2 H,

H-1), 4.30 (dd, J_5,6= 3.6 Hz, J_6,6¢= 12.0 Hz, 2 H, H-6), 4.17 (d, 2 H,

H-6¢), 3.86 (dd, 2 H, H-5), 2.13, 2.07, 2.03, 1.94 (4 s, 24 H,

OCOCH₃).

J

_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.83

(dq, 1 H, H-5), 2.10, 2.06, 2.01, 1.92 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.3, 182.7 (2 C=O, benzo-

quinone), 171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 156.7

(CONH), 147.0, 146.4 (2 C_q, Ar), 146.0 (CH_Ar), 138.5 (C_q, Ar),

130.7 (CH_Ar), 117.7, 114.7, 113.5 (3 CH_Ar), 76.6 (C-5), 73.9 (C-3),

73.2 (C-2), 72.1 (C-1), 68.7 (C-4), 62.4 (C-6), 21.2, 21.0, 21.0, 20.9

(4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 548 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₅H₂₆N₁O₁₃:

548.1404; found: 548.1406.

¹³C NMR (75.5 MHz, CDCl₃): d = 186.6, 186.6, 182.9, 182.9 (4

C=O, benzoquinone), 171.1, 171.1, 170.4, 170.4, 170.3, 170.3,

170.0, 170.0 (8 C=O, acetyl), 162.2, 162.2 (2 CONH), 148.3, 148.3,

146.5, 146.5 (4 C_q, Ar), 140.6 (CH_py), 138.3, 138.3 (2 C_q, Ar),

131.0, 131.0, 127.2, 127.2, 115.5, 115.5 (6 CH_Ar), 76.5, 76.5 (2 C-

5), 73.9, 73.9 (2 C-3), 73.3 (2 C-2), 72.2 (2 C-1), 68.6 (2 C-4), 62.3

(2 C-6), 21.2, 21.2, 21.0, 21.0, 21.0, 21.0, 20.9, 20.9 (8 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-thienyl-

carboxamido)-1,4-benzoquinone (13k)

Treatment of compound 9k (60 mg) according to procedure B af-

forded 13k (54 mg, 95%) as golden-yellow crystals; mp 168–

169 °C (CH₂Cl₂–Et₂O–PE); R_f= 0.44 (EtOAc–PE, 1:1); [a]_D

–20.1 (c 1.0, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.64 (s, 1 H, CONH), 7.68 (dd,

J_o= 3.9 Hz, J_m= 0.9 Hz, 1 H_thienyl), 7.65 (dd, J_o= 5.1 Hz, J_m= 0.9

Hz, 1 H_thienyl), 7.61 (s, 1 H, Ar), 7.16 (dd, J_o= 3.9 Hz, J_o= 5.1 Hz,

1 H_thienyl), 6.94 (d, J = 0.9 Hz, 1 H, Ar), 5.36 (t, J_3,4= 9.3 Hz, 1 H,

H-3), 5.12 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.92 (t, J_2,3= 9.3 Hz, 1 H, H-

2), 4.98 (dd, J_1,2= 9.6 Hz, J = 0.9 Hz, 1 H, H-1), 4.25 (dd, J_5,6= 4.8

Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.13 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢),

3.81 (dq, 1 H, H-5), 2.09, 2.04, 1.99, 1.90 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.3, 182.9 (2 C=O, benzo-

quinone), 171.0, 170.3, 170.3, 170.0 (4 C=O, acetyl), 160.5

(CONH), 146.6, 138.6, 138.0 (3 C_q, Ar), 133.4, 130.6, 130.3, 128.7,

114.7 (5 CH_Ar), 76.6 (C-5), 73.9 (C-3), 73.2 (C-2), 72.1 (C-1), 68.7

(C-4), 62.4 (C-6), 21.2, 21.0, 21.0, 20.9 (4 CH₃, acetyl).

20

MS (ESI+): m/z (%) = 1060.2 (35, [M + Na]⁺), 1037.9 (100, [M +

H]⁺).

Reduction of 13a–l and 13n to 14a–l and 14n; General Proce-

dure C

The C-glycosyl benzoquinone (1 equiv) was dissolved in CHCl₃(3

mL). A solution of Na₂S₂O₄(85% tech., 400 mg, 0.978 mmol, 6

equiv) in H₂O (3 mL) was added to the solution. After stirring the

mixture vigorously for 45 min at r.t., TLC showed the starting ma-

terial was still present while a new more polar compound appeared.

Another portion of Na₂S₂O₄(132 mg, 2 equiv) was added to the

mixture and after 1 h, TLC showed the complete conversion of the

starting material. After extracting the mixture with CHCl₃(3 × 15

mL), the combined organic phases were washed with brine (15 mL),

H₂O (15 mL), and dried (MgSO₄). After filtration and concentra-

tion, the residue was chromatographed (PE–EtOAc, 1:1) on silica

gel to afford the desired hydroquinone.

MS (CI, isobutane): m/z (%) = 564 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₅H₂₆NO₁₂S:

564.1176; found: 564.1175.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(acryl-

amido)hydroquinone (14a)

Treatment of compound 13a (45 mg) according to procedure C af-

forded 14a (29 mg, 65%); yellow syrup; R_f= 0.17 (PE–EtOAc,

1:1); [a]_D²²+14.6 (c 0.57, CHCl₃).

¹H NMR (300.13 MHz, CDCl₃): d = 8.34, 8.07 (2 s, 2 H, CONH and

OH, exch. D₂O), 6.93 (s, 1 H, Ar), 6.65 (s, 1 H, Ar), 6.40 (d, J = 17.1

Hz, 1 H_alkene), 6.23 (dd, J = 10.8, 17.1 Hz, 1 H_alkene), 5.76 (d, J = 10.8

Hz, 1 H_alkene), 5.29 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.22 (t, J_2,3= 9.0 Hz,

1 H, H-2), 5.18 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.57 (d, J_1,2= 9.3 Hz, 1

H, H-1), 4.26 (dd, J_5,6= 4.2 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.09 (dd,

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-nicotinamido-

1,4-benzoquinone (13l)

Treatment of compound 9l (92 mg) according to procedure B af-

forded 13l (67 mg, 77%); yellow-green syrup; R_f= 0.24 (PE–

EtOAc, 1:3); [a]_D²³–29.0 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 9.14 (s, 1 H_py), 8.86 (s, 1 H,

CONH) 8.84 (br s, 1 H_py), 8.20 (dt, J = 7.8, 2.1, 1.8 Hz, 1 H_py), 7.71

(s, 1 H, Ar), 7.50 (dd, J = 8.1, 4.8 Hz, 1 H_py), 6.99 (s, 1 H, Ar), 5.39

(t, J_3,4= 9.3 Hz, 1 H, H-3), 5.15 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.94 (t,

J_2,3= 9.6 Hz, 1 H, H-2), 4.74 (d, J_1,2= 9.6 Hz, 1 H, H-1), 4.28 (dd,

J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.16 (dd, J_5,6¢= 2.1 Hz, 1 H,

H-6¢), 3.84 (dq, 1 H, H-5), 2.10, 2.06, 2.01, 1.92 (4 s, 12 H,

OCOCH₃).

J

_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.81 (dq, 1 H, H-5), 2.03, 2.00, 1.94, 1.80

(4 s, 12 H, OCOCH₃).

¹³C NMR (75 MHz, CDCl₃): d = 170.8, 170.0, 170.0, 169.7 (4 C=O,

acetyl), 165.3 (CONH), 150.8, 148.9, 141.5, 129.0 (4 C_q, Ar), 127.5

(CH_{2 alkene}), 127.4 (CH_alkene), 110.4, 110.3 (2 CH_Ar), 76.5, 74.5, 74.2,

¹³C NMR (75.5 MHz, CDCl₃): d = 186.0, 182.4 (2 C=O, benzo-

quinone), 170.6, 170.0, 170.0, 169.6 (4 C=O, acetyl), 164.2

(CONH), 154.0, 148.7 (2 CH_py), 146.4, 138.1 (2 C_q, Ar), 135.2

3484

Y. Z. Zhang et al.

PAPER

71.4, 68.6 (C-1/C-5), 62.2 (C-6), 21.2, 21.1, 21.0, 20.9 (4 CH₃,

acetyl).

MS (CI, isobutane): m/z (%) = 510 (100, [M + H]⁺).

J_3,4= 9.0 Hz, 1 H, H-3), 5.26 (s, 1 H, OH, exch. D₂O), 5.20 (t,

J_2,3= 9.3 Hz, 1 H, H-2), 5.14 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.71 (d,

J_1,2= 9.6 Hz, 1 H, H-1), 4.22 (dd, J_5,6= 4.2 Hz, J_6,6¢= 12.3 Hz, 1 H,

H-6), 4.06 (dd, J_5,6¢= 1.2 Hz, 1 H, H-6¢), 3.80 (hidden, 1 H, H-5),

3.78 (s, 3 H, OCH₃), 1.98, 1.98, 1.92, 1.75 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.3, 170.8, 170.1, 169.9 (4

C=O, acetyl), 166.9, 163.3, 149.0, 141.2, 140.8 (CONH_q, 4 Ar),

129.8, 129.8 (2 CH_Ar), 126.1 (C_q, Ar), 118.7 (1 C_q, Ar), 117.3,

114.5, 114.5, 110.0 (4 CH_Ar), 77.2, 76.4, 74.5, 71.8, 68.9 (C-1/C-5),

62.6 (C-6), 55.9 (OCH₃), 21.1, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

(E)-2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(cinnam-

amido)hydroquinone (14b)

Treatment of compound 13b (95 mg) according to procedure C af-

forded 14b (89 mg, 93%); pale yellow foam; R_f= 0.11 (PE–EtOAc,

1:1); [a]_D²¹–29.9 (c 0.7, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.54 (s, 1 H, OH exch. D₂O),

8.45 (s, 1 H, CONH, exch. D₂O), 7.72 (d, J = 15.6 Hz, 1 H_alkene),

7.69 (s, 1 H, OH exch. D₂O), 7.51–7.48 (m, 2 H, Ar), 7.35 (s, 1 H,

Ar), 7.33–7.29 (m, 3 H, Ar), 6.79 (s, 1 H, Ar), 6.61 (d, J = 15.6 Hz,

1 H_alkene), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.31 (t, J_2,3= 9.6 Hz, 1 H,

H-2), 5.24 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.74 (d, J_1,2= 9.6 Hz, 1 H, H-

1), 4.30 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.15 (br d,

MS (CI, isobutane): m/z (%) = 590 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₈H₃₂NO₁₃:

590.1873; found: 590.1875.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(3,5-di-

methoxybenzamido)hydroquinone (14e)

Treatment of compound 13e (75 mg) according to procedure C af-

forded 14e (68 mg, 90%); pale yellow foam; R_f= 0.12 (PE–EtOAc,

1:1); [a]_D²¹–21.1 (c 0.97, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.67 (s, 1 H, CONH, exch.

D₂O), 7.98, 7.80 (2 s, 2 H, OH exch. D₂O), 7.35 (d, J = 4.2 Hz, 2 H,

Ar), 6.98 (d, J = 1.5 Hz, 1 H, Ar), 6.78 (s, 1 H, Ar), 6.61 (br s, 1 H,

Ar), 5.34 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.26 (t, J_2,3= 9.0 Hz, 1 H, H-

2), 5.22 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.79 (d, J_1,2= 9.3 Hz, 1 H, H-1),

J

_5,6¢= 1.5 Hz, 1 H, H-6¢), 3.86 (dq or ddd, 1 H, H-5), 2.06, 2.03,

2.00, 1.84 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.4, 170.8, 170.3, 170.1 (4

C=O, acetyl), 165.9 (CONH), 148.8 (C_q, Ar), 143.8 (CH_alkene),

141.1, 134.8 (2 C_q, Ar), 130.7, 129.4, 129.0, 128.5, 128.1 (5 CH_Ar),

127.8 (C_q, Ar), 127.5 (CH_Ar), 120.1 (CH_alkene), 119.2 (C_q, Ar), 110.0

(CH_Ar), 77.2 (C-1), 76.5 (C-5), 74.5 (C-3), 72.0 (C-2), 68.9 (C-4),

62.6 (C-6), 21.1, 21.1, 21.1, 21.0 (4 CH₃, acetyl).

MS (ESI+): m/z (%) = 1778.6 (25, [3 M + Na]⁺), 1192.9 (50, [2 M

+ Na]⁺), 1170.9 (100, [2 M + H]⁺), 608.1 (15, [M + Na]⁺), 586.0 (90,

[M + H]⁺).

4.30 (dd, J_5,6= 4.2 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.16 (br d, J_5,6¢=

1.2 Hz, 1 H, H-6¢), 3.90 (dq, 1 H, H-5), 3.84 (s, 6 H, OCH₃), 2.08,

2.05, 2.00, 1.82 (4 s, 12 H, OCOCH₃).

HRMS (ESI+): m/z [M + H]⁺calcd for C₂₉H₃₂NO₁₂: 586.1924;

found: 586.1924.

¹³C NMR (75.5 MHz, CDCl₃): d = 171.4, 170.8, 170.2, 170.1 (4

C=O, acetyl), 167.1 (CONH), 161.3, 149.2, 141.1, 140.3, 136.3 (5

C_q, Ar), 129.0, 128.1 (2 CH_Ar), 127.9 (C_q, Ar), 127.5 (CH_Ar), 118.6

(C_q, Ar), 105.7, 104.6 (2 CH_Ar), 76.5 (C-5 and C-1), 74.5 (C-3), 72.0

(C-2), 70.3 (C-4), 62.6 (C-6), 56.0, 56.0 (2 OCH₃), 21.1, 21.1, 21.1,

20.9 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-methyl-

benzamido)hydroquinone (14c)

Treatment of compound 13c (57 mg) according to procedure C af-

forded 14c (54 mg, 94%); colorless syrup; R_f= 0.13, (PE–EtOAc,

1:1); [a]_D²¹–25.0 (c 0.8, CH₂Cl₂).

MS (ESI+): m/z (%) = 1260.9 (45, [2 M + Na]⁺), 1238.9 (100, [2 M

+ H]⁺), 620.0 (60, [M + H]⁺).

¹H NMR (300.13 MHz, CDCl₃): d = 8.63 (s, 1 H, CONH), 8.08 (s,

1 H, OH exch. D₂O), 7.75 (d, J = 8.4 Hz, 2 H, Ar), 7.56 (br s, 1 H,

exch. D₂O, OH), 7.44 (s, 1 H, Ar), 7.26 (d, J = 8.4 Hz, 2 H, Ar), 6.79

(s, 1 H, Ar), 5.36 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.28 (t, J_2,3= 9.3 Hz, 1

H, H-2), 5.22 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.73 (d, J_1,2= 9.6 Hz, 1 H,

H-1), 4.29 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.13 (dd,

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-nitro-

benzamido)hydroquinone (14f)

Treatment of compound 13f (63 mg) according to procedure C af-

forded 14f (57 mg, 90%); yellow-green foam; R_f= 0.20 (PE–

EtOAc, 1:1); [a]_D²²–26.8 (c 1.27, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.69 (s, 1 H, CONH), 8.29 (d,

J = 8.7 Hz, 2 H, Ar), 8.01 (d, J = 8.7 Hz, 2 H, Ar), 7.59 (br s, 1 H,

OH exch. D₂O), 7.38 (s, 1 H, Ar), 7.24 (br s, 1 H, OH exch. D₂O),

6.76 (s, 1 H, Ar), 5.37 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.30 (t, J_2,3= 9.6

Hz, 1 H, H-2), 5.24 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.71 (d, J_1,2= 9.3 Hz,

1 H, H-1), 4.31 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.19

(dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.91 (dq, 1 H, H-5), 2.07, 2.07, 2.01,

1. 86 (4 s, 12 H, OCOCH₃).

J

_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.86 (dq, 1 H, H-5), 2.40 (s, 3 H, CH₃),

2.06, 2.06, 2.00, 1.83 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.3, 170.8, 170.2, 170.1 (4

C=O, acetyl), 167.4 (CONH), 149.1, 143.5, 140.9, 131.2 (4 C_q, Ar),

129.9, 129.0 (2 CH_Ar), 128.1 (C_q, Ar), 127.8, 127.5 (2 CH_Ar), 118.8

(C_q, Ar), 117.3, 110.0 (2 CH_Ar), 77.1 (C-1), 76.4 (C-5), 74.4 (C-3),

71.8 (C-2), 68.9 (C-4), 62.5 (C-6), 21.9 (ArCH₃), 21.1, 21.1, 21.1,

20.9 (4 CH₃, acetyl).

MS (ESI+): m/z (%) = 1741.5 (40, [3 M + Na]⁺), 1720.4 (20, [3 M

+ H]⁺), 1168.9 (55, [2 M + Na]⁺), 1146.8 (100, [2 M + H]⁺), 596.1

(15, [M + Na]⁺), 573.9 (90, [M + H]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₂₈H₃₂NO₁₂: 574.1924;

found: 574.1926.

¹³C NMR (75.5 MHz, CDCl₃): d = 171.4, 170.8, 170.2, 170.2 (4

C=O, acetyl), 165.0 (CONH), 150.4, 149.1, 140.8, 139.6 (4 C_q, Ar),

129.0 (2 CH_Ar), 127.2 (C_q, Ar), 124.5 (2 CH_Ar), 119.4 (C_q, Ar),

117.4 (CH_Ar), 110.2 (CH_Ar), 77.5 (C-1), 76.6 (C-5), 74.3 (C-3), 71.7

(C-2), 68.8 (C-4), 62.5 (C-6), 21.2, 21.1, 21.1, 21.0 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 605 (10, [M + H]⁺), 498 (100).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-methoxy-

benzamido)hydroquinone (14d)

Treatment of compound 13d (53 mg) according to procedure C af-

forded 14d (51 mg, 89%); pale yellow foam; R_f= 0.17 (PE–EtOAc,

1:1); [a]_D–26.3 (c 0.9, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.51 (s, 1 H, CONH), 7.74 (d,

J = 8.7 Hz, 2 H, Ar), 7.34 (s, 1 H, OH, exch. D₂O), 7.26 (d, J = 1.2

Hz, 1 H, Ar), 6.86 (d, J = 8.7 Hz, 2 H, Ar), 6.70 (s, 1 H, Ar), 5.28 (t,

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₇H₂₉N₂O₁₄:

605.1619; found: 605.1623.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-biphenyl-

carboxamido)hydroquinone (14g)

Treatment of compound 13g (70 mg) according to procedure C af-

forded 14g (60 mg, 85%); pale yellow syrup; R_f= 0.12 (PE–EtOAc,

1:1); [a]_D²²–33.5 (c 0.95, CH₂Cl₂).

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

MS (CI, isobutane): m/z (%) = 610 (60, [M + H]⁺).

3485

¹H NMR (300.13 MHz, CDCl₃): d = 8.70 (s, 1 H, CONH), 7.98 (s,

1 H, OH exch. D₂O), 7.91 (d, J = 8.4 Hz, 2 H, Ar), 7.66 (d, J = 8.1

Hz, 2 H, Ar), 7.59–7.51 (m, 3 H, Ar), 7.44–7.36 (m, 4 H, 3 Ar and

OH, exch. D₂O), 6.82 (s, 1 H, Ar), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3),

5.32 (t, J_2,3= 9.6 Hz, 1 H, H-2), 5.25 (t, J_4,5= 9.3 Hz, 1 H, H-4), 4.75

(d, J_1,2= 9.0 Hz, 1 H, H-1), 4.31 (dd, J_5,6= 4.2 Hz, J_6,6¢= 12.6 Hz, 1

H, H-6), 4.15 (dd, J_5,6¢= 1.5 Hz, 1 H, H-6¢), 3.89 (m, 1 H, H-5), 2.06,

2.06, 1.99, 1.84 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.3, 170.8, 170.2, 170.1 (4

C=O, acetyl), 167.2 (CONH), 149.1, 145.5, 141.0, 140.0, 132.6 (5

C_q, Ar), 129.9, 129.0, 128.7, 128.4, 128.4, 127.8, 127.8 (7 CH_Ar),

127.8 (C_q, Ar), 127.6, 127.6 (2 CH_Ar), 119.0 (C_q, Ar), 117.6, 110.2

(2 CH_Ar), 77.4 (C-1), 76.5 (C-5), 74.4 (C-3), 71.8 (C-2), 68.9 (C-4),

62.5 (C-6), 21.1, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₁H₃₂NO₁₂:

610.1924; found: 610.1923.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-furyl-

carboxamido)hydroquinone (14j)

Treatment of compound 13j (44 mg) according to procedure C af-

forded 14j (37 mg, 84%); yellow-green foam; R_f= 0.13 (EtOAc–

PE, 1:1); [a]_D¹⁷–22.5 (c 1.0, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.74 (s, 1 H, CONH), 8.14 (s,

1 H, OH exch. D₂O), 7.77 (s, 1 H, Ar), 7.55 (br s, 1 H_furyl), 7.52 (s,

1 H, OH exch. D₂O), 7.32 (d, J = 3.6 Hz, 1 H_furyl), 6.83 (s, 1 H, Ar),

6.60 (br d, J = 0.6 Hz, 1 H_furyl), 5.42 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.28

(t, J_2,3= 9.6 Hz, 1 H, H-2), 5.24 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.87 (d,

J_1,2= 9.9 Hz, 1 H, H-1), 4.32 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.6 Hz, 1 H,

H-6), 4.19 (br d, 1 H, H-6¢), 3.93 (dq, 1 H, H-5), 2.08, 2.08, 2.02,

1.86 (4 s, 12 H, OCOCH₃).

MS (ESI+): m/z (%) = 1927.6 (25, [3 M + Na]⁺), 1906.5 (20, [3 M

+ H]⁺), 1292.9 (70, [2 M + Na]⁺), 1270.8 (100, [2 M + H]⁺), 658.2

(20, [M + Na]⁺), 636.0 (85, [M + H]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₃₃H₃₄NO₁₂: 636.2081;

found: 636.2079.

¹³C NMR (75.5 MHz, CDCl₃): d = 171.4, 170.9, 170.2, 170.1 (4

C=O, acetyl), 157.4 (CONH), 149.4, 147.3 (2 C_q, Ar), 145.5

(CH_furyl), 139.9, 127.2, 118.5 (3 C_q), 116.9 (CH_furyl), 116.3 (CH_Ar),

113.3 (CH_furyl), 109.3 (CH_Ar), 76.5 (C-5), 76.1 (C-1), 74.6 (C-3),

72.1 (C-2), 69.1 (C-4), 62.7 (C-6), 21.2, 21.1, 21.1, 21.0 (4 CH₃,

acetyl).

MS (CI, isobutane): m/z (%) = 550 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₅H₂₈NO₁₃:

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(1-naphthami-

do)hydroquinone (14h)

Treatment of compound 13h (37 mg) according to procedure C af-

forded 14h (32 mg, 86%); yellow syrup; R_f= 0.24 (EtOAc–PE,

1:1); [a]_D¹⁷–21.6 (c 0.75, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.52 (s, 1 H, CONH, exch.

D₂O), 8.29 (dd, J = 2.4, 9.0 Hz, 1 H, Ar), 8.22 (br s, 1 H, OH, exch.

D₂O), 7.95 (d, J = 8.4 Hz, 1 H, Ar), 7.87 (m, 1 H, Ar), 7.69 (dd,

J = 0.9, 6.9 Hz, 1 H, Ar), 7.54 (m, 2 H, Ar), 7.44 (dd, J = 8.4, 4.5

Hz, 1 H, Ar), 7.10 (br s, 2 H, Ar, and OH exch. D₂O), 6.76 (s, 1 H,

Ar), 5.33 (br t, J_3,4= 9.3 Hz, 1 H, H-3), 5.29 (t, J_2,3= 9.0 Hz, 1 H,

H-2), 5.23 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.58 (dd, J_1,2= 9.6 Hz,

J_1,3= 2.7 Hz, 1 H, H-1), 4.30 (dd, J_5,6= 3.9 Hz, J_6,6¢= 12.3 Hz, 1 H,

H-6), 4.13 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.84 (dq, 1 H, H-5), 2.08,

2.05, 1.96, 1.78 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.0, 170.0 (4

C=O, acetyl), 169.6 (CONH), 148.9, 141.5, 134.1, 133.1 (4 C_q, Ar),

132.1 (CH_Ar), 130.3 (C_q, Ar), 128.9, 128.0 (2 CH_Ar), 127.7 (C_q, Ar),

127.2, 126.2, 125.5, 125.0 (4 CH_Ar), 119.5 (C_q, Ar), 118.9, 110.8 (2

CH_Ar), 78.8 (C-1), 76.5 (C-5), 74.2 (C-3), 71.3 (C-2), 68.5 (C-4),

62.2 (C-6), 21.1, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

550.1561; found: 550.1561.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-thienyl-

carboxamido)hydroquinone (14k)

Treatment of compound 13k (52 mg) according to procedure C af-

forded 14k (38 mg, 76%); pale yellow syrup; R_f= 0.16 (PE–EtOAc,

1:1); [a]_D²³–28.9 (c 0.9, CH₂Cl₂).

¹H NMR (300.14 MHz, CDCl₃): d = 8.55 (s, 1 H, CONH), 7.90 (br

s, 1 H, OH exch. D₂O), 7.69 (dd, J_m= 0.9 Hz, J_o= 3.6 Hz, 1 H_thienyl),

7.58 (dd, J_o= 4.8 Hz, J_m= 0.9 Hz, 1 H_thienyl), 7.32 (s, 2 H, Ar, and

OH, exch. D₂O), 7.12 (dd, J_o= 3.6 Hz, J_o= 4.8 Hz, 1 H_thienyl), 6.78

(s, 1 H, Ar), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.28 (t, J_2,3= 9.6 Hz, 1

H, H-2), 5.23 (t, J_4,5= 9.9 Hz, 1 H, H-4), 4.72 (d, J_1,2= 9.6 Hz, 1 H,

H-1), 4.31 (dd, J_5,6= 4.5 Hz, J_6,6¢= 12.3 Hz, 1 H, H-6), 4.16 (dd,

J

_5,6¢= 1.8 Hz, H-6¢), 3.89 (dq, 1 H, H-5), 2.07, 2.07, 2.01, 1.85 (4 s,

12 H, OCOCH₃).

MS (CI, isobutane): m/z (%) = 610 (20, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₃₁H₃₂NO₁₂:

¹³C NMR (75.5 MHz, CDCl₃): d = 171.3, 170.8, 170.1, 170.1 (4

C=O, acetyl), 161.5 (CONH), 149.0, 140.9, 138.2 (3 C_q, Ar), 132.2,

130.1, 128.5 (3 CH_Ar), 127.5, 119.0 (2 C_q, Ar), 117.5, 110.2 (2

CH_Ar), 77.4 (C-1), 76.5 (C-5), 74.4 (C-3), 71.8 (C-2), 68.8 (C-4),

62.5 (C-6), 21.1, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 566 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₅H₂₈NO₁₂S:

610.1924; found: 610.1923.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(2-naphthami-

do)hydroquinone (14i)

Treatment of compound 13i (32 mg) according to procedure C af-

forded 14i (28 mg, 90%); yellow syrup; R_f= 0.20 (PE–EtOAc, 1:1);

[a]_D¹⁷–28.1 (c 0.8, CH₂Cl₂).

566.1332; found : 566.1333.

¹H NMR (300.14 MHz, CDCl₃): d = 8.54 (s, 1 H, CONH), 8.40 (s,

1 H, Ar), 8.17 (s, 1 H, OH exch. D₂O), 7.96–7.87 (m, 4 H, Ar), 7.63–

7.57 (m, 2 H, Ar), 7.06 (d, J = 1.8 Hz, 1 H, Ar), 6.99 (s, 1 H, OH

exch. D₂O), 6.78 (s, 1 H, Ar), 5.36 (m, J_3,4= 9.0 Hz, 1 H, H-3), 5.32

(t, J_4,5= 9.3 Hz, 1 H, H-4), 5.26 (t, J_2,3= 9.6 Hz, 1 H, H-2), 4.62 (dd,

J_1,2= 9.0 Hz, J_1,3= 2.7 Hz, 1 H, H-1), 4.33 (dd, J_5,6= 4.2 Hz,

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-nicotinamido-

hydroquinone (14l)

Treatment of compound 13l (52 mg) according to procedure C af-

forded 14l (51 mg, 97%); pale yellow-green syrup; R_f= 0.10 (PE–

EtOAc, 1:3); [a]_D²¹–21.4 (c 0.78, CHCl₃).

¹H NMR (300.13 MHz, CDCl₃): d = 9.10 (s, 1 H, CONH, exch.

D₂O), 9.00 (s, 1 H, Ar), 8.72 (s, 1 H, OH exch. D₂O), 8.62 (m, 1 H,

Ar), 8.12 (d, J = 7.8 Hz, 1 H, Ar), 7.51 (m, 2 H, Ar), 6.75 (s, 1 H,

Ar), 5.28 (t, J_3,4= 9.0 Hz, 1 H, H-3), 5.22 (s, 1 H, OH exch. D₂O),

5.19 (t, J_2,3= 9.0 Hz, 1 H, H-2), 5.13 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.74

(d, J_1,2= 9.6 Hz, 1 H, H-1), 4.29 (dd, J_5,6= 4.2 Hz, J_6,6’= 12.3 Hz,

1 H, H-6), 4.14 (br d, J = 0.9 Hz, 1 H, H-6¢), 3.88 (m, 1 H, H-5),

2.06, 2.04, 1.99, 1.83 (4 s, 12 H, OCOCH₃).

J

_6,6¢= 12.3 Hz, 1 H, H-6), 4.17 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 3.88

(dq, 1 H, H-5), 2.09, 2.08, 2.00, 1.87 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 169.9, 169.8 (4

C=O, acetyl), 167.5 (CONH), 149.1, 141.8, 135.5, 132.9, 130.8, (5

C_q, Ar), 129.5, 129.3, 128.9, 128.8, 128.3, 127.6 (6 CH_Ar), 127.6

(C_q, Ar), 123.8 (CH_Ar), 119.4 (C_q, Ar), 119.1, 111.1 (2 CH_Ar), 79.2

(C-1), 76.6 (C-5), 74.1 (C-3), 71.3 (C-2), 68.5 (C-4), 62.2 (C-6),

21.1, 21.1, 21.0, 20.9 (4 CH₃, acetyl).

3486

Y. Z. Zhang et al.

PAPER

¹³C NMR (75.5 MHz, CDCl₃): d = 171.3, 170.8, 170.2, 170.2 (4

C=O, acetyl), 164.7 (CONH), 152.4 (CH_Ar), 149.0 (C_q, Ar), 148.0

(CH_Ar), 141.2, 140.9,136.8 (3 C_q, Ar), 129.0, 128.0, 127.4 (3 CH_Ar),

119.2 (C_q, Ar), 109.8 (CH_Ar), 76.5, 76.2, 74.5, 71.9, 68.9 (C-1/C-5),

62.6 (C-6), 56.0 (2 OCH₃), 21.2, 21.1, 21.1, 20.9 (4 CH₃, acetyl).

H_alkene), 5.41 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.29 (t, J_2,3= 9.6 Hz, 1 H,

H-2), 5.24 (t, J_4,5= 9.3 Hz, 1 H, H-4), 5.00 (d, J_1,2= 9.9 Hz, 1 H, H-

1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.16 (d,

J_5,6= 1.5 Hz, 1 H, H-6¢), 3.89 (s, 3 H, OCH₃), 3.89–3.82 (hidden, 1

H, H-5), 3.82 (s, 3 H, OCH₃), 2.07, 2.04, 2.03, 1.83 (4 s, 12 H,

OCOCH₃).

MS (CI, isobutane): m/z (%) = 561 (100) [M + H]⁺).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.2, 170.1 (4

C=O, acetyl), 165.1, 164.9 (2 CONH), 151.9 (C_q, Ar), 143.3 (CH_Ar),

142.6, 142.3, 134.9 (3 C_q, Ar), 130.6 (CH_Ar), 130.1 (C_q, Ar), 129.4,

128.5, 128.4 (6 CH_Ar), 121.0 (CH_alkene), 119.8 (CH_Ar), 119.8

(CH_alkene), 119.0 (C_q, Ar), 109.6 (CH_Ar), 104.6 (C_q, Ar), 103.8

(CH_Ar), 76.5 (C-5), 74.8 (C-3), 73.4 (C-1), 72.9 (C-2), 69.3 (C-4),

62.9 (C-6), 56.7 (2 OCH₃), 21.2, 21.1, 21.1, 21.0 (4 CH₃, acetyl).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₆H₂₉N₂O₁₂:

561.1721; found : 561.1718.

2,6-Bis[2-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)hydro-

quinone-5-amino-N-carbonyl]pyridine (14n)

Treatment of compound 13n (60 mg) according to procedure C

(note: 16 equiv of Na₂S₂O₄were added) afforded 14n (51 mg, 85%);

yellow green syrup; R_f= 0.15 (PE–EtOAc, 1:1); [a]_D²¹–33.8 (c

0.81, acetone).

MS (ESI+): m/z (%) = 1486.9 (20, [2 M + Na]⁺), 1464.8 (100, [2 M

+ H]⁺), 755.1 (20, [M + Na]⁺), 733.0 (70, [M + H]⁺).

¹H NMR (300.13 MHz, acetone-d₆and CDCl₃): d = 10.40 (s, 2 H,

CONH, exch. D₂O), 8.60 (s, 2 H, OH, exch. D₂O), 8.44 (d, J = 7.8

Hz, 2 H, Ar), 8.27 (dd, J = 7.5 Hz, J = 8.1 Hz, 1 H, Ar), 8.18 (d,

J = 7.8 Hz, 2 H, Ar), 7.88 (s, 2 H, Ar), 6.88 (s, 2 H, Ar), 5.38 (t,

J_3,4= 9.3 Hz, 2 H, H-3), 5.20 (t, J_2,3= 9.6 Hz, 2 H, H-2), 5.19 (t,

J_4,5= 9.3 Hz, 2 H, H-4), 4.99 (d, J_1,2= 9.9 Hz, 2 H, H-1), 4.28 (dd,

J_5,6= 5.1 Hz, J_6,6¢= 12.3 Hz, 2 H, H-6), 4.16 (dd, J_5,6¢= 2.1 Hz, H-

6¢), 3.90 (dq, 2 H, H-5), 1.94, 1.94, 1.86, 1.71 (4 s, 24 H, OCOCH₃).

¹³C NMR (75 MHz, CDCl₃): d = 170.4, 170.0, 169.7, 169.0 (8 C=O,

acetyl), 161.3 (2 CONH), 149.5, 148.6 (4 C_q, Ar), 140.3, 128.5 (2

CH_Ar), 128.5 (C_q, Ar), 127.4 (2 C_q, Ar), 127.2, 127.0 (2 CH_Ar),

127.0 (C_q, Ar), 125.6 (CH_Ar), 119.1 (2 C_q, Ar), 114.8, 108.0 (2

CH_Ar), 76.3, 74.6, 74.4, 72.7, 69.2 (2 C-1/C-5), 62.8 (2 C-6), 20.5,

20.5, 20.4, 20.2 (8 CH₃, acetyl).

HRMS (ESI+): m/z [M + H]⁺calcd for C₃₈H₄₁N₂O₁₃: 733.2609;

found: 733.2609.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-[4-(2-thienylcarboxamido)benzamido]benzene (17)

Treatment of 15 (90 mg) according to procedure A afforded 17 (92

mg, 86%); white solid; mp 116–119 °C; R_f= 0.17 (PE–EtOAc,

1:1); [a]_D²¹–33.4 (c 0.73, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.71, 8.56 (2 s, 2 H, 2 CONH),

8.28 (s, 1 H, Ar), 7.84–7.74 (m, 5 H, 4 H_Ar+ 1 H_thienyl), 7.56 (d,

J = 5.1 Hz, 1 H_thienyl), 7.08 (t, J = 4.2, 4.5 Hz, 1 H_thienyl), 6.93 (s, 1 H,

Ar), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.27 (t, J_2,3= 9.3 Hz, 1 H, H-

2), 5.22 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.99 (d, J_1,2= 9.6 Hz, 1 H, H-1),

4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H, H-6), 4.16 (dd, J_5,6¢= 1.2

Hz, 1 H, H-6¢), 3.91 (s, 3 H, OCH₃), 3.86 (m, 1 H, H-5), 3.82 (s, 3

H, OCH₃), 2.06, 2.06, 2.02, 1.81 (4 s, 12 H, OCOCH₃).

MS (ESI+): m/z (%) = 1064.2 (65, [M + Na]⁺, 1042.1 (100, [M +

H]⁺).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.6, 170.1, 169.9 (4

C=O, acetyl), 165.1, 160.8 (2 CONH), 151.9, 142.6, 141.9, 139.5 (4

C_q, Ar), 131.9 (CH_Ar), 130.5 (C_q, Ar), 129.3, 128.4, 128.4, 128.3,

120.3 (5 CH_Ar), 120.3, 119.1 (2 C_q, Ar), 109.7, 104.5, 104.0 (3

CH_Ar), 76.5 (C-5), 74.9 (C-3), 73.5 (C-1), 72.7 (C-2), 69.3 (C-4),

62.9 (C-6), 56.7 (2 OCH₃), 21.2, 21.1, 21.1, 20.8 (4 CH₃, acetyl).

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-aminobenzamido)benzene (15)

Reduction of 9f (111 mg) according to the procedure applied for

preparing compound 7 afforded 15 (91 mg, 86%); colorless syrup;

R_f= 0.15 (EtOAc–PE, 1:1); [a]_D²¹–19.8 (c 0.85, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.52 (s, 1 H, CONH), 8.33 (s,

1 H, Ar), 7.71 (d, J = 8.7 Hz, 2 H, Ar), 6.93 (s, 1 H, Ar), 6.70 (d,

J = 8.7 Hz, 2 H, Ar), 5.38 (t, J_3,4= 9.0 Hz, 1 H, H-3), 5.30 (t,

J_2,3= 9.6 Hz, 1 H, H-2), 5.24 (t, J_4,5= 9.3 Hz, 1 H, H-4), 5.00 (d,

J_1,2= 9.6 Hz, 1 H, H-1), 4.29 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.3 Hz, 1 H,

H-6), 4.15 (dd, J_5,6¢= 2.1 Hz, 1 H, H-6¢), 4.10 (br s, 2 H, NH₂), 3.90

(s, 3 H, OCH₃), 3.90–3.86 (hidden, 1 H, H-5), 3.86 (s, 3 H, OCH₃),

2.08, 2.06, 2.01, 1.80 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.7, 170.1, 169.8 (4

C=O, acetyl), 165.6 (CONH), 152.1, 150.5, 142.5, 129.9 (4 C_q, Ar),

128.3 (2 CH_Ar), 124.6, 118.3 (2 C_q, Ar), 114.6, 114.6, 109.7, 103.8

(4 CH_Ar), 76.5 (C-5), 75.0 (C-3), 73.5 (C-1), 72.4 (C-2), 68.3 (C-4),

62.9 (C-6), 56.8, 56.8 (2 OCH₃), 21.2, 21.0, 21.0, 20.9 (4 CH₃,

acetyl).

MS (ESI+): m/z (%) = 1446.7 (40, [2 M + Na]⁺), 1424.8 (100, [2 M

+ H]⁺), 713.0 (50 [M + H]⁺).

HRMS (ESI+): m/z [M + H]⁺calcd for C₃₄H₃₇N₂O₁₃S₁: 713.2016;

found: 713.2018.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-dimethoxy-

5-(4-nicotinamidobenzamido)benzene (18)

Treatment of 15 (90 mg) according to procedure A afforded 18 (75

mg, 71%); white syrup; R_f= 0.07 (PE–EtOAc, 1:1); [a]_D²¹–18.1 (c

0.68, CH₂Cl₂).

¹H NMR (300.13MHz, CDCl₃): d = 9.13 (s, 1 H, Ar), 9.06 (br s, 1

H, CONH), 8.73 (br s, 1 H, Ar), 8.60 (s, 1 H, CONH), 8.26 (s, 1 H,

Ar), 8.23 (d, J = 7.8 Hz, 1 H, Ar), 7.85 (m, 4 H, Ar), 7.40 (br s, 1 H,

Ar), 6.94 (s, 1 H, Ar), 5.38 (t, J_3,4= 9.3 Hz, 1 H, H-3), 5.27 (t,

J_2,3= 9.3 Hz, 1 H, H-2), 5.22 (t, J_4,5= 9.6 Hz, 1 H, H-4), 4.99 (d,

J_1,2= 9.6 Hz, 1 H, H-1), 4.28 (dd, J_5,6= 4.8 Hz, J_6,6¢= 12.6 Hz, 1 H,

H-6), 4.16 (d, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.91 (s, 3 H, OCH₃), 3.86

(dq, 1 H, H-5), 3.82 (s, 3 H, OCH₃), 2.07, 2.07, 2.01, 1.81 (4 s, 12

H, OCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 171.2, 170.6, 170.1, 169.8 (4

C=O, acetyl), 165.0, 164.7 (2 CONH), 152.9 (CH_Ar), 152.0 (C_q, Ar),

148.6 (CH_Ar), 142.7 (C_q, Ar), 136.0 (CH_Ar), 131.1, 131.0, 130.9,

129.2 (4 C_q, Ar), 128.5, 128.5, 124.5, 120.5, 120.5 (5 CH_Ar), 119.2

(C_q, Ar), 109.8, 104.0 (2 CH_Ar), 76.5 (C-5), 74.8 (C-3), 73.4 (C-1),

72.6 (C-2), 69.3 (C-4), 62.9 (C-6), 56.7, 56.7 (2 OCH₃), 21.2, 21.1,

21.1, 20.8 (4 CH₃, acetyl).

MS (CI, isobutane): m/z (%) = 603 (100, [M + H]⁺).

HRMS (CI, isobutane): m/z [M + H]⁺calcd for C₂₉H₃₅N₂O₁₂:

603.2190; found: 603.2192.

(E)-2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-1,4-di-

methoxy-5-(4-cinnamamidobenzamido)benzene (16)

Treatment of 15 (40 mg) according to procedure A afforded 16 (48

mg, 98%); white solid; mp 109–112 °C; R_f= 0.17 (PE–EtOAc,

1:1); [a]_D²¹–21.2 (c 0.74, CH₂Cl₂).

¹H NMR (300.13 MHz, CDCl₃): d = 8.53, 8.50 (2 s, 2 H, 2 CONH),

8.31 (s, 1 H, Ar), 7.79 (m, 5 H, 4 H_Arand 1 H_alkene), 7.49 (m, 2 H,

Ar), 7.37 (m, 3 H, Ar), 6.93 (s, 1 H, Ar), 6.66 (d, J = 15.6 Hz, 1

PAPER

C-Glycosyl Amino-Substituted Hydro- and Benzoquinones

3487

MS (ESI+): m/z (%) = 1436.8 (30, [2 M + Na]⁺), 1414.7 (70, [2 M

(5) (a) Meo, P.; Osborn, H. M. I. In Carbohydrates; Osborn, H.

M. I., Ed.; Academic Press: Oxford, 2003, 337.

+ H]⁺), 730.2 (10, [M + Na]⁺), 708.1 (100, [M + H]⁺).

(b) Bertozzi, C.; Bednarsky, M. In Modern Methods in

Carbohydrate Synthesis; Khan, S. H.; O’Neill, R. A., Eds.;

Harwood Academic Publishers: Amsterdam, 1996, 316.

(6) Collette, Y.; Ou, K.; Pires, J.; Baudry, M.; Descotes, G.;

Praly, J.-P.; Barberousse, V. Carbohydr. Res. 1999, 318,

162.

(7) (a) Mignon, L.; Goichot, C.; Ratel, P.; Cagnin, G.; Baudry,

M.; Praly, J.-P.; Boubia, B.; Barberousse, V. Carbohydr.

Res. 2003, 338, 1271. (b) Baudry, M.; Barberousse, V.;

Collette, Y.; Descotes, G.; Pires, J.; Praly, J.-P.; Samreth, S.

Tetrahedron 1998, 54, 13783. (c) Baudry, M.; Barberousse,

V.; Descotes, G.; Pires, J.; Praly, J.-P. Tetrahedron 1998, 54,

7447. (d) Baudry, M.; Barberousse, V.; Descotes, G.; Faure,

R.; Pires, J.; Praly, J.-P. Tetrahedron 1998, 54, 7431.

(8) (a) Aly, M. R. E.; Schmidt, R. R. Eur. J. Org. Chem. 2005,

4382. (b) El Telbani, E.; El Desoky, S.; Hammad, M. A.;

Abdel Rahman, A. R. H.; Schmidt, R. R. Eur. J. Org. Chem.

1998, 2317. (c) El Telbani, E.; El Desoky, S.; Hammad, M.

A.; Abdel Rahman, A. R. H.; Schmidt, R. R. Carbohydr.

Res. 1998, 306, 463.

(9) (a) Sato, S.; Hiroe, K.; Kumazawa, T.; Onodera, J.-i.

Carbohydr. Res. 2006, 341, 1091. (b) Sato, S.; Akiya, T.;

Suzuki, T.; Onodera, J.-i. Carbohydr. Res. 2004, 339, 2611.

(10) Kalvoda, L. Collect. Czech. Chem. Commun. 1973, 38,

1679.

(11) (a) Kuribayashi, T.; Ohkawa, N.; Satoh, S. Tetrahedron Lett.

1998, 39, 4537. (b) Kuribayashi, T.; Mizumo, Y.; Gohya, S.;

Satoh, S. J. Carbohydr. Chem. 1999, 18, 371.

(12) (a) Wiley, P. F.; Mizsak, S. A.; Baczynskyj, L.; Argoudelis,

A. D.; Duchamp, D. J.; Watt, W. J. Org. Chem. 1986, 51,

2493. (b) Schnabelrauch, M.; Vasella, A.; Withers, S. G.

Helv. Chim. Acta 1994, 77, 778. (c) Cipolla, L.; Guerrini,

M.; Nicotra, F.; Torri, G.; Vismara, H. Chem. Commun.

1997, 1617. (d) Yamago, S.; Hashidume, M.; Yoshida, J.-i.

Tetrahedron 2002, 58, 6805. (e) Knapp, S.; Myers, D. S. J.

Org. Chem. 2002, 67, 2995.

(13) Praly, J.-P.; He, L.; Qin, B. B.; Tanoh, M.; Chen, G.-R.

Tetrahedron Lett. 2005, 46, 7081.

(14) He, L.; Zhang, Y. Z.; Tanoh, M.; Chen, G.-R.; Praly, J.-P.;

Chrysina, E. D.; Tiraidis, C.; Kosmopoulou, M.; Leonidas,

D. D.; Oikonomakos, N. G. Eur. J. Org. Chem. 2007, 596.

(15) Galland, S. Ph.D. Thesis; University of Avignon: France,

2006.

HRMS (ESI+): m/z [M + H]⁺calcd for C₃₅H₃₈N₃O₁₃: 708.2405;

found: 708.2406.

2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-5-(4-amino-

benzamido)-1,4-benzoquinone (20)

Compound 14f (48 mg, 0.0794 mmol) was dissolved in MeOH (3

mL). HCO₂NH₄(40 mg, 0.62 mmol, 7.7 equiv) and 10% Pd/C (10

mg) were added to the solution, and the mixture was stirred under

argon. TLC showed that compound 14f had changed completely

into a new polar compound [R_f= 0.12 (EtOAc–PE, 1:1)], assumed

to be hydroquinone 19. The mixture was filtered through a Celite

pad and the filtrate was concentrated. The yellow residue was chro-

matographed (PE–EtOAc, 2:3) on silica gel. When the residue was

added into the column, it turned dark red and a dark-red product

[R_f= 0.36 (PE–EtOAc, 1:1)] eluted from the column very quickly,

yielding upon concentration a dark red syrup (34 mg, 71%), identi-

fied as benzoquinone 20 by NMR spectroscopy (no OH signals,

C=O of quinone in the ¹H and ¹³C NMR spectra, respectively).

¹H NMR (300.13 MHz, CDCl₃): d = 8.72 (s, 1 H, CONH), 7.66 (d,

J = 8.4 Hz, 2 H, Ar), 7.68 (s, 1 H, Ar), 6.94 (s, 1 H, Ar), 6.71 (d,

J = 8.4 Hz, 2 H, Ar), 5.38 (t, J_3,4= 9.6 Hz, 1 H, H-3), 5.14 (t,

J_4,5= 9.9 Hz, 1 H, H-4), 4.94 (t, J_2,3= 9.3 Hz, 1 H, H-2), 4.74 (d,

J_1,2= 9.6 Hz, 1 H, H-1), 4.27 (dd, J_5,6= 5.1 Hz, J_6,6¢= 12.6 Hz, 1 H,

H-6), 4.20 (br s, 2 H, NH₂), 4.14 (dd, J_5,6¢= 1.8 Hz, 1 H, H-6¢), 3.82

(dq, 1 H, H-5), 2.10, 2.06, 2.01, 1.92 (4 s, 12 H, OCOCH₃).

¹³C NMR (75.5 MHz, CDCl₃): d = 186.5, 183.4 (2 C=O, quinone),

171.0, 170.4, 170.3, 170.0 (4 C=O, acetyl), 165.7 (CONH), 151.5,

146.4, 139.1 (3 C_q, Ar), 130.6, 129.9, 129.9 (3 CH_Ar), 122.6 (C_q,

Ar), 114.6, 114.6, 113.9 (3 CH_Ar), 76.6 (C-5), 74.0 (C-3), 73.2 (C-

2), 72.1 (C-1), 68.7 (C-4), 62.5 (C-6), 21.2, 21.0, 21.0, 20.9 (4 CH₃,

acetyl).

Acknowledgment

Région Rhône-Alpes is warmly thanked for a stipend (Y.-Z.Z.) and

generous financial support allocated in the frame of the MIRA col-

laborative program with Shanghai City (P. R. of China). Grants

from the National Science Foundation of China (NSFC, Grant No.

20576034) as well as financial supports from CNRS (France), Uni-

versity Claude-Bernard Lyon 1 (co-tutored Ph.D.), and ARCUS-

Chine 2005 are gratefully acknowledged.

(16) Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration: Methods

and Mechanisms; VCH: New York, 1989.

References

(17) Crivello, J. V. J. Org. Chem. 1981, 46, 3056.

(18) Louw, R. Acetyl Nitrate, In e-EROS: Encyclopedia of

Reagents for Organic Synthesis [Online]; Wiley-

Interscience 2001, DOI: 10.1002/047084289X.ra032.

(19) (a) Hojo, M.; Ueda, T.; Daike, C.; Takezaki, F.; Furuya, Y.;

Miyamoto, K.; Narutaki, A.; Kato, R. Bull. Chem. Soc. Jpn.

2006, 79, 1215; and references cited therein. (b) de

Oliveira, A. P.; Moreira, B. G.; Moran, P. J. S.; Rodrigues,

A. R. Tetrahedron Lett. 1996, 37, 5029. (c) Louw, R.;

Vermeeren, H. P. W.; van Asten, J. J. A.; Ultée, W. J. J.

Chem. Soc., Chem. Commun. 1976, 496.

(20) (a) Filimonov, V. D.; Kulmanakova, Yu. Y.; Yusubov, M.

S.; Perederina, I. A.; Chi, K. i.-Whan.; Poleshchuk, O. K.

Russ. J. Org. Chem. 2004, 40, 917. (b) Syvret, R. G.; Butt,

K. M.; Nguyen, T. P.; Bulleck, V. L.; Rieth, R. D. J. Org.

Chem. 2002, 67, 4487. (c) Bovicelli, P.; Mincione, E.;

Antonioletti, R.; Bernini, R.; Colombari, M. Synth.

Commun. 2001, 31, 2955.

(1) Jay, M. In Flavonoids: Chemistry, Biochemistry and

Applications; Andersen, ∆ . M.; Markham, K. R., Eds.; CRC

Press: Boca Raton, 2006, 857.

(2) Bililign, T.; Griffith, B. R.; Thorson, J. S. Nat. Prod. Rep.

2005, 22, 742.

(3) (a) Levy, D. E. In The Organic Chemistry of Sugars; Levy,

D. E.; Fügedi, P., Eds.; CRC Taylor & Francis: Boca Raton,

2006, 269. (b) Parker, K. A. In Glycomimetics: Modern

Synthetic Methodologies, ACS Symposium Series 896; Roy,

R., Ed.; American Chemical Society: Washington, 2005,

93. (c) Suzuki, K.; Matsumoto, T. In Preparative

Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel Dekker

Inc.: New York, 1997, 527. (d) Jaramillo, C.; Knapp, S.

Synthesis 1994, 1.

(4) Satoh, S.; Shimojima, M.; Ito, K.; Kuribayashi, T. Ann. Rep.

Sankyo Res. Lab. 2002, 54, 85; Chem. Abstr. 2003, 139,

180242.

(21) Sathunuru, R.; Rao, U. N.; Biehl, E. ARKIVOC 2003, (xv),

124.

3488

Y. Z. Zhang et al.

PAPER

(26) Evans, B. R.; O’Neill, H. M.; Malyvanh, V. P.; Lee, I.;

Woodward, J. Biosensors Bioelectronics 2003, 8, 917.

(27) Thompson, A.; Wolfrom, M. L. In Methods in Carbohydrate

Chemistry; Academic Press: New York, 1963, 215.

(28) (a) Yin, H.; Xu, Y.; Qian, X.; Li, Y.; Liu, J. Bioorg. Med.

Chem. Lett. 2007, 17, 2166. (b) Scott, J.; Dorr, R. T.;

Samulitis, B.; Landowski, T. H. Cancer Chemother.

Pharmacol. 2007, 59, 749.

(22) (a) Kabalka, G. W.; Verma, R. S. In Comprehensive Organic

Synthesis, Vol. 8; Trost, B. M.; Fleming, I., Eds.; Pergamon:

Oxford, 1991, 363. (b) Larock, R. C. Comprehensive

Organic Transformations: A Guide to Functional Group

Preparation, 2nd ed.; Wiley-VCH: Weinheim, 1999, 821.

(23) (a) Schröter, R. In Houben-Weyl, 4th ed., Vol. XI/1; Müller,

E., Ed.; Thieme: Stuttgart, 1957, 437. (b) Louis-André, O.;

Gelbard, G. Bull. Soc. Chim. Fr. 1986, 565.

(24) Johnstone, R. A. W.; Wilby, A. H.; Entwistle, I. D. Chem.

(29) (a) Braña, M. F.; Cacho, M.; Gradillas, A.; de Pascual-

Teresa, B.; Ramos, A. Curr. Pharm. Des. 2001, 7, 1745.

(b) Braña, M. F.; Ramos, A. Curr. Med. Chem.: Anti-Cancer

Agents 2001, 1, 237.

Rev. 1985, 85, 129.

(25) Park, K. K.; Oh, C. H.; Sim, W.-J. J. Org. Chem. 1995, 60,

6202.

Article Doi

C-glycosyl amino-substituted hydro- and benzoquinones: Synthesis and preliminary biological evaluation

DOI: 10.1055/S-2007-990856

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Article abstract of DOI:10.1055/S-2007-990856

Full text of DOI:10.1055/S-2007-990856

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