Sulfonamidoacetal cyclization-based synthesis of a tetrahydrooxazaphenalenelactone related to the ABC-ring system of the stephaoxocanes

Article abstract of DOI:10.3987/com-00-9099

The elaboration of a tetrahydrooxazaphenalenelactone embodying the ABC-ring system of the stephaoxocanes, by means of Jackson's sulfonamidoacetal cyclization as the isoquinoline ring-forming strategy, is reported.

Full text of DOI:10.3987/com-00-9099

HETEROCYCLES, Vol. 55, No. 2, 2001, pp. 323 - 330, Received, 2nd November, 2000
SULFONAMIDOACETAL CYCLIZATION-BASED SYNTHESIS OF A
TETRAHYDROOXAZAPHENALENELACTONE RELATED TO THE ABC-
RING SYSTEM OF THE STEPHAOXOCANES
Teodoro S. Kaufman
Instituto de Química Orgánica de Síntesis -IQUIOS- (CONICET-UNR) and
Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de
Rosario, Suipacha 570, (S2002LRK) Rosario, Argentina
Abstract - The elaboration of a tetrahydrooxazaphenalenelactone embodying the
ABC-ring system of the stephaoxocanes, by means of Jackson’s
sulfonamidoacetal cyclization as the isoquinoline ring-forming strategy, is
reported.
Stephania cepharantha Hayata, S. excentrica, and Cissampelos glaberrima are Menispermaceae used as
folk medicines in Taiwan, China and Brazil, respectively.1a,b, 2a, 3 Their tuberous roots contain various
alkaloids, such as bisbenzylisoquinolines, hasubanans, morphinans and aporphines.1 Recently, however, the
groups of Miao,2 da-Cunha,3 and Kashiwaba4 reported the isolation of previously unknown alkaloids
displaying a novel skeleton, for which the name stephaoxocane (1a)4a was coined.
Figure
R2
R1
R1
MeO
MeO
MeO
MeO
A
D
B
N
N
H
H
R
N
H
C
O
O
O
OH
OH
R3
OH
1a R1=R2=H, Stephaoxocane
1b R1=OMe, R2= H, R3= OH,
Stephaoxocanidine
1d R= H, Excentricine
1e R = Me, 2-N-Methylexcentricine
1f Stephaoxocanine
1c R1= R2= OMe, R3= OH
Eletefine
OMe
MeO
R1
OH
MeO
MeO
N
N
N
MeO
MeO
MeO
Ts
O
O
R2
O
R3
OR
4
3a R1= R2=R3= H Triclisine
3b R=R1=H, R2= OH Telitoxine
3c R1= OMe, R2= H, R3= OMe Rufescine
3d R1= OMe, R2= H, R3= OH Norrufescine
3e R1=R2=R3= OMe Imeluteine
2a R= H Grandirubrine
2b R= Me Imerubrine

To date, only 5 stephaoxocanes are known; they are stephaoxocanidine (1b)4b and stephaoxocanine (1f),4a
obtained from S. cepharantha, eletefine3 (1c), isolated from C. glaberrima, and excentricine (1d)2a and
N-methylexcentricine (1e),2b from S. excentrica.
As shown in the Figure, the stephaoxocanes share a tetracyclic ring system composed of an isoquinoline
moiety and an oxocane substructure joined together through a pyran ring, which conforms ring C. They
are structurally reminiscent of tropoisoquinoline (2a,b) and azafluoranthene (3a-e) alkaloids,5 which
display an all carbon five-member C-ring system and were isolated from other Menispermaceae. This may
be indicative of some biosynthetic relationship.5b
Being their natural sources used in folk medicine, the pharmacological evaluation of compounds (1b-f)
could be of interest; nevertheless, the results of such an evaluation have not been described, presumably
due to the small amounts of isolated material. Thus, the synthesis of the stephaoxocanes could provide
material for testing; however, no synthetic work on these natural products has been reported so far.
Therefore, as part of our research effort dedicated to the synthesis of structurally interesting isoquinoline-
type natural products by the use of Jackson’s sulfonamidoacetal cyclization,6 we decided to study the
elaboration of the tetrahydrooxazaphenalenelactone (4) from the commercially available 2,3-
dimethoxytoluene (5). Lactone (4) embodies the unique ABC-ring system of the naturally occurring
stephaoxocanes, and may be a potential key intermediate to their synthesis.
In the start of the synthesis, the pair of carbon atoms required to establish the lactone ring was cleanly
introduced by an AlCl3-mediated Friedel-Crafts acylation of 5 with ethyloxalyl chloride at room
temperature.7 This provided α-keto ester (6) in 94% yield, essentially uncontaminated with other
regioisomers, as depicted in Scheme 1.
Scheme 1
d
OMe
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
a
b
OMe
f
5
+
O
OH
N
N
R
Ts
CO2Et
CO2Et
CO2Et
CO2Et
Me
Me
Me
Me
6
8
7 R= H
9 R= Ts
10
c
e
Reagents and conditions: a. ClOCCO2Et, AlCl3, CH2Cl2, rt (94%); b. NaCNBH3,
H2NCH2CH(OMe)2, AcOH (4.5 equiv), EtOH, reflux (7, 53%; 8, 42%); c. TsCl, Et3N, CH2Cl2, rt
(82%); d. (COCl)2, DMSO, CH2Cl2, -60ºC, then Et3N (89%); e. PdCl2, CuCl2, AcOH (92%); f. 6N
HCl, dioxane, reflux (83%).
Next, reductive amination of glyoxylate (6) with aminoacetal and sodium cyanoborohydride in refluxing
ethanol8 furnished a mixture of the desired secondary amine (7) and α-hydroxy ester (8), the latter
resulting from reduction of the starting ketone. Unfortunately, formation of side product (8) could not be
avoided even by running the reaction at room temperature to improve selectivity, adding molecular sieves

or calcined MgSO4 to promote formation of the Schiff base intermediate, diminishing the amount of acetic
acid to lower the reactivity of the cyanoborohydride towards carbonyl reduction, or allowing the mixture
of ketone and amine to interact for 2 h before addition of the reducing agent. Therefore, synthesis
continued by submitting amine (7) to conventional sulfonamidation with tosyl chloride and triethylamine;
this smoothly afforded sulfonamide (9) in 82% yield, which was uneventfully cyclized to the 1,2-
dihydroisoquinolinesulfonamide (10) upon reaction with 6N HCl under Jackson’s conditions.
Now, formation of the lactone ring by functionalization of the primary benzylic position was undertaken;
however, the selenium dioxide-catalyzed benzylic oxidation of 10 furnished an unseparable mixture of
uncharacterizable compounds in which the required product was not detected, while oxidation of its
precursor (9) was unsuccessful and palladium(II)-mediated acyloxylation of 99 furnished 92% of starting
glyoxylate (6).
These results suggested the need of an early functionalization of the methyl group. Therefore, radical
bromination of glyoxylate (6) with NBS in CCl4, employing AIBN as radical initiator was explored; this
cleanly gave benzyl bromide (11) as the only product, which was immediately transformed into the related
acetate (12) with anhydrous sodium acetate in dry HMPA.10
Now the stage was set to perform Jackson’s synthesis; therefore, α-keto ester (12) was subjected to the
reductive amination protocol8 providing, as anticipated, a mixture of amine (13) and alcohol (14).
Unfortunately, attempts to transform alcohol (14) into tosylacetal (16) in one step by means of a
Mitsunobu-type amination with N-tosylaminoacetal (15) failed under various conditions, as observed by
almost quantitative recoveries of unchanged starting material, presumably due to steric congestion
surrounding the hydroxyl group and poor acidity of sulfonamide (15).11
Scheme 2
e
OH
OMe
MeO
MeO
MeO
MeO
MeO
MeO
MeO
a
c
g
OMe
6
N
O
+
OH
O
N
MeO
Ts
R
CO2Et
CO2Et
CO2Et
O
AcO
R
AcO
11 R= Br
12 R= OAc
4
13 R= H
16 R= Ts
b
f
d
14
X
Reagents and conditions: a. NBS, AIBN, CCl4, reflux (91%); b. AcONa, Ac2O, HMPA, (88%); c.
NaCNBH3, H2NCH2CH(OMe)2 (5 equiv.), AcOH (4.5 equiv), EtOH, reflux (13, 52%; 14, 41%);
d. PPh3, DEAD, TsNHCH2CH(OMe)2 (15), THF, reflux (no reaction); e. (COCl)2, DMSO, CH2Cl2,
-60ºC, then Et3N (91%); f. TsCl, Et3N, CHCl3, reflux (81%); g. 6N HCl, dioxane, reflux (49%).
In light of our previous experience, alcohol (14) was recycled by an efficient Swern oxidation to α-keto
ester (12) and the key amine (13) was conveniently converted into the related tosylamide (16) with tosyl
chloride and triethylamine in refluxing chloroform, as shown in Scheme 2.

With tosylacetal (16) in the hands, the next step consisting in its conversion into 4 was undertaken;
however, in contrast to the easy formation of dihydroisoquinoline (10), cyclization of 16 proved to be
difficult. After many trials it was observed that lactone formation occurred at an early stage; presumably,
the strain and rigidity introduced by the lactone ring difficulted acetal cyclization. In addition, it was
detected that increasing the concentration of acid or prolongued reflux periods caused diminished yields of
the required product.
The conformation of the methoxy group para to the ring closure position could also contribute to the poor
reactivity of 16 towards isoquinoline ring formation. Being flanked by two ortho substituents, the methyl
13
group of the ether must adopt an out of plane conformation, as evidenced by its C NMR chemical shift
of δ 59.97 ppm, compared with δ 55.56 of its neighbouring methyl ether,12 thus hindering the ability of
the lone pairs of electrons of the oxygen to efficiently conjugate with the aromatic ring and thereby
lowering the activation of the ring closure position. It has been reported that improper activation of the
aromatic ring strongly disfavors or hinders cyclization causing diminished product yields due to
undesirable side reactions.13
The best alternative was to cyclize 16 with 15 equivalents of HCl in refluxing dioxane during 2 h. This
furnished a tetrahydroisoquinoline derivative in 49% yield, to which structure (4) was assigned on the
grounds of its IR and NMR spectra. Interestingly, only one diastereoisomer was isolated, indicating that
the rigid bicyclic lactone could be responsible for positioning the protonated intermediate in such a
conformation that the attack of the aromatic ring would be possible only from one face of the carbonyl
moiety.
Curiously, benzylic alcohols are not the usual products of Jackson’s cyclization. Under conventional
reaction conditions, these intermediates are protonated and dehydrate to furnish the related 1,2-
dihydroisoquinolinesulfonamides, as observed with 10. We have shown14 that the dehydration step
involves an anti elimination, being the benzylic alcohol the reaction product in cases where a trans H-3 is
1
absent. Examination of the H NMR spectrum of 4 evidenced that Ha-3 has a large coupling constant
(10.3 Hz) with the adjacent H-4, indicating that the benzylic alcohol adopts a pseudoequatorial
conformation in which its dihedral angle with He-3 is small. Furthermore, in addition to the poor
availability of H-3 to engage in the required β-elimination, it is likely that dehydration of 4 might be
disfavored because of the additional strain that it would introduce into the product.
In conclusion, it has been shown that Jackson’s protocol successfully led to the elaboration of 4, a
polysubstituted tetrahydrooxazaphenalene lactone embodying the ABC-ring system of the natural
stephaoxocanes, and a potential key intermediate for their synthesis.
EXPERIMENTAL
Mps were measured on an Ernst Leitz hot-stage microscope apparatus and are uncorrected. IR spectra
were taken on a Bruker IFS 25 spectrophotometer with solid samples as KBr pellets and liquid samples as
13
films. 1H and C NMR spectra were recorded in deuteriochloroform, on a Bruker AC-200E instrument at

200.13 and 50.33 MHz respectively, with tetramethylsilane as the internal standard; J values are given in
Hz. High resolution MS were obtained from LANAIS-EMAR (Buenos Aires) and microanalytical data
were provided by Atlantic Microlab (Norcross, GA, USA). All reactions were carried out in dry oxygen-
free nitrogen or argon atmospheres. Reactions were monitored by thin layer chromatography on Merck's
pre-coated silica gel 60 F254 TLC plates and detected by examination under UV light and by spraying with
2% p-anisaldehyde-sulfuric acid reagent in 95% ethanol. Careful heating improved the selectivity of the
detection. All new compunds gave a single and homogeneous spot by TLC. Flash chromatography was
carried out on Merck Kieselgel 60 (0.04-0.063 mm), packed in hexane; elution was with mixtures of
hexane-EtOAc, using gradient techniques. Compounds were pre-adsorbed from CH2Cl2 solutions onto the
adsorbent before column chromatography.
Ethyl (2-acetoxymethyl-3,4-dimethoxyphenyl)glyoxylate (12).- A solution of 2,3-dimethoxytoluene (5,
1000 mg, 6.57 mmol) and ethyloxalyl chloride (0.845 mg, 7.56 mmol) in dry CH2Cl2 (4 mL) was
dropwise added to a suspension of anhydrous AlCl3 (1926 mg, 14.44 mmol) in CH2Cl2 (5 mL), cooled in
an ice-bath. The deep-red colored reaction mixture was stirred under argon until completion, then it was
poured over saturated NH4Cl (10 mL) and the reaction product was extracted with EtOAc (5 x 20 mL).
The combined organic fractions were washed with brine (10 mL), dried (Na2SO4), concentrated in vacuo
and chromatographed through a short pad of silica, furnishing glyoxylate (6) (1559 mg, 94%), as a clear
oil; IR (film): 2980, 2860, 1740, 1680, 1600, 1520, 1470, 1330, 1260, 1160, 1040, 900 and 770 cm-1;
1H NMR (δ): 1.40 (t, 3H, J= 7.2, OCH2Me), 2.54 (s, 3H, ArMe), 3.78 (s, 3H, OMe), 3.93 (s, 3H,
OMe), 3.41 (q, 2H, J= 7.2, OCH2Me), 6.82 (d, 2H, J= 8.7, ArH) and 7.49 (d, 2H, J= 8.7, ArH); 13C
NMR (δ): 12,87, 13.92, 55.72, 60.21, 61.93, 108.55, 122.62, 130.38, 135.88, 147.80, 157.38,
164.94 and 187.43.
Without delay, the α-keto ester (6) (750 mg, 2.976 mmol) was dissolved in CCl4 (17 mL) and
successively treated with NBS (636 mg, 3.57 mmol) and AIBN (1 mg), and refluxed in an argon
atmosphere for 90 min. When the reaction was completed, it was diluted with brine (10 mL) and extracted
with EtOAc (4 x 30 mL). The organic extracts were dried (Na2SO4), concentrated and chromatographed,
affording benzyl bromide (11) (897 mg, 91 %) as a yellowish and slightly unstable solid, mp 67-67.5ºC
(hexane/EtOAc); IR (KBr): 3000, 2860, 1740, 1680, 1580, 1470, 1310, 1260, 1100, 1030, 910, 830
1
and 720 cm-1; H NMR (δ): 1.41 (t, 3H, J= 7.3, OCH2Me), 3.97 (s, 3H, OMe), 3.99 (s, 3H, OMe), 4.43
(q, 2H, J= 7.3, OCH2Me), 5.08 (s, 2H, ArCH2Br), 6.94 (d, 2H, J= 8.7, ArH) and 7.56 (d, 1H, J= 8.7,
ArH); 13C NMR (δ): 13.84, 23.13, 55.66, 60.86, 62.01, 110.89, 122.68, 131.02, 134.48, 148.35,
157.38, 164.12 and 186.52; HRMS for C13H15O5Br. Calcd: 330.0102. Found: 330.0111.
Without further purification, anhydrous sodium acetate (100 mg, 1.22 mmol) and acetic anhydride (0.025
mL) were successively added to a solution of bromide (11) (100 mg, 0.30 mmol) in dry HMPA (1.5
mL). The reaction mixture was stirred under argon at rt for 24 h; then, it was diluted with 1N HCl (5 mL)
and extracted with ether (3 x 30 mL). The combined organic extracts were washed with brine (5 mL),
dried (Na2SO4) and concentrated in vacuo to furnish benzylic acetate (12) (82.5 mg, 88%), as an oil; IR

1
(film): 2980, 2860, 1750, 1730, 1660, 1600, 1500, 1460, 1300, 1250, 1110, 1030 and 820 cm-1; H
NMR (δ): 1.41 (t, 3H, J= 7.1, OCH2Me), 2.05 (s, 3H, MeCO2), 3.86 (s, 3H, OMe), 3.96 (s, 3H,
OMe), 4.41 (q, 2H, J= 7.1, OCH2Me), 5.45 (s, 2H, ArCH2O), 6.97 (d, 1H, J= 8.7, ArH) and 7.54 (d,
1H, J= 8.7, ArH); 13C NMR (δ): 13.91, 20.58, 55.91, 55.99, 61.29, 62.19, 111.31, 125.23, 130.11,
149.16, 157.30, 160.43, 163.77, 170.46 and 186.23; Anal. Calcd for C15H18O7: C, 58.06; H, 5.85.
Found: C, 58.16; H, 5.88.
Ethyl (2-acetoxymethyl-3,4-dimethoxyphenyl)-[N-(2,2-dimethoxyethyl)-N-(4-toluenesulfonyl)-amino]-
acetate (16).- Aminoacetal (0.123 mL, 1.13 mmol) and glacial acetic acid (0.052 mL, 0.903 mmol) were
added to a solution of keto ester (12) (70 mg, 0.226 mmol) in absolute ethanol (1.5 mL). The reaction
mixture was left to stand for 1 h at rt, then it was treated with sodium cyanoborohydride (14 mg, 0.226
mmol) at rt overnight. The reaction was quenched with 1N NaOH (5 mL) and extracted with EtOAc (4 x
20 mL); the organic extracts were washed with brine (5 mL), dried (Na2SO4), concentrated and
chromatographed, providing mandelate (14) (29 mg, 41 %) as an oil; IR (film): 3460, 2980, 2850, 1730,
1
1740, 1600, 1500, 1460, 1280, 1090 and 810 cm-1; H NMR (δ): 1.22 (s, 3H, J= 8.6, OCH2Me), 2.07
(s, 2H, MeCO2), 3.84 (s, 3H, OMe), 3.86 (s, 3H, OMe), 4.20 (dq, J= 1, 8.6, OCH2Me), 5.35 (s, 2H,
13
ArCH2O), 5.40 (s, 1H, ArCHOH), 6.92 (d, 1H, J= 8.6, ArH) and 7.10 (d, 1H, J= 8.6, ArH); C NMR
(δ): 13.88, 20.86, 55.56, 57.60, 61.20, 61.97, 69.77, 112.71, 122.97, 128.03, 130.88, 148.46,
142.65, 170.73 and 173.60. Increasing the polarity furnished the desired secondary amine (13) (47 mg,
1
52%), as an oil; IR (film): 3550-2700, 2960, 2840, 1740, 1280, 1090 and 820 cm-1; H NMR (δ): 1.20
(t, 3H, J= 7.1, OCH2Me), 2.05 (s, 3H, MeCO2), 2.59 (dd, 1H, J= 5.5, 13, NCH2), 2.74 (dd, 1H, J=
5.5, 13, NCH2), 3.34 (s, 3H, OMe), 3.36 (s, 3H, OMe), 3.85 (s, 3H, OMe), 3.86 (s, 3H, OMe), 4.13
(dq, 2H, J= 1.0, 7.1, OCH2Me), 4.46 [t, 1H, J= 5.5, CH(OMe)2], 4.61 (s, 1H, NH), 2.60 (2H, s,
ArCH2OAc), 6.92 (t, 1H, J= 8.6, ArH), 7.12 (d, 1H, J= 8.6, ArH) and 7.75 (d, 1H, J= 8.6, ArH); 13C
NMR (δ): 13.95, 20.86, 48.82, 53.46, 53.73, 55.59, 57.59, 60.76, 60.99, 61.22, 103.72, 112.78,
122.53, 128.38, 130.67, 148.42, 152.23, 170.65 and 172.72; HRMS for C19H29NO8. Calcd: 399.1893.
Found: 399.1904
Tosyl chloride (38 mg, 0.2 mmol) was added at once to a solution of amine (13) (39 mg, 0.094 mmol) in
chloroform (1 mL) and triethylamine (0.048 mL, 0.35 mmol). The reaction was stirred 24 h at rt and next
refluxed for 4 h; then, it was diluted with brine (5 mL) and the reaction product was extracted with EtOAc
(4 x 20 mL). The combined organic extracts were dried (Na2SO4), concentrated under reduced pressure
and chromatographed, affording sulfonamide (16) (41.6 mg, 81%) as a solid mp 88.5-90ºC
(hexane/EtOAc); IR (film): 2940, 2840, 1740, 1600, 1500, 1460, 1350, 1290, 1170, 1090, 1080, 830
1
and 670 cm-1; H NMR (δ): 1.14 (t, 3H, J= 7.2, OCH2Me), 2.11 (s, 3H, MeCO2), 2.44 (s, 3H, ArMe),
3.01 (s, 3H, OMe), 3.21 (s, 3H, OMe), 3.26 (dd, 1H, J= 6.9, 15.7, NCH2), 3.49 (dd, 1H, J= 4, 15.7,
NCH2), 3.85 (s, 3H, OMe), 3.86 (s, 3H, OMe), 3.82-4.10 (m, 3H, NCH2CH and OCH2Me), 5.13 (d,
1H, J= 11.9, ArCH2O), 5.40 (d, 1H, J= 11.9, ArCH2O), 6.07 (s, 1H, ArCHNTs), 6.77 (d, 1H, J= 8.6,

ArH), 6.85 (d, 1H, J= 8.6, ArH), 7.29 (d, 2H, J= 8.3, ArH of Tosyl) and 7.72 (d, 2H, J= 8.3, ArH of
Tosyl); 13C NMR (δ): 13.75, 20.92, 21.94, 47.44, 54.48, 54.93, 55.56, 57.50, 59.97, 61.15, 61.20,
104.37, 111.83, 124.70, 125.91, 127.65 (2 x C), 129.26 (2 x C), 130.41, 135.78, 143.55, 146.91,
153.32, 170.11 and 170.52; Anal. Calcd for C26H35NO10S: C, 56.41; H, 6.37; N, 2.53; S, 5.79. Found:
C, 56.53; H, 6.34; N, 2.55; S, 5.83.
Attempted synthesis of (16) by Mitsunobu amination of (14).- A THF solution (1 mL) of alcohol (14)
(40 mg, 0.12 mmol) was successively treated with tosylamidoacetal (15, 65 mg, 0.25 mmol), PPh3 (65.6
mg, 0.25 mmol) and DEAD (0.046 mL, 0.25 mmol). The reaction was stirred at 60ºC for 30 min, when
TLC showed absence of DEAD; then the volatiles were evaporated in vacuo and the oily residue was
chromatographed, allowing the recovery of 14 (37.8 mg, 94.5%).
Recycling of alcohol (14) to glyoxylate (12) by Swern oxidation.- Dry DMSO (434 mg, 5.55 mmol) was
dropwise added to a stirred solution of trifluoroacetic anhydride (777 mg, 3.70 mmol) in CH2Cl2 (7 mL)
cooled to -60ºC. After 5 min at -60ºC, a solution of alcohol (14) (470 mg, 1.85 mmol) in CH2Cl2 (3 mL)
was slowly dropped in via canula and the mixture was left to react for 15 min. Then, TEA (0.91 mL, 6.47
mmol) was added and after another 15 min period the reaction was warmed to rt, when it was diluted with
brine (5 mL) and extracted with EtOAc (4 x 20 mL). Drying (Na2SO4), concentration and chromatography
of the organic extracts furnished α-keto ester (12) (427 mg, 91%).
3-Hydroxy-5,6-dimethoxy-1-(4-toluenesulfonyl)-2,3,7,9a-tetrahydro-1H-8-oxa-1-azaphenalen-9-one
(4).- A stirred solution of tosylacetal (16) (54 mg, 0.1 mmol) in peroxide-free dioxane (1 mL) was treated
with 6N HCl (0.166 mL, 10 equiv.) and refluxed under nitrogen during 1 h; then, more 6N HCl (0.083
mL, 5 equiv.) was added and the mixture was left to react for another 1 h period. After cooling to rt, brine
(5 mL) was added and the product was extracted with EtOAc. Drying (Na2SO4), concentration and
chromatography of the extract finally provided compound (4) (24.2 mg, 49%) as a pale yellow solid, mp
172-173.5ºC (hexane-EtOAc); IR (KBr): 3488, 2924, 2852, 1764, 1496, 1342, 1268, 1160, 1018, 968,
1
848, 730 and 666 cm-1; H NMR (δ): 1.67 (br s, 1H, OH), 2.44 (s, 3H, ArMe), 2.74 (dd, 1H, J= 10.3,
13.3, Ha-3), 3.87 (s, 3H, OMe), 3.89 (s, 3H, OMe), 3.97 (dd, 1H, J= 4.9, 13.3, He-3), 4.85 (br dd,
1H, J= 4.9, 10.3, H-4), 5.26 (d, 1H, J= 14.1, ArCH2O), 5.56 (br s, 1H, OH), 5.59 (d, 1H, J= 14.1,
ArCH2O), 7.20 (s, 1H, ArH), 7.33 (d, 2H, J= 8.0, ArH of Tosyl) and 7.94 (d, 2H, J= 8.0, ArH of
Tosyl); 13C NMR (δ): 21,47, 46,96, 53,42, 55,92, 61,29, 64,27, 64,84, 109,32, 118,65, 124,51,
127,87 (2 x C), 129,54 (2 x C), 133,46, 136,43, 143,93, 144,38, 152,14 and 169,03; Anal. Calcd for
C20H21NO7S: C, 57.27; H, 5.05; N, 3.34; S, 7.64. Found: C, 57.51; H, 5.00; N, 3.26; S, 7.66.
ACKNOWLEDGEMENTS
The author thanks Fundación Antorchas, CONICET, ANPCyT and SECyT-UNR for financial support.

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