An investigation into the synthesis of some molecules related to methyl acarviosin

Article abstract of DOI:10.1071/CH03185

Methyl acarviosin is an impressive inhibitor of some glycoside hydrolases that process substrates containing α-D-glucosidic linkages. In an attempt to provide putative inhibitors for enzymes that process β-D-glucosidic linkages, we report an improved synthesis of a hydroxylated 'methyl β-acarviosin' and our efforts towards various deoxygenated versions of methyl β-acarviosin. As well, the synthesis of a 1,3-linked variant of methyl β-acarviosin is reported, together with an unsuccessful 'tether' approach to construct the crucial nitrogen linkage in the acarviosins.

Full text of DOI:10.1071/CH03185

Full Paper
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2004, 57, 233–241
An Investigation into the Synthesis of Some Molecules Related to
Methyl Acarviosin
Matthew J. McDonough,A Robert V. Stick,A,B D. Matthew G. Tilbrook,A and Andrew G. WattsA
A Chemistry, School of Biomedical and Chemical Sciences M313, University of Western Australia,
Crawley WA 6009, Australia.
B Author to whom correspondence should be addressed (e-mail: rvs@chem.uwa.edu.au).
Methyl acarviosin is an impressive inhibitor of some glycoside hydrolases that process substrates containing
α-d-glucosidic linkages. In an attempt to provide putative inhibitors for enzymes that process β-d-glucosidic link-
ages, we report an improved synthesis of a hydroxylated ‘methyl β-acarviosin’ and our efforts towards various
deoxygenated versions of methyl β-acarviosin.As well, the synthesis of a 1,3-linked variant of methyl β-acarviosin is
reported, together with an unsuccessful ‘tether’approach to construct the crucial nitrogen linkage in the acarviosins.
Manuscript received: 21 July 2003.
Final version: 17 September 2003.
Acarbose 1 (Diagram 1) is an excellent inhibitor of several
enzymes that process substrates containing α-d-glucosidic
linkages and, as such, is used in the treatment of various forms
of diabetes.[1–4] Methyl acarviosin 2, the apparent core of
acarbose, is an even better inhibitor of sucrase than acarbose
itself.[5]
Some years ago, we were inspired to prepare β-acarbose 3,
in the hope that the molecule would inhibit those enzymes
that process β-d-glucosidic linkages.[6,7] After a prolonged
synthetic sequence, we were disappointed to find that
β-acarbose was, in fact, a substrate for various β-glucosidases
and cellulases![8] Putting this result aside, we prepared the
core of β-acarbose, namely ‘methyl β-acarviosin’ 4,[9] and
this molecule did show some ability to inhibit the action of
various β-glucosidases.[8]
Two things still seemed worthy of further investigation: (1)
the synthesis of other, or further, deoxy derivatives of 4, to
probe the importance of hydrophobic contacts in binding; and
(2) the glycosylation of 4 at the non-reducing terminus, to
produce analogues of β-acarbose with a reduced propensity
towards hydrolysis. Therefore, in the first part of these inves-
tigations, we decided to prepare the analogues 5 and 6 and, in
a related approach, the 1,3-linked molecule 7, for possible use
as an inhibitor of hydrolases that process 1,3-β-d-glucosidic
linkages.
Our successful synthesis of methyl β-acarviosin 4 had
resulted from the alkylation of the 1-epivalienamine deriva-
tive 8 by the triflate 9.[9] Before employing such an approach
in the synthesis of the analogues 5 and 6, we decided to
improve upon our previous synthesis of the 6-hydroxylated
version of methyl β-acarviosin, namely 10 (this synthesis
had been rather laborious, being intimately linked with our
synthesis of methyl β-adiposin-2).[10,11]
Thus, methyl β-d-galactopyranoside was converted into
the alcohol 11 and thence the triflate 12 (Scheme 1).[12]
The 1-epivalienamine derivative 8 was prepared according
to the published procedure,[13] except that the final reduc-
tion of the azide to the amine was performed with sodium
sulfide, rather than the noxious hydrogen sulfide. Treat-
ment of 8 with the triflate 12 in 1,3-dimethylimidazolidin-
2-one (DMI) then gave the amine 13 (41%), together with
substantial amounts of the alkene 14 (Diagram 2) and unre-
acted starting materials. The deprotection of 13 (sodium in
methanol, then lithium in ammonia), followed by acetylation,
then yielded the heptaacetate 15, and deacetylation gave the
desired 10.
For a synthesis of 5, we decided to prepare the triflate 16
(Scheme 2). Thus, methyl β-d-galactopyranoside was con-
verted into the diol 17.[9,14] In something of a gamble, we
treated the diol 17 with dibutyltin oxide in refluxing toluene,
and then added O-phenyl chlorothioformate, in the hope of
forming the thiocarbonate 18—unfortunately, only the cyclic
thiocarbonate 19 resulted (Diagram 2).
As an alternative, the diol 17 was converted into the acetate
20 and a modified Barton–McCombie deoxygenation gave
the 3-deoxy derivative 21. Deacetylation of 21 gave the alco-
hol 22, treatment of which with triflic anhydride appeared to
give (1H NMR spectroscopy) the unstable triflate 16. Unfor-
tunately, 16 decomposed readily upon workup, and alkylation
of the 1-epivalienamine derivative 8 proved unsuccessful. In
a slight aside, the less reactive mesylate 23 was prepared but
was found to be unreactive towards 8.
Before these alkylation attempts, we had started our
synthesis towards the triflate 24 (Scheme 3), a necessary
precursor of the dideoxy target 6. Thus, methyl β-d-galacto-
pyranoside was converted into the 6-deoxy derivative 25, and
© CSIRO 2004
10.1071/CH03185
0004-9425/04/030233

234
M. J. McDonough et al.
OH
HO
HO
OH
CH3
HO
HN
HO
HO
HO
O
OH
CH3
HO
HN
HO
HO
O
O
O
HO
OH
HO
HO
OMe
O
O
HO
1
2
OH
HO
OH
OH
HO
HO
OH
O
HO
HO
HO
HN
O
HO
HO
O
O
O
HO
CH
3
HO
OH
3
OH
OH
HO
HO
HO
HO
HO
HO
HO
HN
X
OMe
OMe
HN
O
O
HO
CH
HO
Y
3
4
5 X ϭ H, Y ϭ CH2OH
6 X ϭ H, Y ϭ CH3
10 X ϭ OH, Y ϭ CH2OH
OH
OBn
BnO
TfO
CH3
CH
3
O
O
HO
HO
HO
NH
BnO
BnO
OMe
BzO
NH2
OMe
BnO
HO
HO
7
8
9
Diagram 1.
OR
RO
RЈO
OBz
O
OH
RO
HO
HO
RO
RO
a
c
g
RЈO
OMe
O
10
HN
O
OMe
OMe
BzO
HO
BzO
ORЈ
13 R ϭ Bn, RЈ = Bz
15 R ϭ RЈ = Ac
11 R ϭ H
12 R ϭ Tf
b
d,e,f
Scheme 1. (a) BzCl, pyridine, CH2Cl2, −50◦C; (b) Tf2O, pyridine, CH2Cl2, −10◦C; (c) 8, DMI; (d) Na, MeOH; (e) Li, NH3, THF, −78◦C;
(f) Ac2O, pyridine, DMAP; (g) Na, MeOH.
OBz
OBn
OBn
HO
O
S
O
O
O
O
PhOCSO
OMe
OMe
OMe
BzO
BnO
BnO
BzO
14
18
Diagram 2.
19
selective hydrolysis of 25 gave the diol 26.[9] The diol 26 was
then converted into the alcohol 27 in a sequence parallel to
that used on the diol 17.
Although well aware of the instability of the triflate 16,
we still attempted the conversion of the alcohol 27 into the
triflate 24. Again, the product was a somewhat unstable
oil that did not allow for a successful alkylation of the
1-epivalienamine derivative 8.We did attempt the preparation
of the ‘imidazolate’ 28, generally more stable than a triflate
but no less reactive,[15] but only the products of elimination

Synthesis of Molecules Related to Methyl Acarviosin
235
OBn
O
RO
OBn
O
OH
HO
RЈO
RO
a, b, c
e, f
O
OMe
OMe
OMe
HO
BnO
BnO
HO
21 R ϭ Ac
22 R ϭ H
16 R ϭ Tf
23 R ϭ Ms
17 R ϭ RЈ ϭ H
20 R ϭ H, RЈ ϭ Ac
g
h
d
Scheme 2. (a) Me2C(OMe)2, camphorsulfonic acid (CSA); (b) BnBr, NaH, DMF; (c) 80% aq. AcOH, 60◦C; (d) MeC(OEt)3,CHCl3, CF3COOH,
then MeCN, H2O; (e) ClC(S)OPh, pyridine, CH2Cl2; (f) Bu3SnH, AIBN, PhCH3, 70◦C; (g) Na, MeOH; (h) Tf2O, pyridine, CH2Cl2, −50◦C.
RO
OH
HO
HO
HO
O
Me
Me
Me
a, b, c, d
e
O
f, g, h, i
O
O
O
OMe
OMe
OMe
HO
OMe
O
HO
BnO
BnO
BnO
25
26
27 R ϭ H
24 R ϭ Tf
j
28 R ϭ ImSO2
Scheme 3. (a) Me2C(OMe)2, CSA; (b) I2, Ph3P, imidazole, PhCH3; (c) BnBr, NaH, DMF; (d) LiAlH4, THF; (e) 80% aq. AcOH, 60◦C; (f)
MeC(OEt)3, CHCl3, CF3COOH, then MeCN, H2O; (g) ClC(S)OPh, pyridine, CH2Cl2; (h) Bu3SnH, AIBN, PhCH3, 70◦C; (i) Na, MeOH; (j) Tf2O,
pyridine, CH2Cl2, −50◦C. In structure 28, Im represents imidazol-1-yl.
O
O
Ph
Ph
d
O
O
b
O
O
OMe
OMe
RЈO
BzO
RO
RO
30 R ϭ RЈ ϭ H
32 R ϭ ClCH2CO
33 R ϭ H
a
c
31 R ϭ Bz, RЈ ϭ H
OR
RЈ
CH
O
g
3
BzO
O
RO
RO
RЈO
NH
OMe
OMe
BzO
RO
RЈO
RO
36 R ϭ Bn, RЈ ϭ Bz
37 R ϭ RЈ ϭ Ac
7 R ϭ RЈ ϭ H
34 R ϭ H, RЈ ϭ Br
35 R ϭ RЈ ϭ H
e
h
i
f
29 R ϭ Tf, RЈ ϭ H
Scheme 4. (a) 1-(Benzoyloxy)benzotriazole, Et3N, THF; (b) ClCH2CO2H, Ph3P, diethyl azodicarboxylate (DEAD), THF/C6H6; (c) thiourea,
2,6-lutidine, MeOH/CH2Cl2, 40◦C; (d) N-bromosuccinimide, CaCO3, CCl4, 77◦C; (e) Bu3SnH, PhCH3, 70◦C; (f) Tf2O, pyridine, CH2Cl2,
−20◦C to room temperature; (g) 8, DMI; (h) Na, MeOH/THF, then Na, NH3, THF, −78◦C, then Ac2O, pyridine, DMAP; (i) Na, MeOH.
(alkenes) were observed when the alcohol 27 was treated with
imidazolesulfonic anhydride and pyridine.
Finally, the 1-epivalienamine derivative 8 was treated with
the triflate 29 in DMI to give a satisfactory yield (55%)
of the amine 36. Interestingly, and as noted before in sim-
ilar systems,[6] the 1H NMR spectrum of 36 contained
several broadened signals for the (non-aromatic) ring
hydrogens—thisbroadeningwasfrequency-dependent(obvi-
ous at 500 MHz but not so much at 300 Hz) and clearly
correlated with the NMR time scale. The origin of the line
broadening probably lies in a slow inversion of configura-
tion at the nitrogen atom, substituted with bulky/electron-
withdrawing groups.[6,17]
The 1,3-linked molecule 7 required the preparation of the
triflate 29 (Scheme 4). Thus, the diol 30 was treated with
1-(benzoyloxy)benzotriazole[16] to give the 2-O-benzoyl
derivative 31; this procedure avoids the formation of any
dibenzoate, and the easily separated 3-O-benzoyl derivative
can be recycled.
The alcohol 31 was then subjected to a Mitsunobu reaction
with chloroacetic acid to give the chloroacetate 32; a selective
de-esterification with thiourea then gave the d-allo alcohol
33. A Hanessian–Hullar reaction on 33 gave the bromide 34,
the reduction of which produced the 6-deoxy sugar 35. Treat-
ment of 35 with triflic anhydride then gave the triflate 29.
Deprotection of the amine 36 (sodium in methanol, then
sodium in ammonia), followed by acetylation, gave the hexa-
acetate 37; deacetylation then gave the target 7. The amine 7

236
M. J. McDonough et al.
OH
OH
OR
HO
HO
RЈO
BnO
a
d
HO
O
O
HO
HO
OMe
HO
NH
OMe
OMe
OBn
O
OH
HO
OH
41 R ϭ RЈ ϭ H
b
c
42 R ϭ SiButMe2, RЈ ϭ H
43 R ϭ SiButMe2, RЈ ϭ Tf
OR
AcO
O
f
O
H2N
PO
O
N3
BnO
40
PO
PO
O
OMe
OMe
OP
OBn
OP
44 R ϭ SiBut Me2
45 R ϭ H
Diagram 3. P = protecting group.
e
Scheme5. (a)PhCH(OMe)2, CSA, DMF, 60◦C, thenEt3N, thenBnBr,
NaH, then 80% aq. HOAc, 100◦C; (b) ButMe2SiCl, ImH, DMF; (c)
Tf2O, pyridine, CH2Cl2, 0◦C;(d)NaN3, DMF, 80◦C;(e)80%aq. HOAc,
100◦C; (f) phthalic anhydride, pyridine, DMAP.
O
AcO
O
38
O
O
BnO
BnO
O
N3
BnO
OMe
OBn
OBn
the Grignard reagent derived from benzyl chloromethyl ether
to the enone 46.[13] Here, we required a halomethyl ether that
ultimately provided a protecting group in the product, orthog-
onal to a benzyl ether—t-butyl chloromethyl ether[22] and
(t-butyldimethylsilyloxy)methyl chloride[23] were both tried
but neither allowed for a successful Grignard addition to 46.
However, with an improved preparation of chloromethyl
4-methoxybenzyl ether[24] at hand (just half an equivalent
of sulfuryl chloride added to 4-methoxybenzyl methylthio-
methyl ether), a successful Grignard addition to the enone 46
presumably gave the tertiary alcohol, and thence the acetate
47.The configuration of the new stereogenic centre in 47 was
not determined but predicted on the basis of a related addition
to the enone 46.[13] Treatment of the acetate 47 with 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) did not give the
expected alcohol 39, but instead gave rise to the isomeric 48!
The structure of the rearranged product 48 was derived from
O
AcO
HO
40
BnO
BnO
O
O
OH
O
N3
BnO
OBn
OMe
39
OBn
Diagram 4.
proved to be completely inactive as an inhibitor of a 1,3-β-
glucanase from barley.[18]
While we were carrying out the above synthetic work, we
were cognizant of the popularity of ‘tether’chemistry for the
synthesis of (glycosidic) linkages, pioneered by Ziegler[19]
and Schmidt.[20] It seemed to us that a similar approach,
utilizing well established Pd(0) chemistry,[13] could be used
to construct the crucial nitrogen linkage in the acarviosins
(Diagram 3). It was hoped that the tether would both con-
trol the regioselectivity and confer good stereoselectivity on
the process, two features lacking in a related intermolecu-
lar alkylation by Bols.[21] The tether chosen was the stable
phthalic acid diester, and the synthetic target was the azide
38, seemingly available from the alcohol 39 and the acid 40
(Diagram 4).
Methyl β-d-galactopyranoside was easily converted into
the diol 41 (Scheme 5). A selective silylation of 41 then gave
the alcohol 42, subsequently transformed into the triflate 43
and the azide 44. The d-gluco configuration of 44 was con-
firmed by a measurement of the value of J4,5 (9.4 Hz) in the
1H NMR spectrum. Selective deprotection of 44 gave the
alcohol 45, which was esterified with phthalic anhydride to
give the required acid 40.
1
an inspection of its H NMR spectrum and the subsequent
sluggish esterification (1,3-dicyclohexylcarbodiimide/N,N-
dimethylaminopyridine; DCC/DMAP) with the acid 40.
To circumvent this result, the alcohol 48 was deacetylated
and the resulting diol 49 combined with a slight molar excess
of the acid 40. TLC analysis showed complete consump-
tion of the diol 49, so an excess of acetic acid, and more
DCC/DMAP were added. TLC analysis again showed the
presence of a new compound, eventually isolated in an over-
all yield of 74%, and shown to be the azide 38. Reduction
of this azide with propane-1,3-dithiol then gave the tethered
primary amine 50.
Try as we might, we could not convert the primary amine
50 into the secondary amine 51 using Pd(PPh3)4, in either the
presence or absence of 1,5-bis(diphenylphosphino)pentane.
The amine 50 seemed quite unreactive, with fragmentation
of the ether linkage(s) a seemingly unwanted process.
In conclusion, we have been able to prepare several
carbohydrate triflates, but only those that were not deoxy-
genated on the pyranose ring, namely 12 and 29, were stable
enough to alkylate our key cyclohexenyl amine 8 and so
For the synthesis of the other partner, the alcohol 39, the
enone 46[13] (Scheme 6) was an obvious starting point. In
previous work, we had mastered the rather tricky addition of

Synthesis of Molecules Related to Methyl Acarviosin
237
O
AcO
HO
OPMB
OBn
OAc
OBn
BnO
BnO
BnO
BnO
BnO
BnO
a
b
OBn
46
47
48
HO
OH
e
c
d
BnO
BnO
38
OBn
49
O
O
O
AcO
O
O
O
O
O
BnO
BnO
BnO
BnO
O
O
H2N
BnO
NH
BnO
OMe
OMe
OBn
OBn
OBn
OBn
50
51
Scheme 6. (a) 4-MeOC6H4CH2OCH2Cl, Mg, HgCl2, THF, 0◦C, then Ac2O; (b) DDQ, CH2Cl2/H2O; (c) Na, MeOH, 0◦C; (d) 40, DCC, DMAP,
CH2Cl2, then HOAc, DCC, DMAP; (e) HS(CH2)3SH, Et3N, MeOH.
form, ultimately, analogues of methyl β-acarviosin 4. A
related approach, involving the tethering of a cyclohexene
ring to a pyranose amine, certainly generated a lot of new
chemistry but was unsuccessful in the final intramolecular
alkylation step.
74.88 (C2,3), 74.48, 75.00, 75.60 (3 C, CH2Ph), 76.45 (C5), 79.14 (C4ꢀ),
82.96 (C6ꢀ), 84.24 (C5ꢀ), 101.52 (C1), 127.02 (C2ꢀ), 127.37–138.47
(C3ꢀ,Ph), 165.30, 165.98, 166.91 (3 C, C O). m/z (FAB) 1024.4290
•
[(M + H)+ requires 1024.4272].
Methyl 2,3,6-Tri-O-acetyl-4-deoxy-4-[(1ꢀR,4ꢀR,5ꢀS, 6ꢀS)-
4ꢀ,5ꢀ,6ꢀ-triacetoxy-3ꢀ-(acetoxymethyl)cyclohex-2ꢀ-enyl]amino-
β-D-glucoside 15
Experimental
Sodium (5 mg) was added to the amine 13 (285 mg, 0.278 mmol) in
MeOH (2 mL) and the mixture stirred at room temperature (3 h). The
solution was concentrated, and then the residue taken up in dry THF
(20 mL). NH3 was added to the solution at −78◦C until a precipitate
was just seen. Small pieces of Li (20 mg, 2.8 mmol) were then added to
the mixture with vigorous stirring, and the stirring continued at −78◦C
(1 h). NH4OAc (77 mg, 1.0 mmol) was added to the mixture and the sol-
vents were removed by evaporation. The resulting residue was treated
withAc2O (2 mL), pyridine (1 mL), and DMAP (20 mg) and the mixture
left to stir overnight. Normal workup (CH2Cl2) followed by flash chro-
matography(EtOAc/petrol, 1 : 1)gavetheheptaacetate15asacolourless
oil (133 mg, 74%), [α]D −65◦ (lit.[10] −68◦). Spectroscopic data (1H
and 13C NMR) were consistent with those reported.[10]
General experimental procedures have been given previously.[13]
[(1R,4R,5S,6S)-4,5,6-Tribenzyloxy-3-(benzyloxymethyl)cyclohex-
2-enyl]amine, Tetra-O-benzyl-1-epivalienamine 8
[(1R,4R,5S,6S)-4,5,6-Tribenzyloxy-3-(benzyloxymethyl)cyclohex-2-
enyl] azide[13] (3.3 g, 6.0 mmol), Na2S · 9H2O (2.75 g, 12.0 mmol), and
Et3N (200 µL) were heated in MeOH (50 mL) under reflux (3 h). Con-
centration of the mixture followed by a normal workup (CH2Cl2) and
flash chromatography (toluene/EtOAc/EtOH/Et3N, 60 : 35 : 4 : 1) gave
the amine 8 as a waxy solid (2.4 g, 76%). The 1H NMR (300 MHz)
spectrum was consistent with that reported.[25]
Methyl 2,3,6-Tri-O-benzoyl-4-deoxy-4-[(1ꢀR,4ꢀR,5ꢀS,6ꢀS)-
4ꢀ,5ꢀ,6ꢀ-tribenzyloxy-3ꢀ-(benzyloxymethyl)cyclohex-2ꢀ-enyl]-
amino-β-D-glucoside13
Methyl 4-Deoxy-4-[(1ꢀR,4ꢀR,5ꢀS,6ꢀS)-4ꢀ,5ꢀ,6ꢀ-trihydroxy-
3ꢀ-(hydroxymethyl)cyclohex-2ꢀ-enyl]amino-β-D-glucoside 10
The amine 8 (780 mg, 1.5 mmol) and the triflate 12[12] (465 mg,
0.73 mmol) in DMI (5 mL) were stirred at room temperature under nitro-
gen (4 days). Normal workup (Et2O) gave a pale yellow oil that was puri-
fied by flash chromatography. First to elute (EtOAc/petrol, 3 : 17) was
the alkene 14 as a colourless oil (96 mg, 27%), [α]D −87◦ (lit.[15] –86◦).
The 1H NMR (300 MHz) spectrum was consistent with that reported.[12]
Next to elute (EtOH/toluene/EtOAc, 1 : 6 : 3) was the amine 13 as
a colourless oil (305 mg, 41%) (Found C 74.0, H 6.0. C63H61NO12
requires C 73.9, H 6.0%). δH (500 MHz) 3.15–3.23 (m, H4,7ꢀ), 3.27 (m,
Sodium (5 mg) was added to the heptaacetate 15 (200 mg) in MeOH
(5 mL) and the mixture stirred at room temperature (1 h). The solution
was then neutralized (Amberlite IR-120, H+) and concentrated to give
the polyol 10 as a colourless glass (102 mg), [α]D –75◦ (H2O; lit.[10]
−75◦). Spectroscopic data (1H and 13C NMR) were consistent with
those reported.[10]
Methyl 2,6-Di-O-benzyl-3,4-O-thiocarbonyl-β-D-galactoside 19
A solution of the diol 17[24] (610 mg, 1.63 mmol) and Bu2SnO (850 mg,
3.42 mmol) in toluene (100 mL) was distilled over 3 h to a final vol-
ume of approximately 20 mL. The solution was then cooled to 0◦C and
O-phenyl chlorothioformate (280 µL, 2.12 mmol) was added dropwise
with stirring. The solution was allowed to warm to room temperature
and stirring continued (2 h). Concentration of the mixture followed by
flash chromatography (EtOAc/petrol, 3 : 7) of the residue gave the thio-
carbonate 19 as a colourless oil (510 mg, 75%), [α]D −26◦ (Found
H1ꢀ), 3.36 (dd, J1 ,6 8.5, J5 ,6 9.5, H6ꢀ), 3.44 (s, OMe), 3.63 (ddd, J4,5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.7, J5,6 5.3, 2.0, H5), 3.72 (dd, J4 ,5 7.5, H5 ), 3.76, 3.96 (ABq, J 11.7,
CH2Ph), 4.03 (br d, J 11.4, H7ꢀ), 4.12 (br d, H4ꢀ), 4.55, 4.68 (ABq, J
10.8, CH2Ph), 4.60 (d, J1,2 7.5, H1), 4.66 (dd, J6,6 11.8, H6), 4.73, 4.89
(ABq, J 11.1, CH2Ph), 4.84–4.95 (m, H6, CH2Ph), 5.41–5.45 (m, H2,
3), 5.91 (br s, H2ꢀ), 7.15–7.61 (m, Ph). δC (125.8 MHz) 56.70 (OMe),
58.25 (C4), 60.13 (C1ꢀ), 63.21 (C6), 70.55 (C7ꢀ), 71.67 (CH2Ph), 72.15,

238
M. J. McDonough et al.
C 63.6, H 5.9. C22H24O6S requires C 63.4, H 5.8%). δH (300 MHz)
3.48 (s, OMe), 3.63 (dd, J1,2 5.4, J2,3 4.3, H2), 3.78 (2 H, br d, J5,6
6.6, H6), 4.08 (dt, J4,5 1.8, H5), 4.56 (d, H1), 4.57, 4.91 (ABq, J 12.0,
CH2Ph), 4.68, 4.77 (ABq, J 11.8, CH2Ph), 4.92 (dd, J3,4 8.0, H3),
4.99 (dd, H4), 7.29–7.40 (10 H, m, Ph). δC (75.5 MHz) 56.13 (OMe),
68.06 (C6), 69.38, 75.73 (C2,5), 73.46, 73.58 (2 C, CH2Ph), 78.60,
80.25 (C3,4), 100.73 (C1), 127.63–137.29 (Ph), 190.79 (C S).[26]m/z
Methyl 2,6-Di-O-benzyl-3-deoxy-4-O-methanesulfonyl-
β-D-xylo-hexoside 23
Methanesulfonyl chloride (72 µL, 0.94 mmol) was added to the alcohol
22 (280 mg, 0.78 mmol) and pyridine (76 µL, 0.94 mmol) in CH2Cl2
(10 mL) at 0◦C. The mixture was then stirred at room temperature
(1 h). Normal workup (CH2Cl2) followed by flash chromatography
(EtOAc/petrol, 1 : 3) gave the mesylate 23 as a colourless oil (310 mg,
91%), [α]D −41◦ (Found C 60.5, H 6.5. C16H22O5 requires C 60.5,
H 6.5%). δH (300 MHz) 1.75 (ddd, J2,3 11.7, J3,3 14.5, J3,4 2.6, H3),
2.22 (ddd, J2,3 3.2, J3,4 5.1, H3), 2.88 (s, Me), 3.55–3.67 (3 H, m,
H2,6), 3.64 (s, OMe), 3.79 (ddd, J4,5 1.0, J5,6 ≈ J5,6 6.8, H5), 4.35
(d, J1,2 7.8, H1), 4.52, 4.57 (ABq, J 11.7, CH2Ph), 4.62, 4.83 (ABq,
J 11.7, CH2Ph), 4.94 (m, H4), 7.21–7.49 (10 H, m, Ph). δC (75.5 MHz)
34.70 (C3), 52.37 (Me), 56.60 (OMe), 67.84 (C6), 72.07, 74.49, 75.02
(C2,4,5), 73.01, 73.52 (2 C, CH2Ph), 105.98 (C1), 125.65–138.20 (Ph).
•
(FAB) 417.1349 [(M + H)+ requires 417.1372].
Methyl 4-O-Acetyl-2,6-di-O-benzyl-β-D-galactoside20
Trifluoroacetic acid (1 drop) was added to the diol 17 (1.00 g) and
CH3C(OEt)3 (1 mL) in CHCl3 (10 mL), and the solution stirred at
room temperature (5 min). MeCN (10 mL) and H2O (1 mL) were then
added and the mixture stirred vigorously (30 min). Concentration of
the mixture followed by flash chromatography (EtOAc/petrol, 3 : 7) of
the residue gave the acetate 20 as a colourless oil (1.06 g, 95%), [α]D
−9.0◦ (lit.[27] −9.5◦). The 1H NMR spectrum was consistent with that
reported.[27] δC (75.5 MHz) 20.77 (Me), 56.50 (OMe), 67.98, 68.25,
72.79, 72.83, 73.32, 74.88 (7 C, C2, 3, 4, 5, 6, CH2Ph), 106.07 (C1),
127.39–137.72 (Ph), 170.03 (C O).
Methyl 4-O-Acetyl-2-O-benzyl-6-deoxy-β-D-galactoside
Trifluoroacetic acid (1 drop) was added to the diol 26[9] (1.10 g) and
CH3C(OEt)3 (4 mL) in CHCl3 (15 mL) at room temperature and the
solution stirred (2 min). MeCN (40 mL) and H2O (1 mL) were then
added and the mixture was stirred vigorously (20 min). Concentration
of the mixture followed by flash chromatography (EtOAc/petrol, 1 : 1)
of the residue gave the title alcohol as a colourless oil (1.05 g, 83%),
[α]D +21◦ (Found C 61.9, H 7.1. C16H22O6 requires C 61.9, H 7.2%).
δH (300 MHz) 1.21 (3 H, d, J5,6 6.5, H6), 1.95 (s, Me), 3.48 (dd, J1,2
7.7, J2,3 9.7, H2), 3.58 (s, OMe), 3.69 (dq, J4,5 1.1, H5), 3.76 (dd, J3,4
3.6, H3), 4.29 (d, H1), 4.64, 4.97 (ABq, J 11.3, CH2Ph), 5.17 (dd, H4),
7.13–7.39 (m, Ph). δC (75.5 MHz) 16.21 (C6), 20.77 (Me), 50.02 (OMe),
69.17, 71.83, 72.11, 79.08 (C2, 3, 4, 5), 74.63 (CH2Ph), 104.54 (C1),
Methyl 4-O-Acetyl-2,6-di-O-benzyl-3-O-phenoxythiocarbonyl-
β-D-galactoside
O-Phenyl chlorothioformate (0.32 mL, 2.0 mmol) was added to the
acetate 20 (0.51 g, 1.2 mmol) and pyridine (0.3 mL) in CH2Cl2 (30 mL)
at room temperature and the mixture stirred (4 h). Normal workup
(CH2Cl2) followed by flash chromatography (EtOAc/petrol, 3 : 17) gave
the title thiocarbonate as a colourless oil (465 mg, 70%), [α]D +29◦
(Found C 65.2, H 5.7. C30H32O8S requires C 65.3, H 5.8%). δH
(300 MHz) 3.54 (dd, J5,6 6.7, J6,6 9.6, H6), 3.61 (dd, J5,6 6.7, H6),
3.62 (s, OMe), 3.81 (dd, J1,2 7.5, J2,3 9.9, H2), 3.89 (br t, H5), 4.47
(d, H1), 4.43, 4.59 (ABq, J 12.0, CH2Ph), 4.70, 4.93 (ABq, J 11.5,
CH2Ph), 5.55 (dd, J3,4 3.5, H3), 5.74 (dd, J4,5 0.9, H4), 7.09–7.45 (15
H, m, Ph). δC (75.5 MHz) 20.67 (Me), 57.39 (OMe), 66.95, 71.81, 77.09,
81.91 (C2, 3, 4, 5), 67.74, 73.63, 74.94 (3 C, C6, CH2Ph), 104.48 (C1),
121.87–138.26 (Ph), 153.49 (C S),[26] 169.95 (C O). m/z (FAB)
•
125.24–138.30 (Ph), 171.26 (C O). m/z (FAB) 311.1483 [(M + H)+
requires 311.1495].
Methyl 4-O-Acetyl-2-O-benzyl-6-deoxy-3-O-phenoxythiocarbonyl-
β-D-galactoside
O-Phenyl chlorothioformate (1.1 mL, 7.0 mmol) was added to the above
alcohol (1.46 g, 4.70 mmol) and pyridine (1 mL) in dry CH2Cl2 (30 mL)
at room temperature, and the mixture stirred (6 h). Normal workup
(CH2Cl2) followed by flash chromatography (EtOAc/petrol, 3 : 17) gave
the title thiocarbonate as colourless needles (1.60 g, 76%), mp 85–86◦C
(Et2O), [α]D +39◦ (Found C 61.8, H 5.9. C23H26O7S requires C 61.9,
H 5.9%). δH (300 MHz) 1.22 (3 H, d, J5,6 6.5 Hz, H6), 2.01 (s, Me),
3.59 (s, OMe), 3.81 (dd, J1,2 7.5, J2,3 9.9, H2), 3.89 (br t, H5), 4.47 (d,
H1), 4.63, 4.82 (ABq, J 12.0, CH2Ph), 5.54 (dd, J3,4 3.4, H3), 5.74 (d,
H4), 7.09–7.45 (10 H, m, Ph). δC (75.5 MHz) 16.76 (C6), 21.32 (Me),
57.01 (OMe), 67.56, 72.64, 77.45, 81.89 (C2, 3, 4, 5), 73.56 (CH2Ph),
105.43 (C1), 121.70–139.80 (Ph), 152.99 (C S),[26] 169.90 (C O).
•
553.1896 [(M + H)+ requires 553.1899].
Methyl 4-O-Acetyl-2,6-di-O-benzyl-3-deoxy-β-D-xylo-hexoside 21
Tributyltin hydride (0.53 ml, 1.9 mmol) was added to the above thiocar-
bonate (430 mg, 0.78 mmol) and azobisisobutyronitrile (AIBN; 20 mg)
in toluene (30 mL), and the mixture stirred at 70◦C (5 h). Concen-
tration of the mixture followed by normal workup (EtOAc) and flash
chromatography (EtOAc/petrol, 3 : 17) gave the d-xylo-hexoside 21 as
a colourless oil (220 mg, 71%), [α]D +64◦ (Found C 68.8, H 7.0.
C23H28O6 requires C 69.0, H 7.1%). δH (300 MHz) 1.70 (ddd, J2,3
11.8, J3,3 14.6, J3,4 3.1, H3), 1.93 (s, Me), 2.33 (ddd, J2,3 3.1, J3,4
5.1, H3), 3.48–3.60 (3 H, m, H2,6), 3.59 (s, OMe), 3.81 (dt, J4,5 1.3,
J5,6 ≈ J5,6 6.1, H5), 4.37 (d, J1,2 7.6, H1), 4.45, 4.58 (ABq, J 12.0,
CH2Ph), 4.67, 4.95 (ABq, J 11.7, CH2Ph), 5.11 (m, H4), 7.24–7.49
(10 H, m, Ph). δC (75.5 MHz) 20.76 (Me), 33.67 (C3), 56.48 (OMe),
67.98, 72.83, 74.88 (C2,4,5), 68.25 (C6), 72.79, 73.32 (2 C, CH2Ph),
106.07 (C1), 127.38–137.72 (Ph), 170.03 (C O). m/z (FAB) 399.1832
•
m/z (FAB) 447.1450 [(M + H)+ requires 447.1478].
Methyl 4-O-Acetyl-2-O-benzyl-3,6-dideoxy-β-D-xylo-hexoside
Tributyltin hydride (1.65 mL, 6.10 mmol) was added to the above thio-
carbonate (2.10 g, 4.70 mmol) and AIBN (30 mg) in toluene (30 mL),
and the mixture stirred at 70◦C (5 h). Concentration of the mixture fol-
lowed by flash chromatography (EtOAc/petrol, 3 : 17) of the residue
gave the title D-xylo-hexoside as colourless plates (1.13 g, 82%), mp
63–65◦C (Pr2i O/EtOAc), [α]D −32◦ (Found C 65.3, H 7.7. C16H22O5
requires C 65.3, H 7.5%). δH (300 MHz) 1.22 (3 H, d, J5,6 6.5, H6),
1.73 (ddd, J2,3 11.7, J3,3 14.6, J3,4 3.1, H3), 2.10 (s, Me), 2.28 (ddd,
J2,3 5.1, J3,4 3.1, H3), 3.54 (ddd, J1,2 7.6, H2), 3.59 (s, OMe), 3.73
(dq, J4,5 1.4, H5), 4.34 (d, H1), 4.63, 4.87 (ABq, J 11.8, CH2Ph), 4.94
(ddd, H4), 7.27–7.48 (m, Ph). δC (75.5 MHz) 16.22 (C6), 20.75 (Me),
33.99 (C3), 56.30 (OMe), 70.39, 71.74, 72.75 (C2, 4, 5), 72.65 (CH2Ph),
105.91 (C1), 127.31–138.38 (Ph), 170.35 (C O). m/z (FAB) 293.1387
•
[(M − H)+ requires 399.1808].
Methyl 2,6-Di-O-benzyl-3-deoxy-β-D-xylo-hexopyranoside 22
Sodium (4 mg) was added to the acetate 21 (160 mg) in dry MeOH
(8 mL) and the mixture stirred (1 h). The solution was neutralized
(Amberlite IR-120, H+), and then concentrated. Flash chromatography
(EtOAc/petrol, 1 : 3) of the residue gave the alcohol 22 as a colourless
solid (135 mg, 94%), [α]D +26◦ (lit.[28] +25◦). δH (300 MHz) 1.54 (ddd,
J2,3 11.6, J3,3 14.5, J3,4 3.0, H3), 2.22 (ddd, J2,3 3.2, J3,4 5.2, H3), 2.73
(br s, OH), 3.51 (s, OMe), 3.53–3.70 (4 H, m, H2, 5, 6), 3.90 (m, H4),
4.26 (d, J1,2 7.6, H1), 4.49, 4.53 (ABq, J 11.9, CH2Ph), 4.56, 4.76
(ABq, J 11.7, CH2Ph), 7.05–7.28 (10 H, m, Ph). δC (75.5 MHz) 36.46
(C3), 56.40 (OMe), 67.01, 72.90, 75.79 (C2, 4, 5), 69.86, 72.83, 73.56
(3 C, C6,CH2Ph), 106.50 (C1), 122.49–138.57 (Ph).
•
[(M + H)+ requires 293.1389].
Methyl 2-O-Benzyl-3,6-dideoxy-β-D-xylo-hexopyranoside 27
Sodium (5 mg) was added to the above d-xylo-hexoside (157 mg) in
dry MeOH (10 mL) and the mixture stirred (1 h). The solution was

Synthesis of Molecules Related to Methyl Acarviosin
239
neutralized (Amberlite IR-120, H+), and then concentrated. Flash chro-
matography (EtOAc/petrol, 1 : 3) of the residue gave the alcohol 27
as colourless needles (131 mg, 97%), mp 85◦C (Pr2i O/EtOAc; lit.[28]
84–85◦C), [α]D –24◦ (lit.[28] –23◦). δH (200 MHz) 1.36 (3 H, d, J5,6
10.5, H6), 1.63 (ddd, J2,3 11.1, J3,3 14.2, J3,4 3.2, H3), 1.95 (br s,
OH), 2.31 (ddd, J2,3 5.2, J3,4 3.1, H3), 3.52 (ddd, J1,2 7.9, H2), 3.57
(OMe), 3.61–3.72 (m, H4, 5), 4.29 (d, H1), 4.61, 4.81 (ABq, J 11.7,
CH2Ph), 7.29–7.37 (m, Ph).
and the residue was partitioned between MeCN and petrol. Concentra-
tion of the MeCN extract gave an oil that was purified by flash chro-
matography(EtOAc/petrol, 3 : 20to1 : 3)togivethe alcohol 35asaglass
(420 mg, 81%), [α]D −11◦ (Found C 65.3, H 5.9. C22H22O7 requires C
65.3, H 5.7%). δH (300 MHz) 1.33 (3 H, d, J5,6 6.3, H6), 3.56 (s, OMe),
4.23–4.34 (m, H5), 4.65 (m, H3), 4.94 (dd, J3,4 2.7, J4,5 9.7, H4), 4.99
(d, J1,2 8.1, H1), 5.09 (dd, J2,3 2.9, H2), 7.71–8.13 (10 H, m, Ph). δC
(75.5 MHz) 17.60 (C6), 56.88 (OMe), 67.52, 68.02, 72.16, 74.16 (C2,
3, 4, 5), 99.16 (C1), 128.42–133.46 (Ph), 165.15, 165.27 (2 C, C O).
Attempted Coupling of the Triflate 24 and the 1-Epivalienamine
Derivative 8
Methyl 2,4-Di-O-benzoyl-6-deoxy-3-O-trifluoromethanesulfonyl-
β-D-alloside 29
Trifluoromethanesulfonic anhydride (140 µL, 0.82 mmol) was added to
the alcohol 27 (170 mg, 0.68 mmol) and pyridine (70 µL, 0.85 mmol) in
CH2Cl2 (10 mL) at −15◦C.The mixture was stirred (20 min) at this tem-
perature until TLC analysis showed complete conversion of the starting
material into a less polar product, presumed to be the triflate 24. The
solution was then diluted with DMI (5 mL) and the CH2Cl2 removed
under vacuum, without heating, to give a colourless solution. The
1-epivalienamine derivative 8 (720 mg, 1.35 mmol) was added to this
solution and the mixture kept at room temperature (4 days). Normal
workup (Et2O) and flash chromatography (EtOAc/petrol, 3 : 17) gave
a colourless oil (140 mg) that appeared to be a mixture of alkenes (by
1H and 13C NMR spectroscopy).
Trifluoromethanesulfonic anhydride (190 µL, 1.6 mmol) was added to
the alcohol 35 (390 mg, 0.98 mmol) and pyridine (150 µL, 2.2 mmol)
in CH2Cl2 (5 mL) at −20◦C. The mixture was allowed to warm to
room temperature (2 h) and was then quenched with saturated NaHCO3
solution (5 mL). Normal workup (CH2Cl2) and flash chromatography
(EtOAc/petrol, 3 : 20 to 1 : 4) gave the triflate 29 as a glass (440 mg,
86%), [α]D −2.5◦. δH (300 MHz) 1.38 (3 H, d, J5,6 6.2, H6), 3.57 (s,
OMe), 4.18–4.30 (m, H5), 4.92 (d, J1,2 8.2, H1), 5.10 (dd, J3,4 2.3, J4,5
9.9, H4), 5.28 (dd, J2,3 2.3, H2), 5.64 (m, H3), 7.38–8.12 (10 H, m, Ph).
δC (75.5 MHz) 17.38 (Me), 57.1 (OMe), 67.92, 69.18, 71.02 (C2, 4, 5),
84.52 (C3), 98.90 (C1), 118.19 (q, JC,F 319, CF3), 128.20–138.83 (Ph),
164.87, 164.99 (2 C, C O). m/z (FAB) 519.0951 [(M + H)+• requires
519.0937].
Methyl 2-O-Benzoyl-4,6-O-benzylidene-β-D-alloside33
(a) Diethyl azodicarboxylate (630 µL, 4.00 mmol) was added to
the alcohol 31[16] (780 mg, 2.0 mmol), Ph3P (1.0 g, 4.0 mmol), and
ClCH2COOH (280 mg, 3.0 mmol) in C6H6 (50 mL) and THF (10 mL)
at 0◦C. The solution was then stirred at room temperature (7 h). The
solution was concentrated and the residue subjected to flash chromato-
graphy (EtOAc/petrol, 3 : 20 to 1 : 2) to give the chloroacetate 32 as an
oil that was carried through to the next step. δH (300 MHz) 3.56 (s, Me),
3.80–3.90 (m, H4,6), 4.02–4.08 (m, H5), 4.11, 4.17 (ABq, J 14.4,
CH2Cl), 4.45 (dd, J5,6 5.1, J6,6 10.5, H6), 4.92 (d, J1,2 8.2, H1), 5.18
(dd, J2,3 3.1, H2), 5.59 (s, CHPh), 5.98 (br t, J3,4 3.1, H3), 7.38–8.03 (10
H, m, Ph).
(b) The chloroacetate 32 was treated with thiourea (1.5 g, 20 mmol)
and 2,6-lutidine (230 µL, 2.0 mmol) in CH2Cl2/MeOH (40 mL, 1 : 1)
at reflux (12 h). Concentration of the mixture followed by flash chro-
matography (EtOAc/petrol, 3 : 20 to 1 : 3) of the residue gave the alcohol
33 (640 mg, 83% from 31) as fine needles, mp 177–178◦C (Pr2i O),
[α]D −58◦ (Found C 65.4, H 5.9. C22H22O7 requires C 65.3, H 5.7%).
δH (300 MHz) 3.54 (s, Me), 3.73 (dd, J3,4 2.4, J4,5 9.4, H4), 3.82
(dd, J5,6 ≈ J6,6 10.3, H6), 4.05–4.18 (m, H5), 4.44 (dd, J5,6 5.0, H6),
5.57–5.63 (m, H3), 5.01 (m, H1, 2), 5.61 (s, CHPh), 7.37–8.15 (10 H,
m, Ph). δC (75.5 MHz) 57.38 (Me), 63.19, 67.96, 72.23, 78.41 (C2, 3, 4,
5), 69.06 (C6), 100.03, 101.79 (C1, CHPh), 126.14–136.90 (Ph), 165.39
(C O).
Methyl 2,4-Di-O-benzoyl-3,6-dideoxy-3-[(1ꢀR,4ꢀR,5ꢀS, 6ꢀS)-4ꢀ,5ꢀ,6ꢀ-
tribenzyloxy-3ꢀ-(benzyloxymethyl)cyclohex-2ꢀ-enyl]amino-
β-D-glucoside 36
The triflate 29 (280 mg, 0.50 mmol) and the amine 8 (650 mg,
1.25 mmol) in DMI (1.5 mL) were stirred overnight. Normal
workup (Et2O) followed by flash chromatography (EtOAc/petrol/Et3N,
15 : 84 : 1 to 25 : 74 : 1) gave the amine 36 as a glass (250 mg, 55%),
[α]D −67◦ (Found C 74.3, H 6.2. C56H57NO10 requires C 74.4, H 6.4%).
δH (500 MHz) 1.32 (3 H, d, J5,6 6.2, H6), 3.17–3.28 (m, H1ꢀ), 3.32–
3.37 (m, H3), 3.42–3.56 (m, H6ꢀ,7ꢀ), 3.47 (s, OMe), 3.72–3.89 (m, H5),
ꢀ
ꢀ
3.92–4.03 (m, H5ꢀ), 4.07 (d, J7 ,7 11.7, H7 ), 4.16 (br d, J4 ,5 11.6, H4 ),
4.36–4.65 (9 H, m, H1, CH2Ph), 4.86–4.97 (m, H4), 5.10–5.25 (m, H2),
5.57 (br s, H2ꢀ), 6.95–8.02 (m, Ph). δC (125.8 MHz) 17.89 (C6), 56.61
(OMe), 58.46, 59.87, 71.16, 74.93, 76.46, 78.90, 81.88, 83.74 (C2, 3, 4,
5, 1ꢀ, 4ꢀ, 5ꢀ, 6ꢀ), 70.51, 71.72, 74.18, 74.38 (4 C, C7ꢀ, CH2Ph), 102.29
(C1), 127.44–138.34 (C2ꢀ,3ꢀ, Ph), 165.27, 165.63 (2 C, C O); the signal
for either C7ꢀ or a CH2Ph could not be located.
ꢀ
ꢀ
ꢀ
ꢀ
Methyl 2,4-Di-O-acetyl-3,6-dideoxy-3-[(1ꢀR,4ꢀR,5ꢀS,6ꢀS)-4ꢀ,5ꢀ,6ꢀ-tri-
acetoxy-3ꢀ-(acetoxymethyl)cyclohex-2ꢀ-enyl]amino-β-D-glucoside 37
A small piece of Na was added to the amine 36 (95 mg) in MeOH
(10 mL). The mixture was stirred overnight, after which time it was
concentrated. Small pieces of Na were added to a solution of the residue
in THF (10 mL) and NH3 (30 mL) at −78◦C until the solution remained
blue for 1 h. NH4Cl was added so as to dissipate this colour. Evapo-
ration of the solvents gave an off-white residue that was treated with
Ac2O/pyridine (6 mL, 1 : 2) for 5 h. Normal workup (CH2Cl2) followed
by flash chromatography (EtOAc/petrol, 4 : 6) gave the hexaacetate 37
as needles (37 mg, 59%), mp 158◦C (Pr2i O/EtOH), [α]D −67◦ (Found C
52.9, H 6.6. H26H37NO14 requires C 53.1, H 6.4%). δH (300 MHz) 1.20
(3 H, d, J5,6 6.2, H6), 1.98, 2.02, 2.04, 2.08, 2.10 (18 H, 5 s, Ac), 2.88
(dd, J2,3 ≈ J3,4 10.0, H3), 3.43 (s, OMe), 3.43–3.58 (m, H5,1ꢀ), 4.26 (d,
Methyl 2,4-Di-O-benzoyl-6-bromo-6-deoxy-β-D-alloside 34
A mixture of the alcohol 33 (290 mg, 0.75 mmol), NBS (150 mg,
0.82 mmol) and CaCO3 (80 mg, 0.82 mmol) in CCl4 (10 mL) was heated
under reflux (3 h), during which time the mixture changed from red to
yellow.The mixture was concentrated and subjected to a normal workup
(CH2Cl2) to give a residue that was purified by flash chromatogra-
phy (EtOAc/petrol, 1 : 4) to yield the bromide 34 (350 mg, 77%) as
cubes, mp 140–141◦C (Pr2i O/petrol), [α]D −14◦ (Found C 54.3, H 4.4.
C22H21BrO7 requires C 54.2, H, 4.6%). δH (300 MHz) 3.52 (dd, J5,6
7.0, J6,6 11.2, H6), 3.57 (s, Me), 3.61 (dd, J5,6 2.8, H6), 4.37–4.44 (m,
H5), 4.67–4.68 (m, H3), 5.03 (d, J1,2 7.8, H1), 5.07 (dd, J2,3 2.8, H2),
5.10 (dd, J3,4 2.7, J4,5 9.1, H4), 7.38–8.09 (10 H, m, Ph). δC (75.5 MHz)
32.03 (C6), 56.94 (Me), 67.68, 70.90, 71.58, 71.85 (C2, 3, 4, 5), 99.29
(C1), 128.38–133.64 (Ph), 165.04, 165.14 (2 C, C O).
ꢀ
ꢀ
ꢀ
J1,2 7.9, H1), 4.36 (d, J7 ,7 12.8, H7 ), 4.56 (dd, J4,5 9.7, H4), 4.62 (br s,
H7ꢀ), 4.74 (dd, H2), 4.91 (dd, J1 ,6 8.9, J5 ,6 10.7, H6ꢀ), 5.19 (dd, J4 ,5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
7.7, H5ꢀ), 5.68 (br s, H4ꢀ), 5.72 (br s, H2ꢀ). δC (75.5 MHz) 17.55 (C6),
20.63, 20.67, 20.71, 20.89, 20.97 (6 C, COMe), 56.42, 57.45, 59.98,
70.63, 71.21, 72.85, 74.06, 75.80 (C2, 3, 4, 5, 1ꢀ, 4ꢀ, 5ꢀ, 6ꢀ), 62.93 (C7ꢀ),
101.83 (C1), 120.24 (C2ꢀ), 130.66 (C3ꢀ), 169.98, 170.21, 170.32, 170.37
(6 C, C O).
Methyl 2,4-Di-O-benzoyl-6-deoxy-β-D-alloside 35
The bromide 34 (590 mg, 1.3 mmol) was treated with Bu3SnH (0.42 mL,
2.1 mmol) in toluene (7 mL, 70◦C, 3 h). The solution was concentrated

240
M. J. McDonough et al.
Methyl 3,6-Dideoxy-3-[(1ꢀR,4ꢀR,5ꢀS,6ꢀS)-4ꢀ,5ꢀ,6ꢀ-trihydroxy-
3ꢀ-(hydroxymethyl)cyclohex-2ꢀ-enyl]amino-β-D-glucoside 7
(C6), 74.77, 75.71 (2 C, CH2Ph), 74.88, 77.42, 82.24 (C2, 3, 4, 5),
104.52 (C1), 104.52–138.40 (Ph).
A small piece of Na was added to the hexaacetate 37 (120 mg) in MeOH
(5 mL) at 0◦C. The mixture was stirred at room temperature (1 h), and
then neutralized (Dowex 50W-X8, H+), filtered, and the filtrate concen-
trated to give a yellow oil. This oil was filtered through a Sephadex plug
(A-25, MeOH) to give, after evaporation, the polyol 7 as a colourless
oil (57 mg), [α]D −92◦ (MeOH). δH (600 MHz) 1.29 (d, J5,6 6.2, H6),
3.16–3.24 (m, H3,4), 3.38–3.44 (m, H5), 3.46 (dd, J1,2 7.6, J2,3 9.3,
Methyl 4-Azido-2,3-di-O-benzyl-4-deoxy-β-D-glucoside 45
The silyl ether 44 (1.93 g) was treated with aqueous AcOH (20 mL of
80%, 100◦C, 30 min). Concentration of the mixture gave an oil that
was subjected to flash chromatography (EtOAc/petrol, 2 : 3) to give the
alcohol 45 as needles (1.38 g, 91%), mp 92–93◦C (Pri O), [α]D +128◦
(Found C 63.6, H 6.2, N 10.3. C21H25N3O5 requires 2C 63.2, H 6.3, N
10.5%). δH (300 MHz) 3.11–3.18 (m, H5), 3.32–3.50 (m, H2,3,4), 3.52
(s, Me), 3.70 (dd, J5,6 4.5, J6,6 12.1, H6), 3.84 (dd, J5,6 2.6, H6), 4.28 (d,
J1,2 7.2, H1), 4.61–4.90 (4 H, m, CH2Ph), 7.14–7.48 (10 H, m, Ph). δC
(75.5 MHz) 57.30 (Me), 61.31, 74.19, 82.09, 82.68 (C2, 3, 4, 5), 62.12
(C6), 74.80, 75.57 (2 C, CH2Ph), 104.74 (C1), 127.76–138.16 (Ph).
H2), 3.53 (s, OMe), 3.58 (dd, J4 ,5 7.1, J5 ,6 9.3, H5ꢀ), 3.72 (dd, J5 ,6
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
8.1, H6ꢀ), 4.07–4.14 (m, H1ꢀ,4ꢀ), 4.18 (2 H, br s, H7ꢀ), 4.24 (d, H1), 5.87
(br s, H2ꢀ). δC (150 MHz) 17.86 (C6), 57.37, 61.51, 64.64, 72.71, 73.25,
73.40, 74.25, 76.96 (C2, 3, 4, 5, 1ꢀ, 4ꢀ, 5ꢀ, 6ꢀ), 105.42 (C1), 118.35 (C2ꢀ),
•
144.59 (C3ꢀ). m/z (FAB) 336.1675 [(M + H)+ requires 336.1658].
Methyl 4-Azido-2,3-di-O-benzyl-6-O-(2-carboxybenzoyl)-4-deoxy-
β-D-glucoside 40
Methyl 2,3-Di-O-benzyl-4,6-O-benzylidene-β-D-galactoside
Methyl β-d-galactopyranoside (7.2 g, 37 mmol) in DMF (50 mL) was
treated with benzaldehyde dimethyl acetal (7.6 g, 50 mmol) and CSA
(500 mg) under reduced pressure (60◦C, 2 h). Triethylamine (1 mL) was
added to the solution, which was then concentrated to half its volume.
This solution was diluted with more DMF (50 mL), and NaH (4.4 g, 60%
dispersion in mineral oil, 110 mmol) and BnBr (11.4 mL, 96 mmol) were
then added. The mixture was stirred (1 h) and then MeOH (2 mL) was
cautiously added. Concentration of the mixture followed by a normal
workup (CH2Cl2) gave an orange oil.This oil was purified by rapid silica
filtration (RSF) (EtOAc/petrol, 1 : 10 to 1 : 3) to give the title dibenzyl
etherascolourlesscrystals(11.6 g, 68%), mp112◦C(Et2O/petrol;lit.[29]
116.8◦).
The alcohol 45 (0.94 g, 2.4 mmol) was treated with phthalic anhydride
(1.73 g, 11.7 mmol) and DMAP (100 mg) in pyridine (10 mL, room
temperature, 18 h). Water (1 mL) was added to hydrolyze the excess
phthalic anhydride (TLC). Concentration of the mixture followed by
normal workup (CH2Cl2) and flash chromatography (MeOH/CHCl3,
1 : 9) gave the acid 40 as a colourless oil (1.52 g, 86%), [α]D +93◦.
δH (300 MHz) 3.40–3.59 (m, H2,3,4,5), 3.56 (s, Me), 4.32 (d, J1,2 7.5,
H1), 4.49 (dd, J5,6 4.5, J6,6 12.0, H6), 4.63 (dd, J5,6 2.2, H6), 4.67–4.96
(4 H, m, CH2Ph), 7.21–7.88 (14 H, m, Ar). δC (75.5 MHz) 57.34 (Me),
61.44, 71.94, 81.90, 82.67 (C2, 3, 4, 5), 64.47, 74.81, 75.67 (3 C, C6,
CH2Ph), 104.64 (C1), 127.78–138.16 (Ar), 167.56, 170.07 (2 C, C O).
•
m/z (FAB) 546.1884 [(M − H)+ requires 546.1876].
Methyl 2,3-Di-O-benzyl-6-O-(t-butyldimethylsilyl)-
β-D-galactopyranoside 42
(1R,4S,5R,6S)-1-C-(Acetoxymethyl)-4,5,6-
tribenzyloxycyclohex-2-en-1-ol 48
The above dibenzyl ether (5.6 g, 12 mmol) was treated with aqueous
AcOH (70 mL of 80%; 100◦C, 30 min). Concentration of the mixture
followed by RSF (EtOAc/petrol, 1 : 1 to EtOAc) then gave what was
presumed to be methyl 2,3-di-O-benzyl-β-d-galactopyranoside 41 as
a colourless oil. This oil was treated with t-butyldimethylsilyl chloride
(2.08 g, 13.3 mmol) and imidazole (1.03 g, 15.1 mmol) in DMF (20 mL)
for 1 day. MeOH (1 mL) was added and the mixture was stirred (20 min).
Concentration of the mixture followed by normal workup (CH2Cl2) and
flash chromatography (EtOAc/petrol, 1 : 9 to 1 : 4) gave the silyl ether 42
as an oil (4.46 g, 75%), [α]D −28◦ (Found C 67.2, H 8.3. C28H40O6Si
requiresC67.2, H8.0%). δH (300 MHz)0.11(s, SiMe2), 0.92(s, CMe3),
3.38 (m, H5), 3.48 (dd, J2,3 3.3, J3,4 9.4, H3), 3.55 (s, OMe), 3.64 (dd,
J1,2 7.7, H2), 3.82 (dd, J5,6 5.5, J6,6 10.2, H6), 3.90 (dd, J5,6 6.4, H6),
3.99 (m, H4), 4.28 (d, H1), 4.71–4.93 (4 H, m, CH2Ph), 7.22–7.48 (10 H,
m, Ph). δC (75.5 MHz) −5.46 (SiMe2), 18.24 (CMe3), 25.81 (CMe3),
56.74 (OMe), 62.18 (C6), 66.44, 74.25, 79.06, 80.68 (C2, 3, 4, 5), 72.35,
75.03 (2 C, CH2Ph), 104.68 (C1), 127.48–138.70 (Ph).
(a) Sulfuryl chloride (920 µL, 11.4 mmol) was added dropwise to a solu-
tion of 4-methoxybenzyl methylthiomethyl ether (4.15 g, 22.9 mmol)
in CH2Cl2 (20 mL) at −78◦C. After 30 min, TLC analysis showed
complete consumption of the 4-methoxybenzyl methylthiomethyl ether.
The solution was concentrated to give a colourless oil, presumably
chloromethyl 4-methoxybenzyl ether. This oil in THF (20 mL) was
treated with Mg (680 mg, 28 mmol) and HgCl2 (50 mg, 0◦C, 1 h). The
enone 46[27] (990 mg, 2.4 mmol) was added, and stirring continued
(30 min, 0◦C). Ac2O (3.0 mL, 34 mmol) was then added and the mix-
ture stirred (10 min). The mixture was poured into saturated NaHCO3
solution and then stirred and filtered (Celite). Normal workup (CH2Cl2)
of the filtrate followed by flash chromatography (EtOAc/petrol, 3 : 17)
gave an inseparable mixture of, presumably, the acetate 47 and aromatic
impurities (1H NMR) as a colourless oil.
(b) The above mixture was treated with DDQ (900 mg, 5.6 mmol)
in CH2Cl2/water (20 mL, 95 : 5; 2 h). Saturated NaHCO3 solution
(100 mL) was added and the organic layer was separated. The aqueous
layer was extracted with more CH2Cl2 (50 mL). The combined organic
extracts were dried, filtered, and concentrated to give a dark oil. This oil
was purified by flash chromatography (EtOAc/petrol, 1 : 3) to give the
acetate 48 as a colourless oil (720 mg, 62%), [α]D +24◦ (Found C 74.0,
H 6.6. C30H32O6 requires C 73.8, H 6.6%). δH (300 MHz) 2.04 (s, Ac),
3.72 (d, J5,6 9.8, H6), 3.92 (dd, J4,5 6.6, H5), 4.11 (d, J7,7 11.4, H7),
4.17 (m, H4), 4.47 (d, H7), 4.62–4.93 (6 H, m, CH2Ph), 5.61 (dd, J2,3
10.4, J2,4 2.0, H2), 5.78 (dd, J3,4 2.5, H3), 7.21–7.47 (15 H, m, Ar). δC
(75.5 MHz) 20.94 (Me), 67.65, 72.16, 74.96, 75.49 (4 C, C7, CH2Ph),
74.60 (C1), 79.15, 81.34, 83.65 (C4, 5, 6), 127.74–138.35 (C2, 3, Ar),
171.08 (C O).
Methyl 4-Azido-2,3-di-O-benzyl-6-O-(t-butyldimethylsilyl)-
4-deoxy-β-D-glucoside 44
Trifluoromethanesulfonic anhydride (0.82 mL, 5.8 mmol) was added to
the silyl ether 42 (1.9 g, 3.9 mmol) and pyridine (1.0 mL) in CH2Cl2
(20 mL), and the mixture stirred (2 h, 0◦C). The addition of satu-
rated NaHCO3 solution followed by a normal workup (CH2Cl2) gave,
presumably, methyl 2,3-di-O-benzyl-6-O-(t-butyldimethylsilyl)-4-O-
(trifluoromethanesulfonyl)-β-d-galactoside 43 as a yellow oil. This oil
was treated with NaN3 (0.65 g, 12 mmol) in DMF (1 h, 80◦). Concen-
tration of the mixture and normal workup (CH2Cl2) gave an oil that
was subjected to flash chromatography (EtOAc/petrol, 1 : 9) to give the
azide 44 as an oil (1.93 g, 93%), [α]D +87◦ (Found C 64.2, H 7.6,
N 7.9. C28H39N3O5 requires C 64.0, H 7.5, N 8.0%). δH (300 MHz)
0.10 (s, SiMe2), 0.92 (s, CMe3), 3.12–3.16 (m, J4,5 9.5, H5), 3.40
(dd, J1,2 ≈ J2,3 7.9, H2), 3.46–3.62 (m, H3,4), 3.54 (s, OMe), 3.84 (dd,
J5,6 3.9, J6,6 11.5, H6), 3.98 (dd, J5,6 2.0, H6), 4.27 (d, H1), 4.70–5.05
(4 H, m, CH2Ph), 7.28–7.43 (10 H, m, Ph). δC (75.5 MHz) −5.23, −5.46
(SiMe2), 18.35 (CMe3), 25.87 (CMe3), 56.48 (OMe), 61.62 (C4), 62.66
(1R,4S,5R,6S)-4,5,6-Tribenzyloxy-1-C-(hydroxymethyl)cyclohex-
2-en-1-ol 49
A small piece of Na was added to the acetate 48 (540 mg) in MeOH
(5 mL, 0◦C) and the mixture was stirred (room temperature, 1 h), before
being neutralized (Dowex 50W-X8, H+) and filtered. The filtrate was
concentrated to give a yellow oil. This oil was filtered through a plug
of silica gel (EtOAc/petrol, 1 : 1) to give the diol 49 as a colourless oil

Synthesis of Molecules Related to Methyl Acarviosin
241
(450 mg), [α]D +48◦.The 1H NMR (200 MHz) spectrum was consistent
[2] D. D. Schmidt, W. Frommer, B. Junge, L. Müller, W. Wingender,
E. Truscheit, D. Schäfer, Naturwissenschaften 1977, 64, 535.
[3] J. C. McAuliffe, O. Hindsgaul, Chem. Ind. 1997, 170.
[4] W. Puls, U. Keup, H. P. Krause, G. Thomas, F. Hoffmeister,
Naturwissenschaften 1977, 64, 536.
[5] S. Ogawa, K. Yasuda, T. Takagaki, Y. Iwasawa, T. Suami, Carbo-
hydr. Res. 1985, 141, 329. doi:10.1016/S0008-6215(00)90465-8
[6] R. V. Stick, D. M. G. Tilbrook, S. J. Williams, Aust. J. Chem.
1999, 52, 895. doi:10.1071/CH99031
[7] R. V. Stick, D. M. G. Tilbrook, S. J. Williams, Aust. J. Chem.
1999, 52, 885. doi:10.1071/CH99030
[8] J. K. Fairweather, R. V. Stick, D. M. G. Tilbrook, unpublished
results.
[9] J. C. McAuliffe, R. V. Stick, D. M. G. Tilbrook, A. G. Watts,
Aust. J. Chem. 1998, 51, 91. doi:10.1071/CH97153
[10] J. C. McAuliffe, R. V. Stick, Aust. J. Chem. 1997, 50, 219.
doi:10.1071/CH96155
[11] J. C. McAuliffe, R. V. Stick, Aust. J. Chem. 1997, 50, 225.
doi:10.1071/CH96156
[12] V. Moreau, J. C. Norrild, H. Driguez, Carbohydr. Res. 1997,
300, 271. doi:10.1016/S0008-6215(97)00046-3
[13] J. C. McAuliffe, R. V. Stick, Aust. J. Chem. 1997, 50, 193.
doi:10.1071/CH96151
[14] Y. Shibata, Y. Kosuge, S. Ogawa, Carbohydr. Res. 1990, 199,
37. doi:10.1016/0008-6215(90)84091-8
with that reported.[30]
{Methyl 4-Azido-2,3-di-O-benzyl-4-deoxy-6-(hydrogen benzene-
1,2- dicarboxylate)-β-D-glucoside, Ester with C-[(1ꢀR,4ꢀS,5ꢀR,6ꢀS)-
1ꢀ-Acetoxy-4ꢀ,5ꢀ,6ꢀ-tribenzyloxycyclohex-2ꢀ-enyl]methanol} 38
The diol 49 (230 mg, 0.48 mmol) and the acid 40 (330 mg, 0.60 mmol)
were treated with DCC (125 mg, 0.60 mmol) and DMAP (60 mg,
0.48 mmol) in CH2Cl2 (3 mL). After 2 h, TLC analysis indicated the
complete consumption of the diol. Acetic acid (140 µL, 2.4 mmol) and
more DCC (500 mg, 2.5 mmol) and DMAP (300 mg, 2.5 mmol) were
then added and the solution was left for a further 5 h. Pre-adsorbtion
onto silica gel, followed by purification on a short column of silica
gel (EtOAc/toluene, 1 : 9), gave an oil that was further purified by flash
chromatography (EtOAc/petrol, 1 : 4) to give the azide 38 as a colourless
oil (370 mg, 74%), [α]D +77◦. δH (600 MHz) 1.84 (s, Ac), 3.38–3.42
(m, H5), 3.44 (dd, J1,2 7.9, J2,3 8.6, H2), 3.50–3.57 (m, H3,4), 3.53
(s, OMe), 3.97 (dd, J4 ,5 7.7, J5 ,6 10.4, H5ꢀ), 4.28 (d, H1), 4.33 (ddd,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J2 ,4 ≈ J3 ,4 2.3, H4 ), 4.51 (dd, J5,6 5.0, J6,6 12.0, H6), 4.55, 4.87 (2 H,
ABq, J 11.3, H7ꢀ), 4.57 (d, H6ꢀ), 4.58 (dd, J5,6 2.2, H6), 4.64–4.93 (10
H, m, CH2Ph), 5.74 (dd, J2 ,3 10.5, H2ꢀ), 5.89 (dd, H3ꢀ), 7.25–7.78 (m,
Ar). δC (150 MHz) 21.86 (COMe), 57.15 (OMe), 61.69 (C4), 64.48 (C6),
66.60 (C7ꢀ), 71.95 (C5), 72.17, 74.76, 75.36, 75.61, 75.62 (5 C, CH2Ph),
79.79 (C6ꢀ), 80.26 (C4ꢀ), 81.97 (C2), 82.76 (C3), 82.88 (C5ꢀ), 83.66
(C1ꢀ), 104.63 (C1), 127.52–138.34 (C2ꢀ, 3ꢀ,Ar), 166.50, 167.25, 169.77
ꢀ
ꢀ
[15] S. Hanessian, J.-M. Vatèle, Tetrahedron Lett. 1981, 22, 3579.
doi:10.1016/S0040-4039(01)81963-8
•
(3 C, C O). m/z (FAB) 1018.4028 [(M + H)+ requires 1018.4126].
[16] S. Kim, H. Chang, W. J. Kim, J. Org. Chem. 1985, 50, 1751.
[17] H. Günther, NMR Spectroscopy: Basic Principles, Concepts, and
Applications in Chemistry 1995 (Wiley & Sons: Chichester, UK).
[18] G. B. Fincher, M. Hrmova, J. M. Macdonald, M. J. McDonough,
R. V. Stick, unpublished results.
[19] G. Lemanski, T. Ziegler, Helv. Chim. Acta 2000, 83, 2655. doi:
10.1002/1522-2675(20001004)83:10<2655::AID-HLCA2655>
3.0.CO;2-U
[20] K.-H. Jung, M. Müller, R. R. Schmidt, Chem. Rev. 2000, 100,
4423. doi:10.1021/CR990307K
[21] T. M. Tagmose, M. Bols, Chem. Eur. J. 1997, 3, 453.
[22] J. H. Jones, D. W. Thomas, R. M. Thomas, M. E. Wood, Synth.
Commun. 1986, 16, 1607.
[23] L.-L. Gundersen, T. Benneche, K. Undheim, Acta Chem. Scand.
A 1989, 43, 706.
[24] T. Benneche, P. Strande, K. Undheim, Synthesis 1983, 762.
doi:10.1055/S-1983-30506
[25] F. Nicotra, L. Panza, F. Ronchetti, G. Russo, Gazz. Chim. Ital.
1989, 119, 577.
[26] C. Copeland, R. J. Conway, J. J. Patroni, R. V. Stick, Aust. J.
Chem. 1981, 34, 555.
{Methyl 4-Amino-2,3-di-O-benzyl-4-deoxy-6-(hydrogen benzene-
1,2-dicarboxylate)-β-D-glucoside, Ester with C-[(1ꢀR,4ꢀS,5ꢀR,6ꢀS)-
1ꢀ-Acetoxy-4ꢀ5ꢀ6ꢀ-tribenzyloxycyclohex-2ꢀ-enyl]methanol} 50
The azide 38 (100 mg, 0.10 mmol) was treated with propane-1,3-dithiol
(100 µL, 1.0 mmol) and Et3N (140 µL, 1.0 mmol) in MeOH (5 mL,
8 h). The solution was concentrated to give an orange oil, which was
purified by flash chromatography (EtOAc/petrol/Et3N, 20 : 79 : 1, then
EtOAc/petrol/EtOH/Et3N, 40 : 54 : 5 : 1)togivetheamine50asacolour-
less oil (80 mg, 82%), [α]D +23◦. δH (300 MHz) 1.84 (s, Ac), 2.85 (dd,
J3,4 ≈ J4,5 9.6, H4), 3.30 (dd, J2,3 9.6, H3), 3.36–3.42 (m, H5), 3.43 (dd,
J1,2 7.7, H2), 3.55 (s, OMe), 3.99 (dd, J4 ,5 7.7, J5 ,6 10.4, H5ꢀ), 4.32
(d, H1), 4.27–4.34 (m, H4ꢀ), 4.48–4.99 (15 H, m, H6, 6ꢀ, 7ꢀ, CH2Ph),
ꢀ
ꢀ
ꢀ
ꢀ
5.73 (dd, J2 ,3 10.4, J2 ,4 2.2, H2ꢀ), 5.89 (dd, J3 ,4 2.1 Hz, H3ꢀ),
7.25–7.78 (m, Ar). δC (75.5 MHz) 21.84 (COMe), 52.74 (C4), 57.05
(OMe), 64.93, 66.57 (C6, 7ꢀ), 72.25, 74.55, 75.22, 75.36, 75.57
(5 C, CH2Ph), 74.77, 79.76, 80.16, 82.43, 82.89, 89.83 (C2, 3, 5, 4ꢀ,
5ꢀ, 6ꢀ), 83.58 (C1ꢀ), 105.21 (C1), 127.13–138.23 (C2ꢀ, 3ꢀ, Ar), 166.55,
167.67, 169.76 (3 C, C O). m/z (FAB) 992.4227 [(M + H)+• requires
992.4221].
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Acknowledgments
[27] H. Paulsen, T. Hasenkamp, M. Paal, Carbohydr. Res. 1985, 144,
45. doi:10.1016/0008-6215(85)85005-9
[28] K. Eklind, P. J. Garegg, B. Gotthammar, Acta Chem. Scand. B
1976, 30, 300.
We thank James Macdonald for the inhibition results with 7,
and the Australian Research Council for financial support.
[29] S. Ogawa, K. Sato, Y. Miyamoto, J. Chem. Soc., Perkin Trans.
1 1993, 691.
[30] H. Paulsen, D. Schnell, Chem. Ber. 1981, 114, 333.
References
[1] E. Truscheit, W. Frommer, B. Junge, L. Müller, D. D. Schmidt,
W. Wingender, Angew. Chem., Int. Ed. Engl. 1981, 20, 744.