(1S,2S,3R,6R)-6-aminocyclohex-4-ene-1,2,3-triol (=(-)-conduramine B-1) is a selective inhibitor of α-mannosidases. Its inhibitory activity is enhanced by N-benzylation

Article abstract of DOI:10.1002/hlca.200590220

(-)- and (+)-Conduramine B-1 ((-)- and (+)-5, resp.) have been derived from (+)- and (-)-7-oxabicyclo[2.2.1]hept-5-en-2-one ('naked sugars' of the first generation). Although (-)-5 imitates the structure of β-glucosides, it does not inhibit β-glucosidases

Full text of DOI:10.1002/hlca.200590220

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(1S,2S,3R,6R)-6-Aminocyclohex-4-ene-1,2,3-triol (=(ꢀ)-Conduramine B-1)
Is a Selective Inhibitor of a-Mannosidases. Its Inhibitory Activity Is Enhanced
by N-Benzylation
by Robert Łysek, Catherine Schütz, and Pierre Vogel*
Laboratoire de glycochimie et de synthèse asymétrique, Ecole Polytechnique Fédérale de Lausanne, BCH,
CH-1015 Lausanne-Dorigny
(tel. 0216939371; fax 0216939375; e-mail: pierre.vogel@epfl.ch)
(ꢀ)- and (+)-Conduramine B-1 ((ꢀ)- and (+)-5, resp.) have been derived from (+)- and (ꢀ)-7-oxabicy-
clo[2.2.1]hept-5-en-2-one (‘naked sugars’ of the first generation). Although (ꢀ)-5 imitates the structure of b-glu-
cosides, it does not inhibit b-glucosidases but inhibits a-mannosidases selectively. N-Benzylation of (ꢀ)-5
improves the potency of conduramine B-1 as a-mannosidase inhibitor and also generates compounds inhibiting
b-glucosidases. For instance, (ꢀ)-N-benzyl-conduramine B-1 ((ꢀ)-19a) is a competitive inhibitor of b-glucosi-
dase from almonds (IC50 =32 m
(IC50 =171 m ) and from almonds (IC50 =225 m
is a good inhibitor of a-mannosidase from jack beans (IC50 =29 m
cosidase from almonds (IC50 =32 m , Ki =7.8 m ) (Table 1).
M
, Ki =10 m
M
) and a weak inhibitor of a-mannosidases from jack bean
) whereas (ꢀ)-N-(4-phenylbenzyl)conduramine B-1 ((ꢀ)-19g)
, Ki =4.8 m ) and a weaker inhibitor of b-glu-
M
M
M
M
M
M
Introduction. – Aberrant glycosylation of glycoproteins and glycolipids was
reported to be one of the molecular changes that accompany malignant transforma-
tions [1]. As both catabolic and processing glycosidases are involved in the transforma-
tion of normal cells to cancer cells and in tumor-cell invasion and migration [2], it has
been proposed that the specific inhibition of a-mannosidases involved in the addition of
N-linked carbohydrates to glycoproteins may provide new anticancer strategy [3].
Swainsonine (1), a natural inhibitor of Golgi a-mannosidase II, which contains a 4-
amino-4-deoxy-mannofuranose moiety [4], decreases the growth of solid tumors and
hematological malignancies [5]. Subcutaneous administration of swainsonine com-
pletely inhibited the growth and the formation of lung metastases of sarcoma [6]. Nev-
ertheless, the toxicity observed for this alkaloid as well as the undesired co-inhibition of
lysosomal fucosidases resulted in the search for new, more selective a-mannosidases
inhibitors [7]. Some analogues of swainsonine as well as simpler derivatives have
shown interesting inhibitory properties [8–10]. Our group previously reported that
3,4-dihydroxypyrrolidin-2-yl derivatives such as 2–4 (Fig. 1) are selective and compet-
itive inhibitors of a-mannosidase from jack beans [11–13]. This enzyme is a useful
model for mammalian a-mannosidases such as Golgi a-mannosidase II [14]. We
have found that esters of 4 inhibit the growth of human glioblastoma and melanoma
cells [13].
Recently we reported that (ꢀ)-conduramine B-1 ((ꢀ)-5); Fig. 2) does not inhibit b-
glucosidases and b-xylosidases although this compound mimicks b-glycopyranosides
and b-xylopyranosides [15]. We found, however, that N-benzyl derivatives of (ꢀ)-5
are good competitive inhibitors of these enzymes. The most potent b-glucosidase inhib-
© 2005 Verlag Helvetica Chimica Acta AG, Zürich

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Fig. 1. Examples of a-mannosidase inhibitors from jack bean
itor, (ꢀ)-N-(4-phenylbenzyl)conduramine B-1 (=(ꢀ)-N-[(1,1’-biphenyl]-4-ylmethyl]-
conduramine B-1; 6ꢁ19g) was also the most selective inhibitor in assays involving a-
glucosidases from rice and yeast, amyloglucosidase form Aspergillus niger and Rhizo-
pus mold, b-glucosidases from almonds and Caldocellum saccharolyticum and b-xylo-
sidase form Aspergillus niger [15]. Thus 6 and other N-benzyl derivatives of (ꢀ)-con-
duramine B-1 should be tested for their ability to act as chemical chaperones and for
their therapeutic potential for the Gaucher’s disease [16]. With a structure having
one hydroxymethyl group less than b-valienamine derivative 7 [17], which was
shown to act as a chemical chaperone [18] accelerating transport and maturation of
F2-3I mutant b-glucosidase [17], 6 and analogues are expected to be more hydrophobic
than 7 and thus to have a better chance to become oral active drugs in the treatment of
Gaucher’s disease.
Fig. 2. (ꢀ)-Conduramine B-1 and analogs
Recently, Ogawa and co-workers [19] reported that b-valienamine (8), as (ꢀ)-con-
duramine B ((ꢀ)-5), does not inhibit b-glucosidase from almonds but is a weak inhib-
itor (IC50 =190 m ) of a-mannosidase from jack beans. Interestingly, 1-deoxymannono-
M
jirimycin (9; Fig. 2) is not a much better inhibitor (IC50 =150 m ) of this enzyme than 8.
M
Inspired by these unexpected results, we now assayed (ꢀ)-conduramine B-1 toward gly-
cosidases and found that it inhibits a-mannosidases from jack beans and from almonds,
whereas it does not inhibit any of the other glycosidases (a- -fucosidase, a-galactosi-
L
dases, b-galactosidases, a-glucosidases, amyloglucosidases, b-glucosidases, b-mannosi-
dase, b-xylosidase, a-N-acetylgalactosaminidases, b-N-acetyl glucosaminidases). With
the hope to enhance the inhibitory activity of (ꢀ)-conduramine B-1, we prepared sev-
eral N-substituted derivatives (some of them have been presented in our preliminary
communication [15]) and assayed them toward 21 commercially available glycosidases.
As for the inhibition of b-glucosidases from almonds and from Saccharomyces cer-
evisiae, (ꢀ)-N-(4-phenylbenzyl)conduramine B-1 presented the highest inhibitory

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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
activity toward a-mannosidases from jack bean (Ki =4.8 m
almonds (Ki =16 m , IC50 =32 m ). Expectedly, (+)-conduramine B-1 and its N-substi-
tuted derivatives did not inhibit these enzymes at 1 m concentration.
M
, IC50 =29 m
M
) and from
M
M
M
Results. – (ꢀ)-Conduramine B-1 ((ꢀ)-5) was derived from (+)-7-oxabicyclo[2.2.1]-
hept-5-en-2-one [20] ((+)-10), a naked sugar of the first generation [21], applying
chemistry reported for the synthesis of (ꢀ)-conduritol F [22] (Scheme 1). Reduction of
cyclohexenone (ꢀ)-13 (obtained via (+)-11 and (+)-12) [22] with NaBH4/CeCl3 ·7 H2O
in MeOH (08, 3 h) gave a 2.5 :1 mixture of conduritol F and conduritol B derivatives
(ꢀ)-14 and (ꢀ)-15, respectively, in 98% yield. Treatment of this mixture with phthal-
imide, diethyl azodicarboxylate (=diethyl diazenedicarboxylate; DEAD) and Ph3P
(all to the amount of 1.25 equiv.) [23] in dry toluene (08, 12 h) provided a 3.8 :1 mixture
of N-substituted phthalimides (ꢀ)-16 and (ꢀ)-17 (87%) that were separated by flash
chromatography (silica gel). Under acidic conditions (1% TsOH in MeOH, 658, 3 h),
(ꢀ)-16 was converted into triol (ꢀ)-18 in 95% yield. Transaminolysis of (ꢀ)-18 with
MeNH2 (41% in H2O, 208, 20 min) and purification by ion exchange (Dowex-50W
(H+ form), 2
yield (Scheme 1).
N
NH4OH/H2O) provided pure (ꢀ)-conduramine B-1 ((ꢀ)-5) in 95%
Scheme 1. Synthesis of (ꢀ)-Conduramine B-1 ((ꢀ)-5

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The N-substituted derivatives (ꢀ)-19a–i were prepared by standard reductive ami-
nation of the corresponding aldehyde [11] (Scheme 2). Starting with ‘naked sugar’ (ꢀ)-
7-oxabicyclo[2.2.1]hept-5-en-2-one ((ꢀ)-10 [20]), (+)-conduramine B-1 ((+)-5) and its
derivatives (+)-ent-19a–i were prepared with the same ease. As the latter compounds
had none or only very weak inhibitory activities on the glycosidases assayed (see
below), we continued our exploration of the effect of N-substitution of conduramine
B-1 on its glycosidase inhibitory activities by preparing racemic (ꢂ)-5 and its N-sub-
stituted derivatives (ꢂ)-19j–z and N,N-disubstituted derivatives (ꢂ)-20aa–dd
(Scheme 2).
To learn about the importance of the conformation of the aminotriol unit of (ꢀ)-
and (+)-conduramine B-1 on their glycosidase inhibitory activities, we prepared (ꢂ)-
(1RS,2SR,3SR,4RS)-4-aminocyclohexane-1,2,3-triol (=(ꢂ)-dihydroconduramine B-1;
(ꢂ)-211)) by catalytical hydrogenation of (ꢂ)-5 (Scheme 3).
Aldehydes 23n–p and 23t,u used in the syntheses of (ꢂ)-19n–p and (ꢂ)-19t,u were
prepared by nucleophilic displacement of 4-fluorobenzaldehyde with the correspond-
ing 4-substituted or fused phenols 22 following known procedures [25] (Scheme 4).
Aldehyde 23q was obtained in a similar way via enol ether 24.
Reduction of (ꢂ)-19q by NaBH4 (MeOH, 258) gave a 1:1 mixture of diastereoiso-
mers (ꢂ)-19r (see above, Scheme 2) in 89% yield. The synthesis of (ꢂ)-19s started with
the reductive amination of aldehyde 24 with (ꢂ)-5 and NaBH(OAc)3 (258, MeOH).
Staying overnight in dry MeOH, the intermediate aryl enol ether was completely meth-
anolyzed into dimethyl acetal (ꢂ)-19s (60% yield).
To evaluate the role of the aromatic appendage of conduramine B-1 derivatives
(ꢂ)-19p,t,u, we prepared the simpler secondary amines 26–30 from aldehydes
23p,t,u and primary amines 25 (Scheme 4) and submitted them to the enzymatic assays
in parallel with the testing of (ꢀ)- and (+)-conduramine B-1 and their N-substituted
derivatives (see below).
All compounds shown in the Table were tested for their inhibitory activity toward
21 commercially available glycosidases [26]. At 1 m concentration they did not inhibit
M
a-fucosidase from bovine epididymis, a-galactosidase from Escherichia coli, b-galacto-
sidase from E. coli, from Aspergillus niger, and from Aspergillus orizae, a-glucosidase
form yeast and from rice, b-mannosidase from Helix pomatia, a-N-acetylgalactosami-
nidase from chicken liver and b-N-acetylglucosaminidase from jack bean and from
bovine epididymis A and B. Compounds 26 and 27 showed ca. 50% inhibition of a-
fucosidase from bovine epididymis and 29 62% inhibition of a-glucosidase from
yeast at 1 m
L-
M
concentration. The phthalimide (ꢂ)-18 was also assayed and shown to
be a weak inhibitor of b-mannosidase from Helix pomatia (37% inhibition at 1 mM con-
centration). The results for nine other enzymes are summarized in the Table.
Discussion. – The most striking finding is that (ꢀ)-conduramine B-1 ((ꢀ)-5), that
imitates b-glucopyranosides, is not recognized by b-glucosidases from almonds and
from Saccharomyces cerevisiae but inhibits a-mannosidases from jack beans and
from almonds. Interestingly, (+)-conduramine B-1 ((+)-5) and dihydroconduramine
1
)
Dihydroconduramine B-1 has not been described yet. For other stereoisomers, see [24].

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Scheme 2. Synthesis of N-Substituted Conduramine B-1 Derivatives

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Scheme 3. Synthesis of (ꢂ)-Dihydrocondramine B-1 ((ꢂ)-21)
B-1 ((ꢂ)-21) do not inhibit any of the enzymes assayed, except for a weak (57% at
1 mM) inhibition of b-xylosidase from Aspergillus niger by (ꢂ)-21. We attribute the
ability of (ꢀ)-5 to recognize a-mannosidases to its most stable pseudo-chair conforma-
tion shown in Fig. 3. Interestingly, this conformation can be superposed with an enve-
lope conformation of (2R,3R,4S)-2-(aminomethyl)pyrrolidine-3,4-diol (31), an a-man-
nosidase inhibitor. Thus the 3,4-dihydroxy and 1-amino moieties of (ꢀ)-5 (trivial atom
numbering) coincide with the 3,4-diol and the primary amine units of 31 (Fig. 3).
Fig. 3. Representation of the functional groups of (ꢀ)-5 and 31 that can occupy the same sites in the active
site of a-mannosidases (trivial atom numbering of (ꢀ)-5)
Although (ꢀ)-5 does not inhibit b-glucosidases, we found that N-benzyl derivatives
are good and competitive inhibitors of these enzymes (see, e.g., (ꢀ)-19a (N-benzyl) and
(ꢀ)-19g (N-(4-phenylbenzyl)) that showed Ki =10 and 7.8 m
M
, respectively, toward b-
glucosidase from almonds). Now we find that the inhibitory activity of conduramine
B-1 ((ꢀ)-5) toward a-mannosidase is also enhanced by N-benzylation, and it is also
(ꢀ)-19g that is the most potent a-mannosidase inhibitor (Ki =4.8 m
M
, a-mannosidase
from jack beans). Comparing the IC50 values of the Table, one finds that (ꢀ)-19g is
the most selective inhibitor of a-mannosidases, whereas (ꢀ)-19a is a better inhibitor
of b-glucosidase from almonds than of a-mannosidases.
Although many structural variations have been carried out in this work, we have not
found yet the N-substituted conduramine B-1 derivative that is either a highly selective
inhibitor of b-glucosidases or a highly selective inhibitor of a-mannosidases. Not unex-
pectedly, (+)-conduramine B-1 ((+)-5) and its N-substituted derivatives (+)-ent-19 are
not recognized at all neither by b-glucosidases, nor by a-mannosidases. However, one
notes that (+)-ent-19a,c–f are weak to moderate inhibitors of amyloglucosidases from
Aspergillus niger and from Rhizopus mold, whereas (+)-5 is not. This demonstrates
again the importance of the N-benzyl appendages of these inhibitors in their ability
to recognize the glycosidases.
Except for 28, that inhibits a-mannosidase from jack bean moderately (85% inhib-
ition at 1 m concentration), amines 26, 27, 29, and 30 do not recognize this enzyme. All
M
compounds 26–30 ignore a-mannosidase from almonds. Thus, the (ꢀ)-conduramine B-
1 moiety is required for efficient recognition of a-mannosidases. Interestingly, 26–28
are weak inhibitors of b-glucosidase from almonds (34, 32, and 69%, resp., at 1 m con-
M

2794
HELVETICA CHIMICA ACTA – Vol. 88 (2005)
Table. Inhibitory Activities of Conduramine B-1 and Its Derivatives and of Amines 26–30. Percentage of
inhibiton at 1 m concentration, IC50 (italic) and Ki (italic) at optimal pH. When established (Ki measurements,
M
Lineweaver-Burk plots), inhibitions are competitive, except when indicated. M=Mixed-type inhibition;
n.i.=no inhibition at 1 mM, n.m.=not measured.
a-Gal
b-Gal
Amyloglu.
b-Glucosidase
a-Mannosidases
b-Xylosidase
a
b
c
d
e
f
g
h
i
)
)
)
)
)
)
)
)
)
(ꢀ)-5
(ꢀ)-19a
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
72%
67%
n.i.
46%
96%
32j)
43%
78%
171j)
79%
225j)
74%
10k)
95%
52j)
(ꢀ)-19b
n.i.
76%
n.i.
n.i.
68%
91%
91
86%
86j)
74%
25k)
93%
72j)
(ꢀ)-19c
(ꢀ)-19d
(ꢀ)-19e
n.i.
n.i.
n.i.
23%
46%
76%
31%
n.i.
57%
20%
n.i.
56%
27%
90%
100j)
40%
86%
183j)
60%
67%
n.i.
62%
553j)
96%
35j)
n.i.
84%
185j)
39%
94%
35j)
92%
91j)
90%
97%
29j)
4.8k)
96%
40j)
14k)
79%
154j)
n.i.
90%
77j)
80%
94%
32j)
16k) (M)
90%
63j)
n.i.
(ꢀ)-19f
(ꢀ)-19g
n.i.
n.i.
41%
97%
n.i.
n.i.
n.i.
n.i.
85%
97%
32j)
n.i.
n.i.
7.8k)
97%
43j)
(ꢀ)-19h
(ꢀ)-19i
n.i.
n.i.
96%
34%
n.i.
n.i.
n.i.
n.i.
71%
52j)
n.i.
n.i.
13k)
n.i.
43%
51%
(+)-5
(+)-ent-19a
(+)-ent-19b
n.i.
n.i.
n.i.
n.i.
n.i.
33%
n.i.
67%
n.i.
n.i.
72%
n.i.
n.i.
51%
31%
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
(+)-ent-19c
n.i.
n.i.
94%
85%
29%
n.i.
n.i.
n.i.
n.i.
(+)-ent-19d
(+)-ent-19e
(+)-ent-19f
(+)-ent-19g
(+)-ent-19h
(+)-ent-19i
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
42%
45%
50%
n.i.
n.i.
n.i.
41%
72%
72%
n.i.
n.i.
n.i.
n.i.
82%
n.i.
56%
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
27%
47%
63%
60%
n.i.
(ꢂ)-21
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
57%
(ꢂ)-19j
(ꢂ)-19k
(ꢂ)-19l
(ꢂ)-19m
(ꢂ)-19n
n.i.
n.i.
n.i.
n.i.
n.i.
56%
74%
n.i.
n.i.
89%
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
75%
59%
n.i.
37%
82%
82j)
77%
60j)
69%
81%
82j)
29%
77%
n.i.
n.i.
n.m.
81%
84%
63%
83%
74%
287j)
83%
210j)
85%
82%
206j)
76%
76%
73%
88%
n.m.
n.i.
n.i.
n.i.
n.i.
n.i.
39%
29%
68%
n.i.
(ꢂ)-19o
n.i.
91%
n.i.
n.i.
n.m.
n.m.
n.i.
(ꢂ)-19p
(ꢂ)-19q
n.i.
n.i.
91%
89%
n.i.
n.i.
65%
n.i.
n.m.
n.m.
n.m.
n.m.
n.i.
n.i.

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Table (cont.)
a-Gal
b-Gal
Amyloglu.
b-Glucosidase
a-Mannosidases
b-Xylosidase
a
b
c
d
e
f
g
h
i
)
)
)
)
)
)
)
)
)
(ꢂ)-19r
(ꢂ)-19s
n.i.
n.i.
85%
92%
n.i.
n.i.
n.i.
n.i.
n.i.
n.m.
n.m.
76%
275j)
84%
202j)
85%
75%
185j)
61%
n.m
n.i.
n.i.
80%
64j)
69%
77%
98j)
80%
66j)
92%
32j)
85%
69j)
80%
66j)
n.m.
(ꢂ)-19t
(ꢂ)-19u
n.i.
n.i.
90%
82%
n.i.
n.i.
n.i.
n.i.
n.m.
n.m.
n.m.
n.m.
n.i.
n.i.
(ꢂ)-19v
(ꢂ)-19w
(ꢂ)-19x
(ꢂ)-19y
n.i.
n.i.
n.i.
n.i.
36%
67%
74%
75%
n.i.
n.i.
n.i.
n.i.
30%
n.i.
n.m.
n.m.
n.m.
n.m.
74%
77%
77%
74%
n.i.
n.i.
n.i.
n.i.
79%
88%
61%
n.i.
30%
(ꢂ)-19z
n.i.
25%
n.i.
n.i.
n.i.
37%
n.i.
67%
39%
43%
n.i.
n.i.
n.i.
n.i.
n.i.
23%
n.i.
n.i.
n.i.
n.i.
75%
36%
83%
36%
n.i.
31%
n.i.
n.i.
n.i.
n.i.
82%
n.i.
n.i.
n.i.
n.i.
83%
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
(ꢂ)-20aa
(ꢂ)-20bb
(ꢂ)-20cc
(ꢂ)-20dd
26
27
n.i.
n.i.
79%
71%
34%
45%
74%
58%
34%
32%
n.m.
n.m.
n.i.
n.i.
n.m.
n.m.
n.i.
n.i.
28
29
30
n.i.
n.i.
n.i.
90%
66%
61%
n.i.
n.i.
n.i.
n.i.
n.i.
n.i.
69%
n.i.
n.i.
n.m.
n.m.
n.m.
85%
n.i.
n.i.
n.m.
n.i.
n.i.
n.i.
n.i.
n.i.
a) a-Galactosidase from coffee beans. b) b-Galactosidase from bovine liver. c) Amyloglucosidase from Aspergil-
lus niger. d) Amyloglucosidase from Rhizopus mold. e) b-Glucosidase from almonds. f) b-Glucosidase from Sac-
charomyces cerevisiae. g) a-Mannosidase from jack beans. h) a-Mannosidase from almonds. i) b-Xylosidase from
Aspergillus niger. j) IC50 in m k) Ki in m
M. M.
centration). This suggests that the aromatic moieties of these systems contribute to the
recognition of the b-glucosidases.
Probably for steric reasons, the N,N-disubstituted analogues of conduramines B-1
do not inhibit a-mannosidases. A different situation is seen with b-glucosidase from
almonds which is inhibited by (ꢂ)-20aa, (ꢂ)-20bb, and (ꢂ)-20cc, however, with low
potencies. Most of our amines are weak inhibitors of b-galactosidase from bovine
liver. The data shown in the Table demonstrate that this is not typical of the (ꢀ)- or
(+)-conduramine B-1 moiety.
Conclusion. – Although (ꢀ)-conduramine B-1 ((ꢀ)-5) that imitates b-glucopyrano-
sides is not recognized by b-glucosidases, it is a moderate inhibitor of a-mannosidases.
(ꢀ)-N-Benzylconduramine B-1 ((ꢀ)-19a) is a better inhibitor of b-glucosidases than of
a-mannosidases. In contrast, (ꢀ)-N-(4-phenylbenzyl)conduramine B-1 ((ꢀ)-19g) is a
slightly better inhibitor of a-mannosidases than of b-glucosidases. The ability of (ꢀ)-
conduramine B-1 and its N-substituted derivatives to inhibit a-mannosidases is attrib-

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Scheme 4. Preparation of Aldehydes and Amine Derivatives

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uted to the fact that their 3,4-diol and 1-amino moieties (trivial atom numbering, see
Fig. 3) might occupy the same sites of the active site of a-mannosidases as the 3,4-
diol and 2-(aminomethyl) units of (2R,3R,4S)-2-(aminomethyl)pyrrolidine-3,4-diol
and derivatives of this diamine that are potent a-mannosidase inhibitors.
This work was supported by the Secretariat d’Etat à l’Education et à la Recherche (SER) and the FP6 Euro-
pean TRIoH project (No. 03.0738 OFES). We thank Mr. Martial Rey and S. Reddy Dubbaka for their technical
help.
Experimental Part
1. General. All commercially available reagents (Fluka, Aldrich, Acros Organics) were used without further
purification. Solvents were dried by standard methods. Light petroleum ether used refers to the fraction boiling
between 40–608. Solvents after reactions and extractions were evaporated in a rotatory evaporator in vacuo.
TLC (reaction monitoring): Merck silica gel 60F254 plates; detection by UV light, Pancaldi reagent ((NH4)6
MoO4, Ce(SO4)2, H2SO4, H2O), KMnO4, or 1% ninhydrin in MeOH. Liquid/solid flash chromatography (FC):
silica gel 60 (Merck No. 9385, 240–400 mesh) or neutral alumina CC=Column chromatography. M.p.:
Büchi-SMP-20 apparatus; uncorrected. Optical rotations: at 258; Jasco DIP-370 polarimeter or Jasco P-1020
polarimeter; [a]D in 10ꢀ1 deg cm2 gꢀ1. IR Spectra: Perkin-Elmer 1420 spectrometer; in cmꢀ1. NMR Spectra:
1
Bruker ARX-400 spectrometer (1H at 400 MHz; 13C at 100.6 MHz); d in ppm rel. to the solvent’s residual H
1
or to the 13C signal (CDCl3: d(H) 7.27, d(C) 77.0; CD3OD: d(H) 3.31, d(C) 49.8) as internal reference; all H
assignments were confirmed by 2D-COSY-45 and 2D-NOESY experiments and all 13C assignments by 2D-
HMQC; coupling constants J in Hz. MS: Nermag R-10-10C, chemical-ionization (NH3) mode; m/z (% rel. to
the base peak (=100%)). Elemental analyses: Ilse Beetz, D-96301 Kronach, Germany.
2. Glycosidase Inhibition Assays. See [26].
3. (ꢂ)-(1RS,2SR,3SR,4RS)- and (ꢂ)-(1RS,2SR,3SR,4SR)-1,2,3-Tris{[(tert-butyl)dimethylsilyl]oxy}-4-
phthalimidocyclohex-5-ene2) (=(ꢂ)-2-{(1RS,4RS,5SR,6SR)-4,5,6-Tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-
2-en-1-yl}- and (ꢂ)-2-{(1RS,4SR,5RS,6RS)-4,5,6-Tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-yl}-1H-iso-
indole-1,3(2H)-dione, resp.; (ꢂ)-16 and (ꢂ)-17, resp.). A soln. of DEAD (2.26 ml, 14.57 mmol, 1.25 equiv.) in
dry toluene (15 ml) was added dropwise to (ꢂ)-14/(ꢂ)-15 ca. 2.5 :1 [22] (5.70 g, 11.66 mmol), phthalimide
(2.14 g, 14.57 mmol, 1.25 equiv.), and PPh3 (3.82 g, 14.57 mmol, 1.25 equiv.) in dry toluene (85 ml) at 08, and
the mixture was stirred at 08 for 12 h (TLC monitoring). After 12 h, the suspension was filtered off, and H2O
was added. The mixture was extracted with Et2O (3×), the combined org. extract was washed with brine,
dried (MgSO4), and evaporated, and the residue was subjected to FC (silica gel, AcOEt/light petroleum
ether 4 :96). The obtained white solid (6.2 g, 87%) resubjected to CC (AcOEt/hexane 1 :99 ! 5 :95): (ꢂ)-16
(3.7 g) and (ꢂ)-17 (0.64 g).
Data of (ꢂ)-16. White needles. M.p. 83–858. UV (MeCN): 233 (7533), 225 (6855), 221 (6456), 195 (816). IR
(KBr): 2933, 2857, 1776, 1719, 1473, 1387, 1258, 1160, 1128, 1059, 1003, 891, 781, 716. 1H-NMR (400 MHz,
3
3
CDCl3): 7.85–7.80 (m, 2 arom. H); 7.74–7.69 (m, 2 arom. H); 5.93 (ddd, J(6,5)=10.0, J(6,4)=3J(6,1)=3.0,
HꢀC(6)); 5.59 (ddd, 3J(5,6)=10.0, 3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 4.90–4.86 (m, HꢀC(4)); 4.35–4.31 (m,
HꢀC(1)); 4.23 (dd, J(3,2)=3J(3,4)=6.0, HꢀC(3)); 3.83 (dd, J(2,3)=3J(2,1)=6.0, HꢀC(2)); 0.93, 0.86, 0.78
3
3
(3s, 3 BuSi); 0.13, 0.12, 0.07, 0.05 (4s, 6 MeSi). 13C-NMR (100.6 MHz, CDCl3): 168.0 (s, 2 arom. C); 133.9 (d,
t
1J(C,H)=164, 2 arom. C); 132.1 (s, 2 arom. C); 132.0 (d, J(C,H)=162, C(6)); 125.2 (d, J(C,H)=162, C(5));
1
1
1
1
1
1
123.1 (d, J(C,H)=170, 2 arom. C); 78.1 (d, J(C,H)=146, C(2)); 73.3 (d, J(C,H)=145, C(3)); 72.2 (d, J(C,
1
1
H)=144, C(1)); 53.8 (d, J(C,H)=142, C(4)); 26.4, 26.2, 26.0 (3q, J(C,H)=125, 3 Me3C); 18.3, 18.1, 17.8 (3s,
3 Me3C); ꢀ3.1, ꢀ3.2, ꢀ3.5, ꢀ3.7, ꢀ4.1, ꢀ4.7 (6q, 1J(C,H)=119, 6 MeSi). CI-MS (NH3): 560 (23), 428 (9),
354 (12), 329 (48), 314 (8), 288 (17), 231 (6), 167 (4), 147 (29), 115 (14), 99 (5), 75 (52), 73 (100). HR-
MALDI-TOF-MS: 640.3283 (C32H55NNaO5Siþ3 , [M+Na]+; calc. 640.3286). Anal. calc. for C32H55NO5Si3
(617.339): C 62.19, H 8.97, N 2.27; found: C 61.89, H 8.70, N 2.11.
(ꢀ)-(1R,2S,3S,4R)-1,2,3-Tris{[(tert-butyl)dimethylsilyl]oxy}-4-phthalimidocyclohex-5-ene2) (=(ꢀ)-2-{(1R,
4R,5S,6S)-4,5,6-Tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-yl}-1H-isoindole-1,3(2H)-dione; (ꢀ)-16).
As described for (ꢂ)-16/(ꢂ)-17, with (ꢀ)-14/(ꢀ)-15 2.5 :1 derived from (+)-10 [22]: 69% of the major isomer
2
)
Systematic names are given in parentheses

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(ꢀ)-16; ½aꢃ589 =ꢀ126, ½aꢃ577 =ꢀ132, ½aꢃ435 =ꢀ274, ½aꢃ405 =ꢀ340 (c=0.54, CHCl3). HR-MALDI-TOF-MS:
640.3281 (C32H55NNaO5Siþ3 , [M+Na]+; calc. 640.3286).
Enatiomer (+)-16. As described for (ꢂ)-16/(ꢂ)-17, starting from (ꢀ)-10: 66% of the major isomers (+)-16.
25
25
25
25
½aꢃ589 =+118, ½aꢃ577 =+122, ½aꢃ435 =+260, ½aꢃ405 =+327 (c=0.545, CHCl3). HR-MALDI-TOF-MS: 640.3209
(C32H55NNaO5Siþ3 , [M+Na]+; calc. 640.3286).
Data of (ꢂ)-17. Colorless oil. UV (MeCN): 293 (2150), 260 (995), 235 (7188). IR (KBr): 2930, 2858, 1778,
1719, 1742, 1391, 1325, 1257, 1189, 1079, 1006, 867, 835, 774, 719. 1H-NMR (400 MHz, CDCl3): 7.85–7.82 (m, 2
arom. H); 7.74–7.69 (m, 2 arom. H); 6.01 (br. d, 3J(6,5)=10.0, HꢀC(6)); 5.81 (br. d, 3J(5,6)=10.0, HꢀC(5)); 5.09
(br. m, HꢀC(4)); 4.04–3.94 (2 br. m, HꢀC(3), HꢀC(2), HꢀC(1)); 0.97 , 0.94, 0.76 (3s, 3 tBuSi); 0.22, 0.16, 0.14,
1
0.13, ꢀ0.02, ꢀ0.4 (6s, 6 MeSi). 13C-NMR (100.6 MHz, CDCl3): 168.3 (s, 2 arom. C); 133.8 (d, J(C,H)=164, 2
arom. C); 132.1 (s, 2 arom. C); 127.0 (d, 1J(C,H)=160, C(6)); 123.0 (d, 1J(C,H)=160, C(5)); 122.9 (d, 1J(C,
H)=165, 2 arom. C); 74.5 (d, 1J(C,H)=148, C(2)); 70.5, 69.1 (2d, 1J(C,H)ꢄ144, C(1), C(3)); 49.8 (d, 1J(C,
1
H)=139, C(4)); 26.2, 25.8, 25.7 (3q, J(C,H)=125, 3 Me3C); 18.5, 17.9, 17.8 (3s, 3 Me3C); ꢀ4.3, ꢀ4.35, ꢀ4.4,
1
ꢀ4.5, ꢀ4.6, ꢀ5.4 (6q, J(C,H)=119, 6 MeSi). HR-MALDI-TOF-MS: 640.3143 (C32H55NNaO5Siþ3 , [M+Na]+;
calc. 640.3286). Anal. calc. for C32H55NO5Si3 (617.339): C 62.19, H 8.97, N 2.27; found: C 62.03, H 9.05, N 2.10.
(ꢀ)-(1R,2S,3S,4S)-1,2,3-Tris{[(tert-butyl)dimethylsilyl]oxy}-4-phthalimidocyclohex-5-ene2) (=(ꢀ)-2-{(1S,
4R,5S,6S)-4,5,6-Tris{[(tert-butyl)dimethylsilyl]oxy}cyclohex-2-en-1-yl}-1H-isoindole-1,3(2H)-dione; (ꢀ)-17).
25
25
25
As described above for (ꢂ)-16/(ꢂ)-17 starting from (+)-10: ½aꢃ589 =ꢀ50, ½aꢃ577 =ꢀ51, ½aꢃ435 =ꢀ99,
25
½aꢃ405 =ꢀ128 (c=0.44, CHCl3). HR-MALDI-TOF-MS: 640.3283 (C32H55NNaO5Siþ3 , [M+Na]+; calc. 640.3286).
Enantiomer (+)-17. As described above for (ꢂ)-16/(ꢂ)-17 starting with (ꢀ)-10: 21% of the minor isomer
25
25
25
25
(+)-17. ½aꢃ589 =+49, ½aꢃ577 =+50, ½aꢃ435 =+99, ½aꢃ405 =+114 (c=0.29, CHCl3). HR-MALDI-TOF-MS:
640.3263 (C32H55NNaO5Siþ3 , [M+Na]+; calc. 640.3286).
4. (ꢂ)-(1RS,2SR,3SR,4RS)-4-Phthalimidocyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-2-[(1RS,4RS,5SR,6SR)-4,5,6-
Trihydroxycyclohex-2-en-1-yl]-1H-isoindole-1,3(2H)-dione; (ꢂ)-18). Compound (ꢂ)-16 (2.5 g, 4.04 mmol) was
dissolved in 1% TsOH in MeOH (30 ml) and stirred under reflux for 30 min (TLC monitoring). The solvent
was evaporated and the residue subjected to FC (AcOEt/hexane 4 :1, then pure AcOEt, then MeOH/AcOEt
5 :95): 1.05 g (95%) of (ꢂ)-18. White crystals. M.p. 227–2298 (from MeOH/Et2O). UV (MeOH): 293 (1736),
237 (3937), 196 (537). IR (KBr): 3551, 3462, 3401, 1768, 1703, 1467, 1399, 1264, 1132, 1110, 1066, 1029, 995,
945, 871, 791. 1H-NMR (400 MHz, CD3OD): 7.90–7.82 (m, 4 arom. H); 5.75 (ddd, 3J(5,6)=10.2, 3J(5,
3
3
4)=3J(5,1)=2.6, HꢀC(5)); 5.55 (ddd, J(6,5)=10.2, J(6,4)=3J(6,1)=2.6, HꢀC(6)); 4.85–4.82 (m, HꢀC(4));
3
4.29–4.25 (m, HꢀC(1)); 4.23 (dd, 3J(3,2)=10.1, 3J(3,4)=9.4, HꢀC(3)); 3.58 (dd, 3J(2,3)=10.1, J(2,1)=8.0,
HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 169.6 (s, 2 CO); 135.4 (d, 1J(C,H)=164, 2 arom. C); 133.3 (s, 2
1
1
1
arom. C); 132.3 (d, J(C,H)=162, C(5)); 126.8 (d, J(C,H)=162, C(6)); 124.1 (2d, J(C,H)=165, 2 arom. C);
78.5 (d, 1J(C,H)=140, C(2)); 73.7 (d, 1J(C,H)=144, C(1)); 71.9 (d, 1J(C,H)=147, C(3)); 55.6 (d, 1J(C,
H)=140, C(4)). CI-MS (NH3): 228 (15), 215 (17), 186 (23), 160 (8), 148 (18), 130 (34), 110 (100), 104 (52), 99
(27), 82 (52), 76 (74), 71 (5). HR-MALDI-TOF-MS: 298.1320 (C14H13NNaOþ5 , [M+Na]+; calc. 298.0691).
(ꢀ)-(1R,2S,3S,4R)-4-Phthalimidocyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-2-[(1R,4R,5S,6S)-4,5,6-Trihydroxycy-
clohex-2-en-1-yl]-1H-isoindole-1,3(2H)-dione; (ꢀ)-18). As described for (ꢂ)-18, with (ꢀ)-16: (ꢀ)-18 (95%).
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½aꢃ589 =ꢀ229, ½aꢃ577 =ꢀ227, ½aꢃ435 =ꢀ476, ½aꢃ405 =ꢀ612 (c=0.105, MeOH). HR-MALDI-TOF-MS: 298.0693
(C14H13NNaOþ5 , [M+Na]+; calc. 298.0691).
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Enantiomer (+)-18. As described for (ꢂ)-18, with (+)-16: (+)-18 (92%). ½aꢃ589 =+226, ½aꢃ577 =+227,
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½aꢃ435 =+474, ½aꢃ405 =+605 (c=0.105, MeOH). HR-MALDI-TOF-MS: 298.0610 (C14H13NNaOþ5 , [M+Na]+;
calc. 298.0691).
5. (ꢂ)-(1RS,2SR,3SR,4RS)-4-Aminocyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-Aminocy-
clohex-4-ene-1,2,3-triol=rac-Conduramine B-1; (ꢂ)-5). A 40% aq. MeNH2 soln. (15 ml) was added to (ꢂ)-18
(1.1 g, 3.99 mmol). Stirring at 208 was continued for ca. 45 min (TLC monitoring). After evaporation, the residue
was purified by ion exchange (Dowex-50 W (H+ form), 2
N
NH4OH): pure (ꢂ)-5 (0.55 g; 95%). Pure (ꢂ)-5 was
also obtained by FC (silica gel, 25% aq. NH3 soln./MeCN 1 :4). Very hygroscopic crystals. UV(MeOH): 207
(965). IR (film): 3342, 2862, 1648, 1618, 1577, 1402, 1373, 1343, 1296, 1267, 1124, 1083, 1019, 962, 786, 624.
1H-NMR (400 MHz, CD3OD): 5.62 (ddd, 3J(5,6)=10.2, 3J(5,4)=3J(5,1)=2.4, HꢀC(5)); 5.54 (ddd, 3J(6,
5)=10.2, 3J(6,4)=3J(6,1)=2.4, HꢀC(6)); 4.10–4.08 (m, HꢀC(1)); 3.42 (dd, 3J(2,3)=9.8, 3J(2,4)=7.8, Hꢀ
C(2)); 3.47–3.26 (m, H-C(4), HꢀC(3)). 13C-NMR (100.6 MHz, CD3OD): 131.3 (d, J(C,H)=162, C(5)); 129.7
1
1
1
1
1
(d, J(C,H)=162, C(6)); 77.8, 77.7 (2d, J(C,H)ꢄ143, C(3), C(2)); 73.8 (d, J(C,H)=144, C(1)); 55.7 (d, J(C,
H)=139, C(4)). CI-MS (NH3): 117 (2), 104 (5), 98 (4), 86 (4), 85 (100), 76 (2). HR-MALDI-TOF-MS:
146.0815 (C6H12NOþ3 , [M+H]+; calc. 146.0817). Anal. calc. for C6H11NO3 (145.074): C 49.65, H 7.64; found:
C 50.01, H 7.51.

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(ꢀ)-(1R,2S,3S,4R)-4-Aminocyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-Aminocyclohex-4-ene-1,2,
25
3-triol=(ꢀ)-Conduramine B-1; (ꢀ)-5). As described for (ꢂ)-5, with (ꢀ)-18: (ꢀ)-5 (90%). ½aꢃ589 =ꢀ173,
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½aꢃ577 =ꢀ174, ½aꢃ435 =ꢀ341, ½aꢃ405 =ꢀ421 (c=0.29, MeOH). HR-MALDI-TOF-MS: 146.0837 (C6H12NOþ3 ,
[M+H]+; calc. 146.0817).
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Enantiomer (+)-5. As described for (ꢂ)-5, with (+)-18: (+)-5 (90%). ½aꢃ589 =+173, ½aꢃ577 =+175,
½aꢃ435 =+350, ½aꢃ405 =+428 (c=0.29, MeOH). HR-MALDI-TOF-MS: 146.0837 (C6H12NOþ3 , [M+H]+; calc.
146.0817).
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(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Acetylamino)cyclohex-5-ene-1,2,3-triyl Triacetate2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-(Acetylamino)cyclohex-4-ene-1,2,3-triyl Triacetate). To (ꢂ)-5 (0.15 g, 0.103 mmol) were added pyridine
(1 ml), Ac2O (1 ml), and N,N-dimethylpyridin-4-amine (DMAP; 0.01 g), and after stirring at 208 for 20 h,
AcOEt was added. The soln. was washed successively with dil. aq. HCl soln., sat. aq. Na2CO3 soln., and
brine, dried (MgSO4), and evaporated and the residue subjected to pure FC (hexanes/AcOEt 1 :1 and hex-
ane/AcOEt 5 :95): pure (ꢂ)-tetra-N,O,O,O-acetylconduramine B-1 (0.023 g, 72%). Colorless crystals. M.p.
141–1438 (light petroleum ether/AcOEt). UV (CHCl3): 241 (608). IR (KBr): 3264, 2958, 1750, 1653, 1569,
1
3
1374, 1252, 1225, 1052, 961. H-NMR (400 MHz, CDCl3): 5.75 (br. d, J =8.4, NHAc); 5.72–5.60 (2ddd, J(6,
5)=10.2, J(6,4)=3J(6,1)=3J(5,4)=3J(5,1)=2.0, HꢀC(6), HꢀC(5)); 5.58–5.53 (m, HꢀC(1)); 5.39 (dd, 3J(2,
3
3
3
3
3)=10.7, J(2,1)=8.0, HꢀC(2)); 5.09 (dd, J(3,2)=10.7, J(3,4)=9.3, HꢀC(3)); 4.93–4.85 (m, HꢀC(4)); 2.07,
2.06, 2.05, 1.97 (4s, 4 MeCO). 13C-NMR (100.6 MHz, CDCl3): 171.6, 170.8, 170.4, 170.1 (4s, 4 MeCO); 131.0,
126.4 (2d, 1J(C,H)=167, C(6), C(5)); 72.3 (d, 1J(C,H)=140, C(3)); 72.1 (d, 1J(C,H)=146, C(1)); 71.8 (d,
1J(C,H)=140, C(2)); 51.3 (d, J(C,H)=136, C(4)); 23.6, 21.3, 21.1, 21.0 (4q, J(C,H)=130, 4 MeCO). CI-MS
(NH3): 255 (9), 183 (4), 152 (57), 140 (20), 133 (13), 127 (28), 110 (100), 99 (13), 85 (26), 81 (33), 77 (2), 70
(9). HR-MALDI-TOF-MS: 352.0781 (C14H19KNOþ7 , [M+K]+; calc. 352.0799).
1
1
6. N-Benzyl- and N-Alkyl-Substituted Derivatives 19 of Conduramine B-1. General Procedure (G.P.):
NaBH(OAc)3 (1.4 equiv.) was added portionwise to a stirred soln. of (ꢂ)-5 (0.4 mmol) and an appropriate alde-
hyde (0.4 mmol) in abs. MeOH (2 ml) at 208. After complete disappearance of (ꢂ)-5 (TLC control; longer reac-
tion time for the formation of aliphatic imines than for aromatic imines, i.e., 12 h vs. 2–5 h), the solvent was
evaporated and the residue subjected to FC (light petroleum ether/AcOEt 1 :1 ! AcOEt ! MeCN ! 25%
aq. NH3 soln./MeCN 1:9 ! 1:4).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Benzylamino)cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-(Ben-
zylamino)cyclohex-4-ene-1,2,3-triol; (ꢂ)-19a). According to the G.P., from (ꢂ)-5 and benzaldehyde (TLC mon-
itoring, MeOH/AcOEt 3 :7): (ꢂ)-19a (81%). Solid foam. UV (MeOH): 260 (358), 258 (352), 215 (3290). IR
(KBr): 3406, 1612, 1543, 1420, 1211, 1126, 1036, 1012, 668. 1H-NMR (400 MHz, CD3OD): 7.45–7.30 (m, 5
3
3
arom. H); 7.76–7.72 (m, HꢀC(6), HꢀC(5)); 4.12 (dd, J(1,2)=7.9, J(1,6)=3.2, HꢀC(1)); 4.05 (d, 3J=12.9,
3
1 H, ArCH2N); 3.93 (d, J=12.9, 1 H, ArCH2N); 3.59 (dd, 3J(3,2)=10.0, 3J(3,4)=8.7, HꢀC(3)); 3.46 (dd,
3J(4,3)=8.7, 3J(4,5)=3.2, HꢀC(4)); 3.43 (dd, 3J(2,3)=10.0, 3J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6 MHz,
1
1
CD3OD): 138.8 (s, arom. C); 132.9, 126.1 (2d, J(C,H)=162, C(6), C(5)); 130.0 (d, J(C,H)=158, 2 arom. C);
129.7 (d, J(C,H)=160, 2 arom. C); 128.8 (d, 1J(C,H)=160, arom. C); 77.9 (d, J(C,H)=145, C(2)); 73.9 (d,
1J(C,H)=138, C(3)); 73.4 (d, 1J(C,H)=147, C(1)); 61.4 (d, 1J(C,H)=136, C(4)); 50.8 (t, 1J(C,H)=137,
ArCH2N). CI-MS (NH3): 237 (2, [M+2H]+), 176 (33), 175 (100), 161 (16), 149 (4), 132 (9), 117 (8), 106 (34),
104 (17), 91 (94), 84 (73), 80 (3), 77 (7). HR-MALDI-TOF-MS: 258.1102 (C13H17NNaOþ3 , [M+Na]+; calc.
258.1106). Anal. calc. for C13H17NO3 (235.121): C 66.36, H 7.28, N 5.95; found: C 65.87, H 7.01, N 6.04.
(ꢀ)-(1R,2S,3S,4R)-4-(Benzylamino)cyclohex-5-ene-1,2,3-triol (=(ꢀ)-(1S,2S,3R,6R)-6-(Benzylamino)cy-
clohex-4-ene-1,2,3-triol; (ꢀ)-19a). According to the G.P., with (ꢀ)-5 and benzaldehyde: (ꢀ)-19a (79%).
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½aꢃ589 =ꢀ135, ½aꢃ577 =ꢀ148, ½aꢃ435 =ꢀ244, ½aꢃ405 =ꢀ267 (c=0.11, MeOH). HR-MALDI-TOF-MS: 258.1102
(C13H17NNaOþ3 , [M+Na]+; calc. 258.1106).
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Enantiomer (+)-ent-19a. According to the G.P., with (+)-5 and benzaldehyde: (+)-19 (82%). ½aꢃ589 =+87,
½aꢃ577 =+91, ½aꢃ435 =+184, ½aꢃ405 =+224 (c=0.075, MeOH). HR-MALDI-TOF-MS: 258.1102 (C13H17NNaOþ3 ,
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[M+Na]+; calc. 258.1106).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(4-Methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(4-Methoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19b). According to the G.P., with (ꢂ)-5 and
4-methoxybenzaldehyde (TLC monitoring, MeOH/AcOEt 2 :3): (ꢂ)-19b (96%). Solid foam. UV (MeOH):
274 (1208), 230 (4234), 198 (366). IR (KBr): 3382, 1613, 1560, 1516, 1411, 1253, 1181, 1122, 1032, 818, 653.
1H-NMR (400 MHz, CD3OD): 7.36 (d, 3J=8.6, 2 arom. H); 6.96 (d, 3J=8.6, 2 arom. H); 5.81 (ddd, 3J(5,
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6)=10.3, J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.74 (ddd, J(6,5)=10.3, J(6,4)=3J(6,1)=2.0, HꢀC(6)); 4.13–4.09
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(m, HꢀC(1)); 4.08 (d, J=12.9, 1 H, ArCH2N); 3.98 (d, J=12.9, 1 H, ArCH2N); 3.62 (dd, J(3,2)=9.8, J(3,
4)=9.0, HꢀC(3)); 3.57–3.52 (m, HꢀC(4)); 3.43 (dd, 3J(2,3)=9.8, 3J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6

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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
MHz, CD3OD): 161.6 (s, arom. C); 135.4 (d, 1J(C,H)=163, C(5)); 132.1 (d, 1J(C,H)=158, 2 arom. C); 126.8 (s,
arom. C); 123.0 (d, 1J(C,H)=163, C(6)); 115.4 (d, 1J(C,H)=161, 2 arom. C); 77.6 (d, 1J(C,H)=143, C(2)); 73.0
(d, 1J(C,H)=141, C(1)); 72.6 (d, 1J(C,H)=141, C(3)); 61.3 (d, 1J(C,H)=142, C(4)); 55.8 (q, 1J(C,H)=144,
MeO); 49.6 (t, 1J(C,H)=139, ArCH2N). CI-MS (NH3): 267 (2, [M+2H]+), 205 (1), 136 (4), 122 (21), 121
(100), 84 (2), 77 (2). HR-MALDI-TOF-MS: 288.1219 (C14H19NNaOþ4 , [M+Na]+; calc. 288.1212).
(ꢀ)-(1R,2S,3S,4R)-4-[(4-Methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(4-
Methoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19b). According to the G.P., with (ꢀ)-5 and 4-methoxy-
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benzaldehyde: (ꢀ)-19b (83%). ½aꢃ589 =ꢀ85, ½aꢃ577 =ꢀ87, ½aꢃ435 =ꢀ138, ½aꢃ405 =ꢀ212 (c=0.17, MeOH). HR-
MALDI-TOF-MS: 288.1271 (C14H19NNaOþ4 , [M+Na]+; calc. 288.1212).
Enantiomer (+)-ent-19b. According to the G.P., from (+)-5 and 4-methoxybenzaldehyde: (+)-19b (90%).
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½aꢃ589 =+97, ½aꢃ577 =+103, ½aꢃ435 =+201, ½aꢃ405 =+245 (c=0.35, MeOH). HR-MALDI-TOF-MS: 288.1232
(C14H19NNaOþ4 , [M+Na]+; calc. 288.1212).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(4-Hydroxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=((ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(4-Hydroxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19c). According to the G.P., with (ꢂ)-5 and
4-hydroxybenzaldehyde (TLC monitoring, MeOH/AcOEt 2 :3): (ꢂ)-19c (94%). Solid foam. UV (MeOH):
276 (1230), 229 (4178), 197 (402). IR (KBr): 3382, 1616, 1560, 1519, 1410, 1256, 1125, 1017, 834, 654. 1H-
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NMR (400 MHz, CD3OD): 7.27 (d, J=8.4, 2 arom. H); 6.82 (d, J=8.4, 2 arom. H); 5.81 (ddd, J(5,6)=10.0,
3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.74 (ddd, 3J(6,5)=10.0, 3J(6,4)=3J(6,1)=3.0, HꢀC(6)); 4.12–4.08 (m, Hꢀ
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C(1)); 4.08 (d, J=12.8, 1 H, ArCH2N); 4.00 (d, J=12.8, 1 H, ArCH2N); 3.68–3.57 (m, HꢀC(4), HꢀC(3));
3.43 (dd, 3J(2,3)=9.8, 3J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 159.4 (s, arom. C); 135.5 (d,
1J(C,H)=163, C(5)); 132.2 (d, 1J(C,H)=157, 2 arom. C); 125.2 (s, arom. C); 122.9 (d, 1J(C,H)=163, C(6));
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116.8 (d, J(C,H)=159, 2 arom. C); 77.6 (d, J(C,H)=142, C(2)); 73.0 (d, J(C,H)=142, C(1)); 72.7 (d, J(C,
H)=142, C(3)); 61.2 (d, 1J(C,H)=142, C(4)); 49.8 (t, 1J(C,H)=139, ArCH2N). CI-MS (NH3): 252 (38,
[M+H]+), 244 (6), 231 (43), 230 (93), 225 (15), 144 (4), 122 (6), 109 (23), 108 (81), 94 (54), 90 (4), 85 (100),
78 (7). HR-MALDI-TOF-MS: 274.1043 (C13H17NNaOþ5 , [M+Na]+; calc. 274.1055). Anal. calc. for
C13H17NO5 (251.116): C 62.14, H 6.82, N 5.57; found: C 62.40, H 6.70, N 5.43.
(ꢀ)-(1R,2S,3S,4R)-4-[(4-Hydroxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(4-
Hydroxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19c). According to the G.P., with (ꢀ)-5 and 4-hydroxy-
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benzaldehyde: (ꢀ)-19c (90%). ½aꢃ589 =ꢀ88, ½aꢃ577 =ꢀ89, ½aꢃ435 =ꢀ200, ½aꢃ405 =ꢀ256 (c=0.282, MeOH). HR-
MALDI-TOF-MS: 274.1059 (C13H17NNaOþ5 , [M+Na]+; calc. 274.1055).
Enantiomer (+)-ent-19c. According to the G.P., with (+)-5 and 4-hydroxybenzaldehyde: (+)-ent-19c
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(85%). ½aꢃ589 =+101, ½aꢃ577 =+113, ½aꢃ435 =+225, ½aꢃ405 =+278 (c=0.30, MeOH). HR-MALDI-TOF-MS:
274.1034 (C13H17NNaO5þ, [M+Na]+; calc. 274.1055).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(2-Hydroxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(2-Hydroxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19d). According to the G.P., with (ꢂ)-5 and
2-hydroxybenzaldehyde (TLC monitoring, MeOH/AcOEt 2 :3): (ꢂ)-19d (93%). Solid foam. UV (MeOH):
275 (2198), 222 (3434), 198 (409). IR (KBr): 3395, 1560, 1460, 1410, 1255, 1123, 1037, 1015, 760, 655. 1H-
NMR (400 MHz, CD3OD): 7.28–7.22 (m, 2 arom. H); 6.89–6.84 (m, 2 arom. H); 5.84 (ddd, 3J(5,6)=10.0,
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3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.79 (ddd, J(6,5)=10.0, J(6,4)=3J(6,1)=3.0, HꢀC(6)); 4.20 (d, J=13.0, 1
H, ArCH2N); 4.15 (d, 3J=13.1, 1 H, ArCH2N); 4.15–4.10 (m, HꢀC(1)); 3.67 (dd, 3J(3,2)=3J(3,4)=9.1, Hꢀ
C(3)); 3.65–3.61 (m, HꢀC(4)); 3.46 (dd, 3J(2,3)=9.5, 3J(2,1)=8.1, HꢀC(2)). 13C-NMR (100.6 MHz,
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CD3OD): 157.8 (s, arom. C); 134.9 (d, J(C,H)=163, C(5)); 131.8 (d, J(C,H)=157, arom. C); 131.3 (d, J(C,
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H)=159, arom. C); 123.5 (d, J(C,H)=163, C(6)); 121.5 (s, arom. C); 120.8 (d, J(C,H)=161, arom. C); 116.4
(d, 1J(C,H)=158, arom. C); 77.7 (d, J(C,H)=141, C(2)); 73.2, 72.7 (2d, 1J(C,H)ꢄ141, C(3), C(1)); 61.5 (d,
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1J(C,H)=144, C(4)); 46.8 (t, J(C,H)=141, ArCH2N). CI-MS (NH3): 251 (7, M+), 146 (7), 124 (82), 109 (2),
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106 (100), 85 (7), 78 (63), 77 (38). HR-MALDI-TOF-MS: 252.1204 (C13H18NOþ4 , [M+H]+; calc. 252.1236).
Anal. calc. for C13H17NO5 (251.116): C 62.14, H 6.82, N 5.57; found: C 62.33, H 6.68, N 5.40.
(ꢀ)-(1R,2S,3S,4R)-4-[(2-Hydroxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(2-
Hydroxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19d). According to the G.P., with (ꢀ)-5 and 2-hydroxy-
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benzaldehyde: (ꢀ)-19d (93%). ½aꢃ589 =ꢀ101, ½aꢃ577 =ꢀ104, ½aꢃ435 =ꢀ162, ½aꢃ405 =ꢀ191 (c=0.167, MeOH).
HR-MALDI-TOF-MS: 274.1045 (C13H17NNaOþ4 , [M+Na]+; calc. 274.1055).
Enantiomer (+)-ent-19d. According to the G.P., with (+)-5 and 2-hydroxybenzaldehyde: (+)-ent-19d
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(87%). ½aꢃ589 =+97, ½aꢃ577 =+100, ½aꢃ435 =+155, ½aꢃ405 =+183 (c=0.15, MeOH). HR-MALDI-TOF-MS:
274.1069 (C13H17NNaO4þ, [M+Na]+; calc. 274.1055).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(4-Chlorobenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(4-Chlorobenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19e). According to the G.P., with (ꢂ)-5 and 4-

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chlorobenzaldehyde (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19e (99%). Solid foam. UV (MeOH): 275
(1089), 267 (1241), 228 (4266), 197 (554). IR (KBr): 3376, 1612, 1560, 1411, 1093, 1015, 959, 805. 1H-NMR
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(400 MHz, CD3OD): 7.42 (d, J=8.6, 2 arom. H); 7.39 (d, J=8.6, 2 arom. H); 5.74 (br. s, HꢀC(6), HꢀC(5));
4.10 (dd, 3J(1,2)=7.8, 3J(1,6)=3.0, HꢀC(1)); 4.05 (d, 3J=13.2, 1 H, ArCH2N); 3.94 (d, 3J=13.2, 1 H,
ArCH2N); 3.59 (dd, 3J(3,2)=9.9, 3J(3,4)=8.8, HꢀC(3)); 3.45 (dd, 3J(4,3)=8.8, 3J(4,5)=3.0, HꢀC(4)); 3.43
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(dd, J(2,3)=9.9, J(2,1)=7.8, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 135.6 (s, arom. C); 135.3 (s, arom.
C); 134.3 (d, 1J(C,H)=162, C(5)); 132.0 (d, 1J(C,H)=161, 2 arom. C); 129.9 (d, 1J(C,H)=166, 2 arom. C);
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124.4 (d, 1J(C,H)=162, C(6)); 77.7 (d, 1J(C,H)=139, C(2)); 73.2, 73.1 (2d, J(C,H) ꢄ141, C(3), C(1)); 61.5 (d,
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1J(C,H)=140, C(4)); 49.6 (t, J(C,H)=138, ArCH2N). CI-MS (NH3): 271 (23, [M+2H]+), 158 (21), 153 (10),
143 (10), 140 (12), 127 (56), 125 (100), 106 (12), 91 (6), 85 (15), 84 (29). HR-MALDI-TOF-MS: 292.0712
(C13H16ClNNaOþ3 , [M+Na]+; calc. 292.0716).
(ꢀ)-(1R,2S,3S,4R)-4-[(4-Chlorobenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(4-
Chlorobenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19e). According to the G.P., with (ꢀ)-5 and 4-chlorobenz-
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aldehyde: (ꢀ)-19e (95%). ½aꢃ589 =ꢀ143, ½aꢃ577 =ꢀ150, ½aꢃ435 =ꢀ265, ½aꢃ405 =ꢀ309 (c=0.162, MeOH). HR-
MALDI-TOF-MS: 292.0714 (C13H16ClNNaOþ3 , [M+Na]+; calc. 292.0716).
Enantiomer (+)-ent-19e. According to the G.P., with (+)-5 and 4-chlorobenzaldehyde: (+)-ent-19e (94%).
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½aꢃ589 =+144, ½aꢃ577 =+148, ½aꢃ435 =+267, ½aꢃ405 =+301 (c=0.16, MeOH). HR-MALDI-TOF-MS: 292.0721
(C13H16ClNNaOþ3 , [M+Na]+; calc. 292.0716).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(2,6-Difluorobenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(2,6-Difluorobenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19f). According to the G.P., with (ꢂ)-5
and 2,6-difluorobenzaldehyde (TLC monitoring), MeOH/AcOEt 3 :7): (ꢂ)-19f (77%). Solid foam. UV
(MeOH): 261 (665), 214 (2940), 198 (292). IR (KBr): 3365, 1627, 1593, 1560, 1470, 1419, 1266, 1229, 1127,
1048, 1018, 782. 1H-NMR (400 MHz, CD3OD): 7.42–7.33 (m, arom. H); 7.05–6.98 (m, 2 arom. H); 5.75
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(ddd, J(5,6)=10.0, J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.69 (ddd, J(6,5)=10.0, J(6,4)=3J(6,1)=3.0, HꢀC(6));
4.13–4.07 (m, HꢀC(1)); 4.05 (d, 3J=13.3, 1 H, ArCH2N); 3.97 (d, 3J=13.1, 1 H, ArCH2N); 3.49 (dd, 3J(3,
2)=10.0, J(3,4)=8.5, HꢀC(3)); 3.41 (dd, J(2,3)=10.0, J(2,1)=7.6, HꢀC(2)); 3.32–3.27 (m, HꢀC(4)). 13C-
NMR (100.6 MHz, CD3OD): 163.1 (d, 1J(C,F)=247, 2 arom. C); 132.5 (d, 1J(C,H)=162, C(5)); 131.4 (d,
1J(C,H)=165, arom. C); 126.4 (d, 1J(C,H)=162, C(6)); 112.5 (s, arom. C); 112.4 (dd, 1J(C,F)=166, 2J(C,
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F)=25, 2 arom. C); 77.9 (d, J(C,H)=144, C(2)); 73.9 (d, J(C,H)=137, C(1)); 73.6 (d, J(C,H)=143, C(3));
61.3 (d, J(C,H)=140, C(4)); 37.7 (t, J(C,H)=140, ArCH2N). CI-MS (NH3): 272 (3, [M+H]+), 242 (2), 211
(28), 144 (2), 142 (6), 127 (82), 107 (5), 84 (100), 82 (3). HR-MALDI-TOF-MS: 272.1012 (C13H16F2NOþ3 ,
[M+H]+; calc. 272.1098).
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(ꢀ)-(1R,2S,3S,4R)-4-[(2,6-Difluorobenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(2,
6-Difluorobenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19f). According to the G.P., with (ꢀ)-5 and 2,6-difluoro-
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benzaldehyde: (ꢀ)-19f (87%). ½aꢃ589 =ꢀ76, ½aꢃ577 =ꢀ96, ½aꢃ435 =ꢀ228, ½aꢃ405 =ꢀ270 (c=0.105, MeOH). HR-
MALDI-TOF-MS: 294.0981 (C13H15F2NNaOþ3 , [M+Na]+; calc. 294.0918).
Enantiomer (+)-ent-19f. According to the G.P., with (+)-5 and 2,6-difluorobenzaldehyde: (+)-ent-19f
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(85%). ½aꢃ589 =+74, ½aꢃ577 =+95, ½aꢃ435 =+223, ½aꢃ405 =+266 (c=0.105, MeOH). HR-MALDI-TOF-MS:
294.0909 (C13H15F2NNaOþ3 , [M+Na]+; calc. 294.0918).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[([1,1’-Biphenyl]-4-ylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,
2RS,3SR,6SR)-6-[([1,1’-Biphenyl]-4-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19g). According to the
G.P., with (ꢂ)-5 and 4-phenylbenzaldehyde (=[1,1’-biphenyl]-4-carboxaldehyde) (TLC monitoring, MeOH/
AcOEt 3 :7): (ꢂ)-19g (98%). Colorless foam. UV (MeOH): 268 (6370), 249 (7161), 217 (5451), 199 (938). IR
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(KBr): 3363, 2854, 1560, 1409, 1338, 1123, 1040, 1008, 957, 763, 696. H-NMR (400 MHz, CD3OD): 7.68–7.61
(m, 4 arom. H); 7.54–7.32 (m, 5 arom. H); 5.85 (ddd, 3J(5,6)=10.4, 3J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.80
(ddd, 3J(6,5)=10.3, 3J(6,4)=3J(6,1)=2.0, HꢀC(6)); 4.15 (d, 3J=13.0, 1 H, ArCH2N); 4.12 (dd, 3J(1,2)=7.9,
3J(1,6)=3.1, HꢀC(1)); 4.03 (d, 3J=13.0, 1 H, ArCH2N); 3.63 (dd, 3J(3,2)=9.7, 3J(3,4)=8.8, HꢀC(3)); 3.53
(dd, J(4,3)=8.8, J(4,5)=3.1, HꢀC(4)); 3.45 (dd, J(2,3)=9.8, J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6 MHz,
CD3OD): 142.6 (s, arom. C); 141.6 (s, arom. C); 135.1 (s, arom. C); 134.7 (d, 1J(C,H)=163, C(5)); 131.0 (d,
1J(C,H)=159, 2 arom. C); 129.9 (d, 1J(C,H)=161, 2 arom. C); 128.6 (d, 1J(C,H)=160, arom. C); 128.4 (d,
1J(C,H)=160, 2 arom. C); 127.9 (d, 1J(C,H)=159, 2 arom. C); 123.9 (d, 1J(C,H)=158, C(6)); 77.7 (d, 1J(C,
H)=139, C(2)); 73.1, 73.0 (2d, 1J(C,H) ꢄ 144, C(3), C(1)); 61.4 (d, 1J(C,H)=141, C(4)); 49.9 (t, 1J(C,
H)=142, ArCH2N). CI-MS (NH3): 313 (7, [M+2H]+), 252 (19), 168 (51), 167 (100), 165 (22), 152 (14), 128
(8), 117 (8), 106 (11), 89 (5), 84 (17), 76 (24). HR-MALDI-TOF-MS: 334.1414 (C19H21NNaOþ3 , [M+Na]+;
calc. 334.1419).
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(ꢀ)-(1R,2S,3S,4R)-4-[([1,1’-Biphenyl]-4-ylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,
6R)-6-[([1,1’-Biphenyl]-4-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19g). According to the G.P., with
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(ꢀ)-5 and 4-phenylbenzaldehyde: (ꢀ)-19g (96%). ½aꢃ589 =ꢀ98, ½aꢃ577 =ꢀ100, ½aꢃ435 =ꢀ201, ½aꢃ405 =ꢀ238
(c=0.13, MeOH). HR-MALDI-TOF-MS: 334.1413 (C19H21NNaOþ3 , [M+Na]+; calc. 334.1419).
Enantiomer (+)-ent-19a. According to the G.P., with (+)-5 and4-phenylbenzaldehyde: (+)-ent-19g (92%).
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½aꢃ589 =+107, ½aꢃ577 =+125, ½aꢃ435 =+220, ½aꢃ405 =+243 (c=0.15, MeOH). HR-MALDI-TOF-MS: 334.1409
(C19H21NNaOþ3 , [M+Na]+; calc. 334.1419).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(4-Phenoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(4-Phenoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19h). According to the G.P., with (ꢂ)-5 and
4-phenoxybenzaldehyde (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19h (93%). Colorless foam. UV
(MeOH): 271 (1445), 238 (4030), 198 (479). IR (KBr): 3386, 1590, 1560, 1489, 1409, 1243, 1114, 1018, 872,
1
3
3
692. H-NMR (400 MHz, CD3OD): 7.46 (d, J=8.5, 2 arom. H); 7.41–7.36 (m, 2 arom. H); 7.18 (t, J=7.4, 1
arom. H); 7.02 (m, 4 arom. H); 5.86 (ddd, 3J(5,6)=10.0, 3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.78 (ddd, 3J(6,
5)=10.0, J(6,4)=3J(6,1)=3.0, HꢀC(6)); 4.20 (d, J=13.1, 1 H, ArCH2N); 4.15–4.10 (m, HꢀC(1)); 4.13 (d,
3
3
3J=13.1, 1 H, ArCH2N); 3.74–3.61 (m, HꢀC(4), HꢀC(3)); 3.46 (dd, J(2,3)=9.2, J(2,1)=7.7, HꢀC(2)). 13C-
3
3
1
NMR (100.6 MHz, CD3OD): 159.4 (s, arom. C); 158.1 (s, arom. C); 135.2 (d, J(C,H)=163, C(5)); 132.3 (d,
1J(C,H)=159, 2 arom. C); 131.0 (d, 1J(C,H)=159, 2 arom. C); 130.1 (s, arom. C); 124.9 (d, 1J(C,H)=159,
1
1
1
arom. C); 123.4 (d, J(C,H)=163, C(6)); 120.3 (d, J(C,H)=161, 2 arom. C); 119.8 (d, J(C,H)=162, 2 arom.
C); 77.7 (d, 1J(C,H)=143, C(2)); 73.0, 72.8 (2d, 1J(C,H) ꢄ 142, C(3), C(1)); 61.4 (d, 1J(C,H)=144, C(4));
49.6 (t, J(C,H)=138, ArCH2N). HR-MALDI-TOF-MS: 350.1374 (C19H21NNaOþ4 , [M+Na]+; calc. 350.1368).
1
Anal. calc. for C19H21NO4 (327.147): C 69.71, H 6.47, N 4.28; found: C 70.01, H 6.33, N 4.11.
(ꢀ)-(1R,2S,3S,4R)-4-[(4-Phenoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-(1S,2S,3R,6R)-6-[(4-
Phenoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19h). According to the G.P., with (ꢀ)-5 and 4-phenoxy-
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benzaldehyde: (ꢀ)-19h (91%). ½aꢃ589 =ꢀ94, ½aꢃ577 =ꢀ96, ½aꢃ435 =ꢀ196, ½aꢃ405 =ꢀ231 (c=0.142, MeOH). HR-
MALDI-TOF-MS: 350.1358 (C19H21NNaOþ4 , [M+Na]+; calc. 350.1368).
Enantiomer (+)-ent-19h. According to the G.P., with (+)-5 and 4-phenoxybenzaldehyde: (+)-ent-19h
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(90%). ½aꢃ589 =+102, ½aꢃ577 =+109, ½aꢃ435 =+215, ½aꢃ405 =+266 (c=0.27, MeOH). HR-MALDI-TOF-MS:
350.1356 (C19H21NNaO4þ, [M+Na]+; calc. 350.1368).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(2-Bromo-5-hydroxy-4-methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1RS,2RS,3SR,6SR)-6-[(2-Bromo-5-hydroxy-4-methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol; (ꢂ)-
19i). According to the G.P., with (ꢂ)-5 and 2-bromo-5-hydroxy-4-methoxybenzaldehyde (TLC monitoring,
MeOH/AcOEt 3 :7): (ꢂ)-19i (76%). Colorless solid. UV (MeOH): 287 (2721), 260 (899), 233 (4971), 196
(707). IR (KBr): 3358, 1610, 1560, 1508, 1419, 1269, 1211, 1169, 1027, 800, 660. 1H-NMR (400 MHz,
CD3OD): 7.16 (s, arom. H); 7.00 (s, arom. H); 5.79 (br. s, HꢀC(6), HꢀC(5)); 4.13 (dd, 3J(1,2)=7.9, 3J(1,
3
3
3
6)=3.2, HꢀC(1)); 4.06 (d, J=13.2, 1 H, ArCH2N); 3.99 (d, J=13.2, 1 H, ArCH2N); 3.61 (dd, J(3,2)=9.8,
3J(3,4)=8.8, HꢀC(3)); 3.52 (dd, J(4,3)=8.8, J(4,6)=3.2, HꢀC(4)); 3.43 (dd, J(2,3)=9.8, J(2,1)=7.9, Hꢀ
3
3
3
3
C(2)). 13C-NMR (100.6 MHz, CD3OD): 149.9 (s, arom. C); 147.6 (s, arom. C); 133.7 (d, J(C,H)=162, C(5));
1
1
1
1
129.0 (s, arom. C); 125.1 (d, J(C,H)=162, C(6)); 118.9 (d, J(C,H)=159, arom. C); 116.9 (d, J(C,H)=164,
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1
arom. C); 113.8 (s, arom. C); 77.8 (d, J(C,H)=145, C(2)); 73.4, 73.3 (2d, J(C,H)ꢄ142, C(3), C(1)); 61.4 (d,
1J(C,H)=138, C(4)); 56.7 (q, 1J(C,H)=145, MeO); 50.0 (t, 1J(C,H)=139, ArCH2N). CI-MS (NH3): 360 (5,
[M+H]+), 302 (64), 299 (37), 262 (10), 229 (14), 217 (32), 215 (24), 152 (11), 140 (22), 137 (30), 125 (22), 123
(59), 110 (100), 96 (19), 94 (17), 80 (16), 70 (7). HR-MALDI-TOF-MS: 382.0205 (C14H18BrNNaOþ5 ,
[M+Na]+; calc. 382.0266).
(ꢀ)-(1R,2S,3S,4R)-4-[(2-Bromo-5-hydroxy-4-methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢀ)-
(1S,2S,3R,6R)-6-[(2-Bromo-5-hydroxy-4-methoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢀ)-19i). According
25
to the G.P., with (ꢀ)-5 and 2-bromo-5-hydroxy-4-methoxybenzaldehyde: (ꢀ)-19i (80%). ½aꢃ589 =ꢀ70,
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½aꢃ577 =ꢀ73, ½aꢃ435 =ꢀ148, ½aꢃ405 =ꢀ189 (c=0.332, MeOH). HR-MALDI-TOF-MS: 382.0259
(C14H18BrNNaOþ5 , [M+Na]+; calc. 382.0266).
Enantiomer (+)-ent-19i. According to the G.P., with (+)-5 and 2-bromo-5-hydroxy-4-methoxybenzalde-
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hyde: (+)-ent-19i (88%). ½aꢃ589 =+74, ½aꢃ577 =+77, ½aꢃ435 =+156, ½aꢃ405 =+192 (c=0.30, MeOH). HR-
MALDI-TOF-MS: 382.0266 (C14H18BrNNaOþ5 , [M+Na]+; calc. 382.0266).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(3-Methoxybenzyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(3-Methoxybenzyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19j). According to the G.P., with (ꢂ)-5 and
3-methoxybenzaldehyde (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19j (77%). Colorless solid. UV
(MeOH): 280 (845), 274 (907), 220 (2586), 196 (266). IR (KBr): 3373, 1604, 1560, 1516, 1458, 1413, 1268,
1124, 1038, 960, 783, 694. 1H-NMR (400 MHz, CD3OD): 7.34–7.30 (m, 1 arom. H); 7.04–7.00 (m, 2 arom.

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H); 6.95–6.90 (m, 1 arom. H); 5.81 (ddd, 3J(5,6)=10.0, 3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.74 (ddd, 3J(6,5)=10.0,
3J(6,4)=3J(6,1)=3.0, HꢀC(6)); 4.15–4.10 (m, HꢀC(1)); 4.12 (d, 3J=13.0, 1 H, ArCH2N); 4.03 (d, 3J=13.0, 1 H,
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3
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3
ArCH2N); 3.63 (dd, J(3,2)=9.7, J(3,4)=8.9, HꢀC(3)); 3.59–3.54 (m, HꢀC(4)); 3.43 (dd, J(2,3)=9.7, J(2,
1)=8.0, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 161.6 (s, arom. C); 136.9 (s, arom. C); 135.2 (d, 1J(C,
H)=163, C(5)); 131.1 (d, 1J(C,H)=160, arom. C); 123.3 (d, 1J(C,H)=163, C(6)); 122.6 (d, 1J(C,H)=160,
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arom. C); 115.9 (d, J(C,H)=158, arom. C); 115.3 (d, J(C,H)=160, arom. C); 77.6 (d, J(C,H)=140, C(2));
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73.0, 72.8 (2d, J(C,H)ꢄ142, C(3), C(1)); 61.5 (d, J(C,H)=142, C(4)); 55.8 (q, J(C,H)=144, MeO); 50.2 (t,
1J(C,H)=141, 1 C, ArCH2N). CI-MS (NH3): 265 (3, M+), 232 (5), 205 (47), 176 (5), 163 (5), 144 (21), 138 (7),
136 (35), 122 (21), 121 (100), 107 (41), 91 (17), 84 (65), 77 (3). HR-MALDI-TOF-MS: 288.1203
(C14H19NNaOþ4 , [M+Na]+; calc. 288.1212). Anal. calc. for C14H19NO4 (265.131): C 63.38, H 7.22, N 5.58;
found: C 63.02, H 7.00, N 5.69.
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(1-Naphthylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,
6SR)-6-[(Naphthalen-1-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19k). According to the G.P., with (ꢂ)-
5 and 1-naphthaldehyde (=naphthalene-1-carboxaldehyde) (TLC monitoring, MeOH/AcOEt 1 :4): (ꢂ)-19k
(79%). Colorless solid. UV (MeOH): 291 (3582), 280 (4998), 227 (5467), 218 (4853), 208 (3977). IR (KBr):
1
3414, 1610, 1559, 1460, 1419, 1121, 1036, 780, 668. H-NMR (400 MHz, CD3OD): 8.18 (d, 3J=8.5, 1 arom. H);
7.96–7.89 (m, 2 arom. H); 7.67–7.49 (m, 4 arom. H); 5.85 (br. s, HꢀC(6), HꢀC(5)); 4.62 (d, 3J=13.2, 1 H,
ArCH2N); 4.56 (d, 3J=13.2, 1 H, ArCH2N); 4.16 (dd, 3J(1,2)=8.1, 3J(1,6)=3.2, HꢀC(1)); 3.77 (dd, 3J(3,
2)=9.3, J(3,4) =8.8, HꢀC(3)); 3.73 (dd, 3J(4,3)=8.8, 3J(4,6)=3.2, HꢀC(4)); 3.51 (dd, 3J(2,3)=9.3, 3J(2,
1)=8.1, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 135.5 (s, arom. C); 134.4 (d, 1J(C,H)=162, C(5)); 132.9
1
(s, arom. C); 132.4 (s, arom. C); 130.3 (d, J(C,H)=160, arom. C); 130.0 (d, 1J(C,H)=160, arom. C); 129.2 (d,
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1J(C,H)=158, arom. C); 127.9 (d, J(C,H)=160, arom. C); 127.2 (d, J(C,H)=160, arom. C); 126.5 (d, J(C,
H)=161, arom. C); 124.7 (d, 1J(C,H)=162, C(6)); 124.2 (d, J(C,H)=158, arom. C); 77.8 (d, J(C,H)=142,
C(2)); 73.3, 73.1 (2d, 1J(C,H)ꢄ142, C(3), C(1)); 62.2 (d, 1J(C,H)=140, C(4)); 47.7 (t, 1J(C,H)=139,
ArCH2O). CI-MS (NH3): 285 (5, M+), 226 (75), 225 (62), 157 (5), 142 (73), 141 (100), 128 (5), 115 (18), 84
(95), 77 (2). HR-MALDI-TOF-MS: 286.1522 (C17H20NOþ3 , [M+H]+; calc. 286.1443).
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(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(1H-Indol-3-ylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,
3SR,6SR)-6-[(1H-Indol-3-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19l). According to the G.P., with
(ꢂ)-5 and 1H-indole-3-carboxaldehyde (TLC monitoring, 25% aq. NH3 soln./MeCN 1:9): (ꢂ)-19l (30%). Col-
orless solid. UV (MeOH): 287 (3842), 276 (4439), 270 (2261), 225 (4837). IR (KBr): 3382, 1616, 1457, 1419, 1243,
1111, 1034, 748. 1H-NMR (400 MHz, CD3OD): 7.73 (d, 3J=7.8, 1 arom. H); 7.52 (s, 1 arom. H); 7.44 (d, 3J=8.0, 1
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3
3
arom. H); 7.23–7.11 (m, 2 arom. H); 5.93 (ddd, J(5,6)=10.4, J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.83 (ddd, J(6,
5)=10.4, 3J(6,4)=3J(6,1)=2.0, HꢀC(6)); 4.54 (br. s, ArCH2N); 4.15–4.12 (m, HꢀC(1)); 3.86–3.80 (m, Hꢀ
C(4)); 3.80 (dd, 3J(3,4)=3J(3,2)=8.5, HꢀC(3)); 3.45 (dd, 3J(2,3)=3J(2,1)=8.5, HꢀC(2)). 13C-NMR (100.6
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1
MHz, CD3OD): 138.0 (s, arom. C); 136.5 (d, J(C,H)=163, C(5)); 127.9 (s, arom. C); 127.8 (d, J(C,H)=182,
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arom. C); 123.3 (d, J(C,H)=158, arom. C); 121.7 (d, J(C,H)=163, C(6)); 120.9 (d, J(C,H)=159, arom. C);
119.0 (d, 1J(C,H)=158, arom. C); 112.8 (d, 1J(C,H)=159, arom. C); 106.4 (s, arom. C); 77.6 (d, 1J(C,
H)=146, C(2)); 72.9 (d, J(C,H)=143, C(1)); 72.3 (d, 1J(C,H)=142, C(3)); 61.0 (d, J(C,H)=138, C(4)); 41.3
(t, 1J(C,H)=144, ArCH2N). HR-MALDI-TOF-MS: 297.1856 (C15H18N2NaOþ3 , [M+Na]+; calc. 297.1215).
Anal. calc. for C15H18N2O3 (274.1317): C 65.68, H 6.61, N 10.21; found C 66.01, H 6.81, N 10.32.
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(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(1H-Imidazol-5-ylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,
3SR,6SR)-6-[(1H-imidazol-5-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19m). According to the G.P.,
with (ꢂ)-5 and 1H-imidazole-4-carboxaldehyde. FC (25% aq. NH3 soln./MeCN 1:4): (ꢂ)-19m (10%). Yellowish
oil. 1H-NMR (400 MHz, CD3OD): 7.75 (s, 1 arom. H); 7.01 (s, 1 arom. H); 5.81 (ddd, 3J(5,6)=10.4, 3J(5,4)=3J(5,
1)=2.2, HꢀC(5)); 5.74 (ddd, J(6,5)=10.4, J(6,4)=3J(6,1)=2.2, HꢀC(6)); 4.15 (d, J=13.9, 1 H, ArCH2N);
4.10 (m, HꢀC(1)); 4.07 (d, 3J=13.9, 1 H, ArCH2N); 3.68–3.42 (m, HꢀC(4), HꢀC(3)), HꢀC(2)). HR-
MALDI-TOF-MS: 248.1070 (C10H15N3NaOþ3 , [M+H]+; calc. 248.1011).
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(ꢂ)-(1RS,2SR,3SR,4RS)-4-{[4-(4-Methoxyphenoxy)benzyl]amino}cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-
(1RS,2RS,3SR,6SR)-6-{[4-(4-Methoxyphenoxy)benzyl]amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-19n). According
to the G.P., with (ꢂ)-5 and 23n (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19n (84%). Colorless solid. UV
(MeOH): 280 (2708), 274 (2765), 260 (2479), 238 (8066). IR (KBr): 3380, 1614, 1542, 1501, 1441, 1232, 1034,
834. 1H-NMR (400 MHz, CD3OD): 7.45 (d, 3J=8.6, 2 arom. H); 7.00–6.94 (m, 6 arom. H); 5.89 (ddd, 3J(5,
6)=10.3, 3J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.77 (ddd, 3J(6,5)=10.3, 3J(6,5)=3J(6,1)=2.3, HꢀC(6)); 4.23 (d,
3J=13.1, 1 H, ArCH2N); 4.18 (d, 3J=13.1, 1 H, ArCH2N); 4.16–4.12 (m, HꢀC(1)); 3.80 (br. s, Me); 3.76–
3.71 (m, HꢀC(4), HꢀC(3)); 3.46 (dd, 3J(2,3)=9.6, 3J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD):
160.8 (s, arom. C); 157.9 (s, arom. C); 150.8 (s, arom. C); 135.8 (d, 1J(C,H)=164, C(5)); 132.4 (d, 1J(C,

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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
H)=159, 2 arom. C); 128.2 (s, arom. C); 122.5 (d, 1J(C,H)=164, C(6)); 122.1 (d, 1J(C,H)=162, 2 arom. C); 118.6
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1
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(d, J(C,H)=162, 2 arom. C); 116.0 (d, J(C,H)=161, 2 arom. C); 77.6 (d, J(C,H)=144, C(2)); 72.8 (d, J(C,
H)=143, C(1)); 72.5 (d, J(C,H)=142, C(3)); 61.4 (d, J(C,H)=143, C(4)); 56.0 (t, 1J(C,H)=144, MeO); 49.5
(t, 1J(C,H)=142, ArCH2N). CI-MS (NH3): 357 (10, [M]+), 297 (23), 213 (100), 141 (5), 115 (3), 107 (6), 90
(18), 84 (27), 77 (27). HR-MALDI-TOF-MS: 380.1477 (C20H23NNaOþ5 , [M+Na]+; calc. 380.1474).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{[4-(4-Bromophenoxy)benzyl]amino}cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,
2RS,3SR,6SR)-6-{[4-(4-Bromophenoxy)benzyl]amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-19o). According to the
G.P., with (ꢂ)-5 and 23o (TLC monitoring, MeOH/AcOEt 1 :4): (ꢂ)-19o (56%). Colorless solid. UV
(MeOH): 269 (2278), 260 (2555), 238 (8955). IR (KBr): 3382, 1612, 1579, 1483, 1421, 1242, 1010. 1H-NMR
(400 MHz, CD3OD): 7.54–7.51 (m, 4 arom. H); 7.06 (d, 3J=8.6, 2 arom. H); 6.96 (d, 3J=8.9, 2 arom. H);
5.90 (ddd, 3J(5,6)=10.3, 3J(5,4)=3J(5,1)=2.3, HꢀC(5)); 5.80 (ddd, 3J(6,5)=10.3, 3J(6,4)=3J(6,1)=2.3, Hꢀ
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1
3
3
C(6)); 4.27 (d, J=13.1, 1 H, ArCH2N); 4.22 (d, J=13.1, 1 H, ArCH2N); 4.16–4.12 (m, HꢀC(1)); 3.78–3.71
(2m, HꢀC(4), HꢀC(3)); 3.47 (dd, J(2,3)=9.6, J(2,1)=7.9, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 158.9
3
3
1
1
(s, arom. C); 157.6 (s, arom. C); 135.8 (d, J(C,H)=164, C(5)); 134.0 (d, J(C,H)=167, 2 arom. C); 132.7 (d,
1J(C,H)=160, 2 arom. C); 130.0 (s, arom. C); 122.8 (d, J(C,H)=164, C(6)); 122.0 (d, J(C,H)=164, 2 arom.
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C); 120.2 (d, 1J(C,H)=164, 2 arom. C); 117.2 (s, arom. C); 77.6 (d, 1J(C,H)=145, C(2)); 72.9 (d, 1J(C,
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H)=142, C(1)); 72.6 (d, J(C,H)=139, C(3)); 61.5 (d, J(C,H)=145, C(4)); 49.5 (t, J(C,H)=137, ArCH2N).
CI-MS (NH3): 347 (5), 263 (37), 261 (38), 149 (17), 107 (10), 101 (14), 86 (100), 84 (54), 76 (21), 70 (21). HR-
MALDI-TOF-MS: 428.0487 (C19H20BrNNaOþ4 , [M+Na]+; calc. 428.0473).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{{4-[4-(1H-Imidazol-1-yl)phenoxy]benzyl}amino}cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1RS,2RS,3SR,6SR)-6-{{4-[4-(1H-Imidazol-1-yl)phenoxy]benzyl}amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-
19p). According to the G.P., with (ꢂ)-5 and 23p (TLC monitoring, 25% aq. NH3 soln./MeCN 1 :9): (ꢂ)-19p
(57%). Colorless solid. UV (MeOH): 253 (10000), 199 (1270). IR (KBr): 3386, 1519, 1506, 1242, 1115, 1060,
1
3
836. H-NMR (400 MHz, CD3OD): 8.11 (s, 1 arom. H); 7.58 (d, J=8.8, 2 arom. H); 7.56 (s, 1 arom. H); 7.46
(d, 3J=8.5, 2 arom. H); 7.17 (s, 1 arom. H); 7.16 (d, 3J=8.6, 2 arom. H); 7.09 (d, 3J=8.4, 2 arom. H); 5.86,
5.79 (2ddd, 3J(6,5)=3J(5,6)=10.4, 3J(6,4)=3J(5,4)=3J(6,1)=3J(5,1)=2.3, HꢀC(6), HꢀC(5)); 4.22 (d,
3J=13.1, 1 H, ArCH2N)); 4.14 (d, J=13.1, 1 H, ArCH2N); 4.16–4.13 (m, HꢀC(1)); 3.73–3.60 (m, HꢀC(4),
3
HꢀC(3)); 3.47 (t, J(2,3)=3J(2,1)=8.3, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 158.6 (s, arom. C); 157.7
3
(s, arom. C); 137.0 (d, 1J(C,H)=210, arom. C); 135.1 (d, 1J(C,H)=163, C(5)); 134.2 (s, arom. C); 132.5 (d,
1J(C,H)=160, 2 arom. C); 131.2 (s, arom. C); 130.1 (d, 1J(C,H)=191, arom. C); 124.2 (d, 1J(C,H)=163, 2
1
1
1
arom. C); 123.6 (d, J(C,H)=163, C(6)); 121.1 (d, J(C,H)=163, 2 arom. C); 120.2 (d, J(C,H)=162, 2 arom.
1
1
1
C); 120.0 (d, J(C,H)=192, arom. C); 77.7 (d, J(C,H)=141, C(2)); 73.1, 73.0 (2d, J(C,H)=142, C(3), C(1));
61.5 (d, 1J(C,H)=142, C(4)); 49.7 (t, 1J(C,H)=139, ArCH2N). HR-MALDI-TOF-MS: 416.1580
(C22H23N3NaOþ4 , [M+Na]+; calc. 416.1586). Anal. calc. for C22H23N3O4 (393.1689): C 67.16, H 5.89, N 10.68;
found: C 67.10, H 6.00, N 10.82.
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{[4-(4-Acetylphenoxy)benzyl]amino}cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-1-{4-
[4-({[(1RS,2RS,3SR,6SR)-4,5,6-Trihydroxycyclohex-2-en-1-yl]amino}methyl)phenoxy]phenyl}ethanone; (ꢂ)-
19q). According to the G.P., with (ꢂ)-5 and 23q (TLC monitoring, MeOH/AcOEt 1:4): (ꢂ)-19q (64%). Color-
less solid. UV (MeOH): 273 (8340), 259 (7980), 225 (6960). IR (KBr): 3387, 1677, 1594, 1500, 1418, 1260, 1098,
1022. 1H-NMR (400 MHz, CD3OD): 8.03 (d, 3J=8.7, 2 arom. H); 7.56 (d, 3J=8.3, 2 arom. H); 7.14 (d, 3J=8.4, 2
arom. H); 7.06 (d, 3J=8.7, 2 arom. H); 5.87 (ddd, 3J(5,6)=10.3, 3J(5,4)=3J(5,1)=2.1, HꢀC(5)); 5.79 (ddd, 3J(6,
3
3
3
5)=10.3, J(6,4)=3J(6,1)=2.1, HꢀC(6)); 4.24 (d, J=13.0, 1 H, ArCH2N); 4.17 (d, J=13.0, 1 H, ArCH2N);
3
3
4.16–4.12 (m, HꢀC(1)); 3.75–3.65 (m, HꢀC(4), HꢀC(3)); 3.47 (dd, J(2,3)=8.9, J(2,1)=8.1, HꢀC(2)); 2.57
(br. s, Me). 13C-NMR (100.6 MHz, CD3OD): 199.2 (s, COMe); 163.1 (s, arom. C); 157.4 (s, arom. C); 135.2
1
1
(d, J(C,H)=163, C(5)); 133.4 (s, arom. C); 132.6 (d, J(C,H)=160, 2 arom. C); 132.1 (s, arom. C); 132.0 (d,
1J(C,H)=160, 2 arom. C); 123.5 (d, 1J(C,H)=163, C(6)); 121.4 (d, 1J(C,H)=162, arom. C); 118.6 (d, 1J(C,
H)=162, 2 arom. C); 77.7 (d, 1J(C,H)=140, C(2)); 73.0, 72.9 (2d, 1J(C,H)ꢄ142, C(3), C(1)); 61.5 (d, 1J(C,
1
1
H)=141, C(4)); 49.7 (t, J(C,H)=138, ArCH2N); 26.6 (q, J(C,H)=128, COMe). CI-MS (NH3): 309 (15), 225
(100), 167 (11), 149 (35), 121 (22), 110 (18), 98 (16), 84 (42), 76 (41), 70 (12). HR-MALDI-TOF-MS:
370.1590 (C21H24NO5þ, [M+H]+; calc. 370.1654).
1 :1 Mixture of (ꢂ)-(1RS,2SR,3SR,4RS)-4-{{4-{4-[(1RS)- and (ꢂ)-(1RS,2SR,3SR,4RS)-4-{{4-{4-[(1SR)-1-
Hydroxyethyl]phenoxy}benzyl}amino}cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-{{4-{4-[(1RS)
and (ꢂ)-(1RS,2RS,3SR,6SR)-6-{{4-{4-[(1SR)-1-Hydroxyethyl]phenoxy}benzyl}amino}cyclohex-4-ene-1,2,3-
triol; (ꢂ)-19r). A mixture of (ꢂ)-19q (0.03 g, 0.081 mmol) in anh. MeOH (1.5 ml) and NaBH4 (0.0046 g, 0.121
mmol, 1.5 equiv.) was stirred at 208 overnight. After evaporation, the residue was purified by FC (silica gel)
(TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19r (89%). Colorless solid. IR (KBr): 3385, 1602, 1502, 1241,

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1084, 1013, 834. H-NMR (400 MHz, CD3OD): 7.37 (d, 3J=7.9, 4 arom. H); 6.95 (d, 3J=7.2, 4 arom. H); 5.75,
3
5.66 (2ddd, 3J(6,5)=3J(5,6)=10.3, J(6,4)=3J(5,4)=3J(6,1)= 3J(5,1)=2.3, HꢀC(6), HꢀC(5)); 4.83 (q, 3J=6.4,
MeCH(OH); 4.13–4.08 (m, HꢀC(1)); 3.92 (d, 3J=12.8, 1 H, ArCH2N); 3.75 (d, 3J=12.8, 1 H, ArCH2N); 3.52
3
3
3
3
(dd, J(3,2)=9.8, J(3,4)=8.7, HꢀC(3)); 3.46 (dd, J(2,3)=9.8, J(2,1)=7.7, HꢀC(2)); 3.36 (br. m, HꢀC(4));
1.45 (d, J=6.4, Me). 13C-NMR (100.6 MHz, CD3OD): 158.1 (s, arom. C); 157.7 (s, arom. C); 135.5 (s, arom.
3
C); 131.4 (d, 1J(C,H)=161, C(5)); 131.2 (d, 1J(C,H)=161, 2 arom. C); 129.9 (s, arom. C); 128.0 (d, 1J(C,
H)=162, 2 arom. C); 127.8 (d, 1J(C,H)=161, C(5)); 119.7 (d, 1J(C,H)=161, 4 arom. C); 78.0 (d, 1J(C,
H)=144, C(2)); 74.5 (d, 1J(C,H)=141, C(3)); 73.6 (d, 1J(C,H)=142, C(1)); 70.3 (d, 1J(C,H)=143, MeCH(OH);
1
1
1
61.3 (d, J(C,H)=144, C(4)); 50.6 (t, J(C,H)=139, ArCH2N); 25.6 (q, J(C,H)=126, Me). CI-MS (NH3): 372
(13, [M+H]+), 305 (21), 231 (4), 188 (15), 168 (7), 149 (57), 144 (48), 122 (20), 104 (100), 91 (61), 79 (39), 71
(29). HR-MALDI-TOF-MS: 394.5398 (C21H25NNaOþ5 , [M+Na]+; calc. 394.1630).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{{4-[4-(1,1-Dimethoxyethyl)phenoxy]benzyl}amino}cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1RS,2RS,3SR,6SR)-6-{{4-[4-(1,1-Dimethoxyethyl)phenoxy]benzyl}amino}cyclohex-4-ene-1,2,3-triol;
(ꢂ)-19s). According to the G.P., with (ꢂ)-5 and 24 in MeOH (TLC monitoring, MeOH/AcOEt 1 :4): (ꢂ)-19s
(60%). Solid. UV (MeOH): 265 (2965), 236 (6448), 202 (1487). IR (KBr): 3374, 1601, 1502, 1420, 1245, 1094,
1
3
3
3
878. H-NMR (400 MHz, CD3OD): 7.54 (d, J=8.5, 2 arom. H); 7.49 (t, J=8.6, 2 arom. H); 7.05 (d, J=8.5,
2 arom. H); 6.99 (t, 3J=8.7, 2 arom. H); 5.93 (ddd, 3J(5,6)=10.3, 3J(5,4)=3J(5,1)=2.3, HꢀC(5)); 5.82 (ddd,
3J(6,5)=10.3, 3J(6,4)=3J(6,1)=2.3, HꢀC(6)); 4.30 (br. s, ArCH2N); 4.17–4.14 (m, HꢀC(1)); 3.86–3.78 (m,
HꢀC(4), H-C(3)); 3.47 (dd, J(2,3)=8.9, J(2,1)=7.8, HꢀC(2)); 3.18 (br. s, 2 MeO); 1.52 (s, Me). 13C-NMR
(100.6 MHz, CD3OD): 159.6 (s, arom. C); 157.4 (s, arom. C); 136.5 (d, 1J(C,H)=163, C(5)); 133.0 (s, arom.
C); 132.9 (2d, 1J(C,H)=160, 2 arom. C); 132.0 (s, arom. C); 129.1 (d, 1J(C,H)=161, 2 arom. C); 121.8 (d,
1J(C,H)=163, C(6)); 119.9 (d, 1J(C,H)=162, 2 arom. C); 119.7 (d, 1J(C,H)=162, 2 arom. C); 102.7 (s,
3
3
1
1
1
MeC(OMe)2); 77.5 (d, J(C,H)=142, C(2)); 72.8, 72.3 (2d, J(C,H) ꢄ 143, C(3), C(1)); 61.6 (d, J(C,H)=137,
C(4)); 49.4 (t, 1J(C,H)=141, ArCH2N); 49.2 (q, 1J(C,H)=142, 2 MeO); 26.4 (q, 1J(C,H)=127, Me). CI-MS
(NH3): 333 (3), 309 (18), 240 (13), 225 (100), 197 (20), 181 (13), 155 (28), 149 (50), 128 (17), 121 (38), 107
(48), 94 (47), 84 (32), 77 (45). HR-MALDI-TOF-MS: 438.1820 (C23H29NNaOþ6 , [M+Na]+; calc. 438.1893).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{{4-[(2-Methylquinolin-8-yl)oxy]benzyl}amino}cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1RS,2RS,3SR,6SR)-6-{{4-[(2-Methylquinolin-8-yl)oxy]benzyl}amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-
19t). According to the G.P., with (ꢂ)-5 and 23t (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19t (81%). Colorless
solid. UV (MeOH): 292 (4089), 279 (4333), 244 (11828). IR (KBr): 3395, 1609, 1560, 1508, 1430, 1236, 1079. 1H-
NMR (400 MHz, CD3OD): 8.26 (d, 3J=8.5, 1 arom. H); 7.67 (d, 3J=8.0, 1 arom. H); 7.50–7.43 (m, 4 arom. H);
7.16 (d, 3J=7.5, 1 arom. H); 7.08 (d, 3J=8.5, 2 arom. H); 5.87, 5.76 (2ddd, 3J(6,5)=3J(5,6)=10.3, 3J(6,4)=3J(5,
4)=3J(6,1)=3J(5,1)=2.4, HꢀC(6), HꢀC(5)); 4.24 (d, 3J=13.1, 1 H, ArCH2N); 4.18 (d, 3J=13.1, 1 H, ArCH2N);
3
3
4.13–4.11 (m, HꢀC(1)); 3.75–3.70 (m, HꢀC(4), HꢀC(3)); 3.46 (dd, J(2,3)=8.9, J(2,1)=7.8, HꢀC(2)); 2.68
(br. s, Me). 13C-NMR (100.6 MHz, CD3OD): 160.8 (s, arom. C); 159.7 (s, arom. C); 153.3 (s, arom. C); 141.4
(s, arom. C); 138.3 (d, 1J(C,H)=162, arom. C); 135.7 (d, 1J(C,H)=163, C(5)); 132.5 (d, 1J(C,H)=160, 2
arom. C); 129.9 (s, arom. C); 129.7 (s, arom. C); 127.1 (d, 1J(C,H)=163, arom. C); 124.5 (d, 1J(C,H)=161,
arom. C); 124.4 (d, 1J(C,H)=161, arom. C); 122.9 (d, 1J(C,H)=163, C(6)); 120.3 (d, 1J(C,H)=162, 2 arom.
C); 118.6 (d, 1J(C,H) =160, arom. C); 77.6 (d, 1J(C,H)=141, C(2)); 73.0 (d, 1J(C,H)=143, C(1)); 72.7 (d,
1J(C,H)=141, C(3)); 61.6 (d, 1J(C,H)=143, C(4)); 49.6 (t, 1J(C,H)=138, ArCH2N); 24.7 (q, 1J(C,H)=127,
Me). CI-MS (NH3): 393 (3, [M+H]+), 333 (19), 249 (95), 248 (100), 218 (8), 204 (6), 143 (18), 124 (6), 115
(26), 103 (5), 89 (19), 77 (12). HR-MALDI-TOF-MS: 415.1601 (C23H24N2NaOþ4 , [M+Na]+; calc. 415.1634).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{[4-(4-Phenoxyphenoxy)benzyl]amino}cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-
(1RS,2RS,3SR,6SR)-6-{[4-(4-Phenoxyphenoxy)benzyl]amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-19u). According
to the G.P., with (ꢂ)-5 and 23u (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19u (70%). Colorless solid. UV
(MeOH): 271 (3040), 260 (3460), 241 (10357). IR (KBr): 3378, 1609, 1511, 1488, 1225, 1023, 867. 1H-NMR
(400 MHz, CD3OD): 7.48 (d, 3J=8.5, 2 arom. H); 7.36 (t, 3J=7.6, 2 arom. H); 7.11 (t, 3J=7.4, 1 arom. H);
3
3
3
7.05–6.98 (m, 8 arom. H); 5.87 (ddd, J(5,6)=10.3, J(5,4)=3J(5,1)=2.3, HꢀC(5)); 5.77 (ddd, J(6,5)=10.3,
3J(6,4)=3J(6,1)=2.3, HꢀC(6)); 4.22 (d, J=13.1, 1 H, ArCH2N); 4.16 (d, J=13.1, 1 H, ArCH2N); 4.15–4.10
(m, HꢀC(1)); 3.75–3.67 (m, HꢀC(4), HꢀC(3)); 3.46 (dd, 3J(2,3)=8.9, 3J(2,1)=8.2, H-C(2)). 13C-NMR
(100.6 MHz, CD3OD): 160.0 (s, arom. C); 159.1 (s, arom. C); 154.8 (s, arom. C); 153.5 (s, arom. C); 135.5 (d,
3
3
1J(C,H)=161, C(5)); 132.5 (d, J(C,H)=159, 2 arom. C); 130.9 (d, J(C,H)=157, 2 arom. C); 129.5 (s, arom.
1
1
C); 124.3 (d, 1J(C,H)=159, arom. C); 123.0 (d, 1J(C,H)=161, C(6)); 122.0 (d, 1J(C,H)=164, 2 arom. C);
1
1
1
121.5 (d, J(C,H)=162, 2 arom. C); 119.4 (d, J(C,H)=162, 2 arom. C); 119.3 (d, J(C,H)=160, 2 arom. C);
77.6 (d, 1J(C,H)=142, C(2)); 73.0 (d, 1J(C,H)=142, C(1)); 72.8 (d, 1J(C,H)=142, C(3)); 61.5 (d, 1J(C,
H)=137, C(4)); 49.6 (t, 1J(C,H)=141, ArCH2N). CI-MS (NH3): 420 (8, [M+H]+), 359 (28), 290 (5), 275

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HELVETICA CHIMICA ACTA – Vol. 88 (2005)
(100), 181 (13), 154 (10), 141 (10), 115 (17), 107 (11), 84 (30), 77 (62). HR-MALDI-TOF-MS: 442.1644
(C25H25NNaOþ5 , [M+Na]+; calc. 442.1630).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Propylamino)cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-(Pro-
pylamino)cyclohex-4-ene-1,2,3-triol; (ꢂ)-19v). According to the G.P., with (ꢂ)-5 and propanal (TLC monitor-
ing, MeOH/AcOEt 1 :3): (ꢂ)-19v (77%). Pale yellowish oil. UV (MeOH): 213 (867). IR (KBr): 3320, 2924,
1464, 1377, 1132, 1043, 996. 1H-NMR (400 MHz, CD3OD): 5.71–5.63 (br. m, HꢀC(6), HꢀC(5)); 4.11–4.07
3
3
3
(m, HꢀC(1)); 3.48 (dd, J(3,4)=8.2, J(3,2)=10.3, HꢀC(3)); 3.43 (dd, 3J(2,3)=10.3, J(2,1)=7.3, HꢀC(2));
3.34–3.15 (m, HꢀC(4), CH2(1’)); 2.09 (sext., 3J(2’,3’)=3J(2’,1’)=7.4, CH2(2’)); 0.99 (t, J(3’,2’)=7.4, Me). 13C-
3
1
1
NMR (100.6 MHz, CD3OD): 131.3, 126.9 (2d, J(C,H)=162, C(6), C(5)); 77.9 (d, J(C,H)=144, C(2)); 74.1,
1
1
1
1
73.7 (2d, J(C,H) ꢄ 138, C(3), C(1)); 60.7 (d, J(C,H)=131, C(4)); 54.7 (t, J(C,H)=138, C(1’)); 22.0 (t, J(C,
H)=126, C(2’)); 14.3 (q, 1J(C,H)=126, Me). CI-MS (NH3): 167 (26), 146 (2), 122 (2), 110 (3), 98 (6), 84
(100), 81 (6), 70 (8). HR-MALDI-TOF-MS: 226.0818 (C9H17KNOþ5 , [M+K]+; calc. 226.0846).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Hexylamino)cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1RS,2RS,3SR,6SR)-6-
(Hexylamino)cyclohex-4-ene-1,2,3-triol; (ꢂ)-19w). According the the G.P., with (ꢂ)-5 and hexanal (TLC mon-
itoring, MeOH/AcOEt 3 :7): (ꢂ)-19w (62%). Colorless oil. UV (MeOH): 207 (1507). IR (KBr): 3375, 2925,
1
1634, 1456, 1383, 1037, 960. H-NMR (400 MHz, CD3OD): 5.71–5.63 (br. m, HꢀC(6), HꢀC(5)); 4.07 (m, Hꢀ
C(1)); 3.49 (dd, 3J(3,2)=10.0, 3J(3,4)=8.5, HꢀC(3)); 3.43 (dd, 3J(2,3)=10.0, 3J(2,1)=7.6, HꢀC(2)); 3.35–
3.33 (m, HꢀC(4)); 2.85–2.77, 2.68–2.61 (2m, CH2(1’)); 1.60–1.51 (m, CH2(2’); 1.42–1.30 (m, CH2(3’),
CH2(4’), CH2(5’)); 0.92 (t, 3J(6’,5’)=7.0, Me). 13C-NMR (100.6 MHz, CD3OD): 132.5, 126.7 (2d, 1J(C,
H)ꢄ161, C(6), C(5)); 77.9 (d, 1J(C,H)=140, C(2)); 73.8, 73.5 (2d, 1J(C,H)ꢄ144, C(3), C(1)); 62.0 (d, 1J(C,
1
1
1
H)=143, C(4)); 47.0 (t, J(C,H)=131, C(1’)); 32.8 (t, J(C,H)=131, C(2’)); 30.2, 27.9, 23.6 (3t, J(C,H)=124,
1
C(3’), C(4’), C(5’)); 14.4 (q, J(C,H)=124, Me). CI-MS (NH3): 230 (3), 170 (10), 169 (100), 158 (5), 140 (31),
126 (3), 112 (12), 98 (48), 94 (7), 84 (33), 80 (12), 70 (9). HR-MALDI-TOF-MS: 230.1709 (C12H24NOþ3 ,
[M+H]+; calc. 230.1756). Anal. calc. for C12H23NO3 (229.167): C 62.85, H 10.11, N 6.11; found: C 63.11, H
10.40, N 6.27.
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Octylamino)cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-(Octyl-
amino)cyclohex-4-ene-1,2,3-triol; (ꢂ)-19x). According to the G.P., with (ꢂ)-5 and octanal (TLC monitoring,
MeOH/AcOEt 3 :7): (ꢂ)-19x (53%). Oil. UV (MeOH): 207 (1052). IR (KBr): 3374, 2926, 2855, 1560, 1419,
1123, 1034, 781. H-NMR (400 MHz, CD3OD): 5.87 (ddd, J(5,6)=10.4, J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.70
(ddd, 3J(6,5)=10.4, 3J(6,4)=3J(6,1)=2.0, HꢀC(6)); 4.14–4.11 (m, HꢀC(1)); 3.74–3.69 (m, HꢀC(4)); 3.66
(dd, 3J(3,2)=3J(3,4)=9.5, HꢀC(3)); 3.45 (dd, 3J(2,3)=9.5, 3J(2,1)=8.1, HꢀC(2)); 3.10–2.95 (m, CH2(1’));
1.73–1.63 (m, CH2(2’)); 1.46–1.27 (m, CH2(3’), CH2(4’), CH2(5’), CH2(6’), CH2(7’)); 0.92 (t, 3J(8’,7’)=7.0,
1
3
3
Me). 13C-NMR (100.6 MHz, CD3OD): 135.9 (d, J(C,H)=161, C(5)); 122.4 (d, J(C,H)=165, C(6)); 77.5 (d,
1
1
1J(C,H)=140, C(2)); 72.9 (d, 1J(C,H)=139, C(1)); 72.2 (d, J(C,H)=145, C(3)); 61.9 (d, J(C,H)=144, C(4));
1
1
1
1
46.3 (t, J(C,H)=142, C(1’)); 32.9 (t, J(C,H)=125, C(2’)); 30.2, 30.3, 28.1, 27.8, 23.7 (5t, 5 C(3’), C(4’), C(5’),
C(6’), C(7’)); 14.4 (q, J(C,H)=124, Me). CI-MS (NH3): 258 (6, [M+H]+), 198 (43), 197 (100), 168 (53), 158
1
(5), 154 (2), 140 (12), 130 (5), 122 (7), 111 (8), 98 (69), 84 (39), 80 (17), 70 (13). HR-MALDI-TOF-MS:
280.1880 (C14H27NNaO3þ, [M+Na]+; calc. 280.1889).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[(2-Phenylethyl)amino]cyclohex-5-ene-1,2,3-triol2)
(=(ꢂ)-(1SR,2SR,3RS,
6RS)-6-[(2-Phenylethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-19y). According to the G.P., with (ꢂ)-5 and 2-
phenylethanal (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19y (42%). Colorless solid. UV (MeOH): 212
(3652). IR (KBr): 3384, 1569, 1413, 1125, 1030, 753, 701. 1H-NMR (400 MHz, CD3OD): 7.37–7.23 (m, 5
arom. H); 5.87 (ddd, 3J(5,6)=10.4, 3J(5,4)=3J(5,1)=2.0, HꢀC(5)); 5.72 (ddd, 3J(6,5)=10.4, 3J(6,4)=3J(6,
1)=2.0, HꢀC(6)); 4.12 (dd, 3J(1,2)=8.0, 3J(1,6)=2.0, HꢀC(1)); 3.77–3.72 (m, HꢀC(4)); 3.66 (dd, 3J(3,
3
4)=8.5, 3J(3,2)=9.6, HꢀC(3)); 3.46 (dd, J(2,3)=9.6, 3J(2,1)=8.0, HꢀC(2)); 3.35–3.20 (m, CH2(1’)); 3.00 (t,
3J(2’,1’)=7.0, CH2(2’)). 13C-NMR (100.6 MHz, CD3OD): 138.6 (s, arom. C); 135.7 (d, 1J(C,H)=164, C(5));
129.8 (d, 1J(C,H)=160, 2 arom. C); 129.7 (d, 1J(C,H)=161, 2 arom. C); 128.0 (d, 1J(C,H)=154, arom. C);
122.7 (d, 1J(C,H)=164, C(6)); 77.6 (d, 1J(C,H)=140, C(2)); 72.9 (d, 1J(C,H)=140, C(1)); 72.4 (d, 1J(C,
1
1
1
H)=139, C(3)); 61.9 (d, J(C,H)=140, C(4)); 47.7 (t, J(C,H)=142, C(1’)); 34.3 (t, J(C,H)=128, C(2’)). CI-
MS (NH3): 250 (1, [M+H]+), 213 (1), 189 (19), 169 (3), 158 (100), 122 (18), 105 (48), 98 (87), 85 (70), 77
(28), 70 (11). HR-MALDI-TOF-MS: 250.1409 (C14H20NOþ3 , [M+H]+; calc. 250.1443).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-{[(5-Methyl-2-thienyl)methyl]amino}cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,
2RS,3SR,6SR)-6-{[(5-Methyl-2-thienyl)methyl]amino}cyclohex-4-ene-1,2,3-triol; (ꢂ)-19z). According to the
G.P. with (ꢂ)-5 and 5-methyltiophene-2-carboxaldehyde (TLC monitoring, MeOH/AcOEt 3 :7): (ꢂ)-19z
(30%). Colorless solid. UV (MeOH): 248 (1656), 196 (249). IR (KBr): 3378, 1611, 1560, 1542, 1420, 1125,
1036, 1011, 960, 802, 781, 686. 1H-NMR (400 MHz, CD3OD): 6.99 (d, 3J=3.4, arom. H); 6.72 (d, 3J=3.5,

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arom. H); 5.82 (ddd, 3J(5,6)=10.0, 3J(5,4)=3J(5,1)=3.0, HꢀC(5)); 5.73 (ddd, 3J(6,5)=10.0, 3J(6,4)=3J(6,
1)=3.0, HꢀC(6)); 4.35 (d, 3J=14.2, 1 H, ArCH2N); 4.31 (d, 3J=14.2, 1 H, ArCH2N); 4.14–4.09 (m, Hꢀ
3
3
C(1)); 3.70–3.60 (m, HꢀC(4), HꢀC(3)); 3.44 (dd, J(2,3)=9.6, J(2,1)=8.0, HꢀC(2)); 2.49 (s, Me). 13C-NMR
(100.6 MHz, CD3OD): 142.9 (s, arom. C); 135.0 (s, arom. C); 134.9 (d, 1J(C,H)=163, C(5)); 130.1 (d, 1J(C,
1
H)=165, arom. C); 126.5 (d, 1J(C,H)=165, arom. C); 123.6 (d, 1J(C,H)=163, C(6)); 77.6 (d, J(C,H)=141,
C(2)); 73.1, 73.0 (2d, 1J(C,H)ꢄ142, C(3), C(1)); 60.9 (d, 1J(C,H)=143, C(4)); 44.8 (t, 1J(C,H)=142, ArCH2
N); 15.2 (q, 1J(C,H)=129, Me). CI-MS (NH3): 256 (12, [M+H]+), 195 (13), 140 (18), 127 (11), 117 (5), 111
(100), 85 (5), 84 (20). HR-MALDI-TOF-MS: 256.1012 (C12H18NO3S+, [M+H]+; calc. 256.1007).
7. N,N-Disubstituted Derivatives 20 of (ꢂ)-conduramine B-1. NaBH(OAc)3 (5 equiv.) was added portion-
wise within ca. 6 h to a stirred mixture of (ꢂ)-5 (0.4 mmol) and aldehyde (propanal, octanal, 2-phenylethanal,
3 equiv.) in abs. MeOH (3 ml) at 208. After stirring at 208 for ca. 6 h, the solvent was evaporated and the residue
purified by FC (silica gel, light petroleum ether/AcOEt 1:1 ! AcOEt ! MeCN ! 25% aq. NH3 soln./MeCN
0.5 :9.5).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Dipropylamino)cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-
[(Dipropyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-20aa). As described above, with (ꢂ)-5 and propanal in excess
(TLC monitoring, MeOH/AcOEt 1 :4): (ꢂ)-20aa (60%). Colorless oil. UV (MeOH): 216 (1748). IR (KBr):
3372, 1570, 1453, 1411, 1208, 1100, 1025, 966, 736, 699. 1H-NMR (400 MHz, CD3OD): 5.86 (ddd, 3J(5,
3
3
6)=10.4, J(5,4)=3J(5,1)=2.2, HꢀC(5)); 5.73 (ddd, 3J(6,5)=10.4, J(6,4)=3J(6,1)=2.2, HꢀC(6)); 4.15–4.10
(m, HꢀC(1)); 3.85–3.79 (m, HꢀC(4)); (dd, J(3,4)=9.8, 3J(3,2)=9.8, HꢀC(3)); 3.48 (dd, J(2,3)=9.8, 3J(2,
1)=8.1, HꢀC(2)); 2.99–2.80 (m, 2 CH2(1’)); 1.68 (sext., 3J(2’,3’)= 3J(2’,1’)=7.4, 2 CH2(2’)); 0.98 (t, 3J(3’,
2’)=7.4, 2 Me). 13C-NMR (100.6 MHz, CD3OD): 135.7 (d, 1J(C,H)=162, C(5)); 123.2 (d, 1J(C,H)=162,
3
3
1
1
1
1
C(6)); 77.9 (d, J(C,H)=140, C(2)); 72.9 (d, J(C,H)=146, C(1)); 71.3 (d, J(C,H)=140, C(3)); 66.2 (d, J(C,
1
1
1
H)=136, C(4)); 55.0 (t, J(C,H)=137, 2 C(1’)); 21.2 (t, J(C,H)=127, 2 C(2’)); 14.7 (q, J(C,H)=126, 2 Me).
CI-MS (NH3): 230 (12, [M+H]+), 200 (9), 170 (36), 169 (100), 140 (46), 126 (11), 110 (13), 100 (6), 98 (29),
83 (15), 72 (47), 70 (11). HR-MALDI-TOF-MS: 230.2180 (C12H24NOþ3 , [M+H]+; calc. 230.1756). Anal. calc.
for C12H23NO3 (229.168): C 62.85, H 10.11, N. 6.11; found: C 62.50, H 10.47, N 6.00.
(ꢂ)-(1RS,2SR,3SR,4RS)-4-(Dioctylamino)cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,2RS,3SR,6SR)-6-[(Di-
octyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-20bb). As described above, with (ꢂ)-5 and an excess of octanal
(TLC monitoring, MeOH/AcOEt 0.5 :95): (ꢂ)-20bb (68%). Colorless oil. UV (MeOH): 260 (872), 206
1
(3508). IR (KBr): 3381, 2927, 1467, 1378, 1104, 965, 779. H-NMR (400 MHz, CD3OD): 5.66 (br. s, HꢀC(6),
HꢀC(5)); 4.06 (dd, 3J(1,2)=7.9, 3J(1,6)=3.2, HꢀC(1)); 3.54 (dd, 3J(3,2)=9.9, 3J(3,4)=8.7, HꢀC(3)); 3.43
(dd, 3J(2,3)=9.9, 3J(2,1)=7.9, HꢀC(2)); 3.38 (dd, 3J(4,3)=8.7, 3J(4,5)=3.2, HꢀC(4)); 2.65–2.48 (m, 4 Hꢀ
3
C(1’)); 1.51–1.29 (2 br. m, 24 H, CH2(2’) CH4(3’), CH2(4’), CH2(5’), CH2(6’), CH2(7’)); 0.92 (t, J(8’,7’)=7.0,
2 Me). 13C-NMR (100.6 MHz, CD3OD): 132.5, 127.8 (2d, 1J(C,H)=160, C(6), C(5)); 78.4 (d, 1J(C,H)=139,
1
1
1
1
C(2)); 73.4 (d, J(C,H)=140, C(1)); 72.6 (d, J(C,H)=143, C(3)); 65.5 (d, J(C,H)=136, C(4)); 52.8 (t, J(C,
H)=131, 2 C(1’)); 33.0, 30.7, 30.5, 29.9, 28.5, 23.7 (6t, 12 C, C(2’), C(3’), C(4’), C(5’), C(6’), C(7’)); 14.4 (q,
1J(C,H)=125, 2 Me). CI-MS (NH3): 369 (12, M+), 353 (5), 311 (22), 310 (100), 271 (6), 143 (2), 112 (2). HR-
MALDI-TOF-MS: 370.3859 (C22H44NOþ3 , [M+H]+; calc. 370.3321).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[Bis(2-phenylethyl)amino]cyclohex-5-ene-1,2,3-triol2) ((ꢂ)-(1RS,2RS,3SR,
6SR)-6-[Bis(2-phenylethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-20cc). As described above, with (ꢂ)-5 and an
excess of 2-phenylethanal (TLC monitoring, MeOH/AcOEt 5 :95): (ꢂ)-20cc (49%). UV (MeOH): 285
(1017), 260 (1216), 217 (3637). IR (KBr): 3419, 2927, 1559, 1496, 1452, 1261, 1098, 1029, 965. 1H-NMR (400
MHz, CD3OD): 7.30–7.13 (m, 10 arom. H); 5.65, 5.61 (2ddd, 3J(6,5)=3J(5,6) =10.6, 3J(6,4)=3J(5,4)=3J(6,
1)=3J(5,1)=2.2, HꢀC(6), HꢀC(5)); 4.04–4.01 (m, HꢀC(1)); 3.50–3.35 (m, HꢀC(4), HꢀC(3), HꢀC(2));
2.96–2.71 (m, 2 CH2(1’), 2 CH2(2’)). 13C-NMR (100.6 MHz, CD3OD): 141.9 (s, 2 arom. C); 132.4, 128.0 (2d,
1
1
1J(C,H)=161, C(6), C(5)); 129.9 (d, J(C,H)=157, 4 arom. C); 129.4 (d, J(C,H)=159, 4 arom. C); 127.0 (d,
1J(C,H)=160, 2 arom. C); 78.2 (d, 1J(C,H)=143, C(2)); 73.5, 72.8 (2d, 1J(C,H) ꢄ 137, C(3), C(1)); 65.4 (d,
1J(C,H)=132, C(4)); 54.7 (t, 1J(C,H)=133, 2 C(1’)); 36.6 (t, 1J(C,H)=128, 2 C(2’)). CI-MS (NH3): 293 (1),
262 (34), 202 (2), 149 (2), 134 (36), 110 (5), 105 (100), 91 (22), 83 (13), 79 (9), 77 (16), 71 (2). HR-MALDI-
TOF-MS: 354.2095 (C22H28NOþ3 , [M+H]+; calc. 354.2069).
(ꢂ)-(1RS,2SR,3SR,4RS)-4-[Bis(1H-imidazol-5-ylmethyl)amino]cyclohex-5-ene-1,2,3-triol2) (=(ꢂ)-(1RS,
2RS,3SR,6SR)-6-[Bis(1H-imidazol-5-ylmethyl)amino]cyclohex-4-ene-1,2,3-triol; (ꢂ)-20dd). As described
above, with (ꢂ)-5 and an excess of 1H-imidazole-4-carboxaldehyde (TLC monitoring, 25% aq. NH3 soln./
MeCN 1 :4): (ꢂ)-20dd (33%). Colorless solid. UV (MeOH): 217 (6477), 213 (5990). IR (KBr): 3385, 1654,
1
1560, 1438, 1278, 1092, 1051, 1016, 950, 781, 624. H-NMR (400 MHz, CD3OD): 7.79 (s, 2 arom. H); 7.01 (s, 2
3
3
arom. H); 5.82 (br. s, HꢀC(6), HꢀC(5)); 4.06 (dd, J(1,2)=8.0, 3J(1,6)=3.0, HꢀC(1)); 3.80 (d, J=14.3, 1 H,

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ArCH2N); 3.71–3.61 (m, HꢀC(4), HꢀC(3)); 3.68 (d, 3J=14.3, 1 H, ArCH2N); 3.38 (dd, 3J(2,3)=10.0, 3J(2,
1
1)=8.0, HꢀC(2)). 13C-NMR (100.6 MHz, CD3OD): 137.2 (d, J(C,H)=209, 2 arom. C); 136.5 (s, 2 arom. C);
1
1
1
133.8, 127.8 (2d, J(C,H)=160, C(6), C(5)); 121.2 (d, J(C,H)=190, 2 arom. C); 79.1 (d, J(C,H)=142, C(2));
74.4, 73.3 (2d, 1J(C,H) ꢄ 106, C(3), C(1)); 65.8 (d, 1J(C,H)=135, C(4)); 48.2 (t, 1J(C,H)=136, 2 ArCH2N).
HR-MALDI-TOF-MS: 306.1825 (C14H20N5Oþ3 , [M+H]+; calc. 306.1566).
8. (ꢂ)-(1RS,2SR,3SR,4RS)-4-Aminocyclohexane-1,2,3-triol (=(ꢂ)-Dihydroconduramine B-1; (ꢂ)-21). A
soln. of (ꢂ)-5 (0.046 g, 0.32 mmol) in MeOH/AcOEt (10 ml) was stirred under H2 for 5 h in the presence of
10% Pd/C (0.02 g). The soln. was passed trough Celite and evaporated: (ꢂ)-21 (0.045 g, 98%) . White solid.
1
M.p. 171–1738 (dec.). IR (KBr): 3352, 2952, 1618, 1514, 1330, 1075, 1041, 552. H-NMR (400 MHz, CD3OD):
3.47–3.41 (m, HꢀC(1)); 3.59 (dd, 3J(3,2)=10.0, 3J(3,4)=9.0, HꢀC(3)); 3.19 (dd, 3J(2,3)=9.0, 3J(2,1)=9.0,
HꢀC(2)); 3.06–2.97 (m, HꢀC(4)); 2.07–1.96 (m, HaꢀC(5), HaꢀC(6)); 1.57–1.38 (m, HbꢀC(5), HbꢀC(6)).
13C-NMR (100.6 MHz, CD3OD): 79.4 (d, 1J(C,H)=141, C(2)); 75.0 (d, 1J(C,H)=143, C(3)); 73.1 (d, 1J(C,
1
H)=135, C(1)); 55.0 (d, 1J(C,H)=150, C(4)); 30.4, 25.9 (2t, J(C,H) ꢄ 131, C(6), C(5)). CI-MS (NH3): 147 (9,
M+), 135 (16), 132 (29), 130 (12), 112 (61), 109 (100), 100 (20), 98 (98), 94 (43), 91 (10), 88 (43), 86 (73), 82
(30), 79 (22), 73 (36), 70 (26). HR-MALDI-TOF-MS: 148.0971 (C6H14NOþ3 , [M+H]+; calc. 148.0974).
9. Aldehydes 23 and Precursors 22s and 24. 4-(4-Methoxyphenoxy)benzaldehyde (23n) According to [25]:
1
23n (68%). Colorless crystals. M.p. 608 (from hexane) ([25]: 59.5–60.58 (from hexane)). H-NMR (400 MHz,
CDCl3): 9.92 (s, CHO); 7.84 (d, 3J=8.7, 2 arom. H); 7.07–6.93 (m, 6 arom. H); 3.85 (s, MeO). 13C-NMR
(100.6 MHz, CDCl3): 189.7 (d, 1J(C,H)=173, CHO); 164.0 (s, arom. C); 156.8 (s, arom. C); 148.0 (s, arom.
1
1
1
C); 131.9 (d, J(C,H)=161, 2 arom. C); 130.8 (s, arom. C); 121.7 (d, J(C,H)=162, arom. C); 116.6 (d, J(C,
H)=162, arom. C); 115.0 (d, J(C,H)=163, 2 arom. C); 55.5 (q, 1J(C,H)=144, MeO).
1
4-(4-Bromophenoxy)benzaldehyde (23o). According to [25]: 23o (44%). Colorless crystals. M.p. 688 (from
hexane) ([25]: 67–688 (from hexane)). 1H-NMR (400 MHz, CDCl3): 9.95 (s, CHO); 7.88 (d, 3J=8.6, 2 arom. H);
3
3
3
7.54 (d, J=8.7, 2 arom. H); 7.08 (d, J=8.6, 2 arom. H); 6.99 (d, J=8.7, 2 arom. H). 13C-NMR (100.6 MHz,
CDCl3): 189.6 (d, 1J(C,H)=174, CHO); 162.5 (s, arom. C); 154.3 (s, arom. C); 133.1 (d, 1J(C,H)=167, 2
arom. C); 131.9 (d, J(C,H)=162, 2 arom. C); 131.5 (s, arom. C); 122.0 (d, J(C,H)=163, arom. C); 117.7 (d,
1J(C,H)=163, arom. C).
1
1
4-[4-(1H-Imidazol-1-yl)phenoxy]benzaldehyde (23p). According to [25]: 23p (50%). Purification by FC (10
! 15% MeOH/AcOEt). White solid. UV (MeOH): 295 (3342), 271 (3164), 252 (3301). IR (KBr): 1689, 1593,
1579, 1519, 1498, 1236, 1156, 1057, 835. 1H-NMR (400 MHz, CD3OD): 9.92 (s, CHO); 8.15 (s, 1 arom. H);
7.94 (d, 3J=8.7, 2 arom. H); 7.65 (d, 3J=8.8, 2 arom. H); 7.59 (s, 1 arom. H); 7.27 (d, 3J=8.8, 2 arom. H);
7.17–7.14 (m, 3 arom. H). 13C-NMR (100.6 MHz, CD3OD): 192.6 (d, 1J(C,H)=175, CHO); 164.1 (s, arom.
C); 156.0 (s, arom. C); 137.0 (d, 1J(C,H)=211, arom. C); 135.2 (s, arom. C); 133.3 (s, arom. C); 131.1 (d,
1J(C,H)=162, 2 arom. C); 130.3 (d, 1J(C,H)=191, arom. C); 124.3 (d, 1J(C,H)=163, 2 arom. C); 122.6 (d,
1J(C,H)=164, 2 arom. C); 119.9 (d, 1J(C,H)=193, arom. C); 119.0 (d, 1J(C,H)=164, 2 arom. C). CI-MS
(NH3): 265 (27, [M+H]+), 264 (100, M+), 263 (20, [MꢀH]+), 237 (18), 224 (12), 116 (12), 104 (12), 89 (71),
77 (29). HR-MALDI-TOF-MS: 265.0186 (C16H13N2Oþ2 , [M+H]+; calc. 265.0977).
4-(4-Phenoxyphenoxy)benzaldehyde (23u). According to [25]: 23a (60%). Colorless crystals. M.p. 45–478
1
3
(hexane) ([25]: 46–488 (hexane)). H-NMR (400 MHz, CDCl3): 9.94 (s, CHO); 7.87 (d, J=8.4, 2 arom. H);
7.38 (t, 3J=8.0, 2 arom. H); 7.16–7.05 (m, 9 arom. H). 13C-NMR (100.6 MHz, CDCl3): 190.7 (d, 1J(C,
1
H)=173, CHO); 163.5 (s, arom. C); 157.1 (s, arom. C); 154.1 (s, arom. C); 150.2 (s, arom. C); 131.9 (d, J(C,
H)=162, 2 arom. C); 131.1 (s, arom. C); 129.8 (d, 1J(C,H)=159, 2 arom. C); 123.4 (d, 1J(C,H)=159, arom.
C); 121.8 (d, 1J(C,H)=153, arom. C); 120.2 (d, 1J(C,H)=153, arom. C); 118.7 (d, 1J(C,H)=158, arom. C);
117.0 (d, 1J(C,H)=163, 2 arom. C).
4-[(2-Methylquinolin-8-yl)oxy]benzaldehyde (23t). According to [25] followed by FC (20 ! 30% AcOEt/
hexane): 23t (51%). White crystals. M.p. 93–958 (from AcOEt/hexane). UV (CHCl3): 307 (3802), 287 (3743),
272 (3472), 267 (3484), 261 (3404), 256 (3559). IR (KBr): 1688, 1601, 1499, 1427, 1320, 1232, 1158, 820. 1H-
NMR (400 MHz, CDCl3): 9.93 (s, CHO); 8.11 (d, 3J=8.4, 1 arom. H); 7.85 (d, 3J=8.6, 2 arom. H); 7.67 (d,
3J=8.1, arom. H); 7.47 (t, 3J=7.2, 1 arom. H); 7.36–7.25 (m, 2 arom. H); 7.12 (d, 3J=8.5, 2 arom. H); 2.69
1
(br. s, Me). 13C-NMR (100.6 MHz, CDCl3): 190.9 (d, J(C,H)=173, CHO); 164.0 (s, arom. C); 159.6 (s, arom.
1
1
C); 150.9 (s, arom. C); 140.8 (s, arom. C); 136.2 (d, J(C,H)=162, arom. C); 131.8 (d, J(C,H)=161, 2 arom.
C); 131.2 (s, arom. C); 128.3 (s, arom. C); 125.6 (d, 1J(C,H)=164, arom. C); 124.5 (d, 1J(C,H)=160, arom.
1
1
1
C); 123.0 (d, J(C,H)=162, arom. C); 119.4 (d, J(C,H)=162, arom. C); 118.1 (d, J(C,H)=164, 2 arom. C);
25.7 (q, 1J(C,H)=127, Me). CI-MS (NH3): 264 (44, [M+H]+), 263 (87, M+), 262 (100, [MꢀH]+), 234 (13),
204 (5), 103 (6), 88 (15), 84 (84), 77 (11). HR-MALDI-TOF-MS: 264.3860 (C17H14NOþ2 , [M+H]+; calc.
264.1025). Anal. calc. for C16H14O3 (254.094): C 77.55, H 4.98; found: C 77.43, H 5.05.

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4-(4-Acetylphenoxy)benzaldehyde (23q). A soln. of 24 (0.4 g, 1.57 mmol) in 1
M
HCl (5 ml) was stirred at 508
for 30 min. Subsequently, the solvent was evaporated and the residue subjected to FC (10 ! 15% AcOEt/hex-
ane): 0.33 g (87%) of 23q. Colorless crystals. M.p. 57–598 (slow evaporation of hexane). UV (CHCl3): 294
(2491), 287 (2457), 263 (2220), 256 (2392). IR (KBr): 1694, 1681, 1591, 1504, 1416, 1359, 1303, 1245, 1163,
1
3
3
1107, 836. H-NMR (400 MHz, CDCl3): 9.97 (s, CHO); 8.00 (d, J=8.7, 2 arom. H); 7.91 (d, J=8.6, 2 arom.
H); 7.16–7.10 (m, 4 arom. H); 2.63 (s, COMe). 13C-NMR (100.6 MHz, CDCl3): 196.1 (s, COMe); 190.5 (s,
1J(C,H)=173, CHO); 161.4 (s, arom. C); 159.6 (s, arom. C); 133.3 (s, arom. C); 132.2 (s, arom. C); 132.0 (d,
1
1
1J(C,H)=162, 2 arom. C); 130.7 (d, J(C,H)=162, 2 arom. C); 119.1 (d, J(C,H)=163, 2 arom. C); 118.9 (d,
1J(C,H)=164, 2 arom. C); 26.5 (q, 1J(C,H)=128, COMe). CI-MS (NH3): 241 (17, [M+H]+), 240 (36, M]+),
226 (21), 225 (100), 141 (17), 139 (11), 115 (27), 92 (16), 77 (21), 75 (10). HR-MALDI-TOF-MS: 241.0869
(C15H13Oþ3 , [M+H]+; calc. 241.0865). Anal. calc. for C15H12O3 (240.078): C 74.99, H 5.03; found: C 74.97, H 5.10.
4-Hydroxyacetophenone Dimethyl Acetal [=4-(1,1-Dimethoxyethyl)phenol; 22s). A mixture of 4-hydroxy-
acetophenone (8.0 g, 0.059 mol), trimethyl orthoformate (7.12 ml, 0.065 mol), anh. MeOH (20 ml), and conc.
H2SO4 soln. (2 drops) was allowed to stand at 208 for 24 h. After the addition of an excess of anh. Na2CO3,
the precipitate was filtered off, the solvent evaporated [27], and the residue subjected to FC (15% AcOEt/hex-
ane): 22s (9.0 g, 84%). Viscous yellow-red liquid that crystallized at +48 into a greenish solid. UV (MeOH): 273
(2793), 259 (2588), 231 (2601). IR (KBr): 3283, 1615, 1515, 1443, 1375, 1224, 1094, 1026, 838. 1H-NMR (400 MHz,
CDCl3): 7.38–7.35 (m, 2 arom. H); 6.83–6.77 (m, 2 arom. H); 3.19 (s, 2 MeO); 1.54 (s, Me). 13C-NMR (100.6
MHz, CDCl3): 155.3 (s, arom. C); 134.8 (s, arom. C); 127.7 (d, 1J(C,H)=159, 2 arom. C); 114.9 (d, 1J(C,
1
1
H)=158, 2 arom. C); 101.7 (s, MeC(OMe)2); 45.3 (q, J(C,H)=142, 2 MeO); 26.0 (q, J(C,H)=127, Me). CI-
MS (NH3): 167 (2), 151 (15), 149 (100), 133 (13), 121 (24), 120 (39), 107 (22), 94 (6), 91 (26), 77 (9).
4-[4-(1-Methoxyethenyl)phenoxy]benzaldehyde (24). The mixture of 22s (1.5 g, 8.22 mmol) and Cs2CO3
(1.47 g, 4.25 mmol) was stirred and heated at 1208 for 1h. After this time, 4-fluorobenzaldehyde (0.88 ml,
8.22 mmol) was added dropwise. After 2 h, the mixture was allowed to cool to r.t. and diluted with H2O and
CHCl3. The org. layer was separated, dried (Na2SO4), and evaporated, and the resulting crude mixture purified
by FC (6% AcOEt/hexanes): 24 (0.38 g, 18%). M.p. 65–678 (from AcOEt/light petroleum ether). UV (CHCl3):
297 (5001), 292 (4973), 290 (4945), 261 (4335), 257 (4808). IR (KBr): 1686, 1593, 1498, 1308, 1243, 1044, 878, 810.
1H-NMR (400 MHz, CDCl3): 9.94 (s, CHO); 7.86 (d, 3J=8.7, 2 arom. H); 7.68 (d, 3J=8.7, 2 arom. H); 7.07 (t,
3
3
3J=8.1, 4 arom. H); 4.66 (d, J=2.9, 1 H, CH2=C); 4.26 (d, J=2.9, 1 H, CH2=C); 3.78 (s, MeO). 13C-NMR
1
(100.6 MHz, CDCl3): 190.8 (s, J(C,H)=173, CHO); 163.0 (s, CH2=C); 160.0 (s, arom. C); 155.2 (s, arom. C);
133.5 (s, arom. C); 132.0 (d, 1J(C,H)=162, 2 arom. C); 131.3 (s, arom. C); 127.2 (d, 1J(C,H)=162, 2 arom.
1
1
1
C); 120.0 (d, J(C,H)=162, 2 arom. C); 117.7 (d, J(C,H)=160, 2 arom. C); 81.8 (t, J(C,H)=160, CH2=C);
55.4 (q, J(C,H)=144, MeO). CI-MS (NH3): 255 (14, [M+H]+), 254 (64, M+), 253 (100, [MꢀH]+), 225 (20),
1
223 (32), 149 (27), 133 (24), 126 (8), 115 (11), 102 (10), 91 (11), 83 (5), 77 (23). HR-MALDI-TOF-MS:
255.1074 (C16H15Oþ3 , [M+H]+; calc. 255.1021). Anal. calc. for C16H14O3: (254.094): C 75.57, H 5.55; found: C
75.47, H 5.61.
10. Secondary Amines 26–30. N-{4-[4-(1H-Imidazol-1-yl)phenoxy]benzyl}butan-1-amine (26). NaBH-
(OAc)3 (0.112 g, 0.53 mmol, 1.4 equiv.) was added portionwise within ca. 2 h to a stirred soln. of 23p (0.1 g,
0.378 mmol) and butan-1-amine (0.038 ml, 0.378 mmol) in anh. MeOH (4 ml) at 208. After complete disappear-
ance of 23p (TLC monitoring), the solvent was evaporated and the residue subjected to FC (MeOH/AcOEt/
25% aq. NH3 soln. 15 :83 :2): 26 (0.085 g, 70%). Yellowish oil. UV (MeOH): 266 (5730), 255 (6516). IR
(KBr): 3397, 1601, 1517, 1303, 1240, 1171, 1058, 963, 834. 1H-NMR (400 MHz, CD3OD): 8.09 (s, arom. H);
7.56–7.54 (m, 3 arom. H); 7.44 (d, 3J=8.5, 2 arom. H); 7.16 (s, arom. H); 7.13 (d, 3J=8.9, 2 arom. H); 7.06
(d, 3J=8.5, 2 arom. H); 3.90 (br. s, ArCH2N); 2.75 (t, 3J(1,2)=7.6, CH2(1)); 1.60 (quint., 3J(2,3)=3J(2,1)=7.7,
CH2(2)); 1.40 (sext., 3J(3,4)=3J(3,2)=7.6, CH2(3)); 0.97 (t, 3J(4,3)=7.3, Me). 13C-NMR (100.6 MHz, CD3
OD): 158.0 (s, arom. C); 157.9 (s, arom. C); 137.0 (d, 1J(C,H)=210, arom. C); 134.0 (s, arom. C); 133.6 (s,
arom. C); 131.9 (d, 1J(C,H)=162, 2 arom. C); 130.1 (d, 1J(C,H)=191, arom. C); 124.1 (d, 1J(C,H)=163, 2
arom. C); 120.9 (d, 1J(C,H)=163, 2 arom. C); 120.2 (d, 1J(C,H)=161, 2 arom. C); 120.0 (d, 1J(C,H)=192,
1
1
1
arom. C); 53.0 (t, J(C,H)=138, ArCH2NH); 49.2 (t, J(C,H)=138, C(1)); 31.5 (t, J(C,H)=127, C(2’)); 21.3
(t, J(C,H)=125, C(3’)); 14.2 (q, J(C,H)=125, C(4)). CI-MS (NH3): 321 (4, M+), 320 (2, [MꢀH]+), 250 (26),
249 (100), 125 (6), 107 (3), 89 (13), 77 (5). HR-MALDI-TOF-MS: 322.0816 (C20H24N3O+, [M+H]+; calc.
322.1919).
1
1
N-{4-[4-(1H-Imidazol-1-yl)phenoxy]benzyl}cyclohexanamine (27). As described for 26, with 23p and cyclo-
hexanamine. FC (MeOH/AcOEt/25% aq. NH3 soln. 20 :78 :2): 27 (91%). Colorless oil that solidified at +48. IR
(KBr): 3420, 2929, 1515, 1504, 1231, 1060, 873. UV (MeOH): 265 (4457), 263 (4446), 254 (4996). 1H-NMR (400
MHz, CD3OD): 8.09 (s, arom. H); 7.57–7.54 (m, 3 arom. H); 7.41 (d, 3J=8.4, 2 arom. H); 7.16–7.12 (m, 3 arom.

2810
HELVETICA CHIMICA ACTA – Vol. 88 (2005)
H); 7.05 (d, 3J=8.5, 2 arom. H); 3.85 (br. s, ArCH2N); 2.63–2.55 (m, 1 H, chx); 2.03–1.78 (m, 4 H, chx); 1.68 (br.
m, NH); 1.39–1.15 (m, 6 H, chx). 13C-NMR (100.6 MHz, CD3OD): 158.2 (s, arom. C); 157.5 (s, arom. C); 137.0
(d, 1J(C,H)=210, arom. C); 135.5 (s, arom. C); 133.9 (s, arom. C); 131.5 (d, 1J(C,H)=159, 2 arom. C); 130.1 (d,
1J(C,H)=191, arom. C); 124.2 (d, 1J(C,H)=163, 2 arom. C); 120.7 (d, 1J(C,H)=163, 2 arom. C); 120.2 (d, 1J(C,
H)=161, 2 arom. C); 120.0 (d, 1J(C,H)=192, arom. C); 57.3 (d, 1J(C,H)=138, 1 C, chx); 50.3 (t, 1J(C,H)=136,
1
1
ArCH2NH); 33.2 (t, J(C,H)=126, 2 C, chx); 27.0 (t, J(C,H)=128, 1 C, chx); 26.1 (t, 1J(C,H)=127, 2 C, chx).
CI-MS (NH3): 348 (7, [M+H]+), 347 (18, M+), 346 (2, [MꢀH]+), 249 (100), 125 (7), 116 (4), 107 (4), 91 (3),
89 (15), 77 (6). HR-MALDI-TOF-MS: 348.2009 (C22H26N3O+, [M+H]+; calc. 348.2076).
N-{4-[(2-Methylquinolin-8-yl)oxy]benzyl}cyclohexanamine (28). As described for 26, with 23t and cyclo-
hexanamine. FC (MeOH/AcOEt 3 :7): 28 (57%). Colorless solid. UV (CHCl3): 318 (2856), 273 (4455), 269
(4118), 250 (4814). IR (KBr): 3404, 2936, 1603, 1509, 1466, 1430, 1325, 1252, 1174, 1076, 835. 1H-NMR (400
3
3
MHz, CD3OD): 8.30 (d, J=8.5, 1 arom. H); 7.73 (d, J=8.2, 1 arom. H); 7.55–7.48 (m, 4 arom. H); 7.23 (d,
3J=7.7, 1 arom. H); 7.12 (d, 3J=8.6, 2 arom. H); 4.23 (br. s, ArCH2N); 3.18–3.14 (m, 1 H, chx); 2.70 (br. s,
Me); 2.23–1.91 (2m, 4 H, chx); 1.75 (br. m, NH); 1.48–1.25 (m, 6 H, chx). 13C-NMR (100.6 MHz, CD3OD):
160.9 (s, arom. C); 160.4 (s, arom. C); 152.9 (s, arom. C); 141.5 (s, arom. C); 138.3 (d, 1J(C,H)=163, arom.
1
1
C); 132.8 (d, J(C,H)=160, 2 arom. C); 129.8 (s, arom. C); 129.0 (s, arom. C); 127.0 (d, J(C,H)=161, arom.
1
1
1
C); 124.8 (d, J(C,H)=162, arom. C); 124.4 (d, J(C,H)=164, arom. C); 120.2 (d, J(C,H)=163, 2 arom. C);
1
1
1
119.1 (d, J(C,H)=163, arom. C); 58.4 (d, J(C,H)=140, 1 C, chx); 48.8 (t, J(C,H)=144, ArCH2NH); 30.4 (t,
1J(C,H)=128, 2 C, chx); 26.1 (t, 1J(C,H)=127, 1 C, chx); 25.6 (t, 1J(C,H)=129, 2 C, chx); 24.7 (q, 1J(C,
H)=128, Me). CI-MS (NH3): 347 (2, [M+H]+), 346 (6, [M]+), 345 (1, [MꢀH]+), 262 (4), 248 (100), 130 (2),
115 (11), 89 (7), 77 (5). HR-MALDI-TOF-MS: 369.1909 (C23H26N2NaO+, [M+Na]+; calc. 369.1943).
N-[4-(4-Phenoxyphenoxy)benzyl]butan-1-amine (29). As described for 26, with 23u and butan-1-amine: 29
(79%). Colorless solid. M.p. 189–1928 (from CHCl3/light petroleum ether). UV (MeOH): 246 (8773), 199
1
3
(1183). IR (KBr): 3447, 2957, 2799, 1587, 1499, 1244, 1069, 832. H-NMR (400 MHz, CDCl3): 7.55 (d, J=8.3,
2 arom. H); 7.36 (t, 3J=7.6, 2 arom. H); 7.11 (t, 3J=7.3, 1 arom. H); 7.05–6.93 (m, 8 arom. H); 3.99 (br. s,
ArCH2N); 2.79 (t, J(1,2)=7.6, CH2(1)); 1.86 (quint, J(2,3)=3J(2,1)=7.5, CH2(2)); 1.38 (sext., J(3,4)=3J(3,
3
3
3
2)=7.5, CH2(3)); 0.91 (t, J(4,3)=7.3, Me). 13C-NMR (100.6 MHz, CDCl3): 159.2 (s, arom. C); 157.5 (s, arom.
3
C); 153.4 (s, arom. C); 151.3 (s, arom. C); 132.1 (d, 1J(C,H)=160, 2 arom. C); 129.8 (d, 1J(C,H)=159, 2
1
1
arom. C); 124.1 (s, arom. C); 123.2 (d, J(C,H)=159, arom. C); 121.3 (d, J(C,H)=162, 2 arom. C); 120.5 (d,
1J(C,H)=163, 2 arom. C); 118.4 (d, 1J(C,H)=161, 2 arom. C); 117.9 (d, 1J(C,H)=162, 2 arom. C); 49.9 (t,
1J(C,H)=141, ArCH2N); 45.7 (t, 1J(C,H)=141, C(1)); 27.9 (t, 1J(C,H)=125, C(2)); 20.1 (t, 1J(C,H)=125,
C(3)); 13.5 (q, 1J(C,H)=124, Me). CI-MS (NH3): 248 (4, [M+H]+), 247 (10, M+), 246 (4, [MꢀH]+), 275
(100), 181 (6), 138 (7), 115 (10), 90 (19), 77 (30). HR-MALDI-TOF-MS: 348.1908 (C23H26NOþ2 , [M+H]+;
calc. 348.1964).
N-Ethyl-N’-[4-(4-phenoxyphenoxy)benzyl]ethane-1,2-diamine (30). As described for 26, with 23u and N-
ethylethane-1,2-diamine. FC (25% aq. NH3 soln./MeCN 1 :9): 30 (32%). Yellowish oil. UV (MeOH): 270
(3253), 248 (6283), 199 (876). IR (KBr): 3420, 2929, 1515, 1509, 1231, 1060, 813. 1H-NMR (400 MHz,
3
CD3OD): 7.40–7.33 (m, 4 arom. H); 7.11 (t, J=7.4, arom. H); 7.02–6.94 (m, 8 arom. H); 3.91 (br. s, ArCH2
3
3
3
3
NH); 2.99 (t, J(1,2)=6.1, CH2(1)); 2.93 (q, J=7.3, MeCH2N; 2.85 (t, J(2,1)=6.1, CH2(2)); 1.26 (t, J=7.3,
MeCH2N). 13C-NMR (100.6 MHz, CD3OD): 159.2 (s, arom. C); 158.6 (s, arom. C); 154.3 (s, arom. C); 154.2
(s, arom. C); 135.1 (s, arom. C); 131.1 (d, 1J(C,H)=158, 2 arom. C); 130.9 (d, 1J(C,H)=159, 2 arom. C);
124.2 (d, 1J(C,H)=160, arom. C); 121.5 (d, 1J(C,H)=162, 4 arom. C); 119.3 (d, 1J(C,H)=161, 4 arom. C);
53.4 (t, 1J(C,H)=135, ArCH2N); 47.9 (t, 1J(C,H)=140, C(1’)); 46.2 (t, 1J(C,H)=136, C(2’)); 44.0 (t, 1J(C,
H)=137, MeCH2N); 12.4 (q, 1J(C,H)=127, MeCH2N). CI-MS (NH3): 362 (1, [M]+), 305 (16), 303 (13), 276
(27), 275 (100), 115 (10), 90 (10), 77 (17). HR-MALDI-TOF-MS: 362.4928 (C23H26N2Oþ2 , [M+H]+; calc.
362.1994).
REFERENCES
[1] S. Hakomori, Cancer Res. 1985, 45, 2405.
[2] J. W. Dennis, M. Granovsky, C. E. Warren, Biochim. Biophys. Acta 1999, 1473, 21.
[3] K. Olden, P. Breton, K. Grzegorzewski, Y. Yasuda, B. L. Gause, O. A. Oredipe, S. A. Newton, S. L. White,
Pharmacol. Ther. 1991, 50, 285; J. M. van den Elsen, D. A. Kuntz, D. R. Rose, EMBO J 2001, 20, 3008; N.
Asano, Glycobiology 2003, 13, 93R.
[4] S. M. Colegate, P. R. Dorling, C. R. Huxtable, Austr. J. Chem. 1979, 32, 2257.
[5] P. E. Goss, C. L. Reid, D. Bailey, J. W. Dennis, Clin. Cancer Res. 1997, 3, 1077.

H
ELVETICA
CHIMICA
ACTA – Vol. 88 (2005)
2811
[6] T. Kino, N. Inamura, K. Nakahara, S. Kiyoto, T. Goto, H. Terano, M. Kohsaka, H. Aoki, H. Imanaka, J.
Antibiot. 1985, 38, 936.
[7] J. G. Donnelly, Therap. Drug Monitoring 2004, 26, 231.
[8] W. H. Pearson, L. Guo, Tetrahedron Lett. 2001, 42, 8267; J. W. Dennis, S. L. White, A. M. Freer, D. Dime,
Biochem. Pharmacol. 1993, 46, 1459.
[9] W. H. Pearson, E. J. Hembre, Tetrahedron Lett. 2001, 42, 8273.
[10] G. W. J. Fleet, P. W. Smith, S. V. Evans, L. E. Fellows, J. Chem. Soc., Chem. Commun. 1984, 1240; see also
C. W. Ekhart, M. H. Fechter, P. Hadwiger, E. Mlaker, A. E. Stütz, A. Tauss, T. M. Wrodnigg, in ‘Iminosu-
gars as Glycosidase Inhibitors: Nojirimycin and Beyond’, Ed. A. E. Stütz, Wiley-VCH, Weinheim, 1999, p.
253; T. Granier, F. Gaiser, L. Hintermann, A. Vasella, Helv. Chim. Acta 1997, 80, 1443; N. Panday, T. Gra-
nier, A. Vasella, Helv. Chim. Acta 1989, 81, 475; N. Panday, A. Vasella, Synthesis 1999, 1459; N. Panday, Y.
Canac, A. Vasella, Helv. Chim. Acta 2000, 83, 58; A. Vasella, G. J. Davies, M. Boehm, Curr. Opin. Chem.
Biol. 2002, 6, 619; M. Terinek, A. Vasella, Helv. Chim. Acta 2003, 86, 3482; M. Hrmova, R. De Gori, B. J.
Smith, A. Vasella, J. N. Varghese, G. B. Fincher, J. Biol. Chem. 2004, 279, 4970; M. Terinek, A. Vasella,
Helv. Chim. Acta 2004, 87, 3035; M. Terinek, A. Vasella, Helv. Chim. Acta 2005, 88, 10.
[11] F. Popowycz, S. Gerber-Lemaire, R. Demange, E. Rodriguez-García, A. T Carmona Asenjo, I. Robina, P.
Vogel, Bioorg. Med. Chem. Lett. 2001, 11, 2489; F. Popowycz, S. Gerber-Lemaire, E. Rodriguez-García, C.
Schütz, P. Vogel, Helv. Chim. Acta 2003, 86, 1914.
[12] F. Popowycz, S. Gerber-Lemaire, C. Schütz, P. Vogel, Helv. Chim. Acta 2004, 87, 800; see also C. Saotome,
C.-H. Wong, O. Kanie, Chem. Biol. 2001, 8, 1061.
[13] H. Fiaux, F. Popowycz, S. Favre, C. Schütz, P. Vogel, S. Gerber-Lemaire, L. Juillerat-Jeanneret, J. Med.
Chem. 2005, 48, 4237.
[14] S. Howard, S. He, S. G. Withers, J. Biol. Chem. 1998, 273, 2067.
[15] R. Łysek, C. Schütz, P. Vogel, Bioorg. Med. Chem. Lett. 2005, 15, 3071.
[16] A. Beutler, G. A. Grabowski, in ‘The Metabolic and Molecular Bases of Inherited Disease’, 8th edn., Eds.
C. R. Scrvier, A. L. Beaudet, D. Valle, W. S. Sly, B. Childs, K. W. Kinzler, and B. Vogelstein, McGraw-Hill,
New York, 2001, p. 3635.
[17] H. Lin, Y. Sugimoto, Y. Ohsaki, H. Ninomiya, A. Oka, M. Taniguchi, H. Ida, Y. Eto, S. Ogawa, Y. Matsu-
zaki, M. Sawa, T. Inoue, K. Higaki, E. Nanba, K. Ohno, Y. Suzuki, Biochim. Biophys. Acta 2004, 1689, 219.
[18] J.-Q. Fan, Trends Pharmacol. Sci. 2003, 24, 355; T. Kolter, M. Wendeler, ChemBioChem 2003, 4, 260 and
ref. cit therein; J. Matsuda, O. Suzuki, A. Oshima, Y. Yamamoto, A. Noguchi, K. Takimoto, M. Itoh, Y.
Matsuzaki, Y. Yasuda, S. Ogawa, Y. Sakata, E. Nanba, K. Higaki, Y. Ogawa, L. Tominaga, K. Ohno, H.
Iwasaki, H. Watanabe, R. O. Brady, Y. Suzuki, PANS 2003, 100, 15912.
[19] S. Ogawa, Y. Sakata, N. Ito, M. Watanabe, K. Kabayama, M. Itoh, T. Korenaga, Bioorg. Med. Chem. 2004,
12, 995.
[20] A. Forster, T. Kovac, H. Mosimann, P. Renaud, P. Vogel, Tetrahedron: Asymmetry 1999, 10, 567.
[21] P. Vogel, D. Fattori, F. Gasparini, C. Le Drian, Synlett 1990, 173; P. Vogel. J. Cossy, J. Plumet, O. Arjona,
Tetrahedron 1999, 55, 13521; P. Vogel, Curr. Org. Chem. 2000, 4, 455; P. Vogel, in ‘Glycoscience, Chemistry
and Biology’, Eds. B. Fraser-Reid, K. Tatsuta, and J. Thiem, Springer-Verlag, Berlin, 2001, Vol. II, Chapt.
4.4, p. 1023.
[22] C. Le Drian, J.-P. Vionnet, P. Vogel, Helv. Chim. Acta 1990, 73, 161.
[23] O. Mitsunobu, Synthesis 1981, 1; see also P. Renaut, J. Millet, C. Sepulchre, J. Theveniaux, V. Barberousse,
V. Jeanneret, P. Vogel. Helv. Chim. Acta 1998, 81, 2043.
[24] G. Kresze, G. Schulz, J. Firl, Angew. Chem. 1963, 75, 375; T. Hudlicky, H. F. Olivo, Tetrahedron Lett. 1991,
32, 6077; T. Hudlicky, H. Luna, H. F. Olivo, C. Andersen, T. Nugent, J. D. Price, J. Chem. Soc., Perkin Trans
1 1991, 2907; M. G. Banwell, N. Haddad, T. Hudlicky, T. C. Nugent, M. F. Mackay, S. L. Richards, J. Chem.
Soc., Perkin Trans 1 1997, 1779; S. H. Lee, C. S. Cheong, Bull. Korean Chem. Soc. 2000, 21, 1061.
[25] G. W. Yeager, D. N. Schissel, Synthesis 1991, 63; R. C. Desai, W. Han, E. J. Metzger, J. P. Bergman, D. F.
Gratale, K. L. MacNaul, J. P. Berger, T. W. Doebber, K. Leung, D. E. Moller, J. V. Heck, S. P. Sahoo, Bio-
org. Med. Chem. Lett. 2003, 13, 2795.
[26] I. Pastuszak, R. J. Molyneux, L. F. James, A. D. Elbein, Biochemistry 1990, 29, 1886; A, Brandi, S. Cicchi, F.
M. Cordero, R. Frignoli, A. Goti, S. Picasso, P. Vogel, J. Org. Chem. 1995, 60, 6806.
[27] R. A. McClelland, K. M. Engell, T. S. Larsen, P. E. Sørensen, J. Chem. Soc., Perkin Trans 2 1994, 2199.
Recieved June 30, 2005