First glycosylation of decarestrictine B and D: A route to hybrid antibiotics

Article abstract of DOI:10.1002/(SICI)1521-3765(19980710)4:7<1324::AID-CHEM1324>3.0.CO;2-6

The naturally occurring ten-membered lactones decarestrictine B (4) and D (5), which lower cholesterol levels, were glycosylated with deoxygenated 2-selenoglycosyl acetates 7a, 7b, and glycal 10 (obtained from D-glucose), and glycal 13 (obtained from L-rhamnose). Depending on the glycosylation method employed, the triol decarestrictine D was glycosylated with a high degree of regioselectivity. A set of hybrid structures were yielded by O-deblocking and in most cases reductive removal of a halogen or a phenylselenyl group from C-2 of the glycosides 14a-f, 20a, 20b, and 24. These hybrids were subjected to preliminary biological tests in which the novel glycoconjugates 15d and 15e displayed DNA-binding properties. The naturally occurring ten-membered lactones decarestrictine B (4) and D (5), which lower cholesterol levels, were glycosylated with deoxygenated 2-seleno-glycosyl acetates 7a, 7b, and glycal 10 (obtained from D-glucose), and glycal 13 (obtained from L-rhamnose). Depending on the glycosylation method employed, the triol decarestrictine D was glycosylated with a high degree of regioselectivity. A set of hybrid structures were yielded by O-deblocking and in most cases reductive removal of a halogen or a phenylselenyl group from C-2 of the glycosides 14a-f, 20a, 20b, and 24. These hybrids were subjected to preliminary biological tests in which the novel glycoconjugates 15d and 15e displayed DNA-binding properties.

Full text of DOI:10.1002/(SICI)1521-3765(19980710)4:7<1324::AID-CHEM1324>3.0.CO;2-6

FULL PAPER
First Glycosylation of Decarestrictine B and D:
A Route to Hybrid Antibiotics
Gerald Dräger, Alfons Garming, Corinna Maul, Mathias Noltemeyer, Ralf Thiericke,
Marion Zerlin, and Andreas Kirschning*
Abstract: The naturally occurring ten-membered lactones decarestrictine B (4) and
D (5), which lower cholesterol levels, were glycosylated with deoxygenated 2-seleno-
glycosyl acetates 7a, 7b, and glycal 10 (obtained from d-glucose), and glycal 13
(obtained from l-rhamnose). Depending on the glycosylation method employed, the
triol decarestrictine D was glycosylated with a high degree of regioselectivity. A
Keywords: antibiotics ´ DNA rec-
ognition ´ glycosides
tions ´ macrocycles
´ glycosyla-
set of hybrid structures were yielded by O-deblocking and in most cases
reductive removal of a halogen or a phenylselenyl group from C-2 of the glycosides
14a ± f, 20a, 20b, and 24. These hybrids were subjected to preliminary biological
tests in which the novel glycoconjugates 15d and 15e displayed DNA-binding
properties.
pyranose, 2, R ˆ H), and the disaccharide 3, which is
composed of 1 and 2 (Figure 1). These and other rare sugars
are commonly found as constituents of angucycline anti-
biotics,[6] and to a lesser extent in macrolide antibiotics and
Introduction
The frequency of resistance to commonly utilized antiinfec-
tive drugs in bacterial pathogens is increasing at an alarming
rate.[1] The construction of hybrid or composite antibiotics,
among other strategies, is regarded as an important approach
for the development of new therapeutic reagents. This
concept is based upon the combination of structural fragments
commonly found in different antibiotics within one mole-
cule.[2] Apart from the traditional method of chemical syn-
thesis,[3] various research groups have recently employed
genetically engineered hybrid organisms with modified bio-
synthetic genes to achieve this goal.[4]
As part of ongoing synthetic and biosynthetic studies on
glycoconjugates[5] we envisaged constructs that are composed
of a biologically active nonglycosylated secondary metabolite
(aglycons) and a deoxygenated glycan unit. As interesting
sugar moieties we employed d-olivose (2,6-dideoxy-d-arabi-
no-pyranose, 1, R ˆ H), l-rhodinose (2,3,6-trideoxy-l-threo-
Figure 1. Deoxygenated glycosides derived from d-olivose and l-rhodi-
nose and the ten-membered lactones decarestrictine B and D.
[*] Dr. A. Kirschning, Dr. G. Dräger, Prof. Dr. A. Garming
Institut für Organische Chemie der Technischen Universität Clausthal
Leibnizstrasse 6, 38678 Clausthal-Zellerfeld (Germany)
Fax: (‡49)5323-72-2858
anthracycline cytostatics. In all these examples the carbohy-
drate units are essential for biological activity.[7] Apart from
governing the pharmacokinetics of a drug, deoxygenated
sugars also serve as recognition elements for the DNA binding
of natural products.[8, 9] In fact, the contribution of these
oligosaccharides to the energetics and sequence specificity of
preferentially minor-groove DNA binding are only beginning
to be explored.[10]
E-mail: andreas.kirschning@tu-clausthal.de
C. Maul, Dr. R. Thiericke, Dr. M. Zerlin
Hans-Knöll-Institut für Naturstofforschung e. V.
Beutenbergstrasse 11, 07745 Jena (Germany)
Dr. M. Noltemeyer
Institut für Anorganische Chemie, Universität Göttingen
Tammannstrasse 4, 37077 Göttingen (Germany)
1324
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Chem. Eur. J. 1998, 4, No. 7

1324±1333
As aglycons we chose the ten-membered
lactones decarestrictine B (4) and D (5). These
are important new members of the growing
class of ten-membered lactones of natural
origin isolated from the fermentation broth of
Penicillium species.[11] In particular 5 is the most
potent in vivo inhibitor of the de novo choles-
terol biosynthesis.[12] Although they have struc-
tural resemblance to aglycons with 12- and 14-
membered macrolide antibiotics like methymy-
cin and erythromycin A,[7] the decarestrictines
do not exhibit antibacterial, antifungal, or
antiviral activity. Therefore, combination of
the ten-membered lactone moiety of the de-
carestrictines, which serves as an aglycon, with
deoxygenated sugars would lead to hybrid
antibiotics. Glycosylated structures derived
from 4 and 5 are appealing, as a combination
of two components of natural products from a
bacterial and fungal source is achieved.
Scheme 1. Preparation of glycosyl donors 6, 7, 9, and 10.
Results and Discussion
Synthesis of glycosyl donors: In the first phase
of the project, deoxysugars 1 ± 3 had to be
provided in sufficient amounts in an activated form. Glycals
such as 6 and 8, are ideally suited for this purpose as they can
either be directly employed in glycosylation reactions to
preferentially give a glycosides, or they may be transformed
into alternative glycosyl donors that can give access to b
glycosides.[10, 13] As shown in Scheme 1, the tert-butyldime-
thylsilyl-protected (TBS) 6-deoxy-d-glucal 6 was prepared
from glucose by a known synthetic sequence.[14] To obtain a
glycosyl donor suitable for the synthesis of b-glycosylated d-
olivose, 6 was transformed into the seleno acetates 7a and b
following the procedure of Perez and Beau.[15] The isomers
were isolated as a mixture (4:1 ratio) and were difficult to
separate. As the 1H NMR spectrum of the minor component
7a showed a similar size for the diagnostic coupling constant
J1,2 as 7b (5.8 Hz compared with 6.0 Hz), the mixture was
coupled with benzyl alcohol in the presence of trimethylsilyl
trifluoromethanesulfonate (TMSOTf) (yield: 85%). At this
stage both stereoisomers 11a and b were separated and
desilylated (Bu4NF, THF) to afford benzyl glycosides 12a
(94%) and 12b (85%), respectively. With the large protective
groups now removed, both isomers adopt a 4C1(d) conforma-
tion that helped to unequivocally assign the configurations at
C-1 and C-2. Coupling of 7a and 7b (4:1 mixture) with glycal
8[16] at 788C with catalytic amounts of TMSOTf provided
the labile disaccharide 9 in 21% yield along with 52% of
glycal 6, an indication of the well known reversibility for the
addition of PhSeX to glycals.[15] In addition, the following
observations are noteworthy. Only the b-isomer 7b was
glycosylated under the conditions employed. 7a did not react
and was reisolated in high purity. The acetoxy group in
glycosyl acetate 7b can be activated in the presence of another
potential glycosyl donor group, such as the enolether double
bond in 8. The deselenylation of 9 by use of Ph3SnH and
azobisisobutyronitrile (AIBN) in refluxing toluene to gener-
ate the desired glycal 10.
Glycosylation of decarestrictine D: In order to gain access to
a diverse number of glycosylated products for pharmacolog-
ical evaluation, and to assess the relative reactivity of hydroxy
groups in polyhydroxylated decanolides, we employed un-
protected decarestrictine D (5) for glycosylation reactions.
The N-iodosuccinimide (NIS) method,[17] with 5, 4-O-benzoy-
lated l-rhodinal 13,[16] and NIS in acetonitrile, afforded a
mixture of mono- and bisglycosylated decanolides 14a ± f
(11:2.2:4.5:4.5:1:1, 74%) with the expected preference for the
a anomers (Scheme 2 and Figure 2). The ratio between
monoglycosides 14a ± c and bisglycosides 14d ± f could be
manipulated by changing of the molar ratio of 13 and 5. The
ratio of the isolated monoglycosylated products 14a, 14b, and
14c (5:1:2) allowed us to deduce the relative reactivity and
Abstract in German: Die natürlich vorkommenden, den
Cholesterinspiegel senkenden zehngliedrigen Lactone Decare-
strictin B (4) und D (5) wurden mit den aus d-Glucose bzw. l-
Rhamnose erhältlichen desoxygenierten 2-Seleno-glycosylace-
taten 7a,b sowie mit den Glycalen 10 und 13 glycosidisch
verknüpft. In Abhängigkeit von der gewählten Glycosylie-
rungsmethode konnte das Triol Decarestrictin D mit hoher
Positionsselektivität glycosyliert werden. Nach Abspaltung der
Schutzgruppen und in vielen Fällen reduktiver Entfernung von
Halogen oder der Phenylselenyl-Gruppe an C-2 der Glycoside
14a ± f, 20a,b und 24 wurden verschiedene Hybridstrukturen
erhalten, die ersten biologischen Tests unterzogen wurden. Für
die Bisglycoside 15d und 15e wurde DNA-Affinität gefunden.
Chem. Eur. J. 1998, 4, No. 7
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A. Kirschning et al.
FULL PAPER
which are both attached to
3-O of 5. This result implies
an anchimeric assistance by
the lactone carbonyl group
during the glycosylation
process. Kessler et al. ob-
served formation of these
unexpected
glycosylation
products in the NIS-pro-
moted synthesis of O-glyco-
peptides,[18] and encoun-
tered the high electron-do-
nating power of benzyl-
protecting groups in the gly-
cal employed that favors the
ring opening of the inter-
mediate iodonium cation.
In contrast to Kesslerꢁs
results, the benzoyl group
should have an opposite
effect here. Indeed, we
could not detect any 3-O-
1,2-trans-b-glycosides that
would have further support-
ed
their
explanation.
Bu3SnH-promoted deiodi-
nation of the regioisomer
14c yielded 16. In contrast,
reductive exchange of io-
dine by hydrogen in 14a
led to stereoselective 5-
exo-trigonal addition of the
intermediate radical onto
the olefinic double bond,
thereby forming the highly
substituted tetrahydrofuran
18 in excellent yield (88%,
Scheme 3).[19] Also, utiliza-
tion of the reducing system
NiCl2 ´ (H2O)6/NaBH4 could
not suppress this ring clo-
sure. Debenzoylation of
14d ± f and 16 was achieved
without substantial cleavage
of the lactone ring under
mildly basic reaction condi-
tions to afford 15d ± f and
17d.
Scheme 2. Glycosylations of decarestrictine D.
In order to overcome
these problems and to get a
more efficient access to a
wide number of glycosylat-
Figure 2. Bisglycosylated ten-membered lactones derived from decarestrictine D.
ed
decarestrictines
we
accessibility of the hydroxy groups of 5 in acetonitrile as 7-
OH > 3-OH ꢀ 4-OH. The same relative reactivity was also
reflected in the formation of bisglycosides 14d ± f. Surpris-
ingly, 1,2-cis-a-configurated adducts were exclusively found
turned our attention to a proton-induced glycosylation
method.[20] Thus, activation of 13 by triphenylphosphane
hydrobromide (TPHB), coupling with 5 in CH2Cl2 (71%
yield), followed by debenzoylation furnished three monogly-
cosylated adducts 17a ± c and one bisglycoside 17e
(14:5.4:1:2) (Scheme 2).[21] Regioisomer 17d was not detect-
3
3
in rhodinosyl units of 14b (1H NMR: J(1,2) ˆ 2.8, J(2,3a) ˆ
13.2 Hz) and 14 f (1H NMR: 3J(1,2) ˆ 2.8, 3J(2,3a) ˆ 13.6 Hz),
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ªHybrid Antibioticsº
1324±1333
preliminary studies we knew that the benzoyl
group, such as in 13, cannot be removed from a
sugar moiety that is attached to 4 without degra-
dation of the decanolide framework.[25] To restrict
the number of glycosylation products, we did not
apply the NIS-methodology in this case. Instead,
we used two glycosylation methods that are
complementary as far as stereocontrol is con-
cerned. Thus, when a 1:3 mixture of O-silylated
glycals 7a and 7b was treated with 1.1 equiv of 4
Scheme 3. Radical-induced cyclization of 14a.
(0.2 equiv, TMSOTf, 788C) the corresponding 2-
phenylseleno-b-glycoside 20a (89% with reference to 7b),
along with unreacted 7a and 4, was isolated (Scheme 4).
Reductive removal of the phenylseleno substituent in 20a
under radical conditions provided 21a in excellent yield.
Finally, desilylation with tetrabutyl ammonium fluoride
(TBAF) in dry THF afforded the desired hybrid structure
22a. Likewise, pure 7a (vide supra) was glycosylated with 4 at
258C with TMSOTf as promoter to afford 20b in 92% yield.
The target glycoside 22b was eventually obtained in a two step
sequence through the TBS-protected olivoside 21b. In con-
trast, disaccharide 10 was coupled with 4 in the presence of a
catalytic amount of Ph3PHBr. The primary coupling product
24 turned out to be very labile and was immediately
deblocked to generate glycoconjugate 25. The synthetic
strategy could not be reversed. When 9 was subjected to the
glycosylation conditions in the presence of 4 the desired
adduct 23 was detected by HRMS (calcd 842.3359, found
842.3359) in the crude product, but it completely decomposed
upon attempted isolation.
ed. This result clearly disclosed a reversed preference for the
3- and 4-OH groups in 5 compared with the NIS-method. This
observation is further verified by formation of bisglycoside
17e. The difference in regioselectivity can be rationalized
on the basis of the difference of hydrogen-bonding capabil-
ities and dielectric constants of the solvents employed.
From conformational studies of 5 in crystalline form[22]
as well as in solution it was concluded that the 3-OH
group forms a strong hydrogen bond with the lactone
carbonyl. This is reflected in the reactivity pattern of the
proton-induced glycosylation procedure with CH2Cl2 as the
solvent. In contrast, under iodonium induced glycosylation
conditions the conformation of the half of the molecule
containing the 3-OH group of 5 is altered, and the strong
hydrogen bond was not detected; this can be rationalized in
view of the larger polarity of acetonitrile compared with
CH2Cl2.
The structures of all glycosylated products including 18
were comprehensively confirmed by detailed NMR experi-
ments (COSY, HETCOR, NOESY, HMBC, and DQS).
Acetylation of the remaining hydroxy groups followed by
the study of the downfield shifts of adjacent C-bound protons
in the 1H NMR spectra further helped to locate the positions
of glycosylation. Additional structural data were obtained by
recording electrospray mass spectra (ESI-MS). Finally, by X-
ray crystallographic analysis of 19[23] the absolute configura-
tion of the naturally occuring decarestrictine D was unequiv-
ocally established (Figure 3).[24]
Biological properties: Preliminary testing for the evaluation
of the biological activity of these hybrids was conducted, and
revealed DNA-binding activity for 5 and its bisglycosylated
derivatives 15d and 15e by means of a new DNA-binding
assay.[26] This assay works by the application of homogenized
salmon sperma DNA [4 mg] and the test substance [5 mg] on an
RP18 thin-layer chromatography (TLC) plate and determi-
nation of the altered Rf value after development of the
chromatogram. The DNA binding of the substance is ex-
pressed as the quotient of the Rf in the presence of DNA (Rf1)
and without DNA (Rf2); this results in Rf1/Rf2 ˆ 0.1 for 5 and
15d and Rf1/Rf2 ˆ 0.13 for 15e. All other glycosides including 4
showed no alterations in their Rf values under the influence of
DNA. To further validate these results, we measured DNA
melting curves of 5 and
Glycosylation of decarestrictine B: Decarestrictine B (4)
possesses several structural features such as the oxirane ring
and the acid ± base sensitive b-ketoester functionality that
have to be taken into consideration with respect to the
glycosylation and subsequent deblocking reactions. From
15d. The shift of the
DNA melting points of
5 (DTm ˆ 0.78C) and 15d
(DTm ˆ 0.88C) proved
DNA affinity and the
stabilizing effect on
DNA. In this context, it
is worth noting that
Schreiber et al.[27] pro-
posed that the iodine
group in the calicheamy-
cin gI1 oligosaccharide
Figure 3. Structure of glycoside 19 in the crystal.
binds to the exocyclic
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A. Kirschning et al.
FULL PAPER
continued at RT for 12 h and the reaction mixture was
filtered. The resulting solution was concentrated in
vacuo and purified by column chromatography (petro-
leum ether/EtOAc 6:1) to provide a 1:4 mixture of
7a and 7b (1.04 g, 1.81 mmol, 78%) as a colorless oil:
Compound 7a: physical and spectroscopic data are
given below.
Compound 7b: 1H NMR (300 MHz, CDCl3, 258C,
TMS): d ˆ 7.63 ± 7.58 (m, 5H), 6.19 (d, J ˆ 6.0 Hz, 1H),
4.16 (dd, J ˆ 4.4, 2.8 Hz, 1H), 3.94 (dq, J ˆ 2.2, 7.0 Hz,
1H), 3.59 (dd, J ˆ 4.4, 2.2 Hz, 1H), 3.25 (dd, J ˆ 6.0,
2.8 Hz, 1H), 1.88 (s, 3H), 1.39 (d, J ˆ 7.0 Hz, 3H), 0.95,
0.92 (2s, 18H), 0.11, 0.10, 0.08 (3s, 12H); LRMS (DCI):
‡
m/z (%): 592.3 (1) [M‡NH4 ], 532.3 (19), 515.2 (100);
C26H46O5Si2Se: calcd C 54.43, H 8.08; found C 54.81, H
7.89.
Benzyl 3,4-bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-
2-phenylseleno-a-d-manno-pyranoside (11a) and Ben-
zyl 3,4-bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-2-
phenylseleno-b-d-gluco-pyranoside (11b): Freshly dis-
tilled benzyl alcohol (0.2 mL) was added to a solution
of a 1:4 mixture of 7a and 7b (92 mg, 0.16 mmol) in
diethyl ether (15 mL) at 788C, which was stirred.
After 15 min, TMSOTf (43 mL, 1.5 equiv) in diethyl
ether (1.5 mL) was added in small portions, and the
reaction mixture was allowed to slowly warm to 258C
until TLC (petroleum ether/EtOAc 20:1; Rf ˆ 0.32)
showed no further reaction. For the workup, saturated
NH4Cl solution was added, the phases were separated,
and the aqueous phase extracted three times with
CH2Cl2. The combined organic layers were dried
(MgSO4) and concentrated in vacuo. Flash chromatog-
raphy (petroleum ether/EtOAc 30:1) gave two frac-
tions:
Scheme 4. Glycosylations of decarestrictine B.
First fraction: 11a (17.9 mg, 0.03 mmol, 18%); color-
less oil; [a]2D4 ˆ ‡41.8 (c ˆ 1.01 in CHCl3); 1H NMR
(300 MHz, CDCl3, 258C, TMS): d ˆ 7.53 ± 7.17 (m, 10H), 4.93 (d, J ˆ 4.0 Hz,
1H), 4.71, 4.45 (2d, J ˆ 12.0 Hz, 2H), 4.15 (dd, J ˆ 6.0, 3.6 Hz, 1H), 3.77
(dq, J ˆ 7.0, 6.4 Hz, 1H), 3.70 (dd, J ˆ 4.0, 3.6 Hz, 1H), 3.49 (dd, J ˆ 7.0,
6.0 Hz, 1H), 1.29 (d, J ˆ 6.4 Hz, 3H), 0.93, 0.89 (2s, 18H), 0.16, 0.12, 0.11,
0.10 (4s, 12H); 13C NMR (50 MHz, CDCl3): d ˆ 137.9, 133.6, 128.9, 128.4,
128.2, 127.8, 127.4, 127.1, 99.5, 75.8, 74.1, 70.8, 69.4, 50.8, 26.3, 26.0, 18.7, 18.4,
amino group of guanine residues in duplex DNA; this was
confirmed recently.[9, 28] In addition, Crothers et al. observed
enhanced DNA affinity of daunomycin analogues that con-
tain an iodo substituent in the sugar ring. Their data showed
that much of the activity lost upon removing the charged
amino group from the carbodrate framework can be compen-
sated by an iodo substituent at C-2.[29] Further investigations
on the DNA binding properties of decarestrictine D glyco-
sides with a biosensor system[30] are in progress.
18.0,
622.2412, found 622.2412.
Second fraction: 11b (67.6 mg, 0.11 mmol, 67%); colorless oil; [a]D24
3.2,
3.5,
4.1,
4.4; HRMS (EI) calcd for C31H50O4Si2Se
ˆ
17.0 (c ˆ 1.00 in CHCl3); 1H NMR (300 MHz, CDCl3, 258C, TMS): d ˆ
7.59 ± 7.15 (m, 10H), 4.99 (d, J ˆ 7.0 Hz, 1H), 4.90, 4.57 (2d, J ˆ 11.8 Hz,
2H), 4.20 (dd, J ˆ 4.4, 2.4 Hz, 1H), 3.79 (dq, J ˆ 2.0, 6.8 Hz, 1H), 3.56 (dd,
J ˆ 4.4, 2.0 Hz, 1H), 3.23 (dd, J ˆ 7.0, 2.4 Hz, 1H), 1.42 (d, J ˆ 6.8 Hz, 3H),
0.92, 0.87 (2s, 18H), 0.07, 0.06, 0.03 (3s, 12H); 13C NMR (50 MHz, CDCl3):
d ˆ 137.7, 133.5, 131.5, 128.8, 128.0, 127.9, 127.3, 129.6, 102.0, 77.5, 76.7, 74.7,
70.6, 49.6, 26.0, 25.9, 20.2, 18.1, 18.1, 4.2, 4.3, 4.4, 4.5; HRMS (EI)
calcd for C31H50O4Si2Se 622.2412, found 622.2412.
Experimental Section
General techniques: All temperatures quoted are uncorrected. Optical
rotations: Perkin ± Elmer 243b polarimeter. CD-spectra: Jasco J500A
(given in 8cm2 Â 10 1 mol 1). 1H NMR, 13C NMR spectra: Bruker
AMX300, ARX400, and Varian VXR500 spectrometer. 13C NMR multi-
plicities: DEPT 135 method. Mass spectra: Finnigan MAT 95, 70 eV (EI-
MS), and 200 eV (DCI-MS; NH3). Unless otherwise stated, all reactions
were run under a nitrogen atmosphere. All solvents used were of reagent
grade and were further dried. Reactions were monitored by TLC on silica
gel 60PF254 (E. Merck, Darmstadt) and detected either by UV-absorption
or by staining with H2SO4/4-methoxybenzaldehyde in ethanol. Preparative
Column Chromatography: silica gel 60 (E. Merck, Darmstadt). Preparative
Benzyl 2,6-dideoxy-2-phenylseleno-a-d-manno-pyranoside (12a): TBAF ´
3H2O (39.8 mg, 0.13 mmol) was added to a solution of 11a (8.9 mg,
0.014 mmol) in dry THF (2.0 mL) at RT. After 12 h, the reaction mixture
was concentrated in vacuo. The semisolid residue was taken up with water
and extracted three times with CH2Cl2. The combined organic extracts
were dried (MgSO4) and concentrated in vacuo. Flash chromatography
(petroleum ether/EtOAc 4:1) afforded 12a (5.3 mg, 0.013 mmol, 94%) as a
colorless oil. [a]2D3 ˆ ‡14.58 (c ˆ 0.22 in CHCl3); 1H NMR (300 MHz,
CDCl3, 258C, TMS): d ˆ 7.57 ± 7.24 (m, 10H), 5.31 (brs, 1H), 4.69, 4.47 (2d,
J ˆ 11.6 Hz, 2H), 4.05 (brddd, J ˆ 9.6, 9.4, 4.8 Hz, 1H), 3.77 (dq, J ˆ 9.0,
6.2 Hz, 1H), 3.68 (dd, J ˆ 4.8, 1.2 Hz, 1H), 3.17 (brdd, J ˆ 9.4, 9.0 Hz, 1H),
2.49 (brd, J ˆ 9.6 Hz, 1H, exchangeable), 2.49 (brs, 1H, exchangeable),
1.32 (d, J ˆ 6.2 Hz, 3H); 13C NMR (50 MHz, CDCl3): d ˆ 137.2, 133.6, 129.8,
129.4, 128.5, 127.9, 127.9, 127.8, 100.7, 76.3, 70.4, 68.3, 69.4, 55.7, 17.6; HRMS
(EI) calcd for C19H22O4Se 394.0683, found 394.0683; C19H22O4Se: calcd C
58.02, H 5.64; found C 58.11, H 5.79.
HPLC: Abimed/Gilson. Glycal
6 was synthesized according to the
literature,[14] while 8 and 13 have already been reported.[16]
1-O-Acetyl-3,4-bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-2-phenylsele-
no-a-d-manno-pyranose (7a) and 1-O-Acetyl-3,4-bis-O-(tert-butyldime-
thylsilyl)-2,6-dideoxy-2-phenylseleno-b-d-gluco-pyranose (7b): A solution
of 6 (1.0 g, 2.79 mmol) in toluene (30 mL) was stirred at RT, and a small
portion of powdered molecular sieves (4 Š), phenylselenyl chloride (0.69 g,
3.6 mmol), and silver(I) acetate (0.7 g, 4.2 mmol) was added. Stirring was
Benzyl 2,6-dideoxy-2-phenylseleno-b-d-gluco-pyranoside (12b): TBAF ´
3H2O (43.5 mg, 0.14 mmol) was added to a solution of 11b (28.4 mg,
1328
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Chem. Eur. J. 1998, 4, No. 7

ªHybrid Antibioticsº
1324±1333
0.046 mmol) in dry THF (3 mL) at RT. After 30 min, the reaction mixture
was worked up by the procedure described for 12a. Flash chromatography
yielded 14a and 14b (toluene/EtOAc 1.5:1), while the third fraction gave
14c (toluene/EtOAc 2:1) after column chromatography. The total yield of
all isolated products was 74%.
(petroleum ether/EtOAc 10:1) afforded 12b (15.3 mg, 0.039 mmol, 85%)
1
as a colorless oil. [a]D23
ˆ
26.78 (c ˆ 0.89 in CHCl3); H NMR (300 MHz,
7-(4-O-Benzoyl-2-iodo-2,3,6-trideoxy-a-l-lyxo-pyranosyloxy)-decarestric-
tine D (14a): (337 mg, 0.601 mmol, 34%) amorphous, colorless solid, m.p.
CDCl3, 258C, TMS): d ˆ 7.52 ± 7.13 (m, 10H), 4.91, 4.63 (d, J ˆ 12.0 Hz,
1H), 4.39 (d, J ˆ 9.0 Hz, 1H), 3.34 ± 3.20 (m, 3H), 2.99 (dd, J ˆ 10.7, 9.0 Hz,
1H), 3.77 (dq, J ˆ 9.0, 6.2 Hz, 1H), 3.68 (dd, J ˆ 4.8, 1.2 Hz, 1H), 3.17
(brdd, J ˆ 9.4, 9.0 Hz, 1H), 2.49 (brd, J ˆ 9.4 Hz, 1H, exchangeable), 2.49
(brs, 1H, exchangeable), 1.32 (d, J ˆ 6.2 Hz, 3H); 13C NMR (50 MHz,
CDCl3): d ˆ 137.2, 133.6, 129.8, 129.4, 128.5, 127.9, 127.9, 127.8, 100.7, 76.3,
70.4, 68.3, 69.4, 55.7, 17.6; HRMS (EI) calcd for C19H22O4Se 394.0683, found
394.0683; C19H22O4Se: calcd C 58.02, H 5.64; found C 57.95, H 5.81.
748C; Rf ˆ 0.38 (silica gel, petroleum ether/EtOAc 1:1); [a]D20:5
ˆ
122.08
(c ˆ 1.08 in CHCl3); 1H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon)
d ˆ 5.95 (dd, J ˆ 15.8, 2.5 Hz, 1H), 5.81 (ddd, J ˆ 15.8, 9.7, 1.3 Hz, 1H), 5.30
(ddq, J ˆ 9.4, 3.6, 6.2 Hz, 1H), 4.65 (brd, J ˆ 8.4 Hz, 1H, exchangeable),
4.47 (m, 1H), 4.15 (ddd, J ˆ 9.7, 7.6, 2.4 Hz, 1H), 4.07 (m, 1H), 2.65 (dd, J ˆ
14.2, 1.8 Hz, 1H), 2.42 (brs, 1H, exchangeable), 2.41 (dd, J ˆ 14.2, 6.1 Hz,
1H), 1.97 ± 1.88 (m, 2H), 1.27 (d, J ˆ 6.2 Hz, 3H); (rhodinosyl) d ˆ 8.24 ±
7.44 (m, 5H), 5.16 (brs, 1H), 5.13 (ddd, J ˆ 4.6, 3.6, 2.2 Hz, 1H), 4.21 (dq,
J ˆ 2.2, 6.6 Hz, 1H), 4.07 (m, 1H), 2.82 (ddd, J ˆ 15.8, 4.6, 4.6 Hz, 1H), 2.51
(ddd, J ˆ 15.8, 3.6, 3.6 Hz, 1H), 1.28 (d, J ˆ 6.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3): (aglycon) d ˆ 174.9, 133.3, 130.5, 75.4, 73.7, 72.2, 68.0,
41.2, 33.1, 21.2; (rhodinosyl) d ˆ 166.0, 133.1, 130.3, 128.6, 128.3, 97.0, 67.9,
4-O-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-2-phenylseleno-b-d-
gluco-pyranosyl]-1,5-anhydro-2,3,6-trideoxy-l-threo-hex-1-enitol (9):
A
solution of a 1:3 mixture of 7a and 7b (220 mg, 0.383 mmol) in diethyl
ether (15 mL) at 788C was stirred and 8 ( ꢁ 70 mg, 0.61 mmol, in CH2Cl2)
was added. After 15 min, TMSOTf (14 mL, 0.2 equiv) in diethyl ether
(0.3 mL) was added and the solution was stirred for a further 5 min at
ambient temperature. For the workup, saturated NH4Cl solution was
added, the phases separated, and the aqueous phase extratced three times
with CH2Cl2. The combined organic layers were dried (MgSO4) and
concentrated in vacuo. Flash chromatography (petroleum ether/EtOAc
20:1 followed by a second chromatographic step with petroleum ether/
toluene 1:1) afforded 6 (60 mg, 0.2 mmol, 52%) and 9 (51 mg, 0.081 mmol,
‡
65.2, 31.9, 17.5, 16.2; LRMS (ES): m/z (%): 560.8 (88) [M‡H ].
3-(4-O-Benzoyl-2-iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-decarestric-
tine D (14b): (65 mg, 0.116 mmol, 6.5%) semisolid; Rf ˆ 0.28 (silica gel,
petroleum ether/EtOAc 1:1); 1H NMR (400 MHz, CDCl3, 258C, TMS):
(aglycon) d ˆ 5.92 (ddd, J ˆ 16.4, 8.8 Hz, 1H), 5.84 (dd, J ˆ 16.4, 4.8 Hz,
1H), 5.19 (ddq, J ˆ 11.2, 1.4, 6.4 Hz, 1H), 4.34 (m, 1H), 4.21 (ddd, J ˆ 11.2,
8.8, 3.4 Hz, 1H), 3.92 (ddd, J ˆ 9.4, 6.8, 3.4 Hz, 1H), 2.86 (dd, J ˆ 14.0,
3.4 Hz, 1H), 2.36 (dd, J ˆ 14.0, 9.4 Hz, 1H), 1.87 (brs, 1H, exchangeable),
1.86 (ddd, J ˆ 14.0, 3.4, 1.4 Hz, 1H), 1.70 (brs, 1H, exchangeable), 1.75
(ddd, J ˆ 14.0, 11.2, 11.2 Hz, 1H), 1.23 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl) d ˆ
8.08 ± 7.44 (m, 5H), 5.11 (d, J ˆ 2.8 Hz, 1H), 5.0 (m, 1H), 4.49 (ddd, J ˆ 13.2,
4.4, 2.8 Hz, 1H), 4.43 (brq, J ˆ 6.6 Hz, 1H), 2.76 (ddd, J ˆ 14.0, 13.2, 2.4 Hz,
1H), 2.49 (ddd, J ˆ 14.0, 4.4, 2.8 Hz, 1H), 1.11 (d, J ˆ 6.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3): (aglycon) d ˆ 169.9, 137.6, 126.7, 84.4, 72.8, 71.1,
68.3, 42.0, 37.0, 21.5; (rhodinosyl) d ˆ 165.7, 133.4, 129.8, 128.5, 100.6, 72.3,
21%) as colorless oils. [a] V217.0 nm ˆ 134008, V222.0 nm ˆ 129008, V237.4 nm
ˆ
162008, V281.0 nm
ˆ
121008, V349.2 nm
ˆ
3628 (c ˆ 0.0466mm in CH3OH,
1
248C); H NMR (300 MHz, CDCl3, 258C, TMS): (olivosyl) d ˆ 7.69 ± 7.64
and 7.31 ± 7.24 (m, 5H), 5.05 (d, J ˆ 7.0 Hz, 1H), 4.23 (dd, J ˆ 4.4, 3.0 Hz,
1H), 3.82 (dq, J ˆ 2.2, 6.8 Hz, 1H), 3.59 (dd, J ˆ 4.4, 2.2 Hz, 1H), 3.24 (dd,
J ˆ 7.0, 3.0 Hz, 1H), 1.47 (d, J ˆ 6.8 Hz, 3H), 0.99, 0.92 (2s, 18H), 0.15, 0.12,
0.10 (3s, 12H); (rhodinal) d ˆ 6.25 (ddd, J ˆ 6.0, 2.0, 2.0 Hz, 1H), 4.62 (ddd,
J ˆ 6.0, 4.4, 3.2 Hz, 1H), 4.13 (ddq, J ˆ 3.6, 1.0, 6.6 Hz, 1H), 4.0 (ddd, J ˆ
7.8, 5.8, 3.6 Hz, 1H), 2.34 (ddddd, J ˆ 16.8, 5.8, 4.4, 2.0, 1.0 Hz, 1H), 2.18
(dddd, J ˆ 16.8, 7.8, 3.2, 2.0 Hz, 1H), 1.23 (d, J ˆ 6.6 Hz, 3H); 13C NMR
(50 MHz, CDCl3): (olivosyl) d ˆ 133.0, 131.7, 128.8, 126.9, 102.8, 77.7, 76.7,
74.7, 49.8, 26.0, 25.9, 20.3, 18.1, 18.0, 4.2, 4.3, 4.4; (rhodinal) d ˆ 141.4,
97.6, 73.2, 70.9, 25.3, 13.3; HRMS (EI) calcd for C30H52O5Si2Se 628.2518,
found 628.2518; C30H52O5Si2Se: calcd C 57.39, H 8.35; found C 57.31, H 8.45.
‡
65.4, 35.7, 22.3, 16.7; LRMS (ES): m/z (%):560.8 (27) [M‡H ].
3-(4-O-Benzoyl-2-iodo-2,3,6-trideoxy-a-l-lyxo-pyranosyloxy)-decarestric-
tine D (14c): (136 mg, 0.243 mmol, 14%); colorless solid, m.p. 828C; Rf ˆ
0.15 (silica gel, petroleum ether/EtOAc 1:1); [a]D24
ˆ
60.58 (c ˆ 1.02 in
CHCl3); [a] V221.2 nm
ˆ
119008, V242.5 nm ˆ ‡9328, V269.8 nm ˆ 22908 (c ˆ
0.0621mm in MeOH, 258C); 1H NMR (400 MHz, CDCl3, 258C, TMS):
(aglycon) d ˆ 5.92 (ddd, J ˆ 16.3, 9.2, 1.0 Hz, 1H), 5.79 (dd, J ˆ 16.3, 4.2 Hz,
1H), 5.18 (ddq, J ˆ 11.0, 1.8, 6.4 Hz, 1H), 4.24 (brdd, J ˆ 6.6, 4.2 Hz, 1H),
4.21 (ddd, J ˆ 11.0, 9.2, 3.4 Hz, 1H), 3.96 (ddd, J ˆ 8.6, 6.6, 3.6 Hz, 1H), 2.83
(dd, J ˆ 14.2, 3.6 Hz, 1H), 2.67 (brs, 1H, exchangeable), 2.36 (dd, J ˆ 14.2,
8.6 Hz, 1H), 2.10 (brs, 1H, exchangeable), 1.89 (ddd, J ˆ 14.0, 3.4, 3.4 Hz,
1H), 1.77 (ddd, J ˆ 14.0, 11.0, 11.0 Hz, 1H), 1.25 (d, J ˆ 6.4 Hz, 3H);
(rhodinosyl) d ˆ 8.19 ± 7.16 (m, 5H), 5.38 (d, J ˆ 3.4 Hz, 1H), 5.20 (ddd, J ˆ
5.8, 4.8, 2.8 Hz, 1H), 4.53 (dq, J ˆ 2.8, 6.6 Hz, 1H), 4.18 (ddd, J ˆ 5.8, 4.8,
3.4 Hz, 1H), 2.88 (ddd, J ˆ 15.3, 4.8, 4.8 Hz, 1H), 2.49 (ddd, J ˆ 15.3, 5.8,
5.8 Hz, 1H), 1.29 (d, J ˆ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
(aglycon) d ˆ 170.1, 137.2, 127.0, 82.3, 72.7, 71.0, 68.1, 42.2, 36.9, 21.5;
(rhodinosyl) d ˆ 165.9, 133.2, 130.0, 128.4, 125.3, 103.6, 68.7, 66.1, 33.0, 18.2,
4-O-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-b-d-arabino-pyrano-
syl]-1,5-anhydro-2,3,6-trideoxy-l-threo-hex-1-enitol (10): Compound
9
(21.5 mg, 0.034 mmol) and triphenyltin hydride (18 mg, 0.051 mmol) were
mixed and dried in vacuo for 1 h. Dry toluene (4 mL) and a catalytic
amount of AIBN were added, and the reaction mixture was refluxed in a
preheated oil bath at 1208C. This temperature was maintained for 2 h, then
the mixture was cooled to RT and evaporated in vacuo. Flash chromato-
graphy (petroleum ether/CH2Cl2 1:1) afforded 10 (8.3 mg, 0.018 mmol,
51%) as a labile, colorless oil. [a] V319.2 nm
ˆ
1108, V452.6 nm ˆ 25.78 (c ˆ
0.0402mm in CH3OH, 238C); 1H NMR (300 MHz, CDCl3, 258C, TMS):
(olivosyl) d ˆ 4.53 (dd, J ˆ 9.8, 2.0 Hz, 1H), 3.60 (ddd, J ˆ 11.4, 7.8, 5.0 Hz,
1H), 3.20 (dq, J ˆ 8.8, 6.0 Hz, 1H), 3.14 (dd, J ˆ 8.8, 7.8 Hz, 1H), 2.13 (ddd,
J ˆ 12.8, 5.0, 2.0 Hz, 1H), 1.64 (ddd, J ˆ 12.6, 11.4, 9.8 Hz, 1H), 1.23 (d, J ˆ
6.6 Hz, 3H), 0.90, 0.89 (2s, 18H), 0.09, 0.08, 0.07 (3s, 12H); (rhodinal) d ˆ
6.28 (ddd, J ˆ 6.0, 2.0, 2.0 Hz, 1H), 4.61 (ddd, J ˆ 6.0, 3.6, 3.6 Hz, 1H), 4.08
(dq, J ˆ 2.8, 6.6 Hz, 1H), 3.89 (ddd, J ˆ 5.6, 5.6, 2.8 Hz, 1H), 2.40 ± 2.14 (m,
2H), 1.23 (d, J ˆ 6.0 Hz, 3H); 13C NMR (50 MHz, CDCl3): (olivosyl) d ˆ
97.8, 77.7, 73.2, 72.7, 41.0, 26.3, 26.1, 18.7, 18.3, 18.0, 2.7, 3.0, 3.9, 4.1;
(rhodinal) d ˆ 142.1, 100.1, 73.6, 71.3, 26.1, 14.6; LRMS (DCI): m/z (%):
‡
‡
15.6; LRMS (ES): m/z (%): 1143.1 (42) [2M‡H ], 582.9 (98) [M‡Na ],
‡
560.8 (17) [M‡H ].
3,7-Bis-(4-O-benzoyl-2-iodo-2,3,6-trideoxy-a-l-lyxo-pyranosyloxy)-decar-
estrictine D (14d): (102 mg, 0.113 mmol, 13%) colorless solid, m.p. 958C;
Rf ˆ 0.38 (silica gel, toluene/EtOAc 6:1); [a] V216.4 nm
ˆ
91708, V243.0 nm
ˆ
‡4698, V264.8 nm
ˆ
211008 (c ˆ 0.0359mm in MeOH, 258C); 1H NMR
(400 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.93 (dd, J ˆ 16.0, 3.8 Hz,
1H), 5.79 (ddd, J ˆ 16.0, 9.2, 0.8 Hz, 1H), 5.27 ± 5.19 (m, 2H), 4.32 (brdd,
J ˆ 6.7, 3.8 Hz, 1H), 4.20 (m, 1H), 3.98 (ddd, J ˆ 8.4, 6.0, 3.4 Hz, 1H), 2.80
(dd, J ˆ 14.0, 3.4 Hz, 1H), 2.40 (dd, J ˆ 14.0, 8.4 Hz, 1H), 2.0 (brs, 1H,
exchangeable), 1.90 ± 1.82 (m, 2H), 1.26 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl A)
d ˆ 8.24 ± 7.16 (m, 5H), 5.19 (d, J ˆ 3.2 Hz, 1H), 5.27 ± 5.19 (m, 1H), 4.57
(dq, J ˆ 2.8, 6.6 Hz, 1H), 4.18 (ddd, J ˆ 5.2, 5.2, 3.2 Hz, 1H), 2.89 (ddd, J ˆ
15.2, 4.6, 4.6 Hz, 1H), 2.54 ± 2.49 (m, 1H), 1.29 (d, J ˆ 6.6 Hz, 3H);
(rhodinosyl B) d ˆ 8.24 ± 7.16 (m, 5H), 5.19 (d, J ˆ 2.2 Hz, 1H), 5.15 (ddd,
J ˆ 4.4, 3.4, 2.8 Hz, 1H), 4.22 (dq, J ˆ 2.4, 6.6 Hz, 1H), 4.06 (ddd, J ˆ 4.6,
3.8, 2.2 Hz, 1H), 2.82 (ddd, J ˆ 15.8, 5.2, 4.4 Hz, 1H), 2.54 ± 2.49 (m, 1H),
1.29 (d, J ˆ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 170.3,
133.4, 131.0, 82.1, 76.0, 71.4, 68.9, 40.8, 36.5, 21.7; (rhodinosyl A) d ˆ 166.1,
133.3 ± 125.5, 104.0, 68.2, 66.2, 33.1, 18.0, 16.0; (rhodinosyl B) d ˆ 166.1,
133.3 ± 125.5, 97.6, 68.1, 65.4 32.2, 17.4, 16.5.
‡
490.4 (100) [M‡NH4 ], 376.4 (76).
NIS-promoted glycosylation of decarestrictine D:
A suspension of 5
(577 mg, 2.67 mmol), 13 (388 mg, 1.780 mmol), and molecular sieves
(3 Š, 0.2 g) in dry acetonitrile (50 mL) at 08C in the dark was stirred and
three portions of NIS (521 mg, 2.314 mmol; freshly recrystallized from
dioxane/CCl4) were added over a period of 6 h. The reaction mixture was
allowed to warm to RT within the next 12 h. For the workup, saturated
Na2S2O3 solution was added, the phases separated, and the aqueous phase
extracted four times with EtOAc. The combined organic layers were dried
(Na2SO4) and concentrated in vacuo. Gradient column chromatography
(silica gel, petroleum ether/EtOAc 10:1 to EtOAc) afforded three fractions
(Rf ˆ 0.66, Rf ˆ 0.38 ± 0.28, Rf ˆ 0.15; petroleum ether/EtOAc 1:1). The first
fraction was purified again by column chromatography (toluene/EtOAc
6:1)to afford 14d ± 14 f as pure materials. Likewise, the second fraction
Chem. Eur. J. 1998, 4, No. 7
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0407-1329 $ 17.50+.25/0
1329

A. Kirschning et al.
FULL PAPER
3-(4-O-Benzoyl-2-iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-7-(4-O-ben-
zoyl-2-iodo-2,3,6-trideoxy-b-l-lyxo-pyranosyloxy)-decarestrictine D (14e):
(25 mg, 0.028 mmol, 3.1%) amorphous, colorless solid; Rf ˆ 0.27 (silica gel,
d ˆ 5.11 (ddq, J ˆ 11.6, 2.0, 6.0 Hz, 1H), 4.25 (ddd, J ˆ 11.6, 4.6, 3.6 Hz, 1H),
3.56 (m, 1H), 3.44 (ddd, J ˆ 10.8, 5.2, 2.0 Hz, 1H), 2.85 (dd, J ˆ 16.4, 3.6 Hz,
1H), 2.36 (dd, J ˆ 16.4, 11.6 Hz, 1H), 2.19 (ddd, J ˆ 14.0, 2.0, 2.0 Hz, 1H),
2.15 and 1.95 (2brs, 2H, exchangeable), 1.96 (m, 2H), 1.91 (ddd, J ˆ 14.0,
11.6, 10.8 Hz, 1H), 1.32 (d, J ˆ 6.0 Hz, 3H), 1.23 (m, 1H); (pyran) d ˆ 8.08 ±
7.43 (m, 5H), 5.21 (d, J ˆ 4.1 Hz, 1H), 5.07 (ddd, J ˆ 4.8, 3.0, 1.6 Hz, 1H),
4.22 (dq, J ˆ 1.6, 6.4 Hz, 1H), 2.31 (ddd, J ˆ 14.0, 6.2, 4.8 Hz, 1H), 2.08
(dddd, J ˆ 10.8, 6.2, 4.1, 1.5 Hz, 1H), 1.82 (ddd, J ˆ 14.0, 10.8, 3.0 Hz, 1H),
1.23 (d, J ˆ 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): (decanolide) d ˆ
169.4, 81.1, 74.7, 70.1, 68.6, 45.2, 43.2, 40.4, 37.5, 21.0; (pyran) d ˆ 166.2,
133.2, 130.1, 129.7, 128.5, 99.0, 69.2, 67.3, 40.5, 30.2, 16.7; C23H30O8 (434.49):
calcd C 63.58, H 6.96; found C 63.60, H 6.89.
1
toluene/EtOAc 6:1); H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon)
d ˆ 6.02 (dd, J ˆ 16.0, 9.4 Hz, 1H), 5.83 (dd, J ˆ 16.0, 4.0 Hz, 1H), 5.21
(ddq, J ˆ 11.2, 1.0, 6.8 Hz, 1H), 4.25 (brdd, J ˆ 6.5, 4.0 Hz, 1H), 4.24 (ddd,
J ˆ 11.2, 9.4, 2.6 Hz, 1H), 3.97 (ddd, J ˆ 8.6, 6.5, 3.5 Hz, 1H), 2.82 (dd, J ˆ
14.2, 3.5 Hz, 1H), 2.37 (dd, J ˆ 14.2, 8.7 Hz, 1H), 2.20 (brs, 1H; exchang-
able), 2.05 (ddd, J ˆ 14.0, 2.6, 1.0 Hz, 1H), 1.87 (ddd, J ˆ 14.0, 11.2, 11.2 Hz,
1H), 1.27 (d, J ˆ 6.8 Hz, 3H); (rhodinosyl at 7-O) d ˆ 8.15 ± 7.43 (m, 1H),
4.87 (ddd, J ˆ 3.0, 3.0, 0.8 Hz, 1H), 4.56 (d, J ˆ 9.0 Hz, 1H), 4.18 (ddd, J ˆ
13.2, 9.0, 4.5 Hz, 1H), 3.91 (dq, J ˆ 0.8, 6.4 Hz, 1H), 2.78 (ddd, J ˆ 14.8, 4.5,
3.0 Hz, 1H), 2.42 (ddd, J ˆ 14.8, 13.2, 3.0 Hz, 1H), 1.21 (d, J ˆ 6.4 Hz, 3H);
(rhodinosyl at 3-O) d ˆ 8.15 ± 7.43 (m, 1H), 5.39 (d, J ˆ 3.3 Hz, 1H), 5.19
(ddd, J ˆ 5.6, 4.9, 2.8 Hz, 1H), 4.54 (dq, J ˆ 2.8, 6.4 Hz, 1H), 4.19 (ddd, J ˆ
5.6, 4.9, 3.3 Hz, 1H), 2.88 (ddd, J ˆ 15.6, 4.9, 4.9 Hz, 1H), 2.50 (ddd, J ˆ
15.6, 5.6, 5.6 Hz, 1H), 1.29 (d, J ˆ 6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3): (aglycon) d ˆ 170.1, 135.4, 127.5, 81.9, 81.1, 71.2, 68.0, 39.7, 37.0,
21.6; (rhodinosyl at 7-O) d ˆ 165.9, 133.4 ± 128.4, 103.6, 73.7, 71.5, 41.7, 24.8,
17.0; (rhodinosyl at 3-O) d ˆ 165.9, 133.4 ± 128.4, 103.1, 68.7, 66.1, 32.9, 18.0,
15.7.
3-(2,3,6-Trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D (17d): De-
benzoylation of 16 (73 mg, 0.168 mmol) under standard conditions (NaOH,
MeOH, molecular sieves 3 Š, RT, 24 h) afforded 17d (53 mg, 0.160 mmol,
95%) as a colorless solid. M.p. 568C; Rf ˆ 0.09 (silica gel, EtOAc); [a]
V200.0 nm ˆ ‡20508, V223.9 nm
ˆ
4068 (c ˆ 0.176mm in MeOH, 238C); 1H
NMR (400 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.89 (dd, 16.3, 8.8 Hz,
1H), 5.80 (dd, J ˆ 16.3, 4.1 Hz, 1H), 5.17 (ddq, J ˆ 11.2, 1.5, 6.4 Hz, 1H),
4.21 (ddd, J ˆ 12.0, 8.7, 3.6 Hz, 1H), 4.16 (dd, J ˆ 6.8, 4.1 Hz, 1H), 3.93 (ddd,
J ˆ 9.1, 6.8, 3.6 Hz, 1H), 2.84 (dd, J ˆ 13.7, 3.6 Hz, 1H), 2.32 (dd, J ˆ 13.7,
9.1 Hz, 1H), 2.24 (brs, 1H, exchangeable), 1.88 (ddd, J ˆ 13.8, 3.6, 1.5 Hz,
1H), 1.84 (ddd, J ˆ 13.8, 12.0, 11.2 Hz, 1H), 1.85 ± 1.55 (brs, 1H, exchange-
able), 1.24 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl) d ˆ 5.04 (brd, J ˆ 2.0 Hz, 1H),
4.18 (brq, J ˆ 6.6 Hz, 1H), 3.63 (m, 1H), 2.09 (dddd, J ˆ 13.8, 13.8, 3.8,
2.4 Hz, 1H), 1.99 (dddd, J ˆ 13.8, 13.8, 3.8, 3.8 Hz, 1H), 1.85 (m, 1H), 1.85 ±
1.55 (brs, 1H, exchangeable), 1.61 (m, 1H), 1.17 (d, J ˆ 6.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3): (aglycon) d ˆ 170.4, 137.1, 127.3, 82.0, 72.9, 71.1,
68.0, 42.2, 37.0, 21.6; (rhodinosyl) d ˆ 99.6, 67.3, 66.9, 25.7, 24.0, 17.1; LRMS
(ES): m/z (%): 1139.0 (9.2), 1008.3 (29), 678.0 (49), 348.0 (100).
3-(4-O-Benzoyl-2-iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-7-(4-O-ben-
zoyl-2-iodo-2,3,6-trideoxy-a-l-lyxo-pyranosyloxy)-decarestrictine D (14 f):
(24 mg, 0.026 mmol, 3.0%) semisolid; Rf ˆ 0.42 (silica gel, toluene/EtOAc
6:1); 1H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.99 (dd, J ˆ
15.8, 4.0 Hz, 1H), 5.83 (dd, J ˆ 15.8, 9.4 Hz, 1H), 5.25 (m, 1H), 4.46 (brdd,
J ˆ 6.6, 4.0 Hz, 1H), 4.23 (m, 1H), 3.96 (ddd, J ˆ 8.6, 6.6, 3.2 Hz, 1H), 2.86
(dd, J ˆ 14.0, 3.2 Hz, 1H), 2.74 (brs, 1H; exchangable), 2.41 (dd, J ˆ 14.0,
8.6 Hz, 1H), 1.90 ± 1.85 (m, 2H), 1.27 (d, J ˆ 6.6 Hz, 3H); (rhodinosyl at 7-
O) d ˆ 8.25 ± 7.41 (m, 10H), 5.21 (brs, 1H), 5.14 (brdd, J ˆ 6.2, 3.8 Hz, 1H),
4.23 (dq, J ˆ 2.0, 6.8 Hz, 1H), 4.05 (ddd, J ˆ 4.4, 3.8, 2.0 Hz, 1H), 2.82 (ddd,
J ˆ 15.4, 4.4, 3.8 Hz, 1H), 2.55 ± 2.48 (m, 2H), 1.29 (d, J ˆ 6.8 Hz, 3H);
(rhodinosyl at 3-O) d ˆ 8.25 ± 7.41 (m, 10H), 5.12 (brd, J ˆ 2.8 Hz, 1H),
5.04 (m, 1H), 4.55 (brq, J ˆ 6.6 Hz, 1H), 4.51 (ddd, J ˆ 13.6, 4.6, 2.8 Hz,
1H), 2.81 (ddd, J ˆ 13.6, 13.6, 2.6 Hz, 1H), 2.55 ± 2.48 (m, 1H), 1.14 (d, J ˆ
6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 170.0, 130.3,
129.0, 83.7, 75.9, 71.1, 68.1, 40.5, 36.4, 22.2; (rhodinosyl at 7-O) d ˆ 166.0,
133.4 ± 125.3, 97.4, 68.1, 65.4, 32.0, 17.3, 16.3; (rhodinosyl at 3-O) d ˆ 165.7,
133.4 ± 125.3, 100.8, 72.4, 65.2, 35.7, 21.5, 16.7.
3,7-(2-Iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-decarestrictine D
(15d): Debenzoylation of 14d (100 mg, 0.111 mmol) under standard
conditions (NaOH, MeOH, molecular sieves 3 Š, RT, 24 h) afforded 15d
(57 mg, 0.082 mmol, 74%) as a colorless solid. M.p. 668C; Rf ˆ 0.74 (silica
gel, CH2Cl2/CH3OH 1:9); [a] V203.0 nm ˆ ‡243008, V226.2 nm
ˆ
6608,
V244.6 nm ˆ ‡1158 (c ˆ 0.144mm in MeOH, 218C); 1H NMR (400 MHz,
CDCl3, 258C, TMS): (aglycon) d ˆ 5.89 (dd, J ˆ 16.1, 3.9 Hz, 1H), 5.76
(ddd, J ˆ 16.1, 9.4, 0.9 Hz, 1H), 5.20 (ddq, J ˆ 12.9, 2.7, 6.5 Hz, 1H), 4.25
(ddd, J ˆ 6.0, 3.9, 0.9 Hz, 1H), 4.15 (ddd, J ˆ 9.4, 9.4, 5.0 Hz, 1H), 3.95 (ddd,
J ˆ 8.8, 6.0, 3.2 Hz, 1H), 2.78 (dd, J ˆ 14.0, 3.2 Hz, 1H), 2.40 ± 2.33 (m, 1H),
1.84 ± 1.78 (m, 2H), 1.24 (d, J ˆ 6.5 Hz, 3H); (rhodinosyl at 3-O) d ˆ 5.33 (d,
J ˆ 2.8 Hz, 1H), 4.36 (dq, J ˆ 6.6, 2.4 Hz, 1H), 4.12 (ddd, J ˆ 5.0, 4.8, 2.8 Hz,
1H), 3.86 (ddd, J ˆ 4.8, 4.8, 2.4 Hz, 1H), 2.74 (ddd, J ˆ 15.2, 4.8, 4.8 Hz,
1H), 2.40 ± 2.33 (m, 1H), 1.27 (d, J ˆ 6.6 Hz, 3H); (rhodinosyl at 7-O) d ˆ
5.11 (brs, 1H), 4.03 (dq, J ˆ 2.6, 6.6 Hz, 1H), 3.99 (ddd, J ˆ 4.6, 3.5, 0.9 Hz,
1H), 3.77 (ddd, J ˆ 4.5, 3.9, 2.4 Hz, 1H), 2.67 (ddd, J ˆ 15.6, 4.5, 4.5 Hz,
1H), 2.40 ± 2.33 (m, 1H), 1.26 (d, J ˆ 6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): (aglycon) d ˆ 170.1, 133.6, 130.7, 81.4, 75.8, 71.0, 67.9, 40.5, 36.3,
21.5; (rhodinosyl at 3-O) d ˆ 103.2, 67.6, 67.6, 35.1, 20.2, 16.2; (rhodinosyl at
7-O) d ˆ 97.3, 67.4, 66.7, 34.1, 20.0, 15.6; LRMS (DCI): m/z (%): 714.3 (100)
3-(4-O-Benzoyl-2,3,6-trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D
(16): A catalytic amount of AIBN was added to a solution of 14c (121 mg,
0.216 mmol) and tributyltin hydride (65 mL, 0.241 mmol) in toluene
(50 mL), which was stirred, and the reaction mixture was heated at 508C
for 19 h. After cooling, the reaction mixture was evaporated in vacuo and
purified by column chromatography (petroleum ether/EtOAc 1:1) to afford
16 (73 mg, 0.168 mmol, 78%) as an oil. Rf ˆ 0.13 (silica gel, petroleum
ether/EtOAc 1:1); 1H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ
5.90 (dd, J ˆ 16.3, 8.7 Hz, 1H), 5.82 (dd, J ˆ 16.3, 4.1 Hz, 1H), 5.19 (ddq,
J ˆ 10.8, 1.5, 6.4 Hz, 1H), 4.22 (ddd, J ˆ 10.8, 8.7, 3.6 Hz, 1H), 4.19 (dd, J ˆ
6.6, 4.1 Hz, 1H), 3.98 (ddd, J ˆ 8.8, 6.6, 3.6 Hz, 1H), 2.86 (dd, J ˆ 13.8,
3.6 Hz, 1H), 2.36 (dd, J ˆ 13.8, 8.8 Hz, 1H), 2.32, 1.84 (brs, 2H; exchang-
able), 1.89 (ddd, J ˆ 13.7, 3.6, 1.5 Hz, 1H), 1.77 (ddd, J ˆ 13.7, 11.0, 11.0 Hz,
1H), 1.24 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl) d ˆ 8.12 ± 7.44 (m, 5H; OBz),
5.16 ( m, 1H), 5.09 (brs, 1H), 4.36 (brq, J ˆ 6.4 Hz, 1H), 2.23 (dddd, J ˆ
13.6, 13.6, 4.0, 2.8 Hz, 1H), 2.06 (dddd, J ˆ 13.8, 13.8, 4.0, 4.0 Hz, 1H), 1.97
(dddd, J ˆ 13.6, 3.1, 3.1, 3.1 Hz, 1H), 1.69 (brddd, J ˆ 13.8, 3.0, 3.0 Hz, 1H),
1.17 (d, J ˆ 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 170.3,
137.0, 127.3, 82.1, 72.8, 71.1, 67.9, 42.2, 37.0, 21.5; (rhodinosyl) d ˆ 166.1,
133.0 ± 128.4, 99.5, 70.0, 66.0, 24.8, 23.0, 17.2; LRMS (DCI): m/z (%): 452.5
‡
[M‡NH4 ], 474.2 (17), 242.1 (37), 234.2 (14).
3-(2-Iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-7-(2-iodo-2,3,6-trideoxy-
b-l-xylo-pyranosyloxy)-decarestrictine D (15e): Debenzoylation of 14e
(24.5 mg, 0.027 mmol) under standard conditions (NaOH, MeOH, molec-
ular sieves 3 Š, RT, 24 h) afforded 15e (13.5 mg, 0.019 mmol, 72%) as a
colorless solid. M.p. 98.58C; Rf ˆ 0.47 (silica gel, EtOAc); [a] V219.8 nm
ˆ
137008, V244.6 nm ˆ ‡2828, V265.6 nm
ˆ
38208 (c ˆ 0.038mm in MeOH,
1
258C); H NMR (300 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.95 (ddd,
J ˆ 16.1, 9.4, 0.8 Hz, 1H), 5.78 (dd, J ˆ 16.1, 4.1 Hz, 1H), 5.17 (ddq, J ˆ 11.1,
1.7, 6.4 Hz, 1H), 4.21 (ddd, J ˆ 6.4, 4.1, 0.8 Hz, 1H), 4.17 (ddd, J ˆ 11.1, 9.4,
3.0 Hz, 1H), 3.94 (ddd, J ˆ 8.6, 6.4, 3.4 Hz, 1H), 2.78 (dd, J ˆ 14.1, 3.4 Hz,
1H), 2.33 (dd, J ˆ 14.1, 8.6 Hz, 1H), 2.01 (ddd, J ˆ 14.1, 3.0, 1.7 Hz, 1H),
1.82 (ddd, J ˆ 14.1, 11.0, 11.0 Hz, 1H), 1.25 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl
at 7-O) d ˆ 4.50 (d, J ˆ 9.0 Hz, 1H), 4.15 (ddd, J ˆ 13.3, 9.0, 4.9 Hz, 1H),
3.72 (dq, J ˆ 0.9, 6.4 Hz, 1H), 3.38 (ddd, J ˆ 3.2, 3.2, 0.9 Hz, 1H), 2.66 (ddd,
J ˆ 14.0, 4.9, 3.2 Hz, 1H), 2.24 (ddd, J ˆ 14.0, 13.3, 2.8 Hz, 1H), 1.21 (d, J ˆ
6.4 Hz, 3H); (rhodinosyl at 3-O) d ˆ 5.32 (d, J ˆ 2.8 Hz, 1H), 4.33 (dq, J ˆ
2.5, 6.6 Hz, 1H), 4.13 (ddd, J ˆ 4.9, 4.4, 2.8 Hz, 1H), 3.85 (ddd, J ˆ 4.9, 4.5,
2.5 Hz, 1H), 2.72 (ddd, J ˆ 15.0, 4.5, 4.5 Hz, 1H), 2.36 (ddd, J ˆ 15.0, 4.9,
4.9 Hz, 1H), 1.27 (d, J ˆ 6.6 Hz, 3H); 13C NMR (50 MHz, CDCl3):
(aglycon) d ˆ 170.2, 135.4, 127.5, 81.7, 80.8, 71.2, 68.0, 39.7, 36.7, 21.5;
‡
(100) [M‡NH4 ], 234.2 (14), 220.3 (25).
(1aR, 2S, 3S, 4aR, 4bR, 6S, 7S, 11R, 12aS)-3-Benzoyloxy-6,7-dihydrox-
2,11-dimethyl-dodecahydro-1,13-dioxacyclodeca[a]inden-9-one (18):
A
catalytic amount of AIBN was added to a solution of 14a (393 mg,
0.701 mmol) and tributyltin hydride (213 mL, 0.77 mmol) in toluene
(50 mL), which was stirred, and the reaction mixture was heated at 508C
for 19 h. After cooling, the reaction mixture was evaporated in vacuo and
washed twice with petroleum ether. Purification by column chromato-
graphy (petroleum ether/EtOAc 3.5:1) afforded 18 (267 mg, 0.614 mmol,
88%) as a colorless solid. M.p. 818C; Rf ˆ 0.17 (silica gel, petroleum ether/
EtOAc 1:1); [a] V208.4 nm
ˆ
3908, V227.3 nm
ˆ
12308 (c ˆ 0.087mm in
MeOH, 228C); 1H NMR (400 MHz, CDCl3, 258C, TMS): (decanolide)
1330
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0407-1330 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 7

ªHybrid Antibioticsº
1324±1333
(rhodinosyl at 7-O) d 103.5, 74.8, 70.1, 44.5, 24.6, 16.9; (rhodinosyl at 3-O)
d ˆ 103.2, 67.7, 67.6, 35.0, 20.1, 15.6; LRMS (DCI): m/z (%): 714.3 (98)
1.26 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl) d ˆ 4.84 (brd, J ˆ 2.0 Hz, 1H), 3.92
(brq, J ˆ 6.8 Hz, 1H), 3.57 (m, 1H), 1.98 (dddd, J ˆ 13.4, 13.4, 3.8, 2.6 Hz,
1H), 1.96 (brs, 1H; exchangable), 1.91 (dddd, J ˆ 13.4, 13.4, 3.8, 3.8 Hz,
1H), 1.74 (m, 1H), 1.43 (m, 1H), 1.18 (d, J ˆ 6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3): (aglycon) d ˆ 174.9, 132.1, 131.4, 74.6, 73.8, 72.3, 68.4,
41.4, 33.3, 21.3; (rhodinosyl) d ˆ 92.7, 67.4, 66.4, 25.7, 23.3, 17.2; LRMS (ES):
m/z (%): 678.0 (36), 348.0 (100).
‡
[M‡NH4 ], 474.2 (13), 242.1 (40), 234.2 (11).
3-(2-Iodo-2,3,6-trideoxy-a-l-xylo-pyranosyloxy)-7-(2-iodo-2,3,6-trideoxy-
a-l-lyxo-pyranosyloxy)-decarestrictine D (15 f): Debenzoylation of 14 f
(23.5 mg, 0.026 mmol) under standard conditions (NaOH, MeOH, molec-
ular sieves 3 Š, RT, 24 h) afforded 15 f (13.6 mg, 0.02 mmol, 75%) as an
amorphous, colorless solid. Rf ˆ 0.51 (silica gel, EtOAc); [a] V202.2 nm
ˆ
4-(2,3,6-Trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D (17b): De-
benzoylation of the third fraction (Rf ˆ 0.25 vide supra, 44.1 mg,
0.102 mmol) under standard conditions[31] afforded 17b (14.7 mg, 0.2 mmol,
44%; contaminated with ꢁ 30% of the 7-b-anomer, which could not be
separated) after flash chromatography (EtOAc) as a semisolid oil. Rf ˆ 0.13
(silica gel, EtOAc); 1H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon)
d ˆ 5.91 (ddd, J ˆ 15.8, 9.2, 0.8 Hz, 1H), 5.81 (dd, J ˆ 15.8, 2.8 Hz, 1H), 5.27
(ddq, J ˆ 11.0, 1.6, 6.4 Hz, 1H), 4.61 (brs, 1H; exchangable), 4.37 (ddd, J ˆ
4.0, 2.8, 0.8 Hz, 1H), 4.18 (ddd, J ˆ 10.6, 9.2, 3.8 Hz, 1H), 4.06 (m, 1H), 2.56
(dd, J ˆ 14.2, 1.8 Hz, 1H), 2.39 (dd, J ˆ 14.2, 6.3 Hz, 1H), 1.93 (ddd, J ˆ
14.0, 3.8, 1.6 Hz, 1H), 1.90 ± 1.50 (brs, 1H; exchangable), 1.83 (ddd, J ˆ
14.0, 11.0, 11.0 Hz, 1H), 1.25 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl) d ˆ 4.93
(brd, J ˆ 2.8 Hz, 1H), 3.95 (brq, J ˆ 6.6 Hz, 1H), 3.59 (m, 1H), 2.08 (dddd,
J ˆ 13.8, 13.8, 4.0, 2.6 Hz, 1H), 1.99 (dddd, J ˆ 13.8, 13.8, 3.8, 3.8 Hz, 1H),
1.90 ± 1.50 (brs, 1H; exchangable), 1.79 (m, 1H), 1.56 (m, 1H), 1.12 (d, J ˆ
6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 174.9, 134.2,
128.2, 74.8, 72.7, 71.5, 68.2, 42.0, 33.5, 21.3; (rhodinosyl) d ˆ 95.6, 67.2, 66.9,
25.8, 23.6, 17.1; LRMS (ES): m/z (%):678.0 (21), 348.0 (100).
‡93508, V220.6 nm 31408, V239.8 nm ˆ ‡13908, V251.0 nm ˆ ‡17908 (c ˆ
ˆ
0.144mm in MeOH, 228C); 1H NMR (400 MHz, CDCl3, 258C, TMS):
(aglycon) d ˆ 5.94 (dd, J ˆ 16.2, 4.2 Hz, 1H), 5.79 (dd, J ˆ 16.2, 9.2 Hz, 1H),
5.22 (ddq, J ˆ 8.8, 4.0, 6.4 Hz, 1H), 4.37 (brdd, J ˆ 6.6, 4.2 Hz, 1H), 4.17 (m,
1H), 3.90 (ddd, J ˆ 9.0, 6.0, 3.5 Hz, 1H), 2.86 (dd, J ˆ 13.8, 3.4 Hz, 1H),
2.40 ± 2.33 (m, 1H), 1.86 ± 1.78 (m, 2H), 1.25 (d, J ˆ 6.4 Hz, 3H);
(rhodinosyl at 7-O) d ˆ 5.13 (brs, 1H), 4.04 (dq, J ˆ 2.0, 6.6 Hz, 1H), 3.98
(ddd, J ˆ 4.6, 3.6, 2.0 Hz, 1H), 3.77 (brdd, J ˆ 4.8, 4.4 Hz, 1H), 2.70 (ddd,
J ˆ 15.4, 4.8, 4.4 Hz, 1H), 2.40 ± 2.33 (m, 2H), 1.28 (d, J ˆ 6.6 Hz, 3H);
(rhodinosyl at 3-O) d ˆ 5.02 (brd, J ˆ 3.0, 1H), 4.56 (ddd, J ˆ 13.4, 4.6,
3.0 Hz, 1H), 4.32 (brq, J ˆ 6.6 Hz, 1H), 3.60 (ddd, J ˆ 3.8, 2.6, 2.0 Hz, 1H),
2.64 (ddd, J ˆ 13.4, 13.4, 2.6 Hz, 1H), 2.40 ± 2.33 (m, 1H), 1.14 (d, J ˆ
6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 170.0, 134.3,
130.0, 83.4, 76.1, 71.3, 68.1, 40.5, 29.7, 21.6; (rhodinosyl at 7-O) d ˆ 97.5, 67.4,
66.8, 34.2, 19.9, 16.2; (rhodinosyl at 3-O) d ˆ 100.8, 70.4, 66.3, 38.7, 22.6,
‡
16.6; LRMS (DCI): m/z (%): 714.3 (100) [M‡NH4 ], 474.2 (23), 242.1 (31),
234.2 (19).
PPh3HBr-promoted glycosylation of decarestrictine D: A catalytic amount
(5 mol%) of triphenylphosphane hydrobromide was added to a solution of
5 (252 mg, 1.17 mmol) and 13 (130 mg, 0.60 mmol) in dry dichloromethane
(6 mL), and the reaction mixture was stirred for 3 h at RT. For the workup,
it was washed with saturated NaHCO3 solution (3 mL) and brine (3 mL),
and the combined aqueous layers were extracted twice with CH2Cl2. The
combined organic layers were dried (MgSO4) and concentrated in vacuo.
Gradient column chromatography (silica gel, petroleum ether/EtOAc 4:1
to 1:1) afforded four fractions (Rf ˆ 0.62, Rf ˆ 0.36, Rf ˆ 0.25, Rf ˆ 0.15;
petroleum ether/EtOAc 1:1). The total yield of all isolated products (19)
was 71%. The four compounds were purified to high purity and directly
4-(2,3,6-Trideoxy-b-l-threo-pyranosyloxy)-decarestrictine D (17c): Deben-
zoylation of the fourth fraction (Rf ˆ 0.15 vide supra, 8.2 mg, 0.019 mmol)
under standard conditions[31] and chromatographic purification (CH2Cl2/
CH3OH 1:9) afforded 17c (5.3 mg, 0.016 mmol, 84%) as a semisolid oil.
Rf ˆ 0.18 (silica gel, EtOAc); 1H NMR (400 MHz, CDCl3, 258C, TMS):
(aglycon) d ˆ 5.81 (ddd, J ˆ 15.8, 8.8, 0.6 Hz, 1H), 5.73 (dd, J ˆ 15.8, 2.4 Hz,
1H), 5.26 (ddq, J ˆ 11.0, 1.6, 6.2 Hz, 1H), 4.66 (brd, J ˆ 6.0 Hz, 1H;
exchangable), 4.45 (m, 1H), 4.20 (m, 1H), 4.19 (ddd, J ˆ 11.0, 8.8, 3.8 Hz,
1H), 2.55 (dd, J ˆ 14.4, 1.8 Hz, 1H), 2.39 (dd, J ˆ 14.4, 6.6 Hz, 1H), 1.91
(ddd, J ˆ 13.8, 2.8, 1.6 Hz, 1H), 1.82 (ddd, J ˆ 13.8, 11.0, 11.0 Hz, 1H),
1.76 ± 1.62 (brs, 1H; exchangable), 1.25 (d, J ˆ 6.2 Hz, 3H); (rhodinosyl)
d ˆ 4.45 (dd, J ˆ 7.0, 4.6 Hz, 1H), 3.57 (dq, J ˆ 0.6, 6.4 Hz, 1H), 3.48 (m,
1H), 2.00 (dddd, J ˆ 13.4, 2.8, 2.6, 2.6 Hz, 1H), 1.76 ± 1.62 (m, 4H; 1H
exchangable), 1.23 (d, J ˆ 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3):
(aglycon) d ˆ 174.0, 134.7, 127.7, 77.7, 73.2, 72.6, 68.0, 43.1, 33.9, 21.3;
(rhodinosyl) d ˆ 101.0, 74.0, 66.6, 29.8, 25.5, 17.1; LRMS (ES): m/z (%):
1139.0 (5.3), 1008.3 (33), 678.0 (51), 348.0 (100).
Â
debenzoylated (17). This was achieved by employing Zemplen conditions
(NaOMe/MeOH).[31]
7-(4-O-Benzoyl-2,3,6-trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D
(19): colorless solid, m.p. 848C; Rf ˆ 0.36 (silica gel, petroleum ether/
EtOAc 1:1); [a] V217.6 nm
ˆ
7078, V229.0nm ˆ 54208, V253.2 nm
ˆ
8318 (c ˆ
0.130mm in MeOH, 228C); 1H NMR (400 MHz, CDCl3, 258C, TMS):
(aglycon) d ˆ 5.95 (dd, J ˆ 16.0, 2.8 Hz, 1H), 5.76 (ddd, J ˆ 16.0, 9.6, 1.0 Hz,
1H), 5.32 (ddq, J ˆ 12.2, 0.8, 6.5 Hz, 1H), 4.62 (brd, J ˆ 8.8 Hz, 1H;
exchangable), 4.46 (dddd, J ˆ 4.0, 3.4, 2.8, 1.0 Hz, 1H), 4.17 (ddd, J ˆ 9.6,
6.4, 8.2 Hz, 1H), 4.05 (dddd, J ˆ 8.8, 4.0, 6.5, 1.4 Hz, 1H), 2.64 (dd, J ˆ 14.2,
1.4 Hz, 1H), 2.41 (dd, J ˆ 14.2, 6.5 Hz, 1H), 1.94 ± 1.90 (m, 2H), 1.77 (d, J ˆ
3.4 Hz, 1H; exchangable), 1.28 (d, J ˆ 6.6 Hz, 3H); (rhodinosyl) d ˆ 8.10 ±
7.40 (m, 5H), 5.05 (m, 1H), 4.98 (brd, J ˆ 2.6 Hz, 1H), 4.08 (dq, J ˆ 1.0,
6.6 Hz, 1H), 2.15 (dddd, J ˆ 13.4, 13.4, 4.0, 3.0 Hz, 1H), 2.02 (dddd, J ˆ
13.6, 13.4, 3.8, 3.8 Hz, 1H), 1.94 ± 1.90 (m, 1H), 1.52 (brd, J ˆ 13.6 Hz, 1H),
1.19 (d, J ˆ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 174.9,
132.6, 132.3, 74.6, 73.8, 72.4, 68.4, 41.5, 33.2, 21.3; (rhodinosyl) d ˆ 166.2,
133.1, 130.2, 129.8, 128.4, 92.6, 70.0, 65.5, 24.1, 23.0, 17.3; C23H30O8 (434.49):
calcd C 63.58, H 6.96; found C 63.73, H 6.79; Crystal structure data:[23]
crystal dimensions 0.4  0.4  0.4 mm, tetragonal, space group P41212, a ˆ
4,7-Bis-(2,3,6-trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D
(17e):
Debenzoylation of the first fraction (Rf ˆ 0.62 vide supra, 25.5 mg,
0.039 mmol) under standard conditions[31] and chromatographic purifica-
tion with EtOAc afforded 17e (15.5 mg, 0.035 mmol, 89%) as a colorless
solid. M.p. 768C; Rf ˆ 0.10 (silica gel, EtOAc); 1H NMR (400 MHz, CDCl3,
258C, TMS): (aglycon) d ˆ 5.88 (dd, J ˆ 15.8, 3.0 Hz, 1H), 5.72 (ddd, J ˆ
15.8, 9.6, 1.0 Hz, 1H), 5.31 (ddq, J ˆ 12.0, 4.0, 6.4 Hz, 1H), 4.61 (brs, 1H;
exchangable), 4.34 (ddd, J ˆ 4.0, 3.0, 1.0 Hz, 1H), 4.10 (m, 1H), 4.01 (m,
1H), 2.57 (dd, J ˆ 14.2, 1.8 Hz, 1H), 2.40 (dd, J ˆ 14.2, 6.2 Hz, 1H), 1.91 ±
1.86 (m, 2H), 1.27 (d, J ˆ 6.4 Hz, 3H); (rhodinosyl at 7-O) d ˆ 4.80 (brs,
1H), 3.93 (brq, J ˆ 6.6 Hz, 1H), 3.58 ± 3.55 (m, 1H), 2.09 ± 2.00 (m, 1H),
2.00 ± 1.91 (m, 2H; 1H exchangable), 1.82 ± 1.76 (m, 1H), 1.42 ± 1.37 (m,
1H), 1.19 (d, J ˆ 6.6 Hz, 3H); (rhodinosyl at 4-O) d ˆ 4.84 (brs, 1H), 3.92
(brq, J ˆ 6.6 Hz, 1H), 3.58 ± 3.55 (m, 1H), 2.09 ± 2.00 (m, 1H), 2.00 ± 1.91
(m, 2H; 1H exchangable), 1.82 ± 1.76 (m, 1H), 1.59 ± 1.54 (m, 1H), 1.09 (d,
J ˆ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): (aglycon) d ˆ 175.0, 132.0,
130.6, 75.9, 74.5, 71.9, 68.4, 41.4, 33.5, 21.3; (rhodinosyl at 7-O) d ˆ 92.6,
67.3, 66.3, 25.9, 23.6, 17.2; (rhodinosyl at 4-O) d ˆ 96.5, 67.4, 67.0, 25.7, 23.4,
3
10.552(10), c ˆ 40.902(6) Š, Z ˆ 8, Vˆ 4554.2(9) Š3, 1calcd ˆ 1.267 gcm
,
MoKa radiation, (l ˆ 71.073 pm), Tˆ 153(2) K, 3382 reflections, 2966
symmetry-independent reflections, 2Vmax ˆ 458, program SHELXTL, pa-
rameters ˆ 284, R1 ˆ 0.0848 (I > 2s) and wR2 ˆ 0.1562.
7-(2,3,6-Trideoxy-a-l-threo-pyranosyloxy)-decarestrictine D (17a): De-
benzoylation of the second fraction (Rf ˆ 0.36 vide supra, 116.3 mg,
0.268 mmol) under standard conditions[31] afforded 17a (66.1 mg,
0.20 mmol, 75%) after flash chromatography (CH2Cl2/CH3OH 9:1) as a
colorless solid. M.p. 418C; Rf ˆ 0.08 (silica gel, CH2Cl2/CH3OH 9:1); [a]
‡
17.0; LRMS (DCI): m/z (%): 462.5 (100) [M‡NH4 ].
5-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-2-phenylseleno-b-d-glu-
co-pyranosyloxy]-decarestrictine B (20a): A 1:3 mixture of 7a and 7b
(162 mg, 0.282 mmol) was added to a solution of decarestrictine B (4)
(67 mg, 0.313 mmol) in dry diethyl ether (10 mL) at 788C and the
reaction was stirred. After 15 min TMSOTf (11.3 mL, 0.2 equiv) in diethyl
ether (0.2 mL) was added and stirring was continued for 5 min at ambient
temperature. For the workup, the reaction mixture was hydrolyzed with a
saturated NH4Cl solution and allowed to warm to RT. After washing three
times with CH2Cl2, the combined organic phases were dried (MgSO4) and
V201.5 nm ˆ ‡5398, V209.1 nm ˆ 08, V218.3 nm
ˆ
5858 (c ˆ 0.303mm in MeOH,
218C); 1H NMR (400 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.90 (dd,
J ˆ 15.8, 2.8 Hz, 1H), 5.73 (ddd, J ˆ 15.8, 9.6, 1.2 Hz, 1H), 5.28 (ddq, J ˆ 9.6,
3.2, 6.4 Hz, 1H), 4.63 (brs, 1H; exchangable), 4.11 (ddd, J ˆ 9.6, 9.6, 5.2 Hz,
1H), 4.03 (ddd, J ˆ 6.4, 4.0, 1.8 Hz, 1H), 2.62 (dd, J ˆ 14.2, 1.8 Hz, 1H), 2.41
(brs, 1H; exchangable), 2.39 (dd, J ˆ 14.2, 6.4 Hz, 1H), 1.90 ± 1.86 (m, 2H),
Chem. Eur. J. 1998, 4, No. 7
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0407-1331 $ 17.50+.25/0
1331

A. Kirschning et al.
FULL PAPER
evaporated in vacuo. Flash chromatography (toluene/EtOAc 20:1) gave
three fractions:
treated with triphenyltin hydride (39 mg, 0.111 mmol) and a catalytic
amount of AIBN as described for 16. Flash chromatography (toluene/
EtOAc 20:1) afforded 21b (40.2 mg, 0.07 mmol, 94%) as a colorless oil. [a]
First fraction: 4 (25.4 mg, 0.119 mmol, 38% with reference to starting 4).[12]
Second fraction: 7a (33.3 mg; 0.058 mmol); colorless oil; [a]2D4:5 ˆ ‡17.2
V216.0 nm
ˆ
106008, V244.8 nm
ˆ
15908, V284.0 nm
ˆ
59108, V341.0 nm
ˆ
1238,
V472.6 nm ˆ ‡7518 (c ˆ 0.0337mm in MeOH, 258C); 1H NMR (300 MHz,
CDCl3, 258C, TMS): (aglycon) d ˆ 5.09 (brdq, J ˆ 11.4, 6.2 Hz, 1H), 3.73
(ddd, J ˆ 9.0, 4.4, 3.2 Hz, 1H), 3.42 (s, 2H), 3.08 (ddd, J ˆ 10.2, 4.2, 3.8 Hz,
1H), 2.99 (dd, J ˆ 9.0, 3.8 Hz, 1H), 2.94 (dd, J ˆ 14.0, 4.4 Hz, 1H), 2.58 (dd,
J ˆ 14.0, 3.2 Hz, 1H), 2.36 (brdd, J ˆ 14.6, 4.4 Hz, 1H), 1.53 (ddd, J ˆ 14.6,
11.4, 10.2 Hz, 1H), 1.32 (d, J ˆ 6.2 Hz, 3H); (olivosyl) d ˆ 5.11 (brd, J ˆ
3.8 Hz, 1H), 3.93 (ddd, J ˆ 10.8, 8.0, 4.8 Hz, 1H), 3.85 (dq, J ˆ 9.0, 6.2 Hz,
1H), 3.14 (dd, J ˆ 9.0, 8.0 Hz, 1H), 2.03 (ddd, J ˆ 13.2, 4.8, 1.2 Hz, 1H), 1.70
(ddd, J ˆ 13.2, 11.0, 3.8 Hz, 1H), 1.17 (d, J ˆ 6.2 Hz, 3H), 0.89, 0.89 (2s,
18H), 0.09, 0.07 (2s, 12H); 13C NMR (50 MHz, CDCl3): (aglycon) d ˆ
199.6, 165.6, 71.4, 69.0, 58.8, 54.2, 51.9, 47.8, 36.7, 20.7; (olivosyl) d ˆ 94.8,
78.3, 70.5, 68.8, 39.7, 26.3, 26.1, 18.5, 18.3, 18.1, 2.8, 3.1, 4.0, 4.4;
1
(c ˆ 1 in CHCl3); H NMR (300 MHz, CDCl3, 258C, TMS): d ˆ 7.60 ± 7.54
(m, 2H), 7.33 ± 7.24 (m, 3H), 6.17 (d, J ˆ 5.8 Hz, 1H), 4.14 (dd, J ˆ 5.0,
3.4 Hz, 1H), 3.83 (dq, J ˆ 6.2, 6.6 Hz, 1H), 3.68 (dd, J ˆ 5.8, 3.4 Hz, 1H),
3.53 (dd, J ˆ 6.2, 5.0 Hz, 1H), 1.92 (s, 3H), 1.34 (d, J ˆ 6.6 Hz, 3H), 0.94,
0.90 (2s, 18H), 0.16, 0.13, 0.12, 0.10 (4s, 12H); 13C NMR (50 MHz, CDCl3):
d ˆ 169.5, 133.8, 129.0, 127.4, 93.6, 74.9, 74.6, 73.5, 48.6, 26.1, 25.9, 21.0, 18.3,
18.2, 18.0, 3.6, 3.6, 4.31, 4.6; HRMS (EI) calcd for C26H46O5Si2Se
574.2049, found 574.2048.
3rd fraction: 20a (136.6 mg, 0.188 mmol, 89% with reference to starting
7b) colorless oil; [a] V204.0 nm
ˆ
128008, V237.2 nm ˆ ‡148008, V251.2 nm ˆ
1268, V280.6nm
ˆ
145008 (c ˆ 0.0314mm in MeOH, 248C); 1H NMR
(300 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.11 (ddq, J ˆ 11.4, 0.8,
6.4 Hz, 1H), 3.93 (ddd, J ˆ 8.8, 5.4, 3.4 Hz, 1H), 3.49 (d, J ˆ 14.2 Hz, 1H),
3.38 (d, J ˆ 14.8 Hz, 1H), 3.07 (dd, J ˆ 14.0, 3.4 Hz, 1H), 3.05 ± 2.95 (m,
2H), 2.82 (dd, J ˆ 14.0, 5.4 Hz, 1H), 2.31 (ddd, J ˆ 14.6, 4.0, 0.8 Hz, 1H),
1.51 (ddd, J ˆ 14.6, 11.4, 10.2 Hz, 1H), 1.35 (d, J ˆ 6.4 Hz, 3H); (olivosyl)
d ˆ 7.75 ± 7.20 (m, 5H), 5.35 (d, J ˆ 7.0 Hz, 1H), 4.19 (dd, J ˆ 4.6, 3.0 Hz,
1H) 3.82 (dq, J ˆ 2.8, 6.8 Hz, 1H), 3.58 (dd, J ˆ 4.6, 2.8 Hz, 1H), 3.18 (dd,
J ˆ 7.0, 3.0 Hz, 1H), 1.39 (d, J ˆ 6.8 Hz, 3H), 0.97, 0.89 (2s, 18H), 0.11, 0.10,
0.07, 0.04 (4s, 12H); 13C NMR (50 MHz, CDCl3): (aglycon) d ˆ 199.6, 165.3,
74.0, 69.0, 59.3, 53.3, 52.1, 46.9, 36.8, 20.6; (olivosyl) d ˆ 131.3, 128.6, 127.0,
104.2, 101.7, 77.6, 76.2, 75.1, 50.2, 25.9, 25.8, 20.2, 18.1, 4.0, 4.2, 4.3,
4.3; HRMS (EI) calcd for C34H56O8Si2Se 728.2679, found 728.2678.
‡
LRMS (DCI): m/z (%): 590.4 (100) [M‡NH4 ], 392.3 (7), 376.2 (40), 359.3
(8), 232.1 (11).
5-(2,6-Dideoxy-b-d-arabino-pyranosyloxy)-decarestrictine B (22a): Com-
pound 21a (61.2 mg, 0.107 mmol) was treated with anhydrous TBAF
(112 mg, 0.428 mmol, 4 equiv) in dry THF (5 mL) for 2 h at 08C. Flash
chromatography (silica gel, EtOAc) of the concentrated solution followed
by a second chromatogaphic purification (CH2Cl2/MeOH 9:1) afforded 22a
(31.8 mg, 0.092 mmol, 87%) as a colorless oil. [a] V216.8 nm
V248.4 nm 2658, V286.8 nm
22708, V348.2 nm ˆ 1358, V445.2 nm
ˆ
89508,
2988 (c ˆ
ˆ
ˆ
ˆ
0.0947mm in MeOH, 238C); 1H NMR (500 MHz, CDCl3, 258C, TMS): d ˆ
5.11 (ddq, J ˆ 11.4, 1.2, 6.2 Hz, 1H), 4.86 (dd, J ˆ 9.6, 2.0 Hz, 1H), 3.88
(ddd, J ˆ 9.0, 5.2, 3.6 Hz, 1H), 3.61 (ddd, J ˆ 11.6, 8.8, 5.0 Hz, 1H), 3.48 (d,
J ˆ 14.4 Hz, 1H), 3.42 (d, J ˆ 14.4 Hz, 1H), 3.31 (dq, J ˆ 9.0, 6.0 Hz, 1H),
3.13 (dd, J ˆ 9.0, 8.8 Hz, 1H), 3.04 (ddd, J ˆ 10.4, 4.0, 4.0 Hz, 1H), 3.03 (dd,
J ˆ 13.8, 3.6 Hz, 1H), 3.01 (dd, J ˆ 9.0 4.0 Hz, 1H), 2.85 (dd, J ˆ 13.8,
5.2 Hz, 1H), 2.34 (ddd, J ˆ 14.8, 4.0, 1.2 Hz, 1H), 2.28 (ddd, J ˆ 12.4, 5.0,
2.0 Hz, 1H), 1.65 (ddd, J ˆ 12.4, 11.6, 9.6 Hz, 1H), 1.51 (ddd, J ˆ 14.8, 11.4,
10.4 Hz, 1H), 1.35 (d, J ˆ 6.2 Hz, 3H), 1.34 (d, J ˆ 6.0 Hz, 3H); 13C NMR
(50 MHz, CDCl3): d ˆ 199.8, 165.4, 99.1, 77.3, 74.0, 71.8, 71.6, 69.1, 59.5, 53.8,
52.1, 47.0, 39.1, 36.6, 20.6, 17.8; LRMS (DCI): m/z (%): 706.5 (10)
5-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-2-phenylseleno-a-d-m-
anno-pyranosyloxy]-decarestrictine B (20b): Compound 7a (100 mg;
0.174 mmol)was added to a solution of decarestrictine B (4) (41 mg,
0.19 mmol) in dry diethyl ether (10 mL) at 788C, which was stirred. After
15 min, TMSOTf (47 mL, 1.5 equiv) in diethyl ether (1 mL) was added and
stirring was continued for 30 min at 258C. Workup in the usual manner
and purification by flash chromatography (toluene/EtOAc 20:1) gave 20b
(117 mg, 0.16 mmol, 92%) as a colorless oil. [a] V208.0 nm
ˆ
149008,
V232.8 nm ˆ ‡20108, V291.6nm
ˆ
56708 (c ˆ 0.0221mm in MeOH, 248C); 1H
‡
‡
[2M‡NH4 ], 362.3 (100) [M‡NH4 ].
NMR (300 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.11 (ddq, J ˆ 11.4, 0.8,
6.4 Hz, 1H), 3.78 (ddd, J ˆ 9.2, 4.8, 3.2 Hz, 1H), 3.44 (s, 2H), 3.10 (ddd, J ˆ
10.2, 4.0, 4.0 Hz, 1H), 2.97 (dd, J ˆ 9.2, 4.0 Hz, 1H), 2.84 (dd, J ˆ 14.0,
4.8 Hz, 1H), 2.64 (brdd, J ˆ 14.0, 3.2 Hz, 1H), 2.35 (ddd, J ˆ 14.6, 4.0,
0.8 Hz, 1H), 1.57 (ddd, J ˆ 14.6, 11.4, 10.2 Hz, 1H), 1.35 (d, J ˆ 6.4 Hz, 3H);
(olivosyl) d ˆ 7.64 ± 7.20 (m, 5H), 5.26 (d, J ˆ 4.8 Hz, 1H), 4.14 (dd, J ˆ 5.0,
3.4 Hz, 1H), 3.93 (dq, J ˆ 7.2, 6.4 Hz, 1H), 3.66 (dd, J ˆ 4.8, 3.4 Hz, 1H),
3.52 (dd, J ˆ 7.2, 5.0 Hz, 1H), 1.32 (d, J ˆ 6.4 Hz, 3H), 1.04, 0.92 (2s, 18H),
0.21, 0.17, 0.12, 0.12 (4s, 12H); 13C NMR (50 MHz, CDCl3): (aglycon) d ˆ
199.6, 165.5, 72.3, 69.0, 58.8, 54.4, 51.9, 47.3, 36.6, 20.6; (olivosyl) d ˆ 133.2,
130.3, 128.9, 126.9, 98.0, 76.1, 75.0, 70.7, 50.5, 26.2, 26.0, 18.8, 18.3, 18.0,
3.5, 4.2, 4.4; HRMS (EI) calcd for C34H56O8Si2Se 728.2679, found
728.2678.
5-(2,6-Dideoxy-a-d-arabino-pyranosyloxy)-decarestrictine B (22b): Com-
pound 21b (33.5 mg, 0.058 mmol) was treated with anhydrous TBAF
(76 mg, 0.29 mmol) in dry THF (3 mL) for 12 h at RT. For the workup, the
solution was purified directly by flash chromatography (EtOAc, followed
by a second chromatographic purification CH2Cl2/MeOH 9:1) to afford the
starting material 21b (4.7 mg, 8.0 mmol) and 22b (11.0 mg, 0.032 mmol,
55%) as a colorless oil. [a] V215.0 nm
42808, V342.0 nm ˆ 1208, V443.6 nm
ˆ
83408, V247.8 nm
4258 (c ˆ 0.0848mm in MeOH, 238C);
ˆ
1148, V286.4 nm
ˆ
ˆ
1H NMR (500 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.10 (ddq, J ˆ 11.4,
1.0, 6.2 Hz, 1H), 3.76 (ddd, J ˆ 9.2, 4.6, 3.2 Hz, 1H), 3.44 (s, 2H), 3.09 (ddd,
J ˆ 10.4, 4.4, 4.0 Hz, 1H), 2.99 (dd, J ˆ 9.2, 4.0 Hz, 1H), 2.96 (dd, J ˆ 14.0,
4.6 Hz, 1H), 2.60 (dd, J ˆ 14.0, 3.2 Hz, 1H), 2.45 (ddd, J ˆ 14.6, 4.4, 1.0 Hz,
1H), 1.51 (ddd, J ˆ 14.6, 11.4, 10.4 Hz, 1H), 1.33 (d, J ˆ 6.2 Hz, 3H);
(olivosyl) d ˆ 5.22 (brd, J ˆ 3.6 Hz, 1H), 3.95 (ddd, J ˆ 11.6, 8.8, 5.0 Hz,
1H), 3.92 (dq, J ˆ 9.6, 6.2, 1H), 3.12 (dd, J ˆ 9.6, 8.8 Hz, 1H), 2.13 (ddd, J ˆ
13.0, 5.0, 0.8 Hz, 1H), 2.05 (brs, 1H, exchangeable), 1.77 (ddd, J ˆ 13.0,
11.5, 3.6 Hz, 1H), 1.58 (brs, 1H, exchangeable), 1.26 (d, J ˆ 6.2 Hz, 3H);
13C NMR (50 MHz, CDCl3): (aglycon) d ˆ 200.2, 165.5, 70.9, 69.1, 58.7, 54.4,
51.9, 47.4, 36.6, 20.7; (olivosyl) d ˆ 94.5, 78.1, 69.1, 67.6, 37.6, 17.6; LRMS
5-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-b-d-arabino-pyranosy-
loxy]-decarestrictine B (21a): 20a (30.8 mg, 0.042 mmol) was treated with
triphenyltin hydride (22.3 mg, 0.064 mmol) and a catalytic amount of
AIBN as described before for 16. Flash chromatography (toluene/EtOAc
15:1) afforded 21a (22.7 mg, 0.04 mmol, 94%) as a colorless oil. [a]
V214.8 nm
ˆ
116008, V246.8 nm
ˆ
14508, V283.0 nm
ˆ
34908, V342.6 nm
ˆ
4898,
V441.8 nm
ˆ
618 (c ˆ 0.0302mm in MeOH, 258C); 1H NMR (300 MHz,
‡
‡
(DCI): m/z (%): 706.5 (1) [2M‡NH4 ], 362.3 (100) [M‡NH4 ].
CDCl3, 258C, TMS): (aglycon) d ˆ 5.10 (ddq, J ˆ 11.7, 0.8, 6.4 Hz, 1H), 3.89
(ddd, J ˆ 8.8, 5.4, 3.6 Hz, 1H), 3.48 (d, J ˆ 14.4 Hz, 1H), 3.40 (d, J ˆ
14.4 Hz, 1H), 3.05 (dd, J ˆ 13.8, 3.6 Hz, 1H), 3.04 ± 2.98 (m, 2H), 2.83
(dd, J ˆ 13.8, 5.4 Hz, 1H), 2.33 (ddd, J ˆ 14.6, 4.0, 0.8 Hz, 1H), 1.50 (ddd,
J ˆ 14.6, 11.4, 10.4 Hz, 1H), 1.34 (d, J ˆ 6.4 Hz, 3H); (olivosyl) d ˆ 4.81 (dd,
J ˆ 9.8, 2.0 Hz, 1H), 3.63 (ddd, J ˆ 11.6, 7.8, 4.8 Hz, 1H), 3.24 (dq, J ˆ 8.8,
6.0 Hz, 1H), 3.15 (dd, J ˆ 8.8, 7.8 Hz, 1H), 2.16 (ddd, J ˆ 12.6, 4.8, 2.0 Hz,
1H), 1.61 (ddd, J ˆ 12.6, 11.6, 9.8 Hz, 1H), 1.26 (d, J ˆ 6.0 Hz, 3H), 0.90,
0.89 (2s, 18H), 0.09, 0.08, 0.07 (3s, 12H); 13C NMR (50 MHz, CDCl3):
(aglycon) d ˆ 199.6, 165.4, 72.8, 69.0, 59.5, 53.7, 52.1, 47.1, 36.8, 20.6;
(olivosyl) d ˆ 98.8, 77.8, 73.6, 73.1, 41.0, 26.3, 26.1, 18.8, 18.3, 18.0, 2.7,
5-{4-O-[3,4-bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-b-d-arabino-pyra-
nosyl]-2,3,6-trideoxy-a-l-threo-pyranosyl}-decarestrictine B (24): A cata-
lytic amount of Ph3PHBr was added to a solution of decarestrictine B (4)
(1.8 mg, 8.3 mmol) and 10 (3.3 mg, 6.9 mmol) in dry CH2Cl2 (0.5 mL) at 08C,
and the reaction mixture was stirred for 2 h. For the workup, the reaction
mixture was hydrolyzed with a saturated NaHCO3 solution and additional
water (5 mL). After washing three times with CH2Cl2, the combined
organic phases were dried (MgSO4) and evaporated in vacuo. Flash
chromatography (CH2Cl2/MeOH 20:1) afforded 24 (3.2 mg, 4.7 mmol,
68%) as a colorless oil. [a] V218.0 nm
44908, V380.0 nm
in MeOH, 248C); 1H NMR (300 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ
5.10 (ddq, J ˆ 11.4, 1.0, 6.2 Hz, 1H), 3.91 (ddd, J ˆ 8.8, 4.4, 3.8 Hz, 1H), 3.43
(s, 2H), 3.03 ± 2.97 (m, 2H), 2.87 (dd, J ˆ 13.6, 4.4 Hz, 1H), 2.65 (dd, J ˆ
ˆ
92908, V248.4 nm
ˆ
3118, V286.4 nm
ˆ
‡
3.0, 3.9, 4.1; LRMS (DCI): m/z (%): 590.4 (100) [M‡NH4 ], 392.3
ˆ
1608, V449.4 nm ˆ 6588, V489.0 nm ˆ
83.78 (c ˆ 0.0313mm
(10), 376.3 (38), 359.3 (8), 232.1 (22).
5-[3,4-Bis-O-(tert-butyldimethylsilyl)-2,6-dideoxy-a-d-arabino-pyranosy-
loxy]-decarestrictine B (21b): Compound 20b (54 mg, 0.074 mmol) was
1332
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Chem. Eur. J. 1998, 4, No. 7

ªHybrid Antibioticsº
1324±1333
[7] U. Gräfe, in Biochemie der Antibiotika: Struktur, Biosynthese,
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Thiericke, ibid. 1992, 45, 66 ± 73.
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454; Angew. Chem. Int. Ed. Engl. 1990, 29, 425 ± 427.
13.6, 3.8 Hz, 1H), 2.31 (ddd, J ˆ 14.4, 4.0, 1.0 Hz, 1H), 1.64 ± 1.50 (m, 1H),
1.33 (d, J ˆ 6.2 Hz, 3H); (rhodinosyl) d ˆ 5.21 (brd, J ˆ 3.0 Hz, 1H), 4.08
(dq, J ˆ 1.0, 6.4 Hz, 1H), 3.56 (m, 1H), 2.11 ± 1.97 (m, 2H), 1.96 (m, 1H),
1.64 ± 1.50 (m, 1H), 1.19 (d, J ˆ 6.4 Hz, 3H); (olivosyl) d ˆ 4.44 (dd, J ˆ 9.2,
1.8 Hz1H), 3.60 (ddd, J ˆ 11.4, 7.8, 5.0 Hz, 1H), 3.18 (dq, J ˆ 8.8, 5.8 Hz,
1H), 3.16 ± 3.11 (m, 1H), 2.20 (ddd, J ˆ 12.6, 5.0, 1.8 Hz, 1H), 1.67 (ddd, J ˆ
12.6, 11.6, 9.8 Hz, 1H), 1.24 (d, J ˆ 5.8 Hz, 3H), 0.90, 0.89 (2s, 18H), 0.10,
‡
0.09, 0.08, 0.07 (4s, 12H); LRMS (DCI): m/z (%): 704.6 (100) [M‡NH4 ].
5-[4-O-(2,6-dideoxy-b-d-arabino-pyranosyl)-2,3,6-trideoxy-a-l-threo-pyr-
anosyl]-decarestrictine B (25): Compound 24 (3.1 mg, 4.5 mmol) was
treated with anhydrous TBAF (4.7 mg, 18 mmol) in THF (0.5 mL) at 08C
for 2 h. For the workup, the solution was purified directly by double flash
chromatography (CH2Cl2/MeOH 9:1) to afford 25 (1.5 mg, 3.7 mmol, 73%)
as a colorless oil. [a] V214.0 nm
V340.4 nm ˆ 7398, V445.0 nm
ˆ
53008, V244.2 nm ˆ 6278, V287.8 nm
ˆ
18808,
ˆ
4848 (c ˆ 0.0318mm in MeOH, 248C); 1H NMR
(500 MHz, CDCl3, 258C, TMS): (aglycon) d ˆ 5.10 (ddq, J ˆ 11.4, 6.2,
1.0 Hz, 1H), 3.91 (ddd, J ˆ 8.8, 4.4, 3.8 Hz, 1H), 3.43 (s, 2H), 3.02 ± 2.98 (m,
2H), 2.87 (dd, J ˆ 13.6, 4.4 Hz, 1H), 2.65 (dd, J ˆ 13.6, 3.8 Hz, 1H), 2.31
(ddd, J ˆ 14.8, 4.0, 1.2 Hz, 1H), 1.62 ± 1.51 (m, 1H), 1.33 (d, J ˆ 6.2 Hz, 3H);
(rhodinosyl) d ˆ 5.21 (brd, J ˆ 3.2 Hz, 1H), 4.09 (dq, J ˆ 1.0, 6.4 Hz, 1H),
3.52 (m, 1H), 2.09 ± 2.03 (m, 1H), 1.97 ± 1.93 (m, 2H), 1.62 ± 1.51 (m, 1H),
1.18 (d, J ˆ 6.4 Hz, 3H); (olivosyl) d ˆ 4.52 (dd, J ˆ 9.6, 1.9 Hz, 1H), 3.59
(ddd, J ˆ 11.8, 8.6, 5.0 Hz, 1H), 3.26 (dq, J ˆ 8.0, 6.0 Hz, 1H), 3.12 (dd, J ˆ
9.0, 8.6 Hz, 1H), 2.31 (ddd, J ˆ 12.4, 5.0, 1.9 Hz, 1H), 2.16 (brs, 1H,
exchangeable), 2.03 (brs, 1H, exchangeable), 1.72 (ddd, J ˆ 12.4, 11.8,
9.6 Hz, 1H), 1.32 (d, J ˆ 6.0 Hz, 3H); LRMS (DCI): m/z (%): 476.5 (100)
‡
[M‡NH4 ].
Acknowledgements: This work was supported by scholarships from the
Fonds der Chemischen Industrie for G.D. and the DECHEMA e. V. for
C.M. as well as in part by the Deutsche Forschungsgemeinschaft (SFB 416).
We thank Prof. Dr. E. Schaumann (TU Clausthal) and Prof. S. Grabley
(HKI, Jena) for supporting our work.
Received: November 24, 1997 [F F904]
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ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0407-1333 $ 17.50+.25/0
1333