Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

Article abstract of DOI:10.3762/bjoc.14.274

In this paper, a new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported from a common starting material, (?)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring

Full text of DOI:10.3762/bjoc.14.274

Stereodivergent approach in the protected glycal synthesis of
L-vancosamine, L-saccharosamine, L-daunosamine and
L-ristosamine involving a ring-closing metathesis step
Pierre-Antoine Nocquet1, Aurélie Macé1, Frédéric Legros2, Jacques Lebreton3,
Gilles Dujardin2, Sylvain Collet3, Arnaud Martel2, Bertrand Carboni1
and François Carreaux*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 2949–2955.
1Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de
Rennes), UMR 6226, 263 avenue du Général Leclerc, Campus de
Beaulieu, F-35000 Rennes, France, 2Institut des Molécules et
Matériaux du Mans, UMR 6283 CNRS-Université du Maine, avenue
Olivier Messiaen, 72085 Cedex Le Mans, France and 3Chimie Et
Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR
6230 CNRS-Université de Nantes, 2 chemin de la Houssinière,
44322 Cedex Nantes, France
doi:10.3762/bjoc.14.274
Received: 04 September 2018
Accepted: 15 November 2018
Published: 29 November 2018
This article is part of the thematic issue "Progress in metathesis
chemistry III".
Email:
Guest Editors: K. Grela and A. Kajetanowicz
François Carreaux* - francois.carreaux@univ-rennes1.fr
© 2018 Nocquet et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
3-amino glycals; diastereoselective additions to aldehydes;
pluramycins; ring-closing metathesis; vinyl ethers
Abstract
In this paper, a new access to several chiral 3-aminoglycals as potential precursors for glycosylated natural products is reported
from a common starting material, (−)-methyl-L-lactate. The stereodivergent strategy is based on the implementation of a ring-
closing metathesis of vinyl ethers as key step of reaction sequences developed.
Introduction
Several classes of medicinally useful molecules with antibiotic For constructing aryl C-glycoside bonds, glycal derivatives are
and anticancer activity contain in their structures 3-amino-2- versatile synthetic intermediates (Figure 2). Indeed, they can be
deoxy sugars [1]. For instance, N,N-dimethyl-L-vancosamine is converted into glycosyl donors but can also be considered as
an essential component of pluramycin antibiotics such as potential coupling partners or nucleophilic moieties via the for-
kidamycin and pluramycin A via a C-glycosidic linkage mation of transient metalated species [2]. As example concern-
(Figure 1).
ing their use in pluramycins' syntheses, an approach to the syn-
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evaluated for the synthesis of this kind of nitrogen-containing
substrates. Taking into account our interest about the develop-
ment of new synthetic approaches to pluramycins [22,23], we
speculated that the cyclic vinyl ether derivative I, with the
prerequisite configuration of all stereogenic centers of
the carbamate-protected glycal of L-vancosamine 1, could
be obtained from the alcohol derivative II using an O-vinyl-
ation–ring-closing metathesis sequence (Figure 3). Afterwards,
the introduction of nitrogen in the convenient position (C3)
could be performed by a stereopecific nitrene insertion reaction
catalyzed by rhodium(II) complexes [24,25].
Figure 1: N,N-Dimethyl-L-vancosamine as substructure of kidamycin
and pluramycin.
Herein, we describe our outcomes related to the implementa-
tion of this strategy for the synthesis of L-vancosamine deriva-
thesis of pluraflavin A was developed based on a Stille cou- tive 1, as well as its diastereoisomer, the carbamate-protected
pling to install the C-linked sugar residue [3]. Moreover, the ad- 3-aminoglycal of L-saccharosamine 2, employing the
dition of lithiated glycals to quinone derivatives followed by a (S)-(−)-methyl lactate as common starting material. The effi-
rearrangement was also studied for the synthesis of kidamycin ciency and generality of this methodology was also demon-
according to a “reverse polarity” strategy [4,5].
strated by a new synthesis of C-3 unbranched amino glycals,
L-daunosamine 3 and L-ristosamine 4 derivatives, from the
Considering that the glycal scaffolds are versatile building same source of chirality.
blocks with multiple applications in the field of natural product
synthesis [6], the development of new asymmetric synthetic se- Results and Discussion
quences with stereochemical diversity is still of high interest. Synthesis of vancosamine and saccharosamine glycals. The
Different approaches have been reported for the asymmetric chiral (−)-lactic methyl ester was identified as the privileged
synthesis of protected 3-aminoglycals from non-carbohydrate starting material considering that the Evans aldol reaction via
precursors. Most of them used a common methodology for the boron enolates [26-28] with an appropriately O-protected alde-
construction of the pyranosyl glycal ring which is based on a hyde should afford the desired aldol adduct with a syn relative
cycloisomerization reaction of chiral homopropargylic alcohols configuration between the two newly created chiral centers
[7-10]. In some cases, the strategy used for the preparation of [29,30]. Moreover, the boron-mediated stereoselective aldol
the corresponding alkynyl alcohols requires the handling of reaction is all the more interesting for our synthetic plan as
toxic tin reagents [8,9].
stereochemical diversity can be generated depending on the
absolute configuration of the chiral auxiliary used. The alde-
During these last years, ring-closing metathesis (RCM) of hyde 5 was first prepared according to a described procedure in
vinyl ethers have proved to be an efficient method for the prep- two steps from methyl L-lactate (Scheme 1) [31]. The reaction
aration of chiral glycal scaffolds [11-18] as demonstrated in with (R)- or (S)-oxazolidinones 6 led to the formation of 2,3-syn
some total syntheses of marine polycyclic ethers [19-21]. How- aldol products 7 in good yields with a very high level of dia-
ever, to the best of our knowledge, this methodology was never stereoselection (>20:1 for both).
Figure 2: Glycals as relevant scaffolds for constructing aryl C-glycosidic linkage.
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Figure 3: Strategy including a ring-closing metathesis of vinyl ethers as key step for the preparation of several carbamate-protected 3-aminoglycals.
Scheme 1: Evans aldol reaction for the preparation of diastereomeric compounds 13a and 13b.
After protection of the free hydroxy group, the reduction of the ever the conditions used for this step, moderate yields were ob-
N-acyl oxazolidinones 8 into primary alcohols 9 was accom- tained for the desired products due to the formation of substan-
plished by LiBH4 in presence of water or LiAlH4 [32]. What- tial amounts of ring-opened byproducts 10 resulting from the
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hydride addition to the carbonyl group of the oxazolidinone ring n-butyl vinyl ether as solvent in the presence of bathophenan-
[33,34]. The alcohols 9 were then subjected to a Swern oxida- throline as ligand. In the case of Pd(OAc)2, the reaction was
tion followed by a Wittig reaction to generate the correspond- slower with moderate yields.
ing alkenes 13a,b in 90% and 63% yield, respectively, over two
steps. Alternatively, we envisioned that, from the same α-substi- The ring-closing metathesis reaction was performed with
tuted chiral aldehyde 5, compound 13b could be obtained in a Hoveyda–Grubbs second-generation (HG-II) catalyst to deliver
more straightforward manner employing a strategy based on a the corresponding dihydropyrans 16 in excellent yields given
diastereoselective allylboration reaction (Scheme 2) [35]. that this kind of reaction can be sensitive to the substitution
Indeed, the reaction of achiral pinacol (Z)-crotylboronate with 5 pattern contained in the substrate [11]. After silyl deprotection,
under neat conditions at room temperature gave a good level of the key C–H amination precursors 17a,b for the synthesis of the
diastereoselectivity for the hitherto unreported 3,4-syn-2,3-anti carbamate-protected glycal of L-vancosamine 1 and L-saccha-
product 12b [36-39].
rosamine 2 were prepared in two steps by treatment of alcohols
with the trichloroacetyl isocyanate reagent (TCA-NCO) fol-
The syn relationship between C3 and C4 is controlled by the lowed by basic hydrolysis. The spectroscopic properties of
(Z)-geometry of the crotylboronate, while the 2,3-anti relation- carbamates 17 were identical to those reported in the literature
ship can be rationalized by invoking Cornforth-like transition [7,8]. Although the intramolecular C–H amination of com-
states [40-43]. Eventually, silylation of the homoallylic alcohol pounds 17 under the Du Bois conditions [24] was already de-
12b afforded the expected compound 13b in 68% overall yield scribed in the literature [8,9], the reaction was nevertheless
from 5 after purification, compared to 29% using a strategy achieved with carbamate 17a in order to check the repro-
based on an Evans’ aldol reaction.
ducibility of the final step. As expected, L-vancosamine glycal
1 was obtained in similar yield than one reported [8,47].
Mildly oxidizing conditions using 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) were used for the removal of the Synthesis of daunosamine and ristosamine glycals. As previ-
p-methoxybenzyl (PMB) group to provide alcohols 14 ously, the chiral pool material 5 was used for this unbranched
(Scheme 3). Several palladium(II) catalysts have been tested for glycal synthesis (Scheme 4). The first step was the chelation-
the conversion of alcohols to vinyl ethers 15 [13,44-46]. We controlled addition of allylmagnesium bromide to 5 to provide
found that the best yields were obtained using Pd(TFA)2 and the syn diastereomer 18 in high stereoselectivity (93:7). After
Scheme 2: Alternative preparation of 13b based on a diastereoselective allylboration.
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Scheme 3: O-Vinylation-ring-closing metathesis sequence for access to 3-amino glycals.
Scheme 4: Synthesis of key intermediate 23 for the C-3 unbranched amino glycals preparation.
silylation of the free hydroxy group, the cleavage of the PMB Both diastereomers 23 and 26 were converted to the corre-
ether with DDQ led to alcohol 20 in 77% yield for the two sponding known carbamates using a two step sequence. Reac-
steps. Ring-closing metathesis of diene 21, obtained by O-vinyl- tion with TCA-NCO followed by a basic hydrolysis provided
ation of 20, gave the dihydropyran 22 in 53% overall yield for the desired compounds 24 and 27 in good yields and in full
two steps. The silyl group of compound 22 was cleaved using agreement with all reported spectroscopic data [9]. As an exam-
tetrabutylammonium fluoride (TBAF) in THF to form alcohol ple, the expected protected glycal of L-daunosamine 3 [9,47]
23 which was used directly in the next step [48].
was obtained by regioselective rhodium nitrene insertion thus
demonstrating the usefulness of this strategy for the synthesis of
At this stage, we envisioned that 23 could be also a key inter- such compounds.
mediate to access the ristosamine derivative by reversing the
configuration of the stereogenic center bearing the hydroxy Conclusion
group (Scheme 5). With this in mind, the secondary alcohol 23 We developed an alternative route to 3-aminoglycals through
was engaged in a Mitsunobu reaction using p-nitrobenzoic acid ring-closing metathesis of vinyl ethers as key step in the synthe-
as nucleophile to afford the expected compound 25. Hydrolysis sis and using a common noncarbohydrate starting material. The
of the ester was achieved using potassium carbonate in metha- approach was first validated for the synthesis of protected
nol to afford the epimeric product 26.
L-vancosamine glycal and extended afterwards to prepare a dia-
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Beilstein J. Org. Chem. 2018, 14, 2949–2955.
Scheme 5: Access to diastereoisomeric compounds 3 and 4 from 23.
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