Bicyclic Carbohydrate 1,2-Lactones
COMMUNICATION
ly, we succeeded in synthesizing the 1-deoxy derivative 9k
in 78% yield by hydride opening (Table 2, entry 11).
The last topic of our studies was the reaction of lactone
gluco-4 with C-nucleophiles 8l–p in the presence of scandi-
um triflate (Table 3). This should give easy access to inter-
ates in total synthesis.[18] On the other hand, allyl ester 9d is
predestined for ring-closing metathesis,[19] since due to the
selective a-anomerization during the lactone opening, both
double bonds occupy the same side of the carbohydrate.
Indeed, we were able to synthesize macrolide 11, which,
flanked by the saccharide, might possess interesting biologi-
cal properties.[20]
Table 3. Opening of the lactone gluco-4 with C-nucleophiles 8l–p.[a]
In conclusion, we developed a convenient and general
entry to bicyclic carbohydrate 1,2-lactones in only three
steps from glycals. Opening of the gluco-configured lactone
was demonstrated with various nucleophiles, which enabled
the introduction of hetero and carbon substituents at the
anomeric position. The reactions proceed with good yields
and high stereoselectivities, and the products allow further
interesting transformations.
Entry
Nucleophile 8[b]
Product 9 (%)[c]
1
Me3SiCN
8l
9l (90)
2
3
8m
9m (83)
8n
8o
9n (85)
9o (67)
Experimental Section
General procedure for the synthesis of carbohydrate 1,2-lactones 4: A so-
lution of the 2-C-branched carbohydrate 5 (2.0 mmol) and LiOH·H2O
(210 mg, 5.0 mmol) in MeOH/H2O (4/1, 20 mL) was heated under reflux
for 1 h. After cooling to room temperature, the solvent was removed
under reduced pressure. The crude product was dissolved in toluene, and
the pH value was adjusted to 3 with acetic acid. The solution was heated
under reflux for 1 h. After the solvents were evaporated, the crude prod-
uct was purified by flash chromatography (cyclohexane/ethyl acetate 7:1).
4
5
8p
9p (77)
General procedure for the ring opening with nucleophiles: A solution of
lactone gluco-4 (475 mg, 1.0 mmol), ScACHTNUTRGNEUNG(OTf)3 (740 mg, 1.5 mmol), and
[a] Procedure and conditions see Experimental Section. [b] Yields of ana-
lytically pure products (see the Supporting Information).
Drierite (20–40 mesh) (680 mg, 5.0 mmol) in dry dichloromethane
(20 mL) was stirred at 08C under an argon atmosphere. After 30 min the
nucleophile 8 (5.0 mmol, 5.0 equiv) was added to the mixture. The solu-
tion was stirred at room temperature until TLC showed complete conver-
sion. The reaction was quenched with saturated NaHCO3 solution
(30 mL), and the mixture was extracted with dichloromethane (3ꢁ
20 mL). The combined organic extracts were dried (Na2SO4) and concen-
trated, and the products 9 were isolated by flash chromatography. All
products 4 and 9 were completely characterized (see Supporting Informa-
tion).
esting C-glycosides,[17] which was already demonstrated with
other Lewis acids and 1,6-lactones 2.[5a,b] Indeed, we were
able to isolate 1,2-bis-C-branched glucose derivatives 9l–n
with the silylated nucleophiles 8l–n in high yields (Table 2,
entries 1–3). Additionally, electron-rich arenes enabled the
simple synthesis of C-aryl glycosides 9o,p (Table 3, entries 4
and 5). The opening proceeds for all reactions stereoselec-
tively to b-anomers, since subsequent epimerization is not
possible.
Acknowledgements
Finally, we present interesting applications of the synthe-
sized ring-opening products with two examples (Scheme 2).
Nitrile 9l was smoothly converted into the diester 10 in
86% yield. Such 1,2-bis-C-branched glucose derivatives with
a methyl ester group at the 1-positon are suitable intermedi-
This work was generously supported by the Deutsche Forschungsgemein-
schaft (Li 556/7–3).
Keywords: carbohydrates · lactones · nucleophilic addition ·
ring-opening · synthetic methods
[1] Reviews: a) H. Krçper in Houben-Weyl, Methoden der Organischen
Chemie, Vol. VI/2 (Ed.: E. Mꢂller), Thieme, Stuttgart, 1963,
Ogliaruso, J. F. Wolfe, Synthesis of Lactones and Lactams, Wiley,
thesis 2006, 2418–2439.
[2] Recent review: M. I. Konaklieva, B. J. Plotkin, Mini-Rev. Med.
Chem. 2005, 5, 73–95.
[3] a) J. Lehmann, Kohlenhydrate, Chemie und Biologie, 2nd ed.,
Thieme, Stuttgart, 1996; b) M. Bols, Carbohydrate Building Blocks,
Wiley, New York, 1996; c) T. K. Lindhorst, Essentials of Carbohy-
Scheme 2. Transformations of ring-opening products 9l and d.
Chem. Eur. J. 2009, 15, 49 – 52
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