was synthesized in a total of 33 steps and an overall yield
of <0.01% starting from L- and D-rhamnal, whereupon
L-rhodinosyl tetrazoles7 and D-olivosyl phosphites8 were used
as donors to build the corresponding R-L-rhodinoside and
â-D-olivoside linkages, respectively. The stereoselectivities
for the synthesis of the later linkages were only moderate.
Roush and Bennett achieved the synthesis of the hexasac-
charide glycal in a highly stereoselective manner,9 taking
full advantage of the use of their well-advanced 2-deoxy-
2-iodo-glucopyranosyl trichloroacetimidate donors for the
construction of the required 2-deoxy-â-glycoside linkages.10
In addition, L-rhodinosyl acetates were successfully employed
for the synthesis of the R-L-rhodinoside linkages.11 Statisti-
cally, the whole synthetic route consists of 35 steps and was
achieved in 0.6% overall yield starting from (S)-lactate and
triacetyl D-glucal. In a previous report on the synthesis of
an A-B-C trisaccharide derivative by Kirschning,12 2,6-
dideoxy-2-iodo-glucopyranosyl acetates were employed as
donors for the stereoselective synthesis of the â-D-olivoside
linkages, albeit in lower yields. Here we report a novel and
efficient synthesis of the hexadeoxysaccharide fragment of
landomycin A (1) utilizing our newly developed method of
using phenyl 2,3-O-thionocarbonyl-1-thioglycosides as
2-deoxy-â-glycoside precursors.13
Strategically, coupling of two A-B-C trisaccharide
derivatives to build the final hexasaccharide is a convergent,
and therefore very efficient, synthetic route. And such a tactic
was successfully employed in both Sulikowski’s and Roush’s
syntheses.6,9 Alternatively, stepwise elongation is amenable
to the synthesis of shorter or longer congeners. The finding
that landomycins D, E, and B, having glycans of A-B,
A-B-C, and A-B-C-A-B, respectively, are the biosyn-
thetic intermediates of landomycin A implies a biosynthetic
route that is between completely convergent and stepwise
glycosylation.14 We thus planned our synthesis in a similar
fashion, i.e., elongation from A-B to A-B-C and then to
A-B-C-A-B and finally to the target hexasaccharide.
Accordingly, phenyl 3′-O-acetyl-2,3-O-thionocarbonyl-2′-S-
phenyl-1-thiodisacchride 3 and L-rhodinosyl acetate 2 would
be the key intermediates (Scheme 1).
Scheme 1
which differs from the former only at the configuration of
C-4, which will finally be reduced into a methylene. Another
major modification is the replacement of formylmethylene-
triphenylphosphorane with ethyl (triphenylphosphoranyli-
dene)acetate in the Wittig reaction with tartraldehyde 6; we
Scheme 2a
L-Rhodinose, a constituent of several classes of natural
products, has been synthesized by over a dozen approaches.15
We adopted modifications of Herczegh’s route for prepara-
tion of 216 (Scheme 2). Instead of starting from L-arabinose,
we began the synthesis with the much cheaper D-xylose,
(7) (a) Falahatpisheh, N.; Sulikowski, G. A. Synlett 1994, 672. (b) Sobti,
K.; Kim, K.; Sulikowski, G. A. J. Org. Chem. 1996, 61, 6.
(8) Recently, Sulikowski described a one-pot method using glycosyl
phosphites for the synthesis of 2-deoxy-â-oligosaccharides; see: Pongdee,
R.; Wu, B.; Sulikowski, G. A. Org. Lett. 2001, 3, 3523.
(9) Roush, W. R.; Bennett, C. E. J. Am. Chem. Soc. 2000, 122, 6124.
(10) (a) Roush, W. R.; Bennett, C. E. J. Am. Chem. Soc. 1999, 121,
3541. (b) Roush, W. R.; Gung, B. W.; Bennett, C. E. Org. Lett. 1999, 1,
891.
(11) Roush, W. R.; Bennett, C. E.; Roberts, S. E. J. Org. Chem. 2001,
66, 6389.
(12) Kirschning, A. Eur. J. Org. Chem. 1998, 2267.
(13) Yu, B.; Yang, Z. Y. Org. Lett. 2001, 3, 377.
(14) See ref 5a, pp 25-27.
(15) See relevant citations in ref 11.
(16) (a) Herczegh, P.; Zse´ly, M.; Kova´cs, I.; Batta, Gy.; Sztaricskai, F.
J. Tetrahedron Lett. 1990, 31, 1195. (b) Herczegh, P.; Kova´cs, I.; La´szlo´,
A.; Dinya, Z.; Sztaricskai, J. Liebigs Ann. Chem. 1991, 599.
a Reaction conditions: (a) EtSH (3.0 equiv), HCl (concd), 0 °C;
then (MeO)2CMe2, 69%. (b) 80% HOAc, 40 °C, 82%. (c) Pb(OAc)4
(1.1 equiv), PhMe, 0 °C, 100%. (d) Ph3PdCHCO2Et, CH2Cl2, 30
°C, 78%. (e) Raney Ni, H2, EtOH, 60 °C, 59%. (f) DIBAL-H (1.2
equiv), CH2Cl2, -78 °C, 78%. (g) 67% HOAc, 50 °C, 98%. (h)
Ac2O, pyridine, rt, 98%.
1920
Org. Lett., Vol. 4, No. 11, 2002