Angewandte
Chemie
between the free primary OH and its O-sulfate
(Figure 2, circles). Thus, upon O-sulfation of 23,
the 13C shifts for the side-chain bearing the
sulfate underwent a displacement from d = 83.0
to 79.8 ppm for the CHOMe carbon atom and
d = 61.6 ppm to 66.3 ppm for the HO3SOCH2
carbon atom. Consequently, we proposed that
natural banyaside B was the glycosylated a-
anomer at axial-C-9 OH instead of the equato-
rial-C-7 OH as shown for 3 (Figure 1).
In order to provide additional corroborative
evidence for the structural revision, glycoside 27
was subjected to the sulfation conditions de-
scribed for 23. Sulfated 27 displayed an identical
retention factor by LCMS to that described by
Pluotno and Carmeli[3a] for the natural product
(YMC-Pack, ODS-A, isocratic MeOH/H2O
(1:1), EIC m/z 950.40, UV at 210 nm): k’ = 1.94
(natural banyaside B), and k’ = 1.98 (synthetic
banyaside 3). By contrast, the nominal banyaside
2 elicited k’ = 1.73 (for details, see the Supporting
Information).[3a]
Scheme 4. a) 19 (1.0 equiv), Me3SiOTf (0.1 equiv), 4 ꢁ M.S., THF, 238C, 75% (a/b,
2:1); b) TASF (5.0 equiv), DMF, 238C, 92%; c) 1. F3CCO2H (10.0 equiv), CH2Cl2,
238C; 2. 22 (3.0 equiv), Et3N, CHCl3, 238C, 69%; d) SO3·py (1.0 equiv), CH2Cl2, 238C,
25%; e) F3CCO2H/CH2Cl2 (9:1), 238C, 95%. M.S.=molecular sieves, TES=triethyl-
silyl, TASF=tris(dimethylamino)sulfonium difluorotrimethylsilicate, Tf=trifluorome-
thanesulfonyl.
In conclusion, the total synthesis of nominal
banyaside B (2) has been completed in 23 steps,
During the course of optimizing the glycosylation, we
observed the equatorial-OH (C-7 OH) to be more-reactive
than the axial-OH (C-9 OH). Thus, glycosylation of diol 4
with 1.0 equivalent of 19 furnished an 8:1 product mixture,
assigned as the C-7 (26) and C-9 (25) monoglycosides,
respectively (Scheme 5). Noteworthy, and diagnostic for the
relying on the initially reported synthesis of the Abn core
common to banyasides A (1) and nominal banyaside B (2),
suomilide, and spumigin HKVV. The introduction of the
three peptide side-chains proved to be challenging and in fact
could not be realized following standard peptide coupling
procedures, thereby clearly demarking the limitations of
current methods for the installation of hindered peptide
bonds. The total synthesis of nominal banyaside B (2) was
realized by relying on a late-stage glycosylation and intro-
duction of the guanidine subunit on the sensitive 2,5-
dehydropyrrole. Finally, a key outcome of the investigations
is the revision of the structure for banyaside B with the
glycolipid appended at C-9.
Received: July 2, 2010
Revised: August 17, 2010
Published online: October 22, 2010
Scheme 5. Attempted glycosylations of the banyaside core (4).
Keywords: aeruginosins · banyaside b · glycopeptides ·
.
natural products · total synthesis
C-7 isomer, was HMBC correlations between the anomeric
proton and Abn C-7 as well as a COSY cross-peak between
the H-9 proton and the Abn 9-OH (Figure 2). The minor
isomer (25) lacks a HMBC signal involving the anomeric
proton and the Abn C-9 carbon atom, a feature also noted in
the spectra for natural banyaside B. These results prompted
us in turn to prepare the corresponding regioisomer of 20,
which was converted into 27, following procedures described
above.
[1] For a recent review on the chemistry of the aeruginosins, see: K.
K. Sivonen, K. Adachi, N. Kazuyoshi, Y. Shimizu, H. Sano, K.
5529; c) K. Fuji, K. Harada, M. Suzu, K. Adachi, H. Sano, K.
Noguchi, K. Hirayama, K. Sivonen, Tennen Yuki Kagobutsu
Toronkai Koen Yoshishu 1996, 38, 277.
[4] C. S. Schindler, C. R. J. Stephenson, E. M. Carreira, Angew.
The 13C NMR shift for the anomeric carbon atom in 27
was found to be d = 98.9 ppm, which compares well with d =
98.7 ppm for natural banyaside B. Indeed, 27 shows strong
similarities and chemical shifts in the 13C NMR spectra with
the isolated natural product (Figure 2, triangles with Dd <
1 ppm). The only major differences are in the d-leucine side-
chain (circles, Figure 2, 27), in line with the difference
Angew. Chem. Int. Ed. 2010, 49, 9229 –9232
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9231