Models for the synthesis of pluramycin antibiotics. Rearrangement of mono-protected aminoglycal-substituted cyclohexadienediols

Article abstract of DOI:10.1081/CAR-200059936

A two-step sequence converts protected glycal-substituted quinols to aryl bis C-glycals in which one or both of the substituents is an aminoglycal. First, a lithiated glycal undergoes 1,2-addition to the carbonyl group of a protected glycal-bearing quinol

Full text of DOI:10.1081/CAR-200059936

This article was downloaded by: [University of California, San Francisco]
On: 28 October 2014, At: 15:33
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Carbohydrate Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lcar20
Models for the Synthesis of Pluramycin
Antibiotics. Rearrangement of
Mono‐Protected Aminoglycal‐Substituted
Cyclohexadienediols
Kathlyn A. Parker a & Dai‐Shi Su a
a Department of Chemistry , Brown University , Providence, RI
Published online: 16 Aug 2006.
To cite this article: Kathlyn A. Parker & Dai‐Shi Su (2005) Models for the Synthesis of Pluramycin
Antibiotics. Rearrangement of Mono‐Protected Aminoglycal‐Substituted Cyclohexadienediols, Journal
of Carbohydrate Chemistry, 24:2, 199-208, DOI: 10.1081/CAR-200059936
To link to this article: http://dx.doi.org/10.1081/CAR-200059936
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &
Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Carbohydrate Chemistry, 24:199–208, 2005
Copyright # Taylor & Francis, Inc.
ISSN: 0732-8303 print
DOI: 10.1081/CAR-200059936
Models for the Synthesis
of Pluramycin Antibiotics.
Rearrangement
of Mono-Protected
Aminoglycal-Substituted
Cyclohexadienediols
Kathlyn A. Parker and Dai-Shi Su
Department of Chemistry, Brown University, Providence, RI
A two-step sequence converts protected glycal-substituted quinols to aryl bis C-glycals in
which one or both of the substituents is an aminoglycal. First, a lithiated glycal under-
goes 1,2-addition to the carbonyl group of a protected glycal-bearing quinol, leading to
a mono-protected cyclohexadienediol. Then a BF3-etherate-catalyzed “dienol phenol-
type” rearrangement converts the adduct to an aryl bis C-glycal. The glycal moiety
that was originally a substituent on the quinol substrate is the substituent that
migrates. The presence of the amino group does not introduce complications. This
sequence provides models for the rapid access to intermediates for pluramycin synthesis.
Keywords Pluramycin, Aminoglycal, Bis-C-glycoside, Quinone, Quinol, Dienol–
phenol, Rearrangement, Regiospecific, Polarity, Umplong
INTRODUCTION
Among the naturally occurring aryl C-10-glycoside antibiotics,[1,2] the pluramy-
cins, 1, are particularly challenging synthetic targets because they have two
aryl C-glycoside linkages on the same phenolic ring of the “aglycone.” In all
members of the class, the two sugar moieties are different, and they are both
amino sugars (Fig. 1).[3]
Received January 23, 2005; accepted March 3, 2005.
Address correspondence to Kathlyn A. Parker, State University of New York at Stony
Brook, Stony Brook, NY 11794–3400, USA. E-mail: kparker@notes.cc.sunysb.edu
Dai-Shi Su, Department of Medicinal Chemistry, Merck Research Laboratories,
West Point, PA 19486.
199

K. A. Parker and D. S. Shu
200
Figure 1: Pluramycin bis C-aryl glycosides, 1.

Models for the Synthesis of Pluramycin Antibiotics
201
Although numerous strategies have been developed for the synthesis of
aryl C-glycosides, only a few methods have been applied to a bis glycoside struc-
tural unit such as that in the pluramycins.[4] Furthermore, there is a dearth of
methods for connecting amino glycoside synthons to aromatic aglycones.[5]
Direct synthetic approaches to aryl C-aminoglycosides must accommodate
the presence of the amino groups on the sugars.
BACKGROUND
In an effort to discover new and efficient methods of constructing C-aryl glyco-
sides, we have examined the reduction and rearrangement chemistry of glycal-
substituted quinols. Remarkably, derivatives of these complex but easy to
acquire compounds can be converted to aryl C-glycals with substitution
patterns representative of each of the aryl C-10-glycoside structural classes.[4a,6]
In the previous paper in this series, we reported that the reduction of
glycal-substituted quinols (Fig. 2, Equation (1)) proceeds smoothly with
aminoglycal substrates to give p-hydroxyaryl aminoglycals, models for
ravidomycin.[7] Our next goal was to establish that the rearrangement
methodology (Fig. 2, Equation (2)), previously demonstrated only with a
dihydropyran or a protected rhamnal moiety as the migrating group, could
be extended to aminoglycal systems.
Using a lithiated aminoglycal reagent 2[7] in short schemes developed with
rhamnal reagent 3 for the preparation of the related deaza compounds, we have
found that the aminoglycal substituent behaves well in the role of stationary
appendage and in the role of migrating group. Our studies provide aryl
C-aminoglycal models for the pluramycins.
Models for Group 3 Aryl Bis C-Aminoglycal (Pluramycin)
Synthesis
The “dienol phenol-type” rearrangement[4a] would be an especially attrac-
tive key step in a pluramycin synthesis if it could be applied directly to sub-
strates in which at least one of the glycal substituents is an aminoglycal. In
order to proceed with an efficient synthesis based on this approach, we

K. A. Parker and D. S. Shu
202
Figure 2: Substitution patterns in glycal-substituted phenol derivatives from glycal-substituted
quinol substrates. G1 and G2 are protected glycal substituents. R ¼ trialkylsilyl.
wished to establish (1) that an aminoglycal substituent, which was not the
migrating group, would be stable to the rearrangement conditions; (2) that
an aminoglycal substituent, introduced at the appropriate position, would act
as the migrating substituent; (3) that modification of the substrate by the
incorporation of the desired amino group(s) would not alter the regiospecifici-
ty[4a] of the rearrangement reaction; and (4) that a substrate in which both
glycals were aminoglycals would undergo the rearrangement reaction. There-
fore, we examined three model systems. Substrates were prepared by analogy
to prior art.
The first substrate was prepared by treating protected quinol 4[4a] with
the lithiated aminoglycal reagent 2. Treatment of substrate 5 with BF3
etherate gave a protected phenol, assumed to be the product of migration
of the glycal moiety adjacent to the silyl ether, and therefore assigned struc-
ture 6 (Sch. 1).
The second substrate was prepared from quinol 7[7] by protection of the
tertiary hydroxyl group and then introduction of the second glycal substituent
by addition of the lithiated rhamnal reagent 3. When subjected to BF3 etherate,
substrate 9 was converted to a protected phenol. This product, clearly different
from the compound obtained from the regioisomeric substrate 5, was assigned
structure 10 (Sch. 2).
The third substrate, 11, was prepared by addition of the lithiated
aminoglycal reagent 2 to protected quinol 8. Rearrangement with BF3
etherate proceeded smoothly to provide the protected phenol 12 in high
yield (Sch. 3).

Models for the Synthesis of Pluramycin Antibiotics
203
Scheme 1: Model studies for the synthesis of kidamycin: reactivity of aminoglycal-bearing
substrates. Key: (a) 2, THF, 2788C, 67%, (b) BF3 etherate, THF, 08C ! rt, 80%.
Taken together, these studies show that the aminoglycal substituent is well
behaved in the “cyclohexadienol phenol-type” rearrangement, surviving the
rearrangement conditions in both the migratory and nonmigratory roles. Fur-
thermore, our results support the premise that regiochemistry in reactions of
aminoglycal-containing substrates is determined by the order of introduction
of the glycal substituents.
CONCLUSION
The synthesis of model compounds (6, 10, and 12) demonstrates the generality
of the “reverse polarity” strategy for the preparation of aryl bis C-aminoglyco-
sides of the pluramycin substitution pattern. The reactions are simple and easy
to perform and give good yields.
Scheme 2: Model studies for the synthesis of kidamycin: migration of aminoglycal substituent.
Key: (a) TESCl. Im, DMAP, DMF, rt, 94%. (b) 3, THF, 2788C, 90% (c) BF3 etherate, THF, 08C ! rt, 92%.

K. A. Parker and D. S. Shu
204
Scheme 3: Model study for the synthesis of kidamycin: a bis aminoglycal substrate. Key: (a) 2,
THF, 2788C, 61%, (b) BF3 etherate, THF, 08C ! rt, 83%.
EXPERIMENTAL SECTION
Solvents were dried and purified by standard methods before use. Ether refers
to diethyl ether. Flash chromatography was performed with silica gel (200–425
mesh).
Bisglycal 5. An 86-mg sample (0.22 mmol) of aminoglycal in 0.5 mL of
THF was treated with 0.50 mL (0.68 mmol) of t-BuLi (1.35 M in pentane),
and the resulting solution was added to 80 mg (0.14 mmol) of quinol glycal
4 in 1 mL of THF to give 91 mg (67%) of a brown oil. 1H NMR (CDCl3) d
7.77 (dd, J ¼ 1.6, 7.5 Hz, 2H), 7.67 (dd, J ¼ 1.6, 7.5 Hz, 2H), 7.39 (m, 6H),
6.00 (dt, J ¼ 2.3, 11.1 Hz, 2H), 5.74 (dt, J ¼ 2.3, 11.1 Hz, 2H), 5.24
(d, J ¼ 2.8 Hz, 1H), 4.91 (d, J ¼ 3.3 Hz, 1H), 4.16 (dd J ¼ 3.0, 6.5 Hz, 1H),
3.96 (t, J ¼ 6.5 Hz, 1H), 3.76 (m, 2H), 3.44 (dd, J ¼ 5.6, 7.8 Hz, 1H), 2.84
(bs, 1H), 2.38 (s, 1H), 2.19 (s, 6H), 1.18 (d, J ¼ 6.5 Hz, 3H), 1.04 (s, 12H),
0.85 (m, 27H), 0.58 (m, 6H), 0.09 (m, 12H); 13C NMR (CDCl3): d 154.6,
153.0, 136.3, 136.1, 134.5, 134.1, 133.6, 131.5, 131.4, 129.5, 129.4, 127.5,
127.3, 99.3, 91.8, 75.2, 74.1, 72.5, 71.2, 71.1, 66.7, 57.0, 43.0, 27.1, 26.1,
25.9, 19.5, 18.3, 18.0, 17.8, 17.1, 6.9, 6.2, 23.5, 23.6, 24.0, 24.2; FTIR
(neat): 1674, 1108 cm21
.
Aryl bisglycal 6. To a solution of 14 mg (0.014 mmol) of bisglycal 5 in
.
0.5 mL of THF at 08C was added 10 mL (0.082 mmol) of BF3 OEt2. After
stirring at rt for 1 hr, the solution was poured into 20 mL of saturated
NaHCO3. Extraction with ether (4 ꢀ 15 mL) provided a combined organic
solution, which was dried over MgSO4 and concentrated. Flash column

Models for the Synthesis of Pluramycin Antibiotics
205
chromatography (1% Et3N in 3:1 hexanes/EtOAc) gave 11 mg (80%) of a yellow
1
oil. H NMR (CDCl3) d 7.79 (d, J ¼ 6.0 Hz, 2H), 7.68 (d, J ¼ 6.5 Hz, 2H), 7.55
(d, J ¼ 2.0 Hz, 1H), 7.36 (m, 7H), 6.72 (d, J ¼ 8.5 Hz, 1H), 5.14 (d, J ¼ 3.9 Hz,
1H), 5.07 (d, J ¼ 3.2 Hz, 1H), 4.21 (t, J ¼ 4.0 Hz, 1H), 4.10 (t, J ¼ 6.2 Hz, 2H),
3.87 (t, J ¼ 6.1 Hz, 1H), 3.64 (t, J ¼ 5.0 Hz, 1H), 2.97 (bs, 1H), 2.27 (s, 6H),
1.36 (d, J ¼ 6.7 Hz, 3H), 1.06 (s, 12H), 0.89 (m, 27H), 0.76 (m, 6H), 0.09
(m, 12H); 13C NMR (CDCl3): d 153.3, 15.6, 149.2, 136.3, 136.2, 134.4, 129.5,
128.5, 127.4, 127.3, 126.5, 125.7, 119.5, 103.2, 92.1, 75.5, 74.9, 73.5, 73.3,
70.4, 57.7, 43.1, 27.1, 26.1, 26.0, 25.6, 19.6, 18.2, 17.1, 6.7, 6.6, 5.8, 5.2, 23.7,
23.9, 24.1, 24.2; FTIR (neat): 1651, 1105 cm21
.
Quinol silyl ether 8. To a solution of 26 mg (0.052 mmol) of quinol glycal 7
in 1 mL of DMF was added 21 mg (0.31 mmol) of imidazole, a catalytic amount
of DMAP, and 25 mL (0.15 mmol) of TESCl. The reaction mixture was stirred at
rt overnight, diluted with 5 mL of ether, and poured into 20 mL of H2O. The
resulting mixture was extracted with ether (4 ꢀ 15 mL), and the combined
ether solution was washed with H2O (3 ꢀ 15 mL), dried over MgSO4, and con-
centrated. Preparative TLC (1:9 MeOH/CHCl3) gave 30 mg (94%) of a yellow-
orange oil. 1H NMR (CDCl3) d 7.73 (dd, J ¼ 1.5, 7.6 Hz, 2H), 7.62 (dd,
J ¼ 1.6, 6.7 Hz, 2H), 7.36 (m, 6H), 6.74 (dd, J ¼ 3.0, 10.0 Hz, 1H), 6.65 (dd,
J ¼ 3.0, 10.0 Hz, 1H), 6.23 (dd, J ¼ 1.8, 9.9 Hz, 1H), 6.15 (dd, J ¼ 1.9,
10.0 Hz, 1H), 5.26 (d, J ¼ 2.2 Hz, 1H), 3.85 (q, J ¼ 7.0 Hz, 1H), 3.70
(t, J ¼ 4.8 Hz, 1H), 2.85 (s, 1H), 2.24 (s, 6H), 1.04 (s, 9H), 0.86 (m, 12H), 0.55
(m, 6H); 13C NMR (CDCl3): d 186.1, 151.2, 150.1, 150.0, 136.2, 136.0, 134.4,
133.8, 129.6, 129.5, 128.6, 128.5, 127.4, 127.3, 93.6, 74.8, 71.8, 71.4, 57.4,
43.0, 27.0, 26.3, 19.4, 17.2, 6.9, 6.4; FTIR (CDCl3): 1674 cm21; HRMS (FAB,
NaI): calcd. 640.3254, found: 640.3262 (M þ Na).
Bisglycal 9. To a solution of 60 mg (0.17 mmol) of protected rhamnal glycal
was added 0.31 mL (0.42 mmol) of t-BuLi (1.35 M in pentane) in 0.5 mL of THF
at 2788C. The solution was stirred at 08C for 1 hr, then cooled to 2788C and
added via cannula to a solution of 63 mg (0.10 mmol) of protected quinol
glycal 8 in 1 mL of THF at 2788C. The reaction mixture was stirred at
2788C for 4 hr and then diluted with 10 mL of ether. It was poured into
20 mL of H2O and extracted with ether (4 ꢀ 20 mL). The ether solution was
dried over MgSO4 and concentrated. Preparative TLC (hexanes/EtOAc, 3:1)
1
gave 89 mg (90%) of a brown oil. H NMR (CDCl3) d 7.74 (dd, J ¼ 1.5, 7.6 Hz,
2H), 7.64 (dd, J ¼ 1.5, 7.6 Hz, 2H), 7.38 (m, 6H), 5.96 (m, 2H), 5.80 (dd,
J ¼ 2.5, 10.3 Hz, 1H), 5.66 (dd, J ¼ 1.9, 9.8 Hz, 1H), 5.24 (d, J ¼ 3.2 Hz, 1H),
4.91 (d, J ¼ 3.5 Hz, 1H), 4.08 (t, J ¼ 3.7 Hz, 1H), 3.96 (t, J ¼ 6.6 Hz, 1H), 3.82
(t, J ¼ 6.2 Hz, 1H), 3.72 (t, J ¼ 6.6 Hz, 1H), 3.55 (dd, J ¼ 4.6, 6.0 Hz, 1H),
2.84 (bs, 1H), 2.21 (s, 6H), 1.27 (d, J ¼ 6.7 Hz, 3H), 1.04 (s, 9H), 0.88
(m, 30H), 0.59 (m, 6H), 0.08 (m, 12H); 13C NMR (CDCl3): d 154.0, 153.1,

K. A. Parker and D. S. Shu
206
136.2, 136.0, 134.5, 134.3, 134.2, 133.7, 131.2, 131.0, 129.6, 129.4, 127.5, 127.3,
97.6, 92.2, 75.7, 74.5, 72.3, 71.4, 69.7, 66.5, 57.2, 42.9, 27.1, 26.1, 25.8, 19.5,
18.2, 18.0, 17.4, 16.7, 7.0, 6.2, 23.8, 24.0, 24.1, 24.4; FTIR (neat): 1655,
1110 cm21
.
Aryl bisglycal 10. To a solution of 25 mg (0.026 mmol) of bisglycal 9 in
.
1 mL of THF at 08C was added dropwise 20 mL (0.16 mmol) of BF3 OEt2.
The resulting solution was stirred at rt for 0.5 hr and then poured into 20 mL
of saturated NaHCO3. Extraction with ether (4 ꢀ 15 mL) gave a combined
solution, which was dried over MgSO4 and concentrated. Flash column chrom-
atography (1% Et3N in 3:1 hexanes/EtOAc) gave 23 mg (92%) of a yellow oil. 1H
NMR (CDCl3) d 7.80 (dd, J ¼ 1.4, 7.9 Hz, 2H), 7.71 (dd, J ¼ 1.4, 7.9 Hz, 3H),
7.64 (d, J ¼ 1.3 Hz, 1H), 7.37 (m, 6H), 6.71 (d, J ¼ 8.4 Hz, 1H), 5.29
(d, J ¼ 4.1 Hz, 1H), 5.07 (d, J ¼ 3.2 Hz, 1H), 4.27 (dd, J ¼ 3.3, 5.3 Hz, 1H),
4.12 (t, J ¼ 7.9 Hz, 1H), 4.02 (t, J ¼ 6.6 Hz, 1H), 3.88 (t, J ¼ 6.2 Hz, 1H), 3.58
(dd, J ¼ 5.4, 7.4 Hz, 1H), 2.91 (t, J ¼ 4.8 Hz, 1H), 2.20 (s, 6H), 1.37
(d, J ¼ 6.6 Hz, 3H), 1.18 (d, J ¼ 6.3 Hz, 3H), 1.07 (s, 9H), 0.90 (m, 27H), 0.68
(m, 6H), 0.09 (m, 12H); 13C NMR (CDCl3): d 153.4, 151.0, 150.0, 136.3, 136.2,
134.6, 134.5, 129.5, 129.4, 128.0, 127.4, 127.2, 126.2, 125.6, 119.2, 98.1, 97.8,
75.6, 75.4, 73.7, 73.3, 71.4, 57.9, 43.2, 27.2, 26.2, 26.0, 19.6, 18.4, 18.3, 18.1,
17.4, 6.6, 5.2, 23.5, 23.9, 24.2; FTIR (neat): 1653, 1105 cm21
.
Bisaminoglycal 11. In a procedure similar to that for preparing
compound 5, a 66-mg sample (0.17 mmol) of aminoglycal was treated with
0.35 mL (0.47 mmol) of t-BuLi (1.35 M in pentane). The resulting solution
was added to 64 mg (0.096 mmol) of quinol glycal 8 in 1 mL of THF. Iso-
lation and chromatoraphy afforded 18 mg of recovered 8 and 42 mg (61%,
calculated for 72% conversion) of 11 as a yellow oil. 1H NMR (CDCl3) d
7.74 (dd, J ¼ 1.5, 8.8 Hz, 4H), 7.67 (dd, J ¼ 1.5, 8.0 Hz, 4H), 7.37
(m, 12H), 6.00 (dt, J ¼ 1.9, 9.9 Hz, 2H), 5.80 (dd, J ¼ 2.2, 9.7 Hz, 1H),
5.66 (dd, J ¼ 2.3, 9.8 Hz, 1H), 5.23 (d, J ¼ 3.3 Hz, 1H), 4.91 (d, J ¼ 3.3 Hz,
1H), 3.95 (qn, J ¼ 6.6 Hz, 1H), 3.79 (dd, J ¼ 6.3 Hz, 2H), 3.72
(t, J ¼ 5.7 Hz, 1H), 2.83 (s, 3H), 2.19 (s, 12H), 1.08 (2s, 21H), 0.89 (qn,
J ¼ 8.6 Hz, 12H), 0.55 (q, J ¼ 7.8 Hz, 6H); 13C NMR (CDCl3): d 154.7,
153.0, 136.3, 136.2, 136.1, 136.0, 134.5, 134.3, 134.2, 133.7, 131.4, 131.0,
129.6, 129.5, 129.4, 127.5, 127.4, 127.3, 92.2, 91.9, 74.4, 74.1, 72.5, 72.2,
71.4, 66.7, 57.1, 57.0, 46.0, 43.0, 42.9, 27.1, 19.5, 17.9, 17.4, 7.0, 6.3;
FTIR (neat): 3530, 1670, 1112 cm21; HRMS (FAB, NaI): calcd. 1035.5535,
found: 1035.558 (M þ Na).
Aryl bisglycal 12. To a solution of 13 mg (0.013 mmol) of bis aminoglycal
11 in 0.5 mL of THF at 08C was slowly added 10 mL (0.082 mmol) of
.
BF3 OEt2. The solution was stirred at rt for 1 hr, then poured into 15 mL of

Models for the Synthesis of Pluramycin Antibiotics
207
saturated NaHCO3. Extraction with ether (4 ꢀ 15 mL) provided a combined
ether solution, which was dried over MgSO4 and concentrated. Flash column
chromatography (1:4 hexanes/EtOAc with 1% Et3N) left 10 mg (83%) of a
1
yellow oil. H NMR (CDCl3) d 7.79 (m, 4H), 7.70 (m, 4H), 7.63 (s, 1H), 7.34
(m, 13H), 6.70 (d, J ¼ 8.5 Hz, 1H), 5.22 (d, J ¼ 4.0 Hz, 1H), 5.12
(d, J ¼ 3.9 Hz, 1H), 4.11 (m, 2H), 3.88 (t, J ¼ 6.2 Hz, 2H), 2.98 (bs, 1H), 2.91
(bs, 1H), 2.27 (s, 6H), 2.20 (s, 6H), 1.17 (d, J ¼ 6.3 Hz, 3H), 1.06 (m, 21H),
0.91 (m, 9H), 0.66 (m, 6H); 13C NMR (CDCl3): d 153.2, 151.7, 150.1, 136.3,
136.2, 134.6, 134.5, 129.5, 129.4, 127.4, 127.3, 127.2, 125.9, 125.4, 119.2,
97.7, 92.1, 73.6, 73.4, 73.3, 60.4, 57.9, 57.8, 43.1, 43.0, 27.2, 19.6, 18.4, 18.2,
6.6, 5.2; FTIR (neat): 1653, 1104 cm21
.
ACKNOWLEDGEMENT
Funding for the synthesis of aryl C-glycosides has been provided by the
National Cancer Institute (CA-50720 and CA-87503) and the National
Science Foundation (CHE-9521055). Dai-Shi Su was a Fellow of the Govern-
ment Assistance in Areas of National Need Program of the Department of Edu-
cation. We thank Drs. James van Epp and Meng Chen for assistance in
obtaining mass spectra.
REFERENCES
[1] (a) Postema, M.H.D. In C-Glycoside Synthesis. Rees, C.W., Ed.; CRC Press: Boca
Raton, FL, 1995, especially pp. 265–302. (b) Suzuki, K.; Matsumoto, T.
In Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial
Products; Lukacs, G., Ed.; Springer: Berlin, 1993; Vol. 2, pp. 352–403.
[2] The C-glycosidic angucyclines are surveyed in a review by Rohr, J.; Thiericke, R.
Angucycline group antibiotics. Natural Prod. Rep., 1992, 9, 103–137.
[3] (a) Sequin, U. The antibiotics of the pluramycin group (4H-anthra[1,2-b]pyran
antibiotics). Progr. Chem. Org. Nat. Prod. 1986, 50, 58–122; (b) Yasuzawa, T.;
Saitoh, Y.; Sano, H. Structures of the novel anthraquinone antitumor antibiotics,
DC92–B and DC92–D. II. Isolation, physicochemical properties and structure elu-
cidation. J. Antibiot. 1990, 43, 485; (c) Abe, N.; Enoki, N.; Nakakita, Y.; Uchida, H.;
Nakamura; Munekata, M. Novel antitumor antibiotics, saptomycins. II. Isolation,
physicochemical properties and structure elucidation. J. Antibiot. 1993, 46, 1536.
The altromycins and ankinomycin share the aglycone skeleton but bear only one
amino sugar as a C-glycoside, at the position ortho to the phenolic hydroxyl
group; the pluraflavins bear an amino disaccharide at this position and one
remote O-aminoglycoside moiety. The
urdamycins and saquayamycin share the aglycone skeleton but are not
aminoglycosides.
[4] (a) Parker, K.A.; Koh, Y.H. Methodology for the regiospecific synthesis of bis C-aryl
glycosides. Models for Kidamycin. J. Am. Chem. Soc. 1994, 116, 11149;
(b) Martin, S.F. Unified strategy for the synthesis of C-aryl glycosides. Pure
Appl. Chem. 2003, 75, 63; (c) Kaelin, D.E., Jr.; Sparks, S.M.; Plake, H.R.;
Martin, S.F. Regioselective synthesis of unsymmetrical C-aryl glycosides using

K. A. Parker and D. S. Shu
208
silicon tethers as disposable linkers. J. Am. Chem. Soc. 2003, 125, 12994;
(d) Kaelin, D.E., Jr.; Lopez, O.D.; Martin, S.F. General strategies for the synthesis
of the major classes of C-aryl glycosides. J. Am. Chem. Soc. 2001, 123, 6937; See
also (e) Dubois, E.; Beau, J.M. Synthesis of C-glycopyranosyl compounds by a pal-
ladium-catalyzed coupling reaction of 1-tributylstannyl-D-glucals with organic
halides. Carbohydr. Res. 1992, 228, 103; (f) Dubois, E.; Beau, J.M. Formation of
C-glycosides by
a palladium-catalyzed coupling reaction of tributylstannyl
glycals with organic halides. J. Chem. Soc. Chem. Commun. 1990, 17, 1191;
(g) El Telbani, E.; El Desoky, S.; Hammad, M.A.; Abdel Rahman, A.H.;
Schmidt, R.R. Synthesis of bis(C-glycosyl)flavonoid precursors. Carbohydr. Res.
1998, 306, 463; and (h) Sato, S.; Akiya, T.; Suzuki, T.; Onodera, J.I. Environmen-
tally friendly C-glycosylation of phloroacetophenone with unprotected D-glucose
using scandium(III) trifluoromethanesulfonate in aqueous media: key compounds
for the synthesis of mono- and di-C-glucosylflavonoids. Carbohydr. Res. 2004,
339, 2611.
[5] Although aryl C-aminoglycosides have been prepared by the direct glycosylation of
the aromatic aglycone, indirect methods are used more frequently and in systems
where the direct approach offers poor yields or other disadvantages. See:
(a) Parker, K.A.; Ding, Q.J. Relative reactivities of amino glycosides and their syn-
thetic equivalents in the C-glycosylation of aromatics. Synthesis of the psuedo-
aglycon (D-C-glycoside) of the benzanthrins. Tetrahedron 2000, 56, 10255;
(b) Toshima, K.; Matsuo, G.; Ishizuka, T.; Ushiki, Y.; Nakata, M.;
Matsumura, S.J. Aryl and allyl C-glycosidation methods using unprotected
sugars. Org. Chem. 1998, 63, 2307; (c) Brimble, M.A.; Davey, R.M.;
McLeod, M.D.; Murphy, M. C-Glycosylation of oxygenated naphthols with
3-dimethylamino-2,3,6-trideoxy-L-arabino-hexopyranose
trideoxy-D-arabino-hexopyranose. Aust. J. Chem.
and
2003,
3-azido-2,3,6-
56, 787;
(d) Brimble, M.A.; Davey, R.M.; McLeod, M.D.; Murphy, M. Synthesis of 3-azido-
2,3,6-trideoxy-beta-D-arabino-hexopyranosyl pyranonaphthoquinone analogues
of medermycin. Org. Biomol. Chem. 2003, 1, 1690; (e) Ben, A.; Yamauchi, T.;
Matsumoto, T.; Suzuki, K. Sc(OTf)3 as efficient catalyst for aryl C-glycoside
synthesis. Synlett. 2004, 2, 225; (f) Futagami, S.; Ohashi, Y.; Imura, K.;
Hosoya, T.; Ohmori, K.; Matsumoto, T.; Suzuki, K. Total synthesis of ravidomycin:
revision of absolute and relative stereochemistry. Tetrahedron Lett. 2000, 41, 1063;
(g) Nicolaou, K.C.; Baran, P.S.; Zhong, Y.L.; Barluenga, S.; Hunt, K.W.; Kranich, R.;
Vega, J.A. Iodine(V) reagents in organic synthesis. Part 3. New routes to hetero-
cyclic compounds via o-iodoxybenzoic acid-mediated cyclizations: generality,
scope, and mechanism. J. Am. Chem. Soc. 2002, 124, 2233.
[6] (a) Parker, K.A.; Coburn, C.A. Reductive aromatization of quinol ketals: A new syn-
thesis of C-aryl glycosides. J. Am. Chem. Soc. 1991, 113, 8516; (b) Parker, K.A.;
Coburn, C.A.; Johnson, P.D.; Aristoff, P. Reductive aromatization of quinols. New
convenient methods for the regiospecific synthesis of p-hydroxy C-aryl glycals.
J. Org. Chem. 1992, 57, 5547; (c) Parker, K.A.; Coburn, C.A.; Koh, Y.H. Reductive
and non-reductive aromatization of quinol ketal glycals. Models for the preparation
of C-aryl glycoside natural products. J. Org. Chem. 1995, 60, 2938; (d) Parker, K.A.;
Koh, Y.H. unpublished results.
[7] Parker, K.A.; Su, D.S. previous paper in this issue.