Thieme chemistry journal awardees - Where are they now? Approaches to tagetitoxin and its decarboxy analogue from d -glucose

Article abstract of DOI:10.1055/s-0029-1218525

A fifteen-step route has been developed from 1,6-anhydro-β-d- glucopyranose to a C-alkynyl glycoside precursor of decarboxytagetitoxin. Preparation of 1,6-anhydro-5-C-vinyl-β-d-gluco-pyranose, a potential precursor of tagetitoxin, is also described. Georg

Full text of DOI:10.1055/s-0029-1218525

3258
LETTER
Thieme Chemistry Journal Awardees – Where Are They Now?
Approaches to Tagetitoxin and its Decarboxy Analogue from D-Glucose
A
pproache
u
s
to
T
agetito
l
xin ien R. H. Plet, Amandeep Kaur Sandhu, Moussa Sehailia, Michael J. Porter*
Department of Chemistry, University College London, Christopher Ingold Building, 20 Gordon Street, London, WC1H 0AJ, UK
Fax +44(20)76797463; E-mail: m.j.porter@ucl.ac.uk
Received 16 September 2009
Abstract: A fifteen-step route has been developed from 1,6-anhy-
dro-b-D-glucopyranose to a C-alkynyl glycoside precursor of decar-
boxytagetitoxin. Preparation of 1,6-anhydro-5-C-vinyl-b-D-gluco-
pyranose, a potential precursor of tagetitoxin, is also described.
Key words: carbohydrates, natural products, stereoselective syn-
thesis, alkynes, organometallic reagents
Tagetitoxin, isolated from the phytopathogenic bacterium
Pseudomonas syringae pv. tagetis in 1981,1 has unique
activity as a selective inhibitor of eukaryotic RNA poly-
merase III.2 The bicyclic structure 1 (Figure 1) was pro- Mike Porter was born in Harrogate, England, in 1970. He received
his B.A. degree from the University of Oxford, and remained in Ox-
ford for his D.Phil. studies under the supervision of Professor Sir Jack
Baldwin. In 1996 he was awarded a NATO postdoctoral fellowship to
work with Professor Philip Magnus at the University of Texas at Aus-
posed by Mitchell in 1989 on the basis of NMR and mass
spectrometric measurements;3 however, some doubts per-
sist over the structure – in particular, the acid and amide
groups of 1 may be interchanged, and the absolute config-
uration is unknown. More recently, a publication by Gron-
wald suggested that the mass spectrometric data reported
previously was in error, and that tagetitoxin had a molec-
ular weight 262 Da higher than that of structure 1; howev-
er, neither an alternative structure nor a molecular formula
was proposed.4 Clearly a total synthesis of 1 would help to
settle these structural uncertainties as well as allowing a
fuller exploration of tagetitoxin’s biological profile.
tin, then in 1998 returned to the UK to carry out further postdoctoral
research at the University of Liverpool with Professor Stan Roberts.
He was appointed to a lectureship at University College London in
1999, where he has remained ever since. His research interests focus
on developing new methodology for the synthesis of a wide range of
complex natural products.
ketone to give bicycle 4. In our second route,7 treatment of
carbohydrate-derived diazoester 5 with rhodium(II) ace-
tate led to formation of a sulfonium ylide, which under-
went 1,2-rearrangement upon irradiation to afford the
tetracyclic product 6. In this letter, we describe our efforts
to apply the thiol cyclisation route to the synthesis of
tagetitoxin 1 and its non-natural decarboxy analogue 2.
O
O
OH
OAc
OH
OAc
H2N
H2N
S
S
+
+
NH3
NH3
O
HO2C
O
Br
OPO3H–
OPO3H–
CO2Me
(i) KMnO4, MeOH
S
1
2
(ii) N2H4
HO
O
OBn
OBn
OBn
OBn
Figure 1 Tagetitoxin (1) and decarboxytagetitoxin (2)
62%
AcS
OBn
OBn
O
3
4
At the commencement of our work in 1999, very little
work had been published on synthetic routes towards 1,5
and there were no reported syntheses of the core 9-oxa-3-
thiabicyclo[3.3.1]nonane ring system. Since then, we
have developed two methods for the preparation of such
compounds (Scheme 1). In the first route,6 a C-bro-
moalkynyl glycoside 3 was subjected to oxidation by po-
tassium permanganate in methanol to give an a-ketoester;
subsequent hydrazinolysis of the thioacetyl group was ac-
companied by cyclisation of the revealed thiol onto the
O
O
S
O
O
S
(i) Rh2(OAc)4
N2
(ii) hν
O
O
O
O
O
O
65%
Si
Si
5
6
Scheme 1 Previously reported routes to the tagetitoxin skeleton
SYNLETT 2009, No. 20, pp 3258–3262
x
x
.x
x
.2
0
0
9
Advanced online publication: 27.11.2009
DOI: 10.1055/s-0029-1218525; Art ID: S10709ST
© Georg Thieme Verlag Stuttgart · New York
Our initial target was compound 2, and we chose D-glu-
cose as starting material. Inversion of the stereogenic cen-

LETTER
Approaches to Tagetitoxin
3259
tres at positions 2 and 3 of the sugar, with installation of a Compound 12 has potential as an intermediate for the syn-
nitrogen functionality at C3, was envisaged to arise thesis of tagetitoxin. Unfortunately, the ytterbium-mediat-
through the intermediacy of a 2,3-b-epoxide.
ed addition proved highly capricious, and despite
numerous attempts, this product could not be obtained
again; instead, starting lactone was routinely recovered.
The a-allyl glucoside 7 was prepared by literature chem-
istry (Scheme 2).8 Tosylation was moderately selective
for the 2-hydroxyl and was accompanied by closure to the
desired b-epoxide;9 subsequent treatment with sodium
azide under acidic conditions afforded cleanly the altro-
configured azidosugar 8. This was silylated, then the allyl
protecting group removed10 and the resulting lactol
oxidised11 to give lactone 9.
TMS
OTBS
O
OTBS
O
M
Ph
O
Ph
O
O
O
O
H
N3
N3
OM
TMS
13
14
All attempts to synthesise 10 through addition of lithium
trimethylsilylacetylide to the carbonyl group of 9 proved
unsuccessful. Under conditions which had been
successful6 for a related sugar lactone (LiC≡CTMS,
CeCl3, THF, –78 °C to r.t.), the only compound which was
isolated was the double addition product 11.12 It appears
that in this case initial addition to give the lithium salt of
10 had been followed by ring opening to a ketone and a
second organometallic addition. Migration of the silyl
group onto the tertiary alkoxide – which is presumably
relatively unhindered due to the presence of two sp-hybri-
dised substituents – then occurred to give the observed
product 11.
We next investigated the use of ytterbium triflate13 in
place of cerium chloride as an additive in the lithium
acetylide addition. To our surprise, bicycle 1212 was ob-
tained in 48% yield. In this case, following addition of the
acetylide to give 13 and ring opening to afford a ketone
14, a transannular hydride shift occurred to yield a sec-
ondary alkoxide 15 (Scheme 3). Upon workup, cyclisa-
tion to the cis-fused bicyclic lactol 12 took place.
OTBS
O
M
Ph
O
O
N3
Ph
O
OH
O
H2O
O
O
TMS
H
N3
OTBS
TMS
12
15
Scheme 3 Proposed mechanism for the formation of 12
In light of the difficulties encountered in adding an acetyl-
ide to lactone 9, we decided to introduce the alkyne moi-
ety to a glucose derivative prior to inversion of the C2 and
C3 stereogenic centres.
1,6-Anhydroglucose 16 was prepared by the method of
Boons,14 and converted to its 2,4-di-O-triethylsilyl deriv-
ative (Scheme 4). Vasella’s method15 was then used to
stereoselectively introduce a b-configured alkynyl sub-
stituent at C1. In this procedure, lithium trimethylsilyl-
acetylide is reacted with aluminium trichloride prior to
addition of the carbohydrate substrate. In our hands, it was
found essential to purify the aluminium trichloride by sub-
limation immediately prior to the reaction, and to subject
the lithium acetylide–aluminium trichloride mixture to
sonication. With these precautions, an 81% yield of diol
17 could be obtained.
OH
O
Ph
O
Ph
O
O
i, ii
O
O
HO
HO
OAll
N3
OAll
7
8
Cleavage of the triethylsilyl ethers of 17 and installation
of a p-methoxybenzylidene acetal led to bicycle 18; how-
ever, under a variety of sulfonylation conditions (TsCl,
Ts-imidazole, Ts2O, or MsCl as reagent; NaH or pyridine
as base), no selectivity was obtained for one alcohol over
the other and an inseparable 1:1 mixture of sulfonates was
formed.
iii–v
TMS
OTBS
O
OTBS
O
Ph
O
O
Ph
O
O
O
N3
OH
N3
10
9
vi
vii
A solution to this problem was recognised in the differen-
tial protection of O2 and O3 already present in diol 17. Se-
lective silylation of the primary alcohol of 17 was
followed by acetylation of the remaining secondary alco-
hol. This acetylation proved surprisingly difficult: use of
acetic anhydride with various bases, in the presence of ei-
ther DMAP16 or tributylphosphine17 as catalyst, returned
only starting material, as did the use of acetyl chloride in
pyridine. However, the desired acetate was obtained on
treatment of the alcohol with acetic anhydride and trieth-
ylamine in the presence of 4-(1-pyrrolidino)pyridine,18
and acid hydrolysis of the three silyl ethers and acetal for-
mation afforded the monoacetate 19. Sulfonylation of the
free hydroxyl of 19 also required forcing conditions: treat-
OH N3
OTBS
Ph
O
OH
O
N3
TMS
O
TMS
O
O
OH
OTBS
12
TMS
Ph
11
Scheme 2 Reagents and conditions: (i) NaH, DMF, r.t. then Ts-imi-
dazole, 50 °C, 52% b-epoxide, 10% a-epoxide, 24% ditosylate; (ii)
NaN3, NH4Cl, H2O, 2-methoxyethanol, reflux, 92%; (iii) TBSCl, imi-
dazole, DMF, 80 °C, 98%; (iv) Bu3SnH, ZnCl2, Pd(PPh3)4, THF, r.t.,
90%; (v) DMP, pyridine, CH2Cl2, r.t., 88%; (vi) TMSC≡CH, BuLi,
CeCl3, THF, –78 °C to r.t., 32%; (vii) TMSC≡CH, BuLi, Yb(OTf)3,
THF, –78 °C to r.t., 48%.
Synlett 2009, No. 20, 3258–3262 © Thieme Stuttgart · New York

3260
J. R. H. Plet et al.
LETTER
OH
HO
PMP
O
O
PMP
O
O
O
v–viii
O
ix, x
i, ii
O
TMS
TMS
TMS
TESO
O
O
HO
AcO
O
OH
OTES
OH
OH
17
iii, iv
19
21
20
16
xi
xii–xvi
OAc
O
AcS
HO
O
PMP
O
PMP
O
O
O
O
HO
HO
OH
18
N3
22
xvii, xviii
OAc
O
OAc
O
AcS
TESO
AcS
TESO
O
Br
CO2Me
N3
N3
24
23
Scheme 4 Reagents and conditions: (i) TESCl, pyridine, 0 °C, 79%; (ii) TMSC≡CH, BuLi, AlCl3, 2,4,6-collidine, toluene–THF, sonication,
–15 °C to 50 °C, then add substrate, 130 °C, 81%; (iii) AcOH, MeOH, H2O, r.t., 92%; (iv) 4-MeOC6H4CH(OMe)2, TsOH, 4 Å MS, MeCN,
reflux, 95%; (v) TESCl, pyridine, 0 °C, 92%; (vi) Ac2O, 4-(1-pyrrolidino)pyridine, Et3N, r.t., 70%; (vii) AcOH, THF, H2O, 45 °C, 86%; (viii)
4-MeOC6H4CH(OMe)2, TsOH, 4 Å MS, MeCN, 80 °C, 80%; (ix) TsCl, pyridine, 120 °C, 72%; (x) NaOMe, MeOH, CH2Cl2, r.t., 64%; (xi)
NaN3, DMF, 90 °C, 49%; (xii) TMSN3, Yb(OTf)3, LiOi-Pr, THF, 60 °C, 79%; (xiii) Ac2O, DMAP, pyridine, r.t., 99%; (xiv) AcOH, THF, H2O,
45 °C, 81%; (xv) TsCl, pyridine, r.t., 67%: (xvi) KSAc, DMF, r.t., 76%; (xvii) TESCl, pyridine, 0–40 °C, 82%; (xviii) NBS, AgNO3, acetone,
r.t., 73%.
ment with tosyl chloride in refluxing pyridine afforded a scribed by Rao,23 in which a Grignard reagent is added
rather unstable sulfonate product, which was treated im- stereoselectively to a 5-keto derivative of glucose.
mediately with sodium methoxide in methanol–dichlo-
romethane to remove the acetate and trimethylsilyl
protecting groups and effect concomitant cyclisation to
the epoxide 20.
The free hydroxyl of diacetone-D-glucose 25 was protect-
ed as a p-methoxybenzyl ether, then selective hydrolysis
of the 5,6-acetonide was effected with aqueous acetic acid
(Scheme 5). Silylation of the 6-hydroxyl, Swern oxidation
Attempts to carry out diaxial ring opening of the epoxide of the remaining secondary alcohol, and stereoselective
under acidic conditions were thwarted by partial hydroly- Grignard addition afforded tertiary alcohol 26. We were
sis of the acetal protecting group, while heating with sodi- pleased to find that upon extended heating (72 h) in a mix-
um azide in DMF gave an elimination product 21.19 ture of aqueous acetic and trifluoroacetic acids, in the
Successful ring opening was achieved using Yamamoto’s presence of thioanisole as a cation scavenger, global
procedure,20 in which the epoxide is treated with a combi- deprotection was accompanied by cyclisation to the
nation of ytterbium triisopropoxide (formed in situ) and desired 1,6-anhydro-5-C-vinylglucose 27.24 Extensive
trimethylsilyl azide. Acetylation of the 2-hydroxyl, hy- Fischer esterification also took place under these condi-
drolysis of the p-methoxybenzylidene acetal, selective to- tions, and so the crude material was treated with sodium
sylation of the primary alcohol, and tosylate displacement
with potassium thioacetate led to thioester 22.
OH
O
H
H
O
O
TBSO
O
From 22, completion of a synthesis of decarboxytageti-
toxin would require oxidation of the alkyne to an a-keto-
amide, introduction of the phosphate group, reduction of
the azide, and cleavage of the thioester; we chose first to
investigate the alkyne oxidation. Hence the secondary al-
cohol of 22 was protected as a triethylsilyl ether and the
alkyne brominated with N-bromosuccinimide/silver ni-
trate,21 affording 23.12 However, attempted oxidation to a-
ketoester 24 with potassium permanganate in methanol22
was unsuccessful, resulting only in decomposition of the
substrate.
i–v
O
O
O
O
HO
PMBO
25
26
vi
OH
HO
TESO
O
O
TMS
vii, viii
HO
O
OH
OH
OTES
28
27
Scheme 5 Reagents and conditions: (i) NaH, PMBCl, THF, r.t.,
86%; (ii) 60% aq AcOH, r.t., 80%; (iii) TBSCl, imidazole, DMF, r.t.,
81%; (iv) (COCl)2, DMSO, Et3N, CH2Cl2, –78 °C, 79%; (v)
CH2=CHMgBr, THF, r.t., 76%; (vi) 80% aq AcOH, TFA, PhSMe, re-
flux then NaOMe, MeOH, r.t., 73%; (vii) TESCl, pyridine, r.t., 68%;
(viii) TMSC≡CH, BuLi, AlCl3, 2,4,6-collidine, toluene–THF, sonica-
te, –15 °C to 50 °C, then add substrate, 130 °C, 70%.
Concurrently with our efforts to synthesise decarboxy-
tagetitoxin, we have been investigating methods for the
preparation of tagetitoxin itself. This would require the in-
stallation of an extra carbon substituent, destined to be-
come the carboxylic acid of the natural product, at C5 of
glucose. For this purpose, we chose to use the method de-
Synlett 2009, No. 20, 3258–3262 © Thieme Stuttgart · New York

LETTER
Approaches to Tagetitoxin
3261
70.1 (CH2), 67.1 (C), 63.8 (CH), 60.7 (CH), 25.5 (CH3), 18.7
(C), –0.5 (CH3), –0.6 (CH3), –3.5 (CH3), –3.6 (CH3).
HRMS–FAB+: m/z calcd for C29H47O5N3Si3Na [MNa+]:
624.2721; found: 624.2735.
4-Azido-1,3-O-benzylidene-5-O-tert-butyldimethyl-
silanyl-4,7,8-trideoxy-8-trimethylsilanyl-b-L-manno-oct-
7-yn-2-ulopyranose (12)
methoxide to methanolyse the mixture of acetates, afford-
ing the triol 27 in 73% yield.
Compound 27, like its congener 16, underwent selective
disilylation
followed
by
aluminium-mediated
alkynylation15 to give the b-C-glycoside 28.12
In conclusion, we have developed a route from glucose to
bromoalkyne 23, which incorporates all of the carbon at-
oms and the correct stereochemistry for a synthesis of de-
carboxytagetitoxin 2. Work towards the natural product
tagetitoxin 1 has also commenced, with an efficient intro-
duction of the additional carbon substituent in the form of
a vinyl group. Efforts towards the conversion of 23 into 2,
and of 28 to 1 are ongoing in our laboratories, and the re-
sults of these studies will be reported in due course.
[a]D20 –105.5 (c 0.4, CH2Cl2). IR (CHCl3 cast): nmax = 3445,
3053, 2304, 1633, 1421 cm–1. 1H NMR (500 MHz, CDCl3):
d = 7.47–7.42 (2 H, m), 7.33–7.24 (3 H, m), 5.56 (1 H, s),
4.76 (1 H, d, J = 6.2 Hz), 4.32 (1 H, dd, J = 10.3, 6.2 Hz),
4.23 (1 H, d, J = 2.8 Hz), 4.07 (1 H, dd, J = 10.3, 2.8 Hz),
4.03 (1 H, d, J = 11.9 Hz), 3.74 (1 H, s), 3.69 (1 H, d, J = 11.9
Hz), 0.91 (9 H, s), 0.17 (9 H, s), 0.13 (3 H, s), 0.11 (3 H, s).
13C NMR (125 MHz, CDCl3): d = 136.7 (C), 129.0 (CH),
128.2 (CH), 126.0 (CH), 103.0 (C), 100.8 (CH), 95.0 (C),
91.9 (C), 78.9 (CH), 73.5 (CH2), 67.6 (CH), 66.3 (CH), 58.8
(CH), 25.5 (CH3), 17.8 (C), –0.5 (CH3), –4.7 (CH3), –5.0
(CH3). HRMS–FAB+: m/z calcd for C24H37O5N3Si2Na
[MNa+]: 526.2169; found: 526.2158.
Acknowledgment
1-[2-O-Acetyl-6-S-acetyl-3-azido-3-deoxy-6-thio-4-O-
(triethylsilanyl)-b-D-altropyranosyl]-2-bromoethyne (23)
[a]D18 +5.1 (c 0.3, CHCl3). IR (CHCl3 cast): nmax = 2947,
2110, 1755, 1693 cm–1. 1H NMR (500 MHz, CDCl3): d =
4.94 (1 H, dd, J = 3.1, 1.5 Hz), 4.52 (1 H, d, J = 1.4 Hz),
3.87–3.83 (2 H, m), 3.71 (1 H, td, J = 9.2, 2.6 Hz), 3.60 (1 H,
dd, J = 13.6, 2.7 Hz), 2.74 (1 H, dd, J = 13.6, 9.5 Hz), 2.33
(3 H, s), 2.16 (3 H, s), 0.99 (9 H, t, J = 8.0 Hz), 0.68–0.62 (6
H, m). 13C NMR (125 MHz, CDCl3): d = 195.0 (C), 169.7
(C), 76.0 (CH), 74.2 (C), 71.5 (CH), 70.0 (CH), 65.9 (CH),
61.6 (CH), 47.8 (C), 31.2 (CH2), 30.5 (CH3), 20.7 (CH3), 6.7
(CH3), 4.8 (CH2). HRMS–FAB+: m/z calcd for
We thank EPSRC and UCL for funding, Dr. Abil Aliev for assi-
stance with NMR, and Dr. Lisa Harris and Mr. John Hill for mass
spectrometry.
References and Notes
(1) Mitchell, R. E.; Durbin, R. D. Physiol. Plant Pathol. 1981,
18, 157.
(2) (a) Mathews, D. E.; Durbin, R. D. J. Biol. Chem. 1990, 265,
493. (b) Steinberg, T. H.; Mathews, D. E.; Durbin, R. D.;
Burgess, R. R. J. Biol. Chem. 1990, 265, 499.
(3) Mitchell, R. E.; Coddington, J. M.; Young, H. Tetrahedron
Lett. 1989, 30, 501.
(4) Gronwald, J. W.; Plaisance, K. L.; Marimanikkuppam, S.;
Ostrowski, B. G. Physiol. Mol. Plant Pathol. 2005, 67, 23.
(5) (a) Sammakia, T.; Hurley, T. B.; Sammond, D. M.; Smith, R.
S.; Sobolov, S. B.; Oeschger, T. R. Tetrahedron Lett. 1996,
37, 4427. (b) Dent, B. R.; Furneaux, R. H.; Gainsford, G. J.;
Lynch, G. P. Tetrahedron 1999, 55, 6977.
(6) Plet, J. R. H.; Porter, M. J. Chem. Commun. 2006, 1197.
(7) Mortimer, A. J. P.; Aliev, A. E.; Tocher, D. A.; Porter, M. J.
Org. Lett. 2008, 10, 5477.
C18H29O5N3SSi79Br [MH+]: 506.0781; found: 506.0771.
1-(2,4-Di-O-triethylsilanyl-5-C-vinyl-b-D-glucopyran-
osyl)-2-trimethylsilanylethyne (28)
[a]D22 –65.9 (c 0.7, CHCl3). IR (CHCl3 cast): nmax = 3565,
2182, 1729, 1458 cm–1. 1H NMR (600 MHz, CDCl3): d =
6.00 (1 H, dd, J = 18.0, 11.3 Hz), 5.45 (1 H, dd, J = 18.1, 1.4
Hz), 5.43 (1 H, dd, J = 11.2, 1.2 Hz), 4.21 (1 H, d, J = 9.5
Hz), 3.83 (1 H, d, J = 9.8 Hz), 3.56 (1 H, dd, J = 11.7, 11.0
Hz), 3.48 (1 H, dd, J = 9.5, 8.8 Hz), 3.39 (1 H, dd, J = 11.9,
2.9 Hz), 3.36 (1 H, ddd, J = 9.5, 8.9, 3.0 Hz), 2.19 (1 H, dd,
J = 10.9, 3.1 Hz), 2.09 (1 H, d, J = 2.9 Hz), 0.99 (18 H, m),
0.71 (12 H, m), 0.20 (9 H, s). 13C NMR (150 MHz, CDCl3):
d = 132.5 (CH), 119.2 (CH2), 103.4 (C), 89.9 (C), 81.7 (C),
76.0 (CH), 75.9 (CH), 71.0 (CH), 66.7 (CH), 65.9 (CH2), 6.9
(CH3), 5.2 (CH2), 5.3 (CH2), 5.1 (CH2), –0.2 (CH3). HRMS
(CI+): m/z calcd for C25H50O5Si3 [MH+]: 515.3044;
found:515.3050.
(8) Mehta, S.; Jordan, K. L.; Weimar, T.; Kreis, U. C.;
Batchelor, R. J.; Einstein, F. W. B.; Pinto, B. M.
Tetrahedron: Asymmetry 1994, 5, 2367.
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6, 2611.
(10) Pasetto, P.; Franck, R. W. J. Org. Chem. 2003, 68, 8042.
(11) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
(b) Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899.
(12) Data for Selected Compounds
(13) Burkhardt, E. R.; Molander, G. A.; Weinig, P. J. Org. Chem.
1990, 55, 4990.
(14) Boons, G.-J.; Isles, S.; Setälä, P. Synlett 1995, 755.
(15) Ernst, A.; Schweizer, W. B.; Vasella, A. Helv. Chim. Acta
1998, 81, 2157.
3-Azido-4,6-O-benzylidene-1-O-tert-butyldimethyl-
silanyl-3-deoxy-1,1-di-C-(trimethylsilanylethynyl)-D-
altritol (11)
(16) Steglich, W.; Höfle, G. Angew. Chem., Int. Ed. Engl. 1969,
8, 981.
[a]D20 –72.0 (c 2.35, CH2Cl2). IR (CHCl3 cast): nmax = 3444,
3055, 2121, 1706, 1421, 1361 cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.48–7.43 (3 H, m), 7.36–7.28 (2 H, m), 5.49 (1
H, s), 4.35 (1 H, dd, J = 2.9, 0.9 Hz), 4.21 (1 H, d, J = 2.9
Hz), 4.33 (1 H, dd, J = 11.0, 5.8 Hz), 4.09 (1 H, dddd, J =
10.2, 8.9, 5.8, 2.9 Hz), 3.83 (1 H, dd, J = 9.9, 0.9 Hz), 3.74
(1 H, dd, J = 8.9, 2.9 Hz), 3.63 (1 H, dd, J = 11.0, 10.2 Hz),
3.28 (1 H, d, J = 9.9 Hz), 0.90 (9 H, s), 0.28 (3 H, s), 0.27 (3
H, s), 0.18 (18 H, s). 13C NMR (125 MHz, CDCl3): d = 137.4
(C), 129.0 (CH), 128.3 (CH), 126.1 (CH), 103.1 (C), 102.1
(C), 100.1 (CH), 91.6 (C), 91.5 (C), 84.4 (CH), 75.9 (CH),
(17) Vedejs, E.; Diver, S. T. J. Am. Chem. Soc. 1993, 115, 3358.
(18) (a) Steglich, W.; Höfle, G. Tetrahedron Lett. 1970, 4727.
(b) Hassner, A.; Krepski, L. R.; Alexanian, V. Tetrahedron
1978, 34, 2069. (c) Smith, A. B. III.; Rivero, R. A. J. Am.
Chem. Soc. 1987, 109, 1272.
(19) CAUTION: The byproduct of this procedure is the highly
explosive hydrazoic acid.
(20) Meguro, M.; Asao, N.; Yamamoto, Y. J. Chem. Soc., Chem.
Commun. 1995, 1021.
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J. R. H. Plet et al.
LETTER
the MeOH solution and the mixture stirred for 3 h. The
(21) (a) Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, R.
Angew. Chem., Int. Ed. Engl. 1984, 23, 727. (b)Yamamoto,
Y. Chem. Rev. 2008, 108, 3199.
(22) Li, L. S.; Wu, Y. L. Tetrahedron Lett. 2002, 43, 2427.
(23) Rao, A. V. R.; Gurjar, M. K.; Devi, T. R.; Kumar, K. R.
Tetrahedron Lett. 1993, 34, 1653.
(24) 1,6-Anhydro-5-C-vinyl-b-D-glucopyranose (27)
Thioanisole (0.17 mL, 2.1 mmol) was added to a stirred
solution of glucofuranoside 26 (1.00 g, 2.08 mmol) and TFA
(0.05 mL, 0.4 mmol) in 80% aq AcOH (20.8 mL). The
mixture was stirred under reflux for 3 d, concentrated in
vacuo, and co-evaporated with heptane (3 × 80 mL) to give
a viscous black oil. MeOH (40 mL) was added and the
organic solution removed from the insoluble residue using a
Pasteur pipette. NaOMe (225 mg, 4.16 mmol) was added to
solution was concentrated in vacuo and the residue purified
by flash column chromatography (MeOH–CH2Cl2 1:99 →
10:90) to give compound 27 (284 mg, 73%) as a viscous
brown oil; [a]D20 –73.1 (c 1.0, EtOH). IR (neat): nmax = 3368,
2901, 1646, 1416 cm–1. 1H NMR (600 MHz, CD3OD): d =
6.05 (1 H, dd, J = 17.6, 11.2 Hz), 5.44 (1 H, dd, J = 17.6, 1.3
Hz), 5.44 (1 H, br t, J = 1.6 Hz), 5.31 (1 H, dd, J = 11.2, 1.3
Hz), 4.32 (1 H, d, J = 7.0 Hz), 3.82 (1 H, br q, J = 1.5 Hz),
3.59 (1 H, br s), 3.45 (1 H, br q, J = 1.5 Hz), 3.42 (1 H, d,
J = 7.0 Hz). 13C NMR (150 MHz, CD3OD): d = 135.0 (CH),
115.1 (CH2), 103.1 (CH), 82.6 (C), 74.1 (CH), 72.6 (CH),
69.6 (CH), 69.4 (CH2). HRMS (CI+): m/z calcd for C8H13O5
[MH+]: 189.0763; found: 189.0765.
Synlett 2009, No. 20, 3258–3262 © Thieme Stuttgart · New York

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