Glycochemis y oday CHIMIA 2011, 65, No. 1/2 91
doi:10.2533/chimia.2011.91 Chimia 65 (2011) 91–96 © Schweize ische Chemische Gesellscha
*Co espondence: D . A. J. Mo eno-Va gas
Depa men o O ganic Chemis y
Facul y o Chemis y
Uni e si y o Se ille
P o . Ga cia González, 1, Se ille, Spain
E-mail: [email p o ec ed]
Monosaccha ides and Analogues om
Simple Achi al Unsa u a ed Compounds
An onio J. Mo eno-Va gas*, Ana T. Ca mona, Elena Mo eno-Cla ijo, and Inmaculada Robina
Abs ac : We p esen he ein a selec ion o ingenious me hods ha ha e been de eloped o con e inexpensi e
u an, py ole and unsa u a ed hyd oca bons in o enan iome ically en iched monosaccha ides and analogues o
biological in e es .
Keywo ds: Cycloaddi ions · Fu an · Iminoaldi ols · Monosaccha ides· Polyenes · Py ole
1. Cycloaddi ions o Fu ans and
Py oles
The syn hesis o ca bohyd a es and ana-
logues om 7-oxabicyclo[2.2.1]hep -2-
enes as s a ing ma e ials was pionee ed
by Jus [1] and de eloped ex ensi ely by
Vogel’s g oup. 1-Cyano inyl (1’S)-cam-
phana e adds o u an in he p esence o
ZnI2 as ca alys o gi e a mix u e o dias e-
eome ic Diels-Alde adduc s, om which
adduc 1 can be isola ed pu e by c ys al-
liza ion. S a ing om (1R)-camphanic
acid, la ge quan i ies o pu e adduc 2
we e p epa ed.[2] Enan iome ically pu e
7-oxano bo nenyl de i a i es 1 and 2 and
hei p oduc s o saponi ica ion, ke ones
(+)-3 and (–)-3, a e named ‘naked suga s’
as hey a e chi ons like hose de i ed om
na u al hexoses. They a e also homochi al-
like suga s bu wi h h ee unsubs i u ed
(naked) ca bon cen e s. Thei subs i u ion
ollowing highly s e eoselec i e me hods
gi es polysubs i u ed 7-oxabicyclo[2.2.1]
hep ane-2-ones ha can be egioselec i e-
ly oxidized in o di e en u onolac ones 4,
5 and 6 which a e p ecu so s o d- ibose
de i a i e 7, d-allose and l- alose.[3] S a -
ing om 2, l-allose and d- alose we e also
simila ly p epa ed[4] (Scheme 1).
The ‘naked suga ’ me hodology has
been also used o he syn hesis o deoxy-
polyoxin C (Scheme 2). The a-b omou o-
nolac one (–)-6 gi es an allyl u onic es e
on ea men wi h allyl alcohol and i lic
acid ha was con e ed in o azidode i a-
i e 8. Compound 8 could be ans o med
in o deoxypolyoxin C.[5] I also pe mi ed
he i s syn hesis o (+)-d-allonoji imycin
(Scheme 2).[6] l-Daunosamine[7] was also
ob ained om chi on 1.[8] The ‘naked sug-
a s’ ha e been con e ed in o long-chain
suga s and C-disaccha ides,[9] cas ano-
spe mine and de i a i es,[10] and o he
OCN
OR*
1R* = (1'S)-camphanoyl
2R* = (1'R)-camphanoyl
O
O
OCN
OR
O
O
OO
O
O
OO
O
11. H2O2, OsO4
2. (MeO)2CMe2
TsOH
1. KOH, H2O
THF
2. CH2O/H2O
mCPBA
O
O O
OMeHO
(-)-4
(-)-7
O
O
(-)-3
(+)-3
O
O
O
O
O
OR
5
O
OH OH
OH
HO
HO
(L-allose ← ← 2)
D-allose
O
O
O
O
O
B
6
O
OH OH
OH
OH
HO
(D- alose ← ← 2)
L- alose
saponi ica ion
Scheme 1. Use o ‘ i s -gene a ion naked suga s’.
O
O O
COO
B O O
O O
COOBn
N3O
OH
1. Rh(PPh3)3Cl
E OH/H2O
DABCO
2. CsN3
3. BnB
(-)-6
8
O
HOOC
H2N
HO OH
N
NH
O
O
deoxypolyoxin C
NH
2
Cl
HO
OH
HO OH
HO
1. LiAlH4
2. HCl
(+)-D-allonoji imycin
hyd ochlo ide
T OH
Scheme 2
Scheme 2. To al syn hesis o deoxypolyoxin C and o (+)-d-allonoji imycin.
92 CHIMIA 2011, 65, No. 1/2 Glycochemis y oday
O he enan iome ically pu e 7-azabi-
cyclo[2.2.1]hep ane analogues, such as
compounds (–)-15, (+)-16[18] and (+)-17[19]
and hei co esponding enan iome s, we e
also epo ed by Vogel’s g oup (Scheme 5).
Compounds (–)-15 and (+)-16 and hei
co esponding enan iome s we e success-
ully ans o med in o he iminosuga 18
and i s enan iome , espec i ely, which
i s examples o polyhyd oxyla ed indoli-
zidines[11] and quinolizidines.[12]
Ho mann and co-wo ke s ha e de el-
oped he syn hesis o homochi al 2,6-an-
hyd ohep i ols om 8-oxabicyclo[3.2.1]
oc an-3-one.[13] Enan iome ically pu e
3-oxo-8-oxabicyclo[3.2.1]oc yl-2-yl de-
i a i es we e ob ained by [4+3] addi ion
o u an wi h chi al 1,2-dioxyallyl ca ion
engende ed in si u by acid-ca alyzed he -
e olysis o enan iome ically pu e mixed
ace als de i ed om 1,1-dime hoxyac-
e one and enan iome ically pu e second-
a y benzyl alcohols.[14] Adduc (–)-9 was
ob ained in his manne . This compound
was enolized egioselec i ely and oxidized
wi h mCPBA gi ing, a e es e i ica ion,
pi ala e 10 ha was easily con e ed in o
anhyd ohep i ol 11 (Scheme 3).
Vogel and co-wo ke s ha e also ex-
ended he ‘naked suga ’ me hodology o
he syn hesis o u he p oduc s o in e -
es , such as dideoxyiminoaldi ols and
polyhyd oxyla ed p olines (‘aza naked
suga ’ me hodology). The syn hesis o
he aza-analogue o compound 3, 7-az-
abicyclo[2.2.1]hep -5-en-2-one 12, was
epo ed in 1999[15] by T udell e al. in he
acemic o m, s a ing om N-Boc-py ole
and 2-b ome hynyl p- olyl sul one. This
syn hesis was la e imp o ed[16] (Scheme
4). The enan iome ically pu e o ms o 12
we e ecen ly epo ed.[17]
OMe
O
OMe
+
HO Ph
Me
O Ph
O
OMe
O Ph
OTES
OMe
(i-P )
2
NLi, E
3
SiCl
E
3
N, THF, -78°C
O
O
O
O Ph
H
O
O
O Ph
H
OPi
-95°C
Me
3
SiOT
1. (i-P )
2
NLi, E
3
SiCl
E
3
N, THF
2. mCPBA, THF, H
2
O
3. Pi Cl, E
3
N, DMAP, CH
2
Cl
2
(-)-9
10
O
HO
OTBS
OPi
HO
11
OH
Scheme 3
Scheme 3. Ho mann’s asymme ic [4+3]cycloaddi ion o u an: o al syn hesis o
2,6-anhyd ohep i ols.
Scheme 4.
Syn hesis o
enan iome ically pu e
7-azabicyclo[2.2.1]
hep an-2-ones.
Boc
N
O
Boc
N
O
Ts
N
Boc
B Ts (±)-12
+
SmI2
THF, -78 °C
75%
e . [16]
Boc
NBoc
N
O
(+)-12
Boc
N
N
N
H
H
Ph
Ph
N
N
H
H
Ph
Ph
42%
Boc
N
O
(-)-12
H2N
H2N
Ph
Ph
(R,R)-14
1. (R,R)-14, CH2Cl2
4Åmol. sie es
2. Flash
ch oma og aphy
H3PO4(0.1 M)-THF
43%
95%
96%
e . [17]
(±)-13
Boc
N
O
ac-12
Boc
N
(-)-15
O
O
Boc
N
O
(+)-17
O
O
(±)-13
N3
Ts
Boc
N
O
O
N3
Ts
+
(+)-16
Boc
N
O
ON
Bu3SnH/AIBN
Toluene, e lux
56%
H2
N
OHHO
H3N
OH
Cl Cl
18.(HCl)2
Boc
N
OO
HO COOH
1. H2, Pd-C
MeOH
2. HCl-THF
quan .
e [21]
e [19]
Boc
N
OTBS
O
O
1. O3, MeOH
2. NaBH4
CF3CON(Me)TBS
E 3N, DMF
86% 88%
(-)-19
Boc
N
O
PhSe
Cl
Boc
N
OH
Cl
(4 s eps,
including acemic
esolu ion) 1. O3, MeOH
2. Me2S
PhSeCl
CHCl3, -78 ºC
75%
Boc
N
OR*
R* = camphanoyl
(2 s eps)
Boc
N
+
OR*
Boc
N
Cl
OH
1. O3, MeOH
2. Me2S
ac-21
Boc
N
MeO COOMe
OMe OH
(-)-20
(3 s eps including
addi ion o PhSeCl)
Boc
N
MeO COOMe
MeO OH
Scheme 5. 7-Azabi-
cyclohep anes as
in e media es o
he syn hesis o
dideoxyiminosuga s
and hyd oxyla ed
p oline de i a i es.
Glycochemis y oday CHIMIA 2011, 65, No. 1/2 93
epoxide 35 which can be con e ed in-
o 1,4-dideoxy-1,4-imino-d-lyxi ol 36
(Scheme 10).[35] Simila ly, Sch eibe and
co-wo ke s[36] ha e ob ained (+)-KDO
om he diallyl alcohol 37 (Scheme 11).
4. Kine ic Resolu ion o Racemic
Allylic Alcohols
The Ka suki-Sha pless asymme ic
epoxida ion o acemic diol (±)-38 ga e,
a e ch oma og aphic sepa a ion, he
e y h o-epoxide (+)-39 which was u he
ans o med in o d-oli ose (Scheme 12).
Asymme ic epoxida ion o he kine i-
cally esol ed dienol (–)-40 ga e he co -
showed s ong compe i i e inhibi ion o-
wa ds a-mannosidases.[20] The key s ep o
his ans o ma ion implies a no el ea -
angemen on he bicyclic sys em h ough
aminyl adicals.[21] Ke ones 17 and 12 we e
ans o med in o polyhyd oxyla ed p oline
de i a i es 19,[19] 20 and 21,[22] ollowing
he same me hodology ha was p e iously
employed in he case o oxa-analogues
(‘naked suga ’ chemis y[8a]). These p o-
lines a e expec ed o be use ul in e medi-
a es o he p epa a ion o new dideoxyimi-
nosuga s, such as polyhyd oxyla ed indoli-
zidines and py olizidines, in he sea ch o
new glycosidase inhibi o s.
2. Ca bohyd a es and Analogues
om Achi al Polyenes
An elegan o al syn hesis o acos-
amine and o daunosamine was de eloped
a Roche s a ing om cyclopen adiene.[23]
Monome hyla ion o cyclopen adiene
gi es 5-me hylcyclopen adiene ha is hy-
d obo ina ed asymme ically wi h (–)-di-
3-pinanylbo ane gi ing (S)-alcohol 22.
Epoxida ion syn wi h espec o he ho-
moallylic alcohol p o ides 23, which is
oxidized in o ke one 24. Baeye -Villige
oxida ion o 24 is egioselec i e and leads
o lac one 25. This compound was hen
ans o med in o me hyl-a-acosaminide
and daunosamine⋅HCl (Scheme 6).
Johnson and co-wo ke s epo ed a
o al syn hesis o 1,3-dideoxynoji imycin
s a ing om cyclopen adiene.[24] Pho o-
oxida ion o cyclopen adiene and educ-
i e wo k-up wi h hiou ea gene a es cis-
cyclopen -2-ene-1,4-diol. I s enzyma ic
enan ioselec i e monoacyla ion, silyla ion
and subsequen ea men wi h KOH and
oxida ion, ga e enan iome ically pu e
enone 26[25] which was ans o med in o 27
and (+)-28 as depic ed in Scheme 7. A sim-
ila app oach con e ed enan iome ically
pu e (2R,3R)-2,3-isop opylidenedioxycy-
clopen -4-en-1-one de i ed om cyclo-
pen adiene[26] in o (–)-1-deoxymannono-
ji imycin and (–)-1-deoxy alonoji imy-
cin (1,5-dideoxy-1,5-imino-d- ali ol).[27]
Enone 26 was con e ed o (2R,3S)-2,3-
bis[( e -bu yl)dime hylsilyloxy]cyclo-
pen -4-en-1-one and hen o (+)-1-de-
oxynoji imycin.[28]
Dioxygenases, p esen in he blocked
mu an s o he soil bac e ium Pseudomo-
nas pu ida, deg ades benzene and i s de i -
a i es in o cyclohexa-3,5-diene-1,2-diols.
Wi h chlo obenzene, diol 29 is ob ained
wi h >99% ee. This compound is con e ed
in a ew chemical s eps in o se e al sug-
a s and de i a i es[29] such as l-e y h ose,
KDN,[30] (–)-Neu-5-Ac[31] and Vi amin
C[32] (Scheme 8).
When applied o pen a-1,4-diene,
he Sha pless asymme ic dihyd oxyl-
a ion o ms a 1:1 mix u e o (2S,4S)- and
(2S,4R)-pen a-1,2,4,5- e ols, 30 and 31
(Scheme 9), which can be con e ed o
diepoxides 32 and 33, espec i ely.[33]
The o me was con e ed in o dideoxy-
pen i ol and - hiopen i ol. A s e eo- and
enan ioselec i e syn hesis o 32 is possible
s a ing om 1,5-dichlo open a-2,4-diene
applying Noyo i’s asymme ic hyd ogena-
ion.[34]
3. Desymme iza ion o meso
Dienols
Ka suki-Sha pless desymme iza ion o
pen a-1,4-dien-3-ol (34) gi es he mono-
Me Me
HO
Me
HO
O
MeI
0°C
mCPBA
NaHCO3
1.
2. H2O2/NaOH
)2BH
C O3
py
22 23
Me
O
O
O
O
O
Me
mCPBA
NaHCO3
CH2Cl2
O
OMe
Me
OH
NH2
me hyl α-acosaminide
daunosamine⋅HCl
24
25
Na
O
OH
Me
OH
NH2
.HCl
Scheme 6. Roche’s syn hesis o a-acosamine and daunosamine.
NH
HO
HO
HO
O
RO
OR
RO
OR
1. I
2
, py, CCl
4
2. NaBH
4
, CeCl
3
, MeOH
3. TBSCl, imidazole
4. CO, Bu
3
SnH, Pd(PPh
3
)
4
5. NaBH
4
⋅CeCl
3
, MeOH
6. TBSCl, imidazole
1. O
3
, MeOH, -78
o
C
2. Me
2
S, 20
o
C
3. BnNH
3
Cl
Na(CN)BH
3
4. HCl, MeOH
5. H
2
, Pd-C
26 27 (+)-28
R = TBS = SiMe
2
( -Bu)
Scheme 7
Scheme 7. Johnson’s syn hesis o 1,3-dideoxynoji imycin.
Cl Cl
OH
OH
Cl
O
O
Pseudomonas
pu ida 39D
(MeO)2CMe2
TsOH
29
OO
OOH
L
-e y h ose
ace onide
D
-e y h ose
ace onide
O
O
O
HO
O
O
O
O
L
- ibonic-γ-lac one
ace onide
HO
O
O
O
O
HO
HO
H
O
HO F
OH
OH
HO
2- luo o-
D
-glucose
O
HO
HO OH
OH
OH
OH
COOH
KDN
O
HO OH
OH
OH
OH
COOH
AcNH
(-)-Neu5Ac
OH
OH
O
O
H
HO OH
Vi amin C
D
-mannonic-γ-
lac one ace onide
Scheme 8
Scheme 8. Hudlicky’s syn heses o e ose, pen ose and hexose de i a i es and Banwell’s
syn heses o KDN, Neu5Ac and Vi amin C.
94 CHIMIA 2011, 65, No. 1/2 Glycochemis y oday
esponding epoxide (75%) ha could be
ans o med in o d-digi oxose.[37] In a sim-
ila manne (+)-oliose, (+)-cyma ose,[38]
d- and l-chalcose[39] we e also p epa ed.
Applica ion o he Ka suki-Sha pless enan-
ioselec i e epoxida ion o acemic mono-
O-benzyla ed di inylglycol allowed he
p epa a ion o enan iome ically pu e l-lyxo
and d-lyxo-pen oses and analogues.[40]
5. Enan ioselec i e Sha pless
Dihyd oxyla ion and
Aminohyd oxyla ion
This is an ex emely powe ul me hod
o he syn hesis o monosaccha ides and
selec ed examples o applica ion a e col-
lec ed in his sec ion. Fo ins ance, e i ol
and e ose de i a i es a e ob ained eadily
om asymme ic dihyd oxyla ion o (E)-
bu -2-ene-1,4-diol,[41] and 4-deoxy d- and
l- h eose a e de i ed om benzene-1,2-
dime hyl ace al o (E)-c o onaldehyde. In
a simila way, 2-deoxyxylo u anosides a e
ob ained om 5-[( e -bu yldiphenylsilyl)
oxy]-(E)-pen -3-enal.[42] Asymme ic di-
hyd oxyla ion o 2- inyl u an (41) gi es
diol (+)-42, which a e oxida ion wi h
m-chlo ope benzoic acid and wa e elimi-
na ion u nished (+)-isole oglucosenone
(Scheme 13). This compound can be isom-
e ized in o (–)-le oglucosenone. The l-
hexose de i a i e (–)-isole oglucosenone
is ob ained wi h he same ease.[43]
S a ing om u u al and by applying
he same ou e, d- and l-mannose, d- and
l-gulose, d- and l- alose[44] and 2-deoxy
and 2,3-dideoxyhexoses[45] we e ob ained.
The Sha pless asymme ic aminohy-
d oxyla ion[46] o 2- inyl u an 43 gi es
aminoalcohol 44, ha was con e ed in o
he b-hyd oxy u ylamine de i a i e 45,[47]
use ul building block o he syn hesis
o a ious biologically impo an com-
pounds, including 1,5-dideoxy-1,5-imino-
aldi ols (Scheme 14). A less egioselec i e,
bu sho e way o 45 is he di ec asym-
me ic aminohyd oxyla ion o inyl u an.
Sha pless asymme ic dihyd oxyla ion
o e hyl so ba e gi es diol 46 egio- and s e-
eoselec i ely. This compound was ans-
o med in se e al s eps in o osylamide
47 which is hen con e ed in o me hyl
N- osyl-a-d- olyposaminide (–)-48. Al e -
na i ely, diol 46 is eac ed wi h TsN=C=O
o gi e 49. Hyd ogena ion o he alkene
moie y and subsequen me hanolysis and
acidic ea men p o ides lac one 50,
which was success ully ans o med in o
4-epi-N- osyl-a-d- olyposaminide (+)-51
(Scheme 15).[48]
Linds öm and co-wo ke s[49] ha e
also p esen ed an e icien syn hesis o
i e-membe ed iminoaldi ols in wa e ha
includes asymme ic dihyd oxyla ion and
epoxida ion s eps (Scheme 16).
HO OH
OH OH
HO OH
OH OH
AD-mix-α
(78%) +
30 31
1. TsCl, Py
2. NaH, THF
O O O O
OCuO
ClCl
32 33
{[(R)-BINAP]RuCl2}2
E 3N, 120oC
1200 psi H2
MeOH
OH OH
ClCl
OOH
HO
SOH
OH
S
HO OH
+
KOH, E 2O
(89%)
NaOH, H2O
25oC, 36 h
(78%)
Na2S, E OH
0oC, 7 h
5:1
(54%)
(R)-BINAP: (R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaph hyl
Scheme 9. Con e sion o pen a-1,4-diene in o pen i ol de i a i es.
OH OH
O
OHNH2
OH N
HO OH
Ts B
1. TsCl, py
2. NBS
34
(+)-AE
N
HO OH
HOH
36
35
NH
3
Scheme 10
Scheme 10. Jäge ’s syn hesis o 1,4-dideoxy-1,4-iminopen i ols.
OBn OBn
OH
OBn OBn
OH
O
(-)-AE
(94%)
37
O
HOOC OH
HO OH OH
OH
(+)-KDO
Scheme 11
Scheme 11. Sch eibe ’s o al syn hesis o (+)-KDO.
O
HO
OH
Me
OH
OH
OH
O
OH
+
(-)-AE'
(±)-38
(+)-39 O
O
O
HO
(-)-40
1. PhNCO, Py
2. BF3⋅E 2O1. H3O+
2. O3
3. Me2S
(+)-D-oli ose
(33% yield, >95% e.e.
(+)-AE'
O
HO
OH
Me
OH
OH
O1. H3O+
2. O3
3. Me2S
(+)-D-digi oxose
(75% yield, 95% e.e.)
Scheme 12. To al syn heses o 2,6-dideoxyhexoses.
OO
OH
HO O
O
OH
OH O
O
O
mCPBA
CH
2
Cl
2
TsOH
PhH, 80°C
AD-mix-α
MeSO
2
NH
2
aq. -BuOH
0°C
(+)-42 (+)-isole o-
glucosenone
41
OO
O
(-)-le o-
glucosenone
Scheme 13
Scheme 13. To al syn hesis o (+)-isole oglucosenone and (–)-le oglucosenone.
Glycochemis y oday CHIMIA 2011, 65, No. 1/2 95
OOE
O
O COOE
CbzN
OH
H
44
O
CbzN
OTBS
H
N
O
Cbz
HO
OTBS
45
Sha pless
aminohyd oxyla ion
aza-Achma owicz
eac ion
(41%, e.e.>86%)
43
Scheme 14
Scheme 14. Applica ion o he Sha pless
asymme ic aminohyd oxyla ion and o he
aza-Achma owicz eac ion o he syn hesis
o iminosuga s.
6. Bi ch Reduc ion o Py oles
The Bi ch educ ion o py oles wi h
es e unc ionali y a ei he C(2) o a bo h
C(2) and C(5) is a use ul me hod o he
syn hesis o iminosuga de i a i es ha
has been b oadly exploi ed by Donohoe’s
g oup.[50] N-Boc py ole was doubly li hi-
COOE COOE
OH
OH
AD-mix-α
CH
3
SO
2
NH
2
-BuOH/H
2
O
46 (93% ee)
COOE
OTBS
NHTs
47
1. CF
3
COOH, THF/H
2
O, 20°C
2. (i-Bu)
2
AlH, THF/ace one, -78°C
3. TsOH/py (MeO)
3
CH/MeOH
(-)-48
O
TsHN
Me
OMe
TsN=C=O
Pd(Ph
3
P)
4
THF
O NTs
COOE
O
49
O
O
NHTs
O
TsHN Me
OMe
1. H
2
/Pd-C, E OAc, 20°C
2. NaOH/MeOH
3. CF
3
COOH/THF
50
1. (i-Bu)
2
AlH, THF/ oluene, -78°C
2. TsOH/py, (MeO)
3
CH, MeOH
(+)-51
94%
72%
86%
86%
Scheme 15
Scheme 15.
Syn hesis o
olyposaminide
de i a i es.
B
B
B
B
OH
OH B
OH
OH
OH
AD-mix-α, NaHCO
3
MeSO
2
NH
2
H
2
O/ -BuOH 1:1
0°C, 16 h
(70%, 97% ee)
H
2
O
50°C, 3 h
(98%)
B
OH
OH
OH
H
2
O
2
(1.2 equi .)
H
2
O, 20°C
K
2
[W
2
O
3
(O
2
)
4
(H
2
O)
2
]
(0.02 equi .)
(99%, d 96:4)
O
10% NH
3
/H
2
O
4 h (88%) N
OH
OH
HH
HO OH
Scheme 16
Scheme 16. E icien asymme ic syn hesis o an azasuga in wa e .
N
Boc
LiTMP, MeOCOCI
78 ºCN
Boc
COOMe
MeOOC
N
Boc
COOMe
MeOOC
N
Boc
COOMe
MeOOC
80%
10:1 cis
6:1 ans
Li, NH3, THF,
hen NH4Cl
Li, ca . DBB, THF,
hen 2,6-di- e bu ylphenol
80%
N
H
HO OH
OH
HO
N
H
HO OH
OH
HO
DMDP
N
HO OH
OH
H
HO
(-)-2,3-7- iepiaus aline
52
53
53
54
Scheme 17. Pa ial educ ion o py ole o he syn hesis o DMDP and o he iminosuga s.
a ed wi h li hium 2,2,6,6- e ame hylpi-
pe idide (LiTMP), ollowed by a quench
wi h me hyl chlo o o ma e, o gi e dies e
52 (Scheme 17). Py ole 52 can be educed
o gi e he ans isome o 53 wi h good
dias e eoselec i i y, using li hium in am-
monia and quenching wi h ammonium
chlo ide. Reduc ion unde ‘ammonia- ee’
condi ions (Li, ca aly ic DBB, THF) ol-
lowed by p o ona ion wi h 2,6-di- e bu-
ylphenol gi es cis-53 exclusi ely. These
wo py olines we e success ully ans-
o med (among o he s) in o he na u al
py olizidine alkaloid (–)-2,3,7- iepiaus-
aline,[51] in o he polyhyd oxyla ed py -
olidine 54 and in o he na u al glycosidase
inhibi o DMDP.[52]
7. Conclusion
Fo many yea s ca bohyd a es we e e y
di icul syn he ic a ge s because o hei
complexi y a ising om hei s e eochem-
is y and hei mul i unc ional cha ac e . In
pa allel wi h he ecen e olu ion in o ganic
syn hesis, a la ge numbe o complica ed
and a e monosaccha ides ha e been p e-
pa ed by o al asymme ic syn hesis s a ing
om inexpensi e and eady a ailable s a -
ing ma e ials, including u ans eco e ed
om he le -o e s o ag icul u e (biomass)
and py oles. Me hods a e a ailable ha al-
low one o each bo h enan iome s o any
na u al o non-na u al monosaccha ide, in-
cluding deoxyaminosuga s, hiosuga s and
iminosuga s, and his, qui e o en, in ew
syn he ic s eps. Depending on he a ge ,
pu e chemical p ocedu es can be applied
success ully, alone o in combina ion wi h
chemoenzyma ic me hods.
Acknowledgemen s
We hank he Minis e io de Ciencia e
Inno ación o Spain (CTQ2008-01565/BQU)
and he Jun a de Andalucía (FQM 345) o
inancial suppo .
Recei ed: Sep embe 21, 2010
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