Accep ed Manusc ip
Syn hesis, egioselec i e hyd ogenolysis, pa ial hyd ogena ion and con o ma‐
ional s udy o dioxane and dioxolane ype (9’-an h acenyl)me hylene ace als
o suga s
Zsol Jakab, A ila Mándi, Anikó Bo bás, A ila Bényei, Is án Komá omi,
László Lázá , Sándo An us, And ás Lip ák
PII: S0008-6215(09)00444-3
DOI: 10.1016/j.ca es.2009.09.007
Re e ence: CAR 5156
To appea in: Ca bohyd a e Resea ch
Recei ed Da e: 15 July 2009
Re ised Da e: 26 Augus 2009
Accep ed Da e: 9 Sep embe 2009
Please ci e his a icle as: Jakab, Z., Mándi, A., Bo bás, A., Bényei, A., Komá omi, I., Lázá , L., An us, S., Lip ák,
A., Syn hesis, egioselec i e hyd ogenolysis, pa ial hyd ogena ion and con o ma ional s udy o dioxane and
dioxolane ype (9’-an h acenyl)me hylene ace als o suga s, Ca bohyd a e Resea ch (2009), doi: 10.1016/j.ca es.
2009.09.007
This is a PDF ile o an unedi ed manusc ip ha has been accep ed o publica ion. As a se ice o ou cus ome s
we a e p o iding his ea ly e sion o he manusc ip . The manusc ip will unde go copyedi ing, ypese ing, and
e iew o he esul ing p oo be o e i is published in i s inal o m. Please no e ha du ing he p oduc ion p ocess
e o s may be disco e ed which could a ec he con en , and all legal disclaime s ha apply o he jou nal pe ain.
ACCEPTED MANUSCRIPT
1
Syn hesis, egioselec i e hyd ogenolysis, pa ial hyd ogena ion and con o ma ional
s udy o dioxane and dioxolane ype (9’-an h acenyl)me hylene ace als o suga s
Zsol Jakab, A ila Mándi, Anikó Bo bás*, A ila Bényei, Is án Komá omi, László Lázá ,
Sándo An us and And ás Lip ák
ACCEPTED MANUSCRIPT
2
Syn hesis, egioselec i e hyd ogenolysis, pa ial hyd ogena ion
and con o ma ional s udy o dioxane and dioxolane ype (9’-
an h acenyl)me hylene ace als o suga s
Zsol Jakaba, A ila Mándia, Anikó Bo bása,*, A ila Bényeib, Is án Komá omic, László
Lázá a, Sándo An usa,d, And ás Lip áka
aResea ch G oup o Ca bohyd a es o he Hunga ian Academy o Sciences, Uni e si y o
Deb ecen, H-4010, Deb ecen, PO Box 94, Hunga y
bIns i u e o Physical Chemis y, Facul y o Science, Uni e si y o Deb ecen, Deb ecen, PO
Box 7, H-4010 Hunga y
cHaemos asis, Th ombosis and Vascula Biology Resea ch G oup o he Hunga ian Academy
o Sciences, Uni e si y o Deb ecen, H-4032 Deb ecen, Hunga y
dDepa men o O ganic Chemis y, Uni e si y o Deb ecen, H-4010, Deb ecen, PO Box 20
Dedica ed o P o esso Ká oly Lempe on he occasion o his 85 h bi hday
Abs ac
Dioxane- ype (9’-an h acenyl)me hylene ace al o me hyl 2,3-di-O-me hyl--D-
glucopy anoside was clea ed wi h LiAlH4-AlCl3 (3:1) o wi h Na(CN)BH3-HCl
egioselec i ely o p o ide he 4- o 6-O-(9’-an h acenyl)me hyl e he , espec i ely.
Hyd ogenoly ic eac ion o he exo and endo isome s o dioxolane- ype ace als p o ed o be
di ec ed by he con igu a ion o he ace alic ca bon as well as he in amolecula pa icipa ion
o he adjacen ee hyd oxyl; ing opening eac ion o he endo isome o he me hyl 2,3-O-
(9’-an h acenyl)me hylene-α-L- hamnopy anoside ook place wi h comple e selec i i y
ACCEPTED MANUSCRIPT
3
esul ing in he axial (9’-an h acenyl)me hyl e he , whe eas a 1:1 mix u e o he axial and
equa o ial e he s was o med upon same eac ion o he exo isome . Ca aly ic hyd ogena ion
o he suga ace als esul ed in (9’,10’-dihyd o-9’-an h acenyl)me hylene de i a i es wi hou
a ec ing he ace alic cen e . High- empe a u e molecula dynamics simula ions and DFT
(Densi y Func ional Theo y) geome y op imiza ions we e ca ied ou o s udy he
con o ma ion o he dioxane- ype (9’,10’-dihyd o-9’-an h acenyl)me hylene ace al.
Keywo ds 9-An h acenylme hylene ace al, Regioselec i e, Hyd ogenolysis, High-
empe a u e MD, DFT
Co esponding au ho . Tel.: +36 52512900/22462; ax: +36 52512900/22342.
E-mail add ess: [email p o ec ed] (A. Bo bás).
1. In oduc ion
Regioselec i e ans o ma ion o polyhyd oxy compounds, such as ca bohyd a es,
necessi a es he applica ion o p o ec i e g oups which can be a ached o clea ed in a
selec i e manne o ob ain pa ially subs i u ed molecules. Modi ica ion o simple suga s and
syn hesis o highe oligosaccha ides can no be ca ied ou wi hou he use o hese
me hodologies.1
The ace al- ype p o ec ing g oups possess signi ican ad an ages such as simul aneous
p o ec ion o wo hyd oxyls, he easy emo al and he possibili y o a pa ial dep o ec ion. By
he adequa e selec ion o he hyd ide dono and a ious p o ic o Lewis acid eagen s as well
as sol en s, any o he wo p o ec ed hyd oxyls can be libe a ed egioselec i ely.2
ACCEPTED MANUSCRIPT
4
Mos ecen ly he 9-an h aldehyde ace al as a new p o ec ing g oup was p oposed by
Elle ik3 epo ing he syn hesis o (9’-an h acenyl)me hylene ace als o he 2-
( ime hylsilyl)e hyl -D-glucopy anoside and he phenyl 1- hio--D-galac opy anoside in an
ace al exchange eac ion. The an h aldehyde ace als can be clea ed unde educ i e
condi ions wi h Na(CN)BH3 and HCl/E 2O in THF o gi e 6-O-(9’-an h acenyl)me hyl e he s,
and can be selec i ely emo ed in he p esence o benzylidene ace als. Due o he good
c ys alline p ope ies and s ong abso bance and luo escence he (9’-an h acenyl)me hylene
ace al and (9’-an h acenyl)me hyl e he may become use ul as new p o ec ing g oups.
These esul s p omp ed us o in es iga e he egioselec i e ing opening eac ion and
dep o ec ion p ocedu es o dioxane- and dioxolane- ype (9’-an h acenyl)me hylene-ace als o
suga s.
2. Resul s and discussion
2.1. Syn hesis and eac i i y o dioxane- ype (9’-an h acenyl)me hylene ace als
To p epa e he dioxane- ype ace al 2, me hyl α-D-glucopy anoside 1 was ea ed wi h
an h aldehyde dime hyl ace al in he p esence o (±)10-campho sul onic acid (CSA). The OH
g oups o posi ion 2 and 3 we e me hyla ed o ob ain he ully p o ec ed me hyl 4,6-O-(9’-
an h acenyl)me hylene-2,3-di-O-me hyl--D-glucopy anoside 3 (Scheme 1).
Upon ea men o compound 3 wi h LiAlH4-AlCl34 (3:1) he me hyl 4-O-(9’-
an h acenyl)me hyl-2,3-di-O-me hyl--D-glucopy anoside 4 could be isola ed in c ys alline
o m in a yield o 70%. T ans o ma ion o 3 wi h Na(CN)BH3 and HCl/E 2O in d y THF5
mainly esul ed in me hyl 6-O-(9’-an h acenyl)me hyl-2,3-di-O-me hyl--D-glucopy anoside
5, and i s egioisome 4 was also o med as a mino p oduc .

ACCEPTED MANUSCRIPT
5
I has been known since 1936 ha 4,6-O-benzylidene ace als o glucose can be
ca aly ically educed in o he co esponding 4,6-diols.6 Howe e , ca aly ic hyd ogena ion o 3
su p isingly did no a ec he ace alic cen e , bu a ec ed he an acenyl ing esul ing in
me hyl 4,6-O-(9’,10’-dihyd o-9’-an h acenyl)me hylene-2,3-di-O-me hyl--D-
glucopy anoside 6 which was s able unde hyd ogen a mosphe e in he p esence o Pd ca alys
o as long as 5 days. The s uc u e o compound 6 was de e mined on he basis o 1H- and
13C-NMR spec oscopy and X- ay c ys allog aphy as well. Molecula modeling was also
applied o in es iga e he con o ma ion o he (9’,10’-dihyd o-9’-an h acenyl)me hylene
moie y.
In o de o s udy he selec i e emo al o he (9’-an h acenyl)me hyl e he moie y in he
p esence o ace yl, benzoyl o p-me hoxybenzyl (PMB) g oups he ee hyd oxyl o
compound 4 was subs i u ed by a simple ace yla ion, benzoyla ion and p-me hoxybenzyla ion
o u nish compounds 7-9, espec i ely. All h ee ully p o ec ed de i a i es 7-9 we e ea ed
wi h BF3OE 2 in d y CH2Cl2 a 0 °C. Selec i e clea age o he (9’-an h acenyl)me hyl g oup
o 7 and 8 libe a ing he OH-4 ook place in 20 minu es o a o d compounds 107 and 11,8,9
espec i ely. In he case o compound 9 no only he (9’-an h acenyl)me hyl g oup bu also
he PMB g oup was clea ed unde hese condi ions o gi e he diol 12.10
Reduc i e ing opening eac ion o he pa ially hyd ogena ed ace al de i a i e 6 was
also s udied. We assumed ha he ace alic cen e o 4,6-O-ace al ing ancho ed o he
alipha ic 9’-ca bon is less eac i e unde hyd ogenoly ic condi ions han ha o compound 3
ancho ed o an a oma ic ca bon. Compound 6 was ea ed wi h LiAlH4-AlCl3 (3:1) unde he
condi ions applied o he con e sion o 3 in o 4, howe e no eac ion could be obse ed.
In e es ingly, he eac ion o 6 wi h E 3SiH in he p esence o BF3OE 211 in d y CH2Cl2
esul ed in wo p oduc s, 13 and 14. Un eac ed s a ing ma e ial 6 also emained a e 24 h.
Compound 13 p o ed o be me hyl 6-O-(9’,10’-dihyd o-9’-an h acenyl)me hyl-2,3-di-O-
ACCEPTED MANUSCRIPT
6
me hyl--D-glucopy anoside. The byp oduc 14 could be pu i ied a e ace yla ion (1415)
and was iden i ied as 1,5-anhyd o-4-O-ace yl-6-O-(9’,10’-dihyd o-9’-an h acenyl)me hyl-2,3-
di-O-me hyl-D-gluci ol on he basis o NMR. This esul has expe imen ally p o ed he high
s abili y o his ype o ace al 6 and he o ma ion o 14 is assumed o ake place ia
compound 13. Hyd ogenolysis o he glycosidic ace al esul ing in a gluci ol de i a i e is
ex emely a e upon educ i e clea age o benzylidene ype ace als,12 since glycosides a e
mo e s able han he a oma ic ace als.
Scheme 1. Reagen s and condi ions: (a) an h aldehyde dime hylace al, ca . CSA, d y MeCN,
, 3 h, 79%; (b) MeI, NaH, DMF, 0 °C, 3 h, 90%; (c) om 3: LiAlH4, AlCl3 (3:1), E 2O,
CH2Cl2, , 4 h, 70%; (d) om 3: Na(CN)BH3 in THF, HCl/E 2O, , 5 min, 48% o 5, 12%
o 4; (e) Pd(C), H2, E OH, , 6 h, 90%; ( ) Ac2O, py idine, , 2 h, 80% o 7; (g) BzCl,
py idine, CH2Cl2, 0 °C, 2 h, 89% o 8; (h) PMBCl, NaH, DMF, 0 °C, 2 h, 82% o 9; (i)
ACCEPTED MANUSCRIPT
7
BF3OE 2, CH2Cl2, 0 °C, 20 min, 75% o 10, 76% o 11, 79% o 12; (j) BF3OE 2, E 3SiH,
CH2Cl2, 0 °C, o e nigh , 20% o 13; (k) Ac2O, py idine, , 2 h, 14% o wo s eps.
2.2. Syn hesis and eac i i y o dioxolane- ype (9’-an h acenyl)me hylene ace als
The icinal cis-axial/equa o ial hyd oxyl g oups o py anosides eac wi h ace ala ing
eagen s o o m dioxolane- ype ace al de i a i es. The co esponding an h aldehyde
dime hylace al ha e no been used as p o ec ing g oup o icinal diols so a . Me hyl α-L-
hamnopy anoside was conside ed o be an excellen model compound o s udy he syn hesis
and hyd ogenolysis o dioxolane- ype (9’-an h acenyl)me hylene ace als. T ea men o me hyl
-L- hamnopy anoside 16 wi h an h aldehyde dime hylace al esul ed in a 1:4.5 mix u e o he
17endo and 17exo isome s, in a mode a e yield (55%). Since hese isome s could no be
comple ely sepa a ed by column ch oma og aphy, he mix u e was ace yla ed, and he
sepa a ion o he ob ained mix u e o 18endo and 18exo was success ul. A e deace yla ion
o 18endo and 18exo, espec i ely, he 17endo- and exo-ace als could be ob ained in
c ys alline o m (Scheme 2).
ACCEPTED MANUSCRIPT
8
Scheme 2. Reagen s and condi ions: (a) an h aldehyde dime hylace al, ca . CSA, d y MeCN,
, 1 d, 46% o 17exo, 9% o 17endo. (b) Ac2O, py idine, , 1 h; (c) NaOMe, MeOH, , 1 h.
The de e mina ion o he absolu e con igu a ion o he dioxolane- ype ace als is a a he
complex ask al hough he 1H-NMR spec a can help i bo h isome s a e a ailable. Since he
la e se en ies he chemical shi alues o ace alic p o ons and ca bons ha e been applied o
he s uc u e elucida ion o he dioxolane- ype s uc u es.13 The ace alic con igu a ion o
compounds 17 and 18 we e p o en by 1H-NMR spec oscopy; H-ace alic o 17- and 18endo
isome s esona e a highe ield ( 7.08 and 7.12 ppm) while H-ace alic signals o 17- and
18exo isome s a e a lowe ield ( 7.47 and 7.58 ppm). Resonance alues o he ace alic
ca bons a e he ollowings: 17endo: 102.2 ppm, 18endo: 101.8 ppm and 17exo:100.3 ppm,
18exo:100.8 ppm.
We s udied ing-opening eac ion o he dioxolane- ype ace als 17endo and 17exo
possessing an ex emely bulky an h acenyl subs i uen a he ace alic cen e . I was ea lie
shown ha he clea age o he i e-membe ed benzylidene- ype ace al ings is di ec ed by he
s e eochemis y o he ace alic cen e . Namely, upon exo a angemen o he bulky
subs i uen , he eagen a acks he axial oxygen a om o ming he axial hyd oxyl and
equa o ial benzyl-e he de i a i es, selec i ely. On he con a y, in he case o endo
a angemen o he bulky g oup, he equa o ial oxygen a om is a acked leading o he
o ma ion o he equa o ial hyd oxyl and axial e he ype p oduc s, also wi h ull selec i i y.
Recen ly a ule o humb (x, x, x) was o mula ed o he ing opening eac ions o he
dioxolane ace als by he ollowing way: exo isome gi es axial hyd oxyl.14 In good ag eemen
wi h ou expec a ions he clea age o 17endo wi h LiAlH4-AlCl3 (3:1) ga e me hyl 2-O-(9’-
an h acenyl)me hyl--L- hamnopy anoside 20, exclusi ely. Su p isingly, ea men o 17exo
wi h LiAlH4-AlCl3 (3:1) esul ed in a 1:1 mix u e o he equa o ial (9’-an h acenyl)me hyl-
ACCEPTED MANUSCRIPT
15
exis ence o o he axial con o ma ion also migh ha e con ibu ion o he obse ed p ope ies.
Ano he consequence o he axial ace al con o ma ion and he oo - ype shape o he
hyd ogena ed an h acenyl g oup is he loss o igh i o he su ace o ca alysa o and his
way he loss o ull hyd ogena ion.
4. Expe imen al
4.1. Gene al Me hods
Op ical o a ions we e measu ed a oom empe a u e wi h a Pe kin-Elme 241
au oma ic pola ime e . Mel ing poin s we e de e mined on a Ko le ho -s age appa a us and
a e unco ec ed. TLC was pe o med on Kieselgel 60 F254 (Me ck) wi h de ec ion by 5%
sul u ic acid in e hanol. Column ch oma og aphy was pe o med on Silica Gel 60 (E. Me ck
0.062–0.200 nm). The o ganic solu ions we e d ied o e MgSO4 and concen a ed in acuum.
The 1H (200.13, 360.13 and 500.13 MHz) and 13C NMR (50.3, 90.54, 125.76 MHz) spec a
we e eco ded wi h B uke WP-200SY, B uke AM-360 and B uke DRX-500 spec ome e s
o solu ions in CDCl3. In e nal e e ences: TMS (0.00 ppm o 1H), CDCl3 (77.00 ppm o
13C). MALDI-TOF MS spec a we e eco ded on a B uke Bi lex III spec ome e in posi i e,
linea mode using sa u a ed 2,4,6- ihyd oxy-ace o enon in wa e as ma ix. X- ay di ac ion
da a was collec ed a 293 K, En a Nonius MACH3 di ac ome e , Mo K adia ion =
0.71073 Å. The s uc u e was sol ed by SIR-92 p og am18 and e ined by ull-ma ix leas -
squa es me hod on F2, wi h all non-hyd ogen a oms e ined wi h aniso opic he mal
pa ame e s using he SHELXL-97 package19, publica ion ma e ial was p epa ed wi h he
WINGX- sui e.20 All hyd ogen a oms we e loca ed geome ically and e ined in he igid
mode. The molecula dynamics simula ions and he p elimina y geome y op imiza ions using
he sui ably de eloped GAFF empi ical o ce ield on he ajec o y snapsho geome ies we e

ACCEPTED MANUSCRIPT
16
ca ied ou by means o he Ambe molecula dynamics simula ion package.21 B3LYP/6-
31G(d) densi y unc ional calcula ions we e ca ied ou using he Gaussian 03 package.22 A
he B3LYP/6-31G(d) minima he ze o poin ib a ional ene gy co ec ion a he same le el o
heo y also we e compu ed. Ball-and-s ick ep esen a ions o he con o me s we e gene a ed
by he Molekel23 and VMD24 so wa es.
4.1.1. Me hyl 4,6-O-(9’-an h acenyl)me hylene--D-glucopy anoside (2)
To a mix u e o me hyl -D-glucopy anoside 1 (3.0 g 15.4 mmol) and an h aldehyde
dime hylace al3 (4.56 g 18.1 mmol) in MeCN (20 mL) was added ca aly ic amoun o (±)10-
campho sul onic acid (CSA) and was s i ed a oom empe a u e o 3 h. The mix u e was
neu alized by addi ion o E 3N and concen a ed, hen co-e apo a ed wi h oluene h ee
imes. The esidue was c ys allized om E 2O-hexane o gi e 2 (4.64 g, 79%) as whi e
needles: mp 192-194 °C; []D +106 (c 0.14, CHCl3); 1H NMR (200 MHz, CDCl3): δ (ppm)
8.59 (d, 2H, J 8.5 Hz), 8.46 (s, 1H), 7.97 (d, 2H, J 8.0 Hz), 7.58-7.37 (m, 4H), 6.80 (s, 1H,
ace alic), 4.50 (d, 1H, J1,2 3.9 Hz, H-1), 4.33 (dd, 1H, J 10.4 Hz, J 4.7 Hz), 4.0 (d , 1H, J 9.9
Hz, J 4.7 Hz), 3.87 (dd, 1H, J 9.3 Hz, J 2.4 Hz), 3.82 (d, 1H, J 11.6 Hz), 3.7 (d, 1H, J 10.3
Hz), 3.50-3.35 (m, 2H), 3.31 (s, 3H, OCH3), 2.73 (d, 1H, J 8.7 Hz, OH); 13C NMR: (50 MHz,
CDCl3): δ (ppm) 131.5, 129.9, 129.6, 129.0, 126.6, 126.2, 124.8 (a oma ic), 100.5 (C
ace alic), 99.9 (C-1), 82.1 (C-4), 72.5, 71.3 (C-2, C-3), 69.9 (C-6), 62.3 (C-5), 55.6 (OCH3);
Anal. Calcd. o C22H22O6 (382.41): C 69.10, H 5.80. Found: C 69.43, H 5.71.
4.1.2. Me hyl 4,6-O-(9’-an h acenyl)me hylene-2,3-di-O-me hyl--D-glucopy anoside (3)
ACCEPTED MANUSCRIPT
17
Compound 2 (1.58 g, 4.36 mmol) was s i ed in d y DMF (10 mL), ea ed wi h NaH
(0.40 g, 60%, 3 equi ) a 0 °C. Me hyl iodide (0.70 mL, 11.2 mmol, 2.71 equi ) was added
d opwise and he eac ion empe a u e was kep a 0 °C o 1 h. Then i was allowed o wa m
up o , and no s a ing ma e ial was indica ed by TLC a e 2 h. To he mix u e MeOH was
added o decompose he un eac ed NaH and hen i was concen a ed, dilu ed wi h CH2Cl2,
washed wice wi h wa e , d ied (MgSO4) and concen a ed. A e column ch oma og aphy
(6:4 hexane-E OAc) compound 3 (1.52 g, 90%) was isola ed as a sy up: []D +85 (c 0.16,
CHCl3); 1H NMR (200 MHz, CDCl3): δ (ppm) 8.66 (d, 2H, J 8.7 Hz), 8.42 (s, 1H), 7.93 (dd,
2H, J 8.4 Hz, J 0.8 Hz), 7.55-7.36 (m, 4H), 6.89 (s, 1H, ace alic), 4.89 (d, 1H, J 3.8 Hz, H-1),
4.43 (dd, 1H, J 10.1 Hz, J 4.7 Hz), 4.26-4.11 (m, 1H), 4.09 (dd, 1H, J 14.3 Hz, J 7.2 Hz), 3.90
( , 1H, J 10.2 Hz), 3.80-3.72 (m, 1H), 3.52 (2s, 6H, 2 x OCH3), 3.41 (s, 3H, OCH3), 3.34 (dd,
1H, J2,3 8.9 Hz, H-2); 13C NMR (50 MHz, CDCl3): δ (ppm) 131.4, 129.6, 129.6, 128.8, 126.9,
125.9, 124.9, 124.7 (a oma ic), 100.6 (C ace alic), 98.5 (C-1), 83.1, 81.4, 79.8 (C-2, C-3, C-
4), 69.9 (C-6), 62.3 (C-5), 60.8, 59.2 (2 x OCH3), 55.5 (anome ic OCH3). MALDI-TOF MS
m/z calcd. o C24H26O6 : 410.17. Found: 410.42 [M]+ and 433.38 [M+Na]+. Anal. Calcd. o
C24H26O6: C 70.23, H 6.38. Found: C 70.33, H 6.32.
4.1.3. Me hyl 4-O-(9’-an h acenyl)me hyl-2,3-di-O-me hyl--D-glucopy anoside (4)
To a s i ed suspension o he s a ing ace al 3 (2.1 g, 5.1 mmol) in d y CH2Cl2 and E 2O
(30 mL, 2:1) LiAlH4 (0.86 g, 4.5 equi ) and solu ion o AlCl3 (1.0 g, 1.5 equi ) in E 2O (10
mL) we e added ca e ully unde a gon a 0 °C, hen s i ed o 4 h a . A e comple e
con e sion 2-3 mL o E OAc and 1-5 d ops o wa e we e added, he mix u e was dilu ed wi h
E OAc, washed 3 imes wi h wa e , d ied and concen a ed. The c ude sy up was c ys allized
om E OH o gi e pale yellow c ys alline p oduc and mo he liquo was pu i ied by column
ACCEPTED MANUSCRIPT
18
ch oma og aphy (7:3 hexane-ace one) o gi e 4 wi h 70% o e all yield (1.46 g): mp 145-146
°C; []D +112 (c 0.10, CHCl3); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.47 (d, 2H, J 9.0 Hz,
H-1’, H-8’), 8.44 (s, 1H, H-10’), 7.98 (d, 2H, J 8.5 Hz, H-4’, H-5’), 7.55-7.40 (m, 4H, H-2’,
H-3’, H-6’, H-7’), 5.81 (d, 1H, J 11.0 Hz, A CH2), 5.71 (d, 1H, J 11.0 Hz, A CH2), 4.80 (d,
1H, J1,2 3.6 Hz, H-1), 3.80 (s, 3H, OCH3), 3.75-3.60 (m, 4H), 3.55-3.50 (m, 1H), 3.53 (s, 3H,
OCH3), 3.32 (s, 3H, OCH3), 3.29 (dd, 1H, J2,3 9.1 Hz, H-2), 1.80 (bs, 1H, OH); 13C NMR
(125 MHz, CDCl3): δ (ppm) 131.4, 130.9, 129.0, 128.7, 128.5, 126.3, 124.9, 124.3 (a oma ic),
97.2 (C-1), 83.5, 82.8, 76.6 (C-2, C-3, C-4), 70.6 (C-5), 66.6 (A CH2-), 61.7 (C-6), 61.3, 58.6
(2 x OCH3), 55.0 (OCH3 anome ic); Anal. Calcd. o C24H28O6 (412.48): C 69.88, H 6.84.
Found: C 69.96, H 6.75.
4.1.4. Me hyl 6-O-(9’-an h acenyl)me hyl-2,3-di-O-me hyl--D-glucopy anoside (5) and
compound (4)
To a s i ed suspension o he s a ing ace al 3 (0.39 g, 0.96 mmol) and Na(CN)BH3
(0.54 g, 9 equi ) in d y THF (5 mL) con aining 3 Å MS was added HCl in E 2O d opwise
un il he e olu ion o gas ceased. A e 5 min TLC showed comple e con e sion o he
s a ing ma e ial. The mix u e was dilu ed wi h CH2Cl2 (100 mL), washed wi h sa d NaHCO3
and wa e , hen d ied (MgSO4) and concen a ed. A e column ch oma og aphy (1:1 hexane-
E OAc) compound 5 (227 mg, 48%) was isola ed as a sy up: []D +63 (c 0.17, CHCl3); 1H
NMR (360 MHz, CDCl3): δ (ppm) 8.39 (d, 3H), 7.95 (d, 2H, J 8.4 Hz), 7.47 (d , 4H), 5.55 (d,
1H, J 11.5 Hz, A CH2), 5.47 (d, 1H, J 11.6 Hz, A CH2), 4.84 (s, 1H, J1,2 3.4 Hz, H-1), 3.90-
3.75 (m, 2H), 3.68 (m, 1H, H-5), 3.60-3.33 (m, 12H, incl. 3x OCH3), 3.17 (dd, 1H, J2,3 9.1
Hz, H-2); 13C NMR (90 MHz, CDCl3): δ (ppm) 130.9, 130.5, 128.5, 128.3, 127.9, 125.7,
124.5, 124.0 (a oma ic), 97.0 (C-1, JC1,H1 170 Hz), 82.5, 81.2, 70.2, 70.0 (C-2, C-3, C-4, C-5),
ACCEPTED MANUSCRIPT
19
69.2 (A CH2-), 65.3 (C-6), 60.5, 58.1 (2 x OCH3), 54.7 (OCH3 anome ic); Anal. Calcd. o
C24H28O6 (412.48): C 69.88, H 6.84. Found: C 70.06, H 6.63.
Compound 4 was also o med (56 mg, 12%).
4.1.5. Me hyl 4,6-O-(9’,10’-dihyd o-9’-an h acenyl)me hylene-2,3-di-O-me hyl--D-
glucopy anoside (6)
Compound 3 (0.45 g, 1.1 mmol) was dissol ed in 96% E OH (25 mL) and s i ed unde
H2 a mosphe e in he p esence o 10% Pd/C (75 mg) o 6 h. The ca alys was emo ed by
il a ion h ough a laye o Celi e, washed wi h E OH, and he sol en was e apo a ed. The
esidue was c ys allized om MeOH o gi e 6 (360 mg, 79%) as whi e needles: mp 172-174
°C; []D +51 (c 0.19, CHCl3); 1H NMR (200 MHz, CDCl3): δ (ppm) 7.40-7.10 (m, 8H,
a oma ic), 4.72 (d, 1H, J1,2 3.7 Hz, H-1), 4.63 (d, 1H, J 5.2 Hz, H-ace alic), 4.22 (d, 1H, J 4.4
Hz, H-9’), 4.17 (d, 1H, J 16.9 Hz, H-10’a), 3.99 (dd, 1H, J 10 Hz, J 4.6 Hz), 3.78 (d, 1H, J
18.1 Hz, H-10’b), 3.60-3.40 (m, 8H, incl. 2 x OCH3), 3.33 (s, 3H, anome ic OCH3), 3.30 ( ,
1H, J 10.1 Hz), 3.14 ( , 1H, J 9.4 Hz), 3.12 (dd, 1H, J2,3 9.3 Hz, H-2); 13C NMR (50 MHz,
CDCl3): δ (ppm) 137.3, 137.2, 135.1, 134.9, 130.0, 129.8, 127.4, 127.3, 126.7, 125.6
(a oma ic), 103.5 (C-ace alic), 98.3 (C-1), 81.8, 80.9, 79.8 (C-2, C-3, C-4), 68.6 (C-6), 61.9
(C-5), 60.6, 59.3 (2 x OCH3), 55.0 (anome ic OCH3), 51.0 (C-9’), 35.8 (C-10’). MALDI-TOF
MS m/z calcd. o C24H28O6 : 412.19. Found: 435.40 [M+Na]+. Anal. Calcd. o C24H28O6: C
69.88, H 6.84. Found: C 70.03, H 6.69.
4.1.6. Me hyl 6-O-ace yl-4-O-(9’-an h acenyl)me hyl-2,3-di-O-me hyl--D-
glucopy anoside (7)
ACCEPTED MANUSCRIPT
20
To a solu ion o 4 (250 mg, 0.61 mmol) in py idine (2 mL) was added Ac2O (1 mL),
and s i ed o 2 hou s. Then he eac ion mix u e was concen a ed and co-e apo a ed wice
wi h oluene. A e column ch oma og aphy (7:3 hexane-E OAc) compound 7 was isola ed
(220 mg, 80%) as a sy up: []D +144 (c 0.11, CHCl3); 1H NMR (500 MHz, CDCl3): δ (ppm)
8.42 (d, 2H, J 9.0 Hz, H-1’, H-8’), 8.40 (s, 1H, H-10’), 7.96 (d, 2H, J 8.5 Hz, H-4’, H-5’),
7.60-7.40 (m, 4H, H-2’, H-3’, H-6’, H-7’), 5.75 (d, 1H, J 11.5 Hz, A CH2), 5.70 (d, 1H, J
11.5 Hz, A CH2), 4.80 (s, 1H, J1,2 3.5 Hz, H-1), 4.12-4.08 (m, 1H), 3.95 (dd, 1H, J 12.0 Hz, J
3.5 Hz), 3.81 (s, 3H, OCH3), 3.75-3.60 (m, 3H), 3.59 (s, 3H, OCH3), 3.33 (s, 3H, OCH3),
3.40-3.30 (dd, 1H, J 4.0 Hz), 1.77 (s, 3H, COCH3); 13C NMR (125 MHz, CDCl3): δ (ppm)
170.3 (CO) 131.5, 131.0, 129.0, 128.6, 126.4, 125.0, 124.3 (a oma ic), 97.2 (C-1), 83.9, 82.5,
76.0, 68.4 (C-2, C-3, C-4, C-5), 66.3 (A CH2), 62.9 (C-6) 61.5, 58.7 (2 x OCH3), 55.1
(anome ic OCH3) 20.2 (OCOCH3); Anal. Calcd. o C26H30O7 (454.51): C 68.71, H 6.65.
Found: C 68.52, H 6.77.
4.1.7. Me hyl 4-O-(9’-an h acenyl)me hyl-6-O-benzoyl-2,3-di-O-me hyl--D-
glucopy anoside (8)
To a solu ion o 4 (123 mg, 0.30 mmol) in d y CH2Cl2 (2 mL) and d y py idine (2 mL)
was added BzCl (42 µL, 1.2 equi ) a 0 °C and he mix u e was s i ed o 2 h. Then he
eac ion mix u e was dilu ed wi h CH2Cl2, washed wice wi h wa e , d ied (MgSO4) and
concen a ed. A e column ch oma og aphy (7:3 hexane-E OAc) compound 8 (138 mg, 89%)
was isola ed as a sy up: []D +102 (c 0.12, CHCl3); 1H NMR (500 MHz, CDCl3): δ (ppm)
8.43 (d, 2H, J 9.0 Hz, H-1’, H-8’), 8.26 (s, 1H, H-10’), 7.88 (d, 2H, J 8.5 Hz, H-4’, H-5’),
7.82 (d, 2H, J 9.0 Hz,) 7.55-7.45 (m, 3H) 7.40-7.30 (m, 4H, H-2’, H-3’, H-6’, H-7’), 5.83 (d,
1H, J 11.5 Hz, A CH2), 5.76 (d, 1H, J 11.5 Hz, A CH2), 4.82 (s, 1H, J1,2 3.5 Hz, H-1), 4.42

ACCEPTED MANUSCRIPT
21
(dd, 1H, J 11.8 Hz, J 2.0 Hz), 4.23 (dd, 1H, J 12.0 Hz, J 3.5 Hz), 3.85 (s, 3H, OCH3), 3.85-
3.76 (m, 4H), 3.55 (s, 3H, OCH3), 3.36 (s, 4H, incl. OCH3); 13C NMR (125 MHz, CDCl3): δ
(ppm) 165.8 (COPh) 132.9, 131.4, 131.0, 129.8, 129.5, 129.1, 128.7, 128.4, 126.4, 125.0,
124.2 (a oma ic), 97.2 (C-1), 84.0, 82.7, 76.3, 68.6 (C-2, C-3, C-4, C-5), 66.5 (A CH2), 63.2
(C-6) 61.5, 58.7 (2 x OCH3), 55.2 (anome ic OCH3); Anal. Calcd. o C31H32O7 (516.58): C
72.08, H 6.24. Found: C 72.66, H 6.01.
4.1.8. Me hyl 4-O-(9’-an h acenyl)me hyl-6-O-p-me hoxybenzyl-2,3-di-O-me hyl--D-
glucopy anoside (9)
To a solu ion o 4 (127 mg, 0.31 mmol) in d y DMF (3 mL) was added NaH (20 mg,
80%, 1.5 equi ) a 0 °C and he mix u e was s i ed o 20 min, hen PMBCl (50 µL, 1.2
equi ) was added and s i ed o 4 h. Then he eac ion mix u e was dilu ed ca e ully wi h
MeOH and concen a ed. The esidue was dissol ed in CH2Cl2, washed wice wi h wa e ,
d ied (MgSO4) and concen a ed. A e column ch oma og aphy (7:3 hexane-E OAc)
compound 9 (135 mg, 82%) was isola ed as a sy up: []D +118 (c 0.09, CHCl3); 1H NMR
(500 MHz, CDCl3): δ (ppm) 8.41 (s, 1H, H-10’), 8.41 (d, 2H, J 8.5 Hz, H-1’, H-8’), 7.97 (d,
2H, J 8.0 Hz, H-4’, H-5’), 7.50-7.40 (m, 4H, H-2’, H-3’, H-6’, H-7’), 7.18 (d, 2H, J 8.5 Hz),
6.81 (d, 2H, J 8.5 Hz), 5.77 (d, 1H, J 11.0 Hz, A CH2), 5.66 (d, 1H, J 11.0 Hz, H- A CH2),
4.86 (s, 1H, J1,2 3.5 Hz, H-1), 4.30 (s, 2H, pCH3OPhCH2), 3.82 ( , 1H, J 8.0 Hz), 3.76-3.65
(m, 9H, incl. 2 x OCH3) 3.65-3.60 (m, 4H, incl. OCH3), 3.39-3.35 (m, 4H, incl. OCH3); 13C
NMR (125 MHz, CDCl3): δ (ppm) 159.2, 131.6, 131.0, 130.2, 129.2, 128.0, 126.2, 124.9,
124.6, 113.8 (a oma ic), 97.3 (C-1), 83.8, 82.7, 76.7, 70.1 (C-2, C-3, C-4, C-5), 73.0
(pCH3OPhCH2), 66.5 (an h -CH2), 66.6 (C-6), 61.5, 58.7 (2 x OCH3), 55.2, 55.1
ACCEPTED MANUSCRIPT
22
(pCH3OPhCH2, anome ic OCH3); Anal. Calcd. o C32H36O7 (532.62): C 72.16, H 6.81.
Found: C 72.32, H 6.71.
4.1.9. Me hyl 6-O-ace yl-2,3-di-O-me hyl--D-glucopy anoside (10)
To a solu ion o 7 (42 mg, 0.09 mmol) in d y CH2Cl2 (1 mL) a 0 °C was added
BF3OE 2 (2 µL) and he mix u e was s i ed o 20 min. When TLC (4:6 hexane-E OAc)
showed comple e con e sion o he s a ing ma e ial (R 0.65) in o he i le compound (R
0.22) 1 d op o E 3N was added and he sol en was e apo a ed. A e column
ch oma og aphy (3:7 hexane-E OAc, R 0.27) compound 107 (18 mg, 75%) was isola ed as a
sy up: []D = +85 (c 1.28, CHCl3), li .7 +85 (CH2Cl2); 1H NMR (360 MHz, CDCl3): δ (ppm)
4.86 (d, 1H, J1,2 3.5 Hz, H-1), 4.45 (d, 1H, J6a,6b 12.1 Hz, J6a,5 4.8 Hz, H-6a), 4.27 (d, 1H, J6b,5
2.1 Hz, H-6b), 3.80-3.70 (m, 1H, H-5), 3.65 (s, 3H, OCH3), 3.55-3.35 (m, 8H, 2 x OCH3, H-3,
H-4), 3.25 (dd, 1H, J2,3 9.4 Hz, H-2), 2.77 (bs, 1H, 4-OH), 2.12 (s, 3H, OCOCH3); 13C NMR
(90 MHz, CDCl3): δ (ppm) 97.5 (C-1), 82.5, 81.7 (C-2, C-3), 69.9, 69.3 (C-4, C-5), 63.2 (C-
6), 61.3, 58.6 (2 x OCH3), 55.3 (anome ic OCH3), 20.8 (OCOCH3); Anal. Calcd. o C11H20O7
(264.27): C 49.99, H 7.63. Found: C 50.38, H 7.42.
4.1.10. Me hyl 6-O-benzoyl-2,3-di-O-me hyl--D-glucopy anoside (11)
To a solu ion o 8 (47 mg, 0.09 mmol) in d y CH2Cl2 (1 mL) a 0 °C was added
BF3OE 2 (2 µL) and he mix u e was s i ed o 20 min. TLC (4:6 hexane-E OAc) showed
comple e con e sion o he s a ing ma e ial (R 0.72) in o he i le compound (R 0.32). Then
1 d op o TEA was added and he solu ion was e apo a ed. A e column ch oma og aphy
(3:7 hexane-E OAc, R 0.52) compound 118,9 (22 mg, 76%) was isola ed as a sy up: []D +81
ACCEPTED MANUSCRIPT
23
(c 0.11, CHCl3), li .9 +75 (CH2Cl2); 1H NMR (360 MHz, CDCl3): δ (ppm) 8.06 (d, 2H, J 7.4
Hz, o-H a oma ic), 7.57 ( , 1H, J 7.4 Hz, p-H a oma ic), 7.44 ( , 2H, J 7.7 Hz, m-H a oma ic),
4.87 (d, 1H, J1,2 3.5 Hz, H-1), 4.67 (d, 1H, J6a,6b 12.1 Hz, J6a,5 4.9 Hz, H-6a), 4.55 (d, 1H, J6b,5
2.1 Hz, H-6b), 3.9-3.8 (m, 1H, H-5), 3.66 (s, 3H, OCH3), 3.55-3.4 (m, 8H, 2 x OCH3, H-3, H-
4), 3.25 (dd, 1H, J2,3 9.1 Hz, H-2), 2.96 (bs, 1H, 4-OH); 13C NMR (90 MHz, CDCl3): δ (ppm)
166.8 (OCOPh), 133.2 (m a oma ic), 129.7, 128.4 (o and p a oma ic), 97.4 (C-1), 82.6, 81.7
(C-2, C-3), 70.1, 69.5 (C-4, C-5), 63.7 (C-6), 61.3, 58.6 (2 x OCH3), 55.2 (anome ic OCH3);
Anal. Calcd. o C16H22O7 (326.34): C 58.89, H 6.79. Found: C 58.63, H 6.89.
4.1.11. Me hyl 2,3-di-O-me hyl--D-glucopy anoside (12)
To a solu ion o 9 (67 mg, 0.13 mmol) in d y CH2Cl2 (1 mL) a 0 °C was added
BF3OE 2 (2 µL) and he mix u e was s i ed o 20 min. TLC (1:1 hexane-E OAc) showed
comple e con e sion o he s a ing ma e ial (R 0.82) in o he i le compound (R 0.22). Then
1 d op o TEA was added and he solu ion was e apo a ed. A e column ch oma og aphy
(1:1 hexane-E OAc) compound 1210 (24 mg, 86%) was isola ed as a sy up: []D +170 (c 0.98,
CHCl3), li .10b +174; 1H- and 13C-NMR da as we e in e y good ag eemen wi h hose
epo ed in he li e a u e.10b
4.1.12. Me hyl 6-O-(9’,10’-dihyd o-9’-an h acenyl)me hyl-2,3-di-O-me hyl--D-
glucopy anoside (13) and 1,5-anhyd o-6-O-(9’,10’-dihyd o-9’-an h acenyl)me hyl-2,3-
di-O-me hyl-D-gluci ol (14)
To a solu ion o 6 (250 mg, 0.60 mmol) in d y CH2Cl2 (2 mL) was added E 3SiH (484
µL, 5 equi ) a 0 °C, hen BF3OE 2 (154 µL, 2 equi ) was also added and he mix u e was
ACCEPTED MANUSCRIPT
24
s i ed o e nigh a . A e TLC (7:3 hexane-ace one) indica ed he o ma ion o wo
p oduc s, he eac ion mix u e was dilu ed wi h CH2Cl2, washed wi h wa e , sa d NaHCO3,
hen again wi h wa e , d ied (MgSO4) and concen a ed. A e column ch oma og aphy
(8:27:3 hexane-ace one) compound 13 (R 0.42, 49 mg, 20%), compound 14 (R 0.46, 52
mg) and un eac ed 6 (34 mg, 14%) we e isola ed as sy ups. Compound 13: []D +62 (c 0.14,
CHCl3); 1H NMR (500 MHz, CDCl3) δ (ppm) 7.36-7.19 (m, 8H, a oma ic), 4.78 (d, 1H, J1,2
3.6 Hz, H-1), 4.22 ( , 1H, J 7.3 Hz, H-9’), 4.13 (d, 1H, J 18.5 Hz, H-10’a), 3.88 (d, 1H, J 18.5
Hz, H-10’b), 3.65-3.56 (m, 6H), 3.61 (s, 3H, OCH3), 3.48 (s, 3H, OCH3), 3.47-3.36 (m, 2H),
3.35 (s, 3H, OCH3), 3.15 (dd, 1H, J 9.1 Hz, H-1); 13C NMR (125 MHz, CDCl3): δ (ppm)
137.1, 137.0, 136.1, 128.8, 128.7, 127.7, 127.7, 126.5, 126.1, 126.0 (a oma ic), 97.3 (C-1),
82.6, 81.6 (C-2, C-3) 75.6 (C-11’), 71.0, 69.8 (C-4, C-5), 70.9 (C-6), 61.0, 58.5 (2 x OCH3),
55.0 (OCH3 anome ic), 47.5 (C-9’), 35.1 (C-10’). MALDI-TOF MS m/z calcd. o C24H30O6 :
414.20. Found: 437.42 [M+Na]+. Anal. Calcd. o C24H30O6 (414.49): C 69.54, H 7.30.
Found: C 69.43, H 7.38.
Compound 14 con aining impu i ies was pu i ied and cha ac e ized a e ace yla ion.
4.1.13. 4-O-ace yl-1,5-anhyd o-6-O-(9’,10’-dihyd o-9’-an h acenyl)me hyl-2,3-di-O-
me hyl-D-gluci ol (15)
The isola ed 14 (52 mg) con aining impu i ies was ace yla ed wi h Ac2O (0.5 mL) in
py idine (1 mL). The mix u e was dilu ed wi h CH2Cl2, washed wice wi h wa e , d ied and
concen a ed. A e column c oma og aphy (7:3 hexane-ace one) compound 15 (37 mg, 14%
o wo s eps) was isola ed as a sy up: []D +16 (c 0.14, CHCl3); 1H NMR (500 MHz,
CDCl3): δ (ppm) 7.31-7.19 (m, 8H, a oma ic), 4.66 ( , 1H, J 9.3 Hz), 4.18 ( , 1H, J 7.1 Hz, H-
9’), 4.12 (d, 1H, J 18.0 Hz, H-10’a), 4.02 (dd, 1H, J 11.3 Hz, J 5.3 Hz), 3.87 (d, 1H, J 18.5
ACCEPTED MANUSCRIPT
31
This wo k was suppo ed by he Hunga ian Na ional Fund (NK48798 o A.L. and K62802 o
A.B.).
Re e ences
1. Kocienski, P. J. P o ec ing G oups; Thieme: New Yo k, 1994.
2. Lip ák, A.; Bo bás, A.; Bajza, I. P o ec ing G oup Manipula ions in Ca bohyd a e
Syn hesis. In Comp ehensi e Glycoscience; Kame ling, J. P., Boons, G.-J., Lee, Y. C.,
Suzuki, A., Taniguchi, N., Vo agen, A. G. J., Eds; Else ie , 2007, 1; pp 203-259.
3. Elle ik U. Te ahed on Le . 2003, 44, 2279-2281.
4. Lip ák, A.; Jodál, I.; Nánási, P. Ca bohyd . Res. 1975, 44, 1-11.
5. Ga egg, P. J.; Hul be g, H. Ca bohyd . Res. 1975, 93, C10-C11.
6. Ze as, L. Be . 1939, 64, 2289-2296.
7. Pe i ou, M.; Imbe y, A.; Duchaussoy, P.; D iguez, P.-A.; Cecca o, M.-L.; Gou enec,
F.; Sizun, P.; Hé aul , J.-P.; Pé ez, S.; He be , J.-M. Chem. Eu . J. 2001, 7, 858-873.
8. Sa o, K; Iga ashi, T.; Yanagisawa, Y.; Kawauchi, N.; Hashimo o, H.; Yoshimu a, J.
Chem. Le . 1988, 1699-1702.
9. Luzzio, F. A.; Bobb, R. A. Te ahed on Le . 1997, 38, 1733-1736.
10. (a) I ine, J. C.; Sco , J. P. J. Chem. Soc. 1913, 109, 575-586. (b) Robe son, G. J.,
Lamb, R. A. J. Chem. Soc. 1934, 1321.
11. Debenham, S. D.; Toone, E. J. Te ahed on: Asymme y 2000, 11, 385-387.
12. (a) Lip ák, A.; Neszmélyi, A.; Ko á, P; Hi sch, J. Te ahed on 1981, 37, 2379-2382;
(b) Gigg, R.; Conan , R. J. Ca b. Chem. 1982-83, 1, 331-336; (c) Gigg, R.; Conan , R.
Ca bohyd . Res. 1982, 104, C14-C17.
13. (a) Bage , N.; Buck, K. W.; Fos e , A. B.; Webbe , J. M. J. Chem. Soc. 1965, 3401-
3407; (b) Neszmélyi, A.; Lip ák, A.; Nánási, P. Ca bohyd . Res. 1977, 58, C7-C9.

ACCEPTED MANUSCRIPT
32
14. Osca son, S. P o ec i e G oup S a egies. In The O ganic Chemis y o Suga s;
Fügedi, P., Le y, D. E., Eds.; Taylo & F ancis, 2006; pp 53-87.
15. Bo bás, A.; Hajkó, J.; Kaj á -Pe edy, M.; Lip ák, A. J. Ca bohyd . Chem. 1993, 12,
191-200.
16. Hajkó, J.; Bo bás, A.; Szabo ik, G.; Kaj á -Pe edy, M.; Lip ák, A. J. Ca bohyd .
Chem. 1997, 16, 1123-1144.
17. Rigaudy J, Ta dieu P. Comp . end. 1956, 242, 2730-2733.
18. Al oma e, A.; Casca ano, G.; Giaco azzo, C.; Guaglia di, A. J. Appl. C ys . 1993, 26,
343-350.
19. Sheld ick, G. M. Ac a C ys . 2008, A64, 112-122.
20. Fa ugia, L. J. J. Appl. C ys . 1999, 32, 837-838.
21. Case, D. A.; Da den, T. A.; Chea ham III, T. E.; Simme ling, C. L.; Wang, J.; Duke,
R. E.; Luo, R.; C owley, M.; Walke , R. C.; Zhang, W.; Me z, K. M.; Wang, B.;
Hayik, S.; Roi be g, A.; Seab a, G.; Koloss á y, I.; Wong, K. F.; Paesani, F.; Vanicek,
J.; Wu, X.; B ozell, S. R.; S einb eche , T.; Gohlke, H.; Yang, L.; Tan, C.; Mongan, J.;
Ho nak, V.; Cui, G.; Ma hews, D. H.; See in, M. G.; Sagui, C.; Babin, V.; Kollman,
P.A. AMBER 10, Uni e si y o Cali o nia, San F ancisco, 2008.
22. Gaussian 03, Re ision C.02, F isch, M. J.; T ucks, G. W.; Schlegel, H. B.; Scuse ia,
G. E.; Robb, M. A.; Cheeseman, J. R.; Mon gome y, J ., J. A.; V e en, T.; Kudin, K.
N.; Bu an , J. C.; Millam, J. M.; Iyenga , S. S.; Tomasi, J.; Ba one, V.; Mennucci, B.;
Cossi, M.; Scalmani, G.; Rega, N.; Pe e sson, G. A.; Naka suji, H.; Hada, M.; Eha a,
M.; Toyo a, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Ki ao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; H a chian, H. P.; C oss, J. B.; Bakken,
V.; Adamo, C.; Ja amillo, J.; Gompe s, R.; S a mann, R. E.; Yazye , O.; Aus in, A.
J.; Cammi, R.; Pomelli, C.; Och e ski, J. W.; Ayala, P. Y.; Mo okuma, K.; Vo h, G.
ACCEPTED MANUSCRIPT
33
A.; Sal ado , P.; Dannenbe g, J. J.; Zak zewski, V. G.; Dapp ich, S.; Daniels, A. D.;
S ain, M. C.; Fa kas, O.; Malick, D. K.; Rabuck, A. D.; Ragha acha i, K.; Fo esman,
J. B.; O iz, J. V.; Cui, Q.; Baboul, A. G.; Cli o d, S.; Cioslowski, J.; S e ano , B. B.;
Liu, G.; Liashenko, A.; Pisko z, P.; Koma omi, I.; Ma in, R. L.; Fox, D. J.; Kei h, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakka a, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian, Inc.,
Walling o d CT, 2004.
23. (a) Flükige P.; Lü hi H. P.; Po mann S.; Webe e J. MOLEKEL 5.2 Swiss Cen e o
Scien i ic Compu ing, Manno (Swi ze land) 2000-2002; (b) Po mann S.; Lü hi H. P.
Chimia 2000, 54, 766-770.
24. Humph ey, W.; Dalke, A.; Schul en, K. J. Molec. G aphics 1996, 14, 33-38.
25. Clode, D. M.; Ho on, D.; Wecke le, W. Ca bohyd . Res. 1976, 49, 305-314.