b7synthesis and activity test deoxyribose degradation inhibitor two asymmetric dibenzalacetones pros

(1)

ri

XIX

INTERI{ATIONAL

CHEMISTRY

SEMINAR

Pal

$il

Yoryakart&,

eo May

zoog

Jointll'held

br':

Department

of

Chemistry

Facultl'

of N{athernatics and

Natural

Sciences

LTnir-ersitas

Gadj

air

X'i

ada

and

Indonesian Chemical

Sociefy"

Branch

of

Yog'akarta

Special Region

/)ri;

,{

(2)

lnlmnrtloarltiamlstrytsnhffPm8esdtuo

ISSN NO- 1410-8313

i aq,r *;-ir: 1,:: Ellr ).t.'tty;

CONTENT

covEB

i

EIXTOB

i'

REMARKFROMTHE ORGANIZING COIi}'ITTEE

...

iii

REMARK OF HEAD OF GHEMISTRY

DEPARTMENT

V

BEMABK FROM DEAN OF FACULTy AF MATHEMAnCSATUD

NATUBAL

vi

SGIENCES

REIilARK

FM

THE

BB

TON OF UHIVERSilTAS GA[L'A}I

T'4D4..,...

Vii CONTENT

PAPER

GRUOP

ORGANIC CHEiIISTRT GEOUP

1.

ZnBrd?€lumina

ad

HW-alumina : an lmprp!rcd cdalyst for the highly

selecfive syntheeis ol menthols starting lrom (+)rcitonellal in two-step

process

1

Elvina D. lftitah, M. Muchalal, WegaTrisunaryanti, Ria Armunanto

Z

Erlrymatlc lletilanolysls of Palm OII Uslng Rlce Bran as Llpase

Source...

6

Ptdfi ltastuti,

R*w

ldati,

Tqwin Yuliyanto

3.

ilw

tiothod tor the

S$hesis

ol

llexahydropyidazine.

11

Rrtmabni, Varinder K. Aggarwal

4.

Synthesi s 3, 4-Di methoxybenzyl -2,4-Di h ydroxyphenyl Ketone From

Eugenol

Sabiin

MabW,

Attdt Haifil

Alimt#in, Mdasir,

Eti Narwenirg Sholikhah

5,

Phospholipid

r{cs

prent

at pumpkin

sed

kernels oil (&rcurbita

moschata (Duch)

Poir)...

18

Laily Nurliana, TriJoRo Raharjo, Sabirin Mastjeh

6,

The use of lignin

trun

pulp blacle liquor with palm

emfi

bunch

malsiats in the

prooss

oI slow

rebas

urm

tabbt

fertilizer

24

Lucy Arianie,

Ahrd

Mulyadi, Atghani Jayuska

7.

Santhesis and Gharacterization of Nonionic $rrtactant of Alkanolamide

Derivatives from Castor Oil (Ricinus

communis)...

30

M. ldham. D. M, Musih Anwar, Aditia Diyah, Teguh Apiyanto, Miftah faried

and Tutik Dwi Wahyuningsih

8.

Synthesis and Activity Test as lleoryrlbose

@rdation

lnhibltor of Two

AsymrHric

Dibsaletones...

.

35

Sd llandayani, Sabirin Matsieh, Chahil Anwar, Sri Atun

(3)

SYNTHESIS AND ACTIVITY TEST AS DEOXYRIBOSE DEGRADATION INHIBITOR OF TWO ASYMMETRIC DIBENZALACETONES

Sri Handayani''., sabirin Matsjeh2, Chairil Anwaf ,

SriAtun'

lDepartment of Chemical Education, Faculty of Mathematics and Natural Sciences, State University of Yogyakarta, Karangmalang, Depok, Yogyakarta 55281, lndonesia

2Chemistry Departement, Faculty of Mathematic and Natural Science

Gadjah Mada University, Bulaksumur, Yogyakarta, lndonesia " Co*veffimtdfrlTrg ffiaffiw,r,, Mt:rihx:

Wi!ffi&?ffi2"

e,rnaff:

ABSTRACT

Synfhesis and activity fesf as deoxyribose degradation inhibitor of tuvo asymmetric

dibenzalacetones

have

been

conducted.

The

first

compound,

1(E),4(E)-1-(4'-methoxyphenyl)-5-phenyl-1,4-pentadiene-3-one

was

synthesized

fram

benzaldehyde,

acetone and 4-methoxybenzatdehyde. The second, 1{E),4(E)-1-(3',4'-dimethoxyphenyl)-5-phenyl-1,4-pentadiene-3-one

was from

benzaldehyde,

acetone

and

3,4-dimethoxybenzaldehyde.

Those

compounds

were

synthesized

by

crossed

aldol

condensation

in

base condition

with

water-ethanol solvent.

The

synthesize

of

both

compounds using ice bath throughout the stirring. The precipita.te was purified by coloumn

chromatography. Each product was characteized

by

FTIR, _{'H'NMR, "C-NMR,}HMQC

and

HMBC. Activity

tesf

as

deoxyribose degradation inhibitor showed lCso

of

both compounds are 1,7pM and 1,02 yM respectively.

Keyword s : a sy m m etri c d i b e n z al a ceton e, d e oxy ribose degrad ati o n i n h i bitor

INTRODUCTION

followed by

reaction cynnamaldehyde [3].

Aldol

Condensation

has

been

Handayani

and Arty

have

occurred

by

a

nucleophilic addition

of

synthesized

1(E),4{E)-1-5diphenyl-1,4-enolate ion to a carbonyl group.

Acetone

pentadiene-3-one and its derivatives were

also

undergoes aldol condensation,

but

known

as

symmetrical dibenzalacetone

the

equilibrium

concentration

of the

that

have been made

by

crossed aldol

product was generally small. Cross

aldol

condensation

between

acetone:ben-condensation between

pannisaldehyde

zaldehyde (1:2). lt also tested as a radical

from

fennel

oil

with

acetophenone

hydroryl scavenger

t4l.

Asymmetric

produced

2{rydrory4angftoryc*ralcone

crossed

aldol

mndensation

have

been

compound

[1]. The

influence

of

base

done with various eatalyst _{[5,6,7]. Tutik}D

concentration

and

reaction

time on

the has

synthesized

of

symmetrical

cross

aldol

condensation reaction

has

dibenzalacetone

which have

similar

also been

reported t21. AJnustone

or

skucture with the cinnamic acid derivative

4(E),6{E)-1,7diphenyl-4,6*reptadiene-}

I8l.

Fronr

its

structure,

it

could

be

one

is

an

asymmetric mmpound

*tat

estimated

t'rat

benzalacetone

and

isolated

ftom

Curcuma

xanthonhiza

dibenzalacetone,

which

have

similar (Zingiberaceae).

This

compound

was

structure

with

cinnamic

acid

or

its

synthesized

by

Goksu,

et

al.

using

derivative, have ultraviolet absorption in

crossed

aldol

condensation

between

the

same

range.

Thus,

asymmetric

benzaldehyde

and

acetone, wtrich

then

dibenzalaretane

was

esfimated

as

a

radical scavenger and also a sun screen. with

Htndayani et al. 35

lntornational 8[smistrl Ssminrr Pr0000tiliu

Ibgruftirra 26 i'.{er' ilN&

(4)

htffnatioml 8[smi$try Sonimr Prooooding "lilg.:d;:ttr:ta }ll'i'li*t I{tf}*

ln

this

research

two

of

asymmetric

dibenzalacetones, compounds

5

and

6

namely 1(E),4(E)-1

-(4'-methoxyphenyt)-5-phenyl-1,4-penladiene-3-one

and

1 _{E},4(E}-1-{3',4'dimethoxyphenyt}-5.

phenyl-l,4.pentadiene.3-one

will

_be

synthesized.

EXPERIMENTAL SECTION

Materials

All

materids used frnm.

Merck

afi?eftg

d4rffi

ffi{fiH,

.S-rnethor#mis#dd1@,

3.4-dimethoxybenzaldehyde,

chloroform

ethanol, benzaldehyde, hexane, and ethyl

acetate. TLC was carried out using

0.25-mm plate

Silica

gel

Merck

6A

F254,

column chrornatography were perfonned

by Silica _{get60 {230400}mesh)"

lnstrumentation

The]H, ,.C.NMR, HMQC and HMBC

Spectra were recorded

on

500 MHz Jeol

spectrophotometer.

lR

spectra

were

conducted using

a

Shimadzu 8300 FTIR spectrometer.

Procedure

Synthesis of compounds 5.

lnto a solution

of

_{NaOH @.A25 mol,}

19)

in

aqueous ethanol

{1:1)

trat

was

prepared

at

ambient

temperature,

1

benzaldehyde (0.01 mot, 1,06 g),2 acetone

(0,01

mol,

0,58

g) and 3

4-methoxybenzaldehyde (0,01 mol, 1,66 g)

were added drop wise altemately. Afier

additional stining for 60 minutes, water (20

ml) was

added

to

tfre

reaction mixture which then filtered. The extract was washed

with water (20 ml

x

3)

and separated by

column chromatography

(d

2.5 cm,

h

S0

cm), with silica gel 60 (230400 mesh) as

the

stationary phase

and

ethytaetate-hexane

1

:

I

as

the

eluent. The target

compound

(5) was

identified using thin

layer

chromatography

with

ethylacetate-hexane 5:1 as the mobile phase.

Synthesis of compound 5.

The similar procedure _wasrepeated

for 3,4-dimethorybenzaldehyde to replace

4-methoxybenzaldehyde

in

order

to synthesize compound

6

(Figure '1). Four

fractions

obtained

from

the

column

chromatography,

and the

target

compound was identi:lied using thin layer chromatography

with

chloroform-hexane

4:6.

Deoxyribose assay.

The assay was performed follow the method as described hy Ftaltiwetl

[9]

Att

soluticns

,uws

fre*d,V

exwrcC.

lroto

*

solutlo* CIf S.? ilr$

6

rffi#

Zdeoxyribose was added 0.2 ml ascorbic acid 0.01 mM;

0.2 ml buffer phosphate (pH

7.4);0.2

mt

0.01

mM

HzOz,

0.02

ml

of

various

concentration sample _{{0,24; 0,48;}0,95; '1,89; _3,78_plM)_and_0.2_{ml ferrosulphate}

0"1 mM. After an incubation period of 30

minutes

at

3100K,

the

extent

of deoxyribose degradation

was

measured by the TBA reaction. 3 ml of TBA and 3 ml

of

TCA were

added

to

the

reaction

mixture

and

heated

for

15

minutes at

3530K. After the mixture being cooied, it is

read

at

absorbance

532 nm

against a

blank (the

same

solution

but

without sample).

The

percentage inhibition was calculated by the formula:

4..

_A

I ('/o) ₌"hlauh ":utPtL .f l 00%

4,,t.,n,.

The

lCsr value

represented the

concentration

of

the

compounds that

caused 50% inhibition. BHT was used as

a posrtive control.

RESULTS AND DISCUSSION

lmproved Synthesis of Compound 5

Separation

of the

product

of

crossed

aldol

condensation between

benzaldehyde,

acetone

and

4-methoxybenzaldehyde

was

done

by

coloumn chromatography.

The

product

from coloumn chromatography separation

yielded 3 fractions, which were identified

by TLC with hexane-ethylacetate S:1 as

the eluent. Retardation factor datas from

TLC scanner showed that fraction

ll

was

the

target

of

compound

5

(10,6%)

determined as yellow residue. Fraction I

(5)

hlff!r$$$

c.lrEfi$ry 8!Emr

lrellllbg

fuw,&,ww.3{)3fu1 .M6B

and

fracton

tl

supposed

to

be benzala*et*ne and diamisaia**tcne a$ the

side

produoi$

of

sr&$sed

aldal condensation

reaction-Chame,terization of comp*und

5

hy F?tR {KBri resultad peaks qn _{3S35; 2823;}

2ffr2: 1888

1423:1445:

and

1775

srt1.

A series cf *vre and &va dirnensio*al f*fifrfi

spectro*c*si*

experlr**r* using

I-{MGC

and

Hetersnl,clear

Multiti$e

Bond

Coherence

{HMBC} pattems

wsre

perfonned

to

a*sign

the

praton

and

carbon res*nafice

welation

cf

the

mmpounds.

The

signal pattem

sf

the

arornatic

*ng

showed

th*

in{lu+nce

*f

rnetlrcxy _{#&Ae}

in S

3,8 {3}t, s}

ppnt (Figure 1;'f

able'll-6

Fig,

I

Scfier*e sf cross aldd condensation fo

synthesieed of compound 5 and S.

Table 1. IH, 13C-NMR and ttMBC dates of

oompourd 5 {CDQs}

psr_

_

(5HlMHz)

I

7,7A {tH;

<t} 143

C6", C2,C3

2

6,97 {1H;

d} tf,,3,4

Ci}, CZ

3-188

I

7,aT

(tH;dl 125,7

C3, Cl"

5

7;t1(1H;

d)

143,3

C3

",6'

3'n5o

7.58 S,93

{fi;

{2H;

d}

d)

t1{,6

tP

C{, G3', Ol[' 04'

4'-OMe

3,8; (3H,

s)

56

(}t"

4',

-

162

X

7,61 (1H;

d)

1m,3

C5, C6"

3",5'

7,'l {2H;

d)

r?7,8

04', C2'

q'

7,a, _tlH;

d)

128.5

C1".

Cr

t tr*r1rr1ru, ,&u1* ur.v

6"

7,62

(2H;C) j3!,5

C5,

Cf

frrBrored,$ymf&esis

*f **mpourd

S.

The preparaiion of compouno B was

initiated by the mixing af

1.2

and 4 to giqe

rsstY$o. r4t&83r3

S {Figure 1}. The yiel$

of

crossed atdol

*onde*sation

betw*en acctsne,

3,4-dimetlrexybenzaldehyde

and

benzaldehyde tuas a mixture cqnsist of 4 eompounds.

There

uras

$eparated by

G*lurnn Chr*rnat*graphy {Ac$ft-hexane,

t:9| to

provide

ihe

asymmetric

diknEalacetoile

t

i15,53Dlo) determined

as pale yaltcw oil.

The

rnu{tip{e

bcnd wnelation

sf

HMBC supported the structure (Figure 1;

Table

?). ln the

IH-NMR spectrum (500

&{Hz,

C*Slrl,

M

pattem$.einglet, nine

d*ublet and three

double dublet were sbserurd. The double dublet

at

D

=

7,2;

?,S1;*r'ld 7,41 was assign€hle to H2", H3"

and H5"

respectively.

Two

equivalenee

methcry signals

at

6 3,gl

and 3,9 were asslgncd to C3' and

e4'.

$uppoil spectra

data

prcvided

by the

tR

{KBr}, which indicaies the existence of C=O

{1645cm-1),

aromatic C=C (1514-1417 cm-l) and

CO

etir*r

{1255-113$

rm-l}.

Therefore, the structurc

of

G was

1{E},4{EF1-(3',4'-d im*thcxyphenyl)-5-phenyl-

1,4-pe*t*di*ne-3-on*.

Tabl* 2. tH, _{'*c-h,MR and IIMBC}datas of

compound 6.lCQS'e)

_ ,

--

-C

no.

6l-t _{IH;mi

pgm

SC

pPm

HMBC

,\

$["\

.\-'o.t"r

-A)

J.

2

6,94 {1H;

d}

124

c3

3-180

1

vio $H:

dl

1?5,8

c&

cf

5

7,?4

flH;d) 143

Cg

t

?,6{1}l;d} 110

C3

3'

"

161

3'{Irie

&9 {3tl;

s)

S

C4'

4',-15a

#-gt{e &91(3H;s} 56

C3'

S'

t,83 {1H;

d}

111

O4', C8', Cl'

6'

S,89 {1H;

d)

120

C1', C5', C4'

r

7,6111H;#l

1*

c5

f

?3 (1H;

tldl

1zl.it

G1'.

et'

'*'

7,14 {1H;

d}

1'10

C3"

5"

7,33{11{;

d)

tz$

C1'

Seoxyribosa assay

A*W&

t*sl eS

d*oxyribcs*

degraclauon innrottor^was oon6, by fentot,

reactir:n

i9l

The

iClr

vatue fepresente#

tfr* c*nffintrctisn nf the csmpounds. that

cgrsed

5*%

inhibfir"on.

-+il

ex$rir{rent

I

$rere canied

out

6in

triplicate{.

Ilanilalani

ef aI. 3?

o"

o

[image:5.596.58.522.55.831.2]

(6)

Determination of lCso values were

showed

9. Halliwell,

B.,Gutteridge,

M.C.,

and

in Table

3.

Auroma, O.1., 1987, Analytical Bioch',

165,215-219.

CONCLUSION

ln

conclusion,

two

asymmetric

dibenzalacetones

exhibited

significant

deoxyribose degradation inhibitor activity.

The |CSO of mmpund 5 and 6 are 1,7 and

1,02

pM

respectively. Compound

6

is more potent than 5 to inhibit deoxyribose degradation.

REFERENCES

1.

Handayani,

S.,

Sintesis

4'-metoksiflavanon Menggunakan

G'

hidroksiasetofenon dan p-anisaldehida

dari

minyak

Adas,

Master's Thesis,

Gadjah Mada University, 2000.

2.

Handayani,

S.,

Sunarto

and Kristianingrufi], S., lndonesian Joumal of Chemissy, 5, No.2 (2005), pp 88-93"

3.

Goksu,

S.,

Celik, H- and Secen, H-,

Turk. J. Chem.27 (2003), pp 31-34.

4.

Handayani,

S.

and

Arty,

1.S., 2008,

Joumal of Physical Science,

19{2),61-68.

5. Yamano, Y., Fujitia, Y., Mizugucfti, Y.,

Nakagawa, K-, Okano, T., lto, M. And

Wada, A., Chem. Pharm. Bull., 55(9) (2A07), pp 1365-1370.

6.

Mlynarski, J., 2006, European Journal

of Organic Chemistry, 21,47794786.

7.

M.Manuel

B.

Marques, Asymmetric

Cross-Aldol Reaction of Aldehides : A

Formidable

Synthetic

Chalengge,

Requimte-FGT-New

University

of

Lisbon (2005).

8. Tutik, D., Oksidasi Anetol dan Kajian

Pengaruh

Gugus

Metoksi

Turunan

benzaldehide

Terhadap

Reaksi

Kondensasi Benzoin dan Aldol Silang,

Master Thesis, Gadiah

Mada

University, 1996.

1,7 1,02