Nghien
CLFU- Ky thuat
- Tinh d i u qud ed tac dung khang n i m tdt tren 7 chting n i m vdi MID ttr 8-120 mg/L khdng khi.
- Tinh d i u bac ha chtra menthol mang nhdm chir'c alcohol cd tac dung khang n i m kha manh sau nhdm chu'C aldehyd.
- Hoat tinh khang n i m ctia tinh d i u la do ti le % hoat chit chinh. Ngoai ra cdn do bdi cac thanh phin khac cd trong tinh d i u nhu tar-dng hgp ctia TD tram gid va TD khuynh diep, hay do bdi dp bay hoi, tinh bdn vung ctia e i u tnJc hoat chit chinh...
nhu trong trudng hgp eua tinh d i u sa Java.
Nhan xet bieu dd 1:
So sanh kdt qua khdng n i m etia 5 tinh d i u tren 7 chting n i m . tinh d i u qud cho tac dung khang n i m manh nhit tren nhidu chung n i m , trir A. fumigatus vi A. niger.
K§t luan
Tinh d i u ed hoat tinh khang n i m tdt dwgc dwa vao nghien ciru tao chd p h i m sau nay nhu TD qud, TD sa chanh. TD mang tang, TD bach dan chanh. TD bae ha. Tuy nhien dd tang hoat tinh khang n i m . giam thd tieh tinh d i u thtr nghiem va giam thieu nhugc didm etia tinh d i u e i n su phdi hgp cdc tinh d i u ,
* o d tai thuc hien tai B6 m6n Vi Ky Sinh - Khoa Dugc - DHYD - Tp. Hd Chi Minh, thdi gian 04/2009-9/2010.
Summary
Nowadays, indoor air environments are rather polluted, diseases caused by moulds are increasing, especially on the acquired immune deficiency patients. To kill pathogenic moulds, essential oils are favourable for their natural origin and less harmfulness than chemicals. In
this research, antifungal activities of volatile constituents of some essential oils on 7 fungal species were assayed by vapor contact method for household mould-killing fumigant sprays. Of the ten essential oils containing aldehyde constituents tested, four were the most effectively inhlbitive to moulds ncluding those of Cinnamomum. Symbopogon nardus. Litsea cubeba. Eucalyptus citriodora. Cinnamon oils showed the highest activity against 7 fungal species with - MID 8 to 120mg/L air The antifungal activities of essential oils mainly depended on their major components, but also on the other ones.
Tai lieu tham khao
1. B 5 Huy Bich, Cay thuoc va dong vat lam thuoc d Viet Nam tap II, NXB Khoa hoc va Ky thuat. Ha Noi.
(2004). 65. 118,
2. Kazuhiko Nakahara, Chemical composition and antifungal activity of essential oil from Cymbopogon nardus, JARQ. Japan. (2003), 37(4), 249-252,
3. K.Nakahara. N.SAIzoreky, Growth-inhibitory activity against maize weevil and the antifungal activities of volatile compounds from citronella grass, JARQ {Japan Intemational research center for Argicultural Sciences). (2004), 14.
4. Patrick R.Murray, Manual of clinical microbiology, 8th edition, ASIVI press. Washington DC. (2005). 1887,
5. Robert E. Greene, Indoor air quality investigation protocols. Journal of environmental health. (1996), 59.
6. Shigehaai Inouye, Antibacterial activity of essential oil and their major constituents against respiratory tract pathogens by gaseous contact. Journal ofAntimcrobial Chemotherapy. (2001), 47(5). 565-573,
•7
Nghien cuu tong hop genistein
Hua Kim Dung, Tran Thanh Dao, Huynh Thj Ngoc Phirong Bg mdn Hda Dtrgc - Khoa Dugc. Dgi hgc Y Dugc Tp. Hd Chi Minh
Dat van de
Loang xuang la mpt benh t h i m lang dang trd thanh v i n di sire khde toan c i u va la ganh nang tren ngan saeh y td d mdi qudc gia. Ty le loang xuang lien quan ddn tudi. dac biet d phu
nir- trong dp tudi tren 50, day la thdi ky man kinh. loang xuang x i y ra r i t nhanh do thidu estrogen. Hien nay, dd didu tri loang xuang cho ddi tugng nay. lieu phap thay thd hormon (HRT) dang dugc ap dung rpng rai. Tuy nhien phuang
38 TAP CHI DUQC H Q C - 2 / 2 0 1 1 (SO 418 N.A.M 51)
Nghien CLFU - Ky thuat
phap HRT eung cd nhieu nguy ea nhit dinh nhu nguy ea tang san npi mac ttr cung, nguy ca ung thu vii'^',
Nhirng hpp chat isoflavon ndi chung va genistein ndi rieng de ddng duge tim thiy trong cac cay hp Dau, dac biet trong dau nanh, dang dugc sir dung ngay cang nhidu n h i m ngan chan su mat xuang va cai thien cac trieu chir'ng sau man kinh ma khdng e6 tae dung,ngoai y nhu HRT '^'. N h i m gdp phin vao viee tdng hgp ngudn nguyen lieu hoa duge trong nude, giam gia thanh san phim ddi vdi nhirng chd p h i m didu tri loang xuang d phu nir, ehiing tdi tien hanh nghien ciru tdng hgp isoflavon genistein bing phuang phap dong v6ng va tai s i p xdp ehalcon''^"®'.
D6i tu'O'ng va phu'O'ng phap nghien
CU'U
Nguyen lieu chinh: 2,4,6-trihydroxyaceto phenon; dimethyl sulfat; 4-methoxybenzaldehyd;
thallium (111) nitrat va boron tribromid loai dimg eho tdng hgp ctia Merck,
cae san p h i m mdi giai doan tdng hgp dugc tinh chd bing phuang phap kdt tinh trong dung mdi methanol hoae hdn hgp methanol- dicloromethan, Didm ehay duge do tren may Gallenkamp vdi nhiet kd khdng hieu chinh, Phd
H,CO,
hdng ngoai (IR) do tren may IR FTIR 8101 Shimadzu, Phd NMR do tren may Brucker 500 MHz, Phd khdi (MS) dwgc ghi b i n g may Mieromass-Quartro micro API.
Phu'O'ng phap nghien CLFU: Qua trinh tdng hgp theo 4 giai doan nhu mo ta trong sa dd 1.
Qua trinh tdng hgp duge tidn hanh bing each khao sat tim cac th6ng sd tdi uu eho hieu s u i t va chit lugng san p h i m tdt nhit.
K§t qua va ban luan
Tdng ho'p 2-hydroxy-4,6-dimethoxyaceto phenon (2)
Hoa tan 2,4,6-trihydroxyacetophenon (THAP) trong mdt lugng tdi thidu aceton khan trong binh e i u day tron g i n vdi he thdng sinh han va dugc each i m vdi mdi trudng ben ngoai. Them K2CO3, khuiy ddu. Them tir tir dung dieh dimethyl sulfat (DMS) vao hdn hgp phan irng, khuiy ddu. Dun nhe hdn hgp. Theo ddi phan irng bing s i e ky Idp mdng ddn khi phan irng kdt thiic, San p h i m kdt tinh trong methanol.
Hieu suit trung binh 80%. Diem chay 82°C (theo tai lieu 80-84 °C). Phd khdi [M + H f = 197 (ly thuydt = 197,08 tuang irng vdi C10H13O4).
Phd IR (em'\ KBr): 3085,9 (v C-H, C-H tham);
2848,7 va 2594,1 (v 0 - H ; 0 - H phenol); 1623,0 (v C=0, ceton); 1157,2 (v C - 0 , ether).
HXO OCH,
OCH3O
H3CO
OCH, OCH3O
4 5 S c dd 1: Tdng hgp genistein tu 2,4,6-tnhydroxyacetophenon: 1) Me2S04, K2CO3, aceton. il) p-
methoxy-benzaldehyd, KOH, methanol, iii) thalium (III) nitrat. HCI. iv) BBrs, CHCI3.
San pham thu dugc trong mdi giai doan Bar\g 1: Diiu kien tdi uu cho phin u'ng tdng dugc kidm nghiem: diem chay, SKLM, IR, NMR, hgp 2-hydroxy-4,6-dimethoxyacetophenon MS
Kdt qua khao sat cac ydu td anh hudng ddn hieu suit phan irng da dua ddn eae didu kien phan ii'ng thich hgp ghi trong bang 1.
Cac yeu to anh hwang Nhiet dp phan ung (°C) Tl le moi THAP : DMS : K2CO3
Thdi gian phan irng (gid)
Dieu kien thich hap 40 - 45 °C
1 ; 2 , 5 : 3 3 gid
TAP CHi DUQC H Q C - 2 / 2 0 1 1 (SO 418 NAM 51) 39
Nghien
CLFU- Ky thuat
Tdng hcrp d i n xuat chalcon (3)
Hoa tan 2-hydroxy-4.6-dimethoxyacetophenon (2) vdi mdt lugng tdi thidu MeOH trong binh ndn. Them 4-methoxybenzaldehyd vao hdn hgp phan irng. Dat toan bp binh phan irng len bdp khuiy tir'. Sau d6 cho tir tir' KOH nghidn min vao hdn hgp tren. Theo d6i phan ir-ng bing s i c ky Idp mdng den khi phan u'ng ket thiie, Tinh ehe san phim trong methanol, Hieu suit trung binh 82% Oiem chay: 113 °C (tai lieu 112-116°C), Phd IR (cm"' KBr): 2600 (v O-H, O-H phenol (lien kdt hydro ndi phan ttr); 1622.0 (v C=0, ceton); 1157,2 (V C-0, ether). Phd khdi: [M + H f = 315,01 (ly thuydt = 315,13 tuang irng vdi CisHigOs).
Kdt qua khao sat cic ydu td anh hudng ddn hieu suit phan ir-ng da dua ddn eae didu kien phan ir-ng thich hgp ghi trong bang 2.
Bang 2: Cac diiu kien thich hgp cho phan irng tdng hgp chalcon
Cac yeu to anh hwang Nhiet do phan ung (°C)
Ti le moi (2) : p-methoxybenzaldehyd : KOH
Thai gian phan ung (ngay) Moi truong
Dieu kien thich hap 45 - 50 °C
1 : 1 : 3 4 ngay Khi tro Tong hgp 4',5,7-Trimethoxyisoflavon (4) Hoa tan d i n xuit chalcon (3) vdi mpt lugng tdi thidu MeOH trong binh n6n. Them T1(N03)3.3H20 vao hdn hgp phan ir-ng. Khuiy ddu hdn hgp d nhiet dd phdng va theo ddi phan trng bing SKLM ddn khi khdng edn thiy vdt nguyen lieu chalcon tren ban mdng. Them dung dieh HCI 2M. Khuiy deu hdn hgp d 50 °C trong khoang 5 gid, Theo ddi phan ir-ng bing s i c ky Idp mdng ddn khi phan ir-ng kdt thiic. Tinh ehe san phim trong methanol, Hieu suit trung binh 80%. Oiem chay: 224 °C (tai lieu 225,5 °C). Phd IR (cm"' KBr): 1151.4 (v C-O, ether); 1689,5 (v C=0. ceton), Phd khdi: [M + Na]" = 334,9 (ly thuyet = 335,09 tuang ir-ng vdi CgHisOsNa),
Kdt qua khao sat cac ydu td anh hudng ddn hieu suit phan trng da dua ddn cae didu kien thich hgp ghi trong bang 3.
Bang 3: Diiu kien thich hgp cho phan irng tdng hgp 4'.5.7-tnmethoxyflavon
Cac yeu to anh hwang Dieu kien thich hqp Nhiet do phan ung ("C) 50 - 55°C
Ti le moi chalcon (3) : 1 : 2 : 2 TI(N03)3 : HCI 2M
Thoi gian phan ung 6 gid
Tong hcrp genistein (5)
Hoa tan 4',5,7-trimethoxyisoflavon (4) trong lugng tdi thidu CH2CI2 khan trong binh e i u gin vdi he thdng sinh han va duge each i m vdi mdi trudng ben ngoai.(iam lanh hdn hgp ddn nhiet d6 - 5 °C bing hdn hgp nude da vi mudi hot), Hoa tan BBrs trong CH2CI2 khan dd dupe dung dieh I M , (iam lanh hdn hgp ddn - 5 °C bing hdn hgp nudc da va mudi hat). Them tir- tir- dung dich BBrs I M vao hdn hgp phan ung, Khuiy ddu hdn hgp d nhiet d6 - 5 °C trong 24 gid. Sau dd, khuiy hdn hgp d nhiet dp phdng va theo ddi phan irng b i n g s i e ky ldp mdng den khi phan trng kdt thiie. San pham kdt tinh trong hdn hgp ddng lugng methanol-dicloromethan,
Hieu suit thu duge khdng khae nhau giira cac didu kien (ti le moi) phan ir-ng demethyl hda Do vay nen ehpn tT le moi giir-a isoflavon va BBr3 la 1:3 cho phan ir-ng didu chd genistein, (xem bang 4),
Pho cgng hw&ng tir hat nhan NMR cua genistein tong hgp
' H - N M R (500 MHz, DMSO) : 5 12,9 (s. 1H, OH), 10.8 (s. I H , OH), 9,5 (s, I H , OH), 8.3 (s, I H , H-2), 7,3 (d, J=8.5. 2H. H-2' va H-6'), 6,8 (d.
J=8,5, 2H. H-3' va H-5"), 6.4 (d, J=2, IH, H-8).
6.2 (d, J=2, I H , H-6).
Bang 4: Kdt qua khao sat ti le moi giira isoflavon (4) va dung dieh BBr3/CH2Cl2 I M
Ti le moi Isoflavon : BBri Hieu suat san pham
tho (%)
1 :3
40,5 %
1 :10 42,1 %
1:15
42,5 % Kiem nghiem genistein (5)
Genistein didu chd duge dugc kiem nghiem so sanh vdi m i u genistein nhap ngoai (do Xi nghiep Imexpharm eung c i p ) . kdt qua eho thiy mau nguyen lieu tdng hgp ed the so sanh dupc vdi m i u nguyen lieu ngoai nhap (xem bang 5).
KSt luan
Qua qua trinh thue hien dd tai. ehung tdi da thu dugc mpt sd kdt qua nhu sau:
- Sa b6 xay dung duge quy trinh tdng hgp genistein thich hgp tir- nguyen lieu d i u la 2.4.6- tnhydroxyacetophenon qua bdn giai doan phan ir-ng.
- Khao sat eae ydu td anh hudng den phan ir-ng va tim dugc nhirng dieu kien thich hgp n h i t cua giai doan 1 va 2 de ed duac m6t qui trinh dn dinh va hieu s u i t cao.
40 TAP CHi DUQC HQC - 2/2011 (SQ 418 .N.AM 51)
N g h i e n CLFU - Ky t h u a t
Bang 5: So sinh mdt sd chi tieu kiim nghiem glCra genistein tdng hgp va miu ddi chiiu Chi tieu so sanh
Tinh chat
Diem chay SSc ki ldp mong
He dung moi:
n-hexan:aceton (3:1).
Pho IR (cm'') v C = C v C = 0 v O - H
Quang pho khoi do phan giai thap MSLR
Mau tong hqp bot trSng nga, khong tan
trong nuoc, tan it trong dicloromethan, cloroform va aceton, tan d i trong DMSO
297-298 °C
Rf = 0 , 4
1616,2 1652,9 3411,8 [M + H]* = 271,04
Mau doi chieu bot mau trang, khong tan
trong nudc, tan it trong dicloromethan, cloroform va
aceton, tan de trong DMSO 298 °C
R f = 0 , 4
1616,2 1652,9 3411,8 [M + H]" = 271,04
Nhan xet
Tuong duong
Tuong duong
Tuong duong
Tuong duong
Tuong duong
Lai cam a n
cae tae gia cam an Dai hpc Y Duge thanh phd H6 Chi Minh da tai trg kinh phi nghien etru va giiip eho sir dung eae thiet bi xac dinh e i u true.
Summary
Osteoporosis Is a silent disease which becomes an important matter of health and consumes a lot of money of health budget in every country. General isoftavones. genisteine in particular, which is found easily in Leguminoides.
is used more and more popular to prevent osteoporosis and to improve post-menopause symptoms. In order to contribute to domestic studies of raw material production, the study of synthesis of genisteine by cyclisation and oxidative rearrangement ofchalcone was done.
Synthesize 2-hydroxy-4,6-dimethoxyaceto phenone from 2,4,6-thhydroxyacetophenone and dimethyl sulfate. Synthesize corresponding chalcone by Claisen-Schmldt condensation from 2'-hydroxy-4.6-dimethoxyacetophenone and 4-
methoxylbenzaldehyde. Oxidative reamangement of chalcone with TI(N03)3 as a catalyst formed the corresponding isoflavone. Demethylatlon of the isoflavone provided genisteine.
Keywords: Osteoporosis, genisteine.
Tai lieu tham khao
1. CMP (United Business Media). Progynova. In:
Vidal 2006 Viet Nam. Wong Mei Chan. 434-435.
2. Helen Wiseman, Isoflavonoids and Human Health. In; Flavonoids: Chemistry, Biochemistry and applications. 0yvind, M.; Andersen Kenneth, R. CRC Taylaot&Francis Group, New York, 2006, pp382-384.
3. J. Mark Weber; Andreas Constantinous; Paul E.
Messier. Progress of prepahng genistein, US patent 5554519, 1996.
4. Alexander Mckillop. Applications of thallium (III) nitrate (TTN) to organic synthesis. School of chemical sciences, university of East Anglia, Norwich, UK, 443-479.
5. Arthur E. Harms. Synthesis of isoflavone. US.
20090062555A1, 2009.
6. Bruno, B.; August, P. Manufacture of isoflavones. PCT. 2005. WO 2005/0256321 A l ,
M p t s o y k i e n . . . (Tiip theo trang 56)
Tai lieu tham khao
1, Quyet dinh so 35/2001/QB-TTg ciia Thii tuang Chinh phii ve viec phe duyet Chidn luoc cham soc va bao ve sii'c khoe nhan dan giai doan 2001-2010,
2. Bo Cong an: Kd hoach s6 76/KH-BCA ngay 12/8/2005 ciia Bo tru'ong Bo Cong an ve viec tri§n
khai Chinh sach quoc gia thuoc trong CAND den nam 2010, (2005).
3. Trudng Dai hoc Dup'c Ha Noi: Bo mon Duac lam sang - Duoc lam sang va dieu tri - NXB Y hoc - Ha Noi-2001.
4. Bo Y te: Tai lieu tap huin sir dung thuoc hgp ly trong di§u tri, (2005).
TAP CHi DUQC HQC-2/2011 (SO 418 NAM 51)
