1999-science-cianoglicosidos.pdf

7/22/2019 1999-science-cianoglicosidos.pdf

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N O N - C Y A N O G E N I C C Y A N O G L U C O S I D E SK a z u o Y a m a s a k iInstitute of Pha rmaceu tical Sciences Hiroshima University Schoo l o f Medicine Kasum i 1-2-3Minami-ku Hiroshima 734 JAPAN

Ke y W or d Indexm non-cyano senic ;cyanoglucoside;ni tr i le [ lucos ide; glycoside; s immondsin.AbstractmNatural ly occurring non-cyanogenic glucosides isolated and characterized fromvarious plant sources are reviewed. Their occurrences, characteristic features,structure elucidations, biogenesis, biological activities and promising applicationsare discussed.

I n t r o d u c t i o nM ost o f the cyan oglycosides in Nature are cyanogenic, since they hav e a ni tr ile groupalpha to the glycosidic l inkage. Hydrolysis of these cyanogenic glycosides by certainglycosidase or acid l iberates aldehyde or ketone and hydrogen cyanide throughthe corresponding cyanohydrin. The l iberated hydrogen cyanide is responsible for theirphy siological activities including toxicity.

S u g a r ~ O R2C ~ N

13-glucosidase H R1 ox yn itri las e R1O R2 ; O R2

~ C ~ NH C N

Ho wev er, there is a sm all group of cyanoglycosides possessing a ni t ri le g roup notadjacent to the glycosidic linkage, hence, are non-cyanogenic. In this review, severalexam ples o f these glyc oside s isolated from plants are introduced and their occurrences,structural features, plausible biogenesis, biological activities and promising applicationsare briefly d iscussed.O c c u r r e n c eNon-cyanogenic cyanoglucosides of plant origin are l isted in Table 1 and their st ructuresare shown in Figure 1. Although only a few com pounds of this typ e have been isolated so far,the taxonomical distribution is very wide, occurring in both classes of Angiospermae,the monoc otyledoneae Gram inae) [2 8 ] and the Dicotyledoneae in the subclassesSympetalae Boraginaceae [7, 1 8 ] ) and Archichlamydeae S immo ndsiaceae [1-3 ] ,Leguminosae [5,6, 16, 2 2 ] M eni spermaceae [8 , 1 3 ] , Aqui fo l iaceae [1 0 , 11] ,Euphorbiaceae [1 2] , Ranunculaceae[14, 21], Ochnaceae [1 7 ] , Rosaceae [2 0 ] andCrassulaceae [ 25 , 27]) . The non-cyan ogenic cyano glycosides seem to be ubiquitous andthe l imited ex amp les m ake a discussion on their chem otaxonom y diff icul t.

S t r u c t u r a l e a t u r e sAll of the non-cya nogen ic cyanoglycosides isolated so far are monoglucosides, and theycan be classif ied into two main groups, the cyanom ethylenecyclohe xyl glucosides 1-1 3),including phenylacetonitr ile glucoside 14), and the acyclic isopentenyl cyanogluco sides 15 -21). In this review, the fo rme r group is mainly discussed, while the latter group is only brieflymentioned.

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o

~ . 0 ~

o ~~o ~ m9 . 0 d

0 ~ " 0

= = - - - o , ~ - ~ , a a ~ = : = ~ . .

9 b b~

;a.10

oo ,.,,9 o

- ~ . =0 " . ~= =~ = = =

9 ~ = . = . ~ ~- ~ ~ >

0 . ~ . ,. .~ , - , . , ~ I =I7 m . ~ 7 ~. .~ .~ .~ .~ .== .~ ~o ~ . ~ ~

9~ .~. ~ ~ ! .~. ~= < < < ,~ ~ - - - '~ ~ . -~ ~ .~.~ ~ . ~ = ~ .

o t a ~o_=o

~ ~, ~, ~, g g g g g ~ 8 ~ g g gg g = . = . . = . . . . . . . .= = 9 ~ ~ ~ ~ ~.=

> 1oo,.~

0

rg

2 :0

.,..~

o

~ < ~ ~ ~ < a ~ ~

0

" ' " ~ . , . . .

i ~

, . o[ - - =

336


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N C 8 7 N C1 G I c O oGI cO 4 ~ 2

O H O Hmenisdaur in 1 ) pu rsh ian in 2 )[lit . 8-1 3, 15, 20] [lit . 20]

cf. me nisdauri l ide la )[lit . 8, 9, 12, 13,211

NCGIcO

O RR = N :l i~ osNr m os id e 3 )gliffonin) [lit . 5, 7, 14]

R = M e :bauh inin 4) [lit . 161

R1 R2 R3

GIcO,HO ' ' =

O Hdasycarponin S)[lit. 14, 151

H OGIc (13-D-glucopyranosyl)

N C iG I c O , , , ~ , R1

4 f 3 OR 2OR3

GIcO,

O Heh re t i o s i d e B 1 4 ) [ li t. 1 8 ]

H M e M eH Bz BzBz H BzH Cin BzCin H BzH S en HH H S enS en H H

s immonds in 6 ) [ l i t . 1 -4 , 18 ,29 -321lophiroside A1 7) [ l i t . 17]lophiroside A2 8) [ l i t . 17]lophiroside B 1 9) [ l i t . 17]lophiroside B2 10) [ l i t . 17]ehret ioside A1 11) [ l i t . 181ehret ioside A2 12) [ l i t . 181ehret ioside A3 13) [ l i t . 181

0 0 0

Bz (benzoyl) Cin t rans-cinnamoyl) Sen senecioyl)

R1 R2CH2OH HCH 3 HH CH3H CH2OHH C H 2 O g a l l o y l

s u t h e r l a n d i n 1 5 ) [ l i t . 2 2 -2 4 ]o s m a ro n i n 1 6 ) [l it . 2 3 -2 4 ]rh o d i o c y a n o s i d e A 1 7 ) [ l i t . 2 5s a rm e n t o s i n 1 8 ) [l it . 2 6 -2 7 ]rh o d i o c y a n o s i d e B 1 9 ) [ l i t . 2 5

R~ N , A_ _ / / . . N- .- , t . R1 R2 R3R 2 - - J / ~ O R 3 H H GIc

OGIc OH He p i d e rm i n 2 0 ) [ l i t . 2 8 ]no t r iv ia l name ) 21 ) [ l i t . 28 ]

F i g u re 1 . No n c y a n o g e n i c Cy a n o g l u c o s id e s337


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Tab le 2 . Sp ec t r a l Da ta fo r I - 3 an d 5

C om pd M e n i s d au r i a P u r s h h n h L i t h o s p e m o s i deS truc ure 1 2 3

O r g hF a m . M e n i s pe r m a c e a e M en Jsp en nM e n i s p e m a c e a e P ~ Tha/izt2q2nR o s a c e a e R a n u n cu h c e a eA u th o r T a k a h a s h i e t a l N a k a n i s h i e t a l N a k a n i s h i e t a l W u e t a li iRef. ~ y 8 0978) 20 1994) 20 1994) 14 1979 )

mp 1 7 5 -1 7 6 0 1 7 0 -1 7 2 o 1 6 7 -1 7 0 o 2 7 2 -2 7 4 oh ] D - 1 8 5 o b i e O H ) - 2 1 5 ~ ~ e O H ) - 9 0 0 b l e O H ) - 1 3 8 0 1 42 0)

MS ~n/z) 313 M+ 314 h i+H) + 329 M+IR v 0[B r) 2220, 1625,16 20 2220, 1620 2220

l lU V L (b g c) 26 0 (5.5) 271 (4.0) 25 9 (4.2)13C NM R

S o l v e n tC - 1C - 2C - 3C - 4C - 5C - 6C - 7CNG - 1G - 2G - 3G - 4G - 5G - 6

H NM RS o l v e n t

D20156.4 s127.6 d139.3 d64.5 d35.2 t73.8 d96.9 d118.7 s101.2 d73.1 d76.9 d70.7 d76.9 d61.9 tCD3 0 D1 0 0 MHz6.27 d, 106.20 dd, 10,34.35 m1.87 m2.39 m4.91 dd d, 2,4,85.48 d, 2

4.54 d, 7

3.68 dd, 4 123.88 dd, 2,12

F r e q .H - 2H - 3H - 4H - 5 aH - 5 bH - 6H - 7

CD3 0 D157.8 s128.4 d141.3 d66.0 d36.7 t73.2 d97.6 d118.7 s102.3 d75.2 d78.7 d72.4 d78.8 d63.8 tC D 3 0 D600M H z6.29 ddd6.21 ddd4.36 dddd2.25 ddd2.04 ddd4.9 3 ddd5.5 0 ddd

4.55 d, 83.343.393.293.343.673.89

S - 1 'H - 2H - 3H-4H - 5H - 6H - 6

CD3 0 D157.1 s127.5 d144.3 d65.3 d38.4 t75.2 d98.7 d119.1 s104 .1 d75.8 d79.0 d72.4 d78.8 d63.7 tC D 3 0 D

600M Hz6.25 dddd6.22 dddd4.66 dddd2.57 dddd1.60 ddd4.93 dd5.5 0 dd4.54 d, 83.16 dd3.38 dd3.29 dd3 .3 1 d d d3.68 dd3.86 dd

D20157.6 s129.2 d138.7 d76.2 d78.5 d72.3 d99.4 d120.1 s104.9 d75.3 d78.4 d72.3 d78.3 d63.5 t

D2090M Hz6.33 dd, 10,16.12 dd, 10,34.28 m

5.61 d, 14.7 4.9

3.3 4.1

D a s y c a r p o n hS

Tha./i:rtnm~R a n u n c u h c e a eW u e t a l

14 (1979)2 5 3 - 2 5 5 ~

- 1 1 ~ 1 4 2 0329 M+

2230, 1633261 4.2)

D20155.4 s128.5 d139.8 d68.1 d79.4 d7 2 d102.5 d120.1 s105.3 d75.6 d78.6 d71.3 d78.3 d63.2 t

D209 0 MHz6.35 d, lO6.05 d, lO4.28 m

5.70 s4.6 5.0

3.1 4.0

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Table 3. S e c t r a l D a t a f o r 6, 7 , I I a n d 1 4Co mp d Simmondsin Lophiroside A1 Ehre tio sid e A1 Ehr eti osi de B

St ru ct ur e 6 7 11 14Ori gin Ehr e t i a Loph ir a Ehr e t i a Ehr e t i a

Fam. Boragi naceae Ochnaceae Bo rag i naceae Bo rag i naceaeAuth. Simpol et al Murakami et al Simpol et al Simpol et al

Ref. (y) 18 (1994) 17 (1993) 18 (1994) 18 (1994)mp 95-1 O0~ amorphous Amorphous Amorphous

[a ] D -73 ~ (MeOH) -1 1. 5 ~ (MeOH) +39 ~ (p yr id in e) -72 ~ (MeOH)MS (m/z) 374 (M-H)- 556 (M+H) 428 (M-H)- 310 (M-H)-IR v(KBr) 2218, 164011] 2210,16 00 2230, 1645UV~(log~) 217 (4. 0) 274 (3.2)

13C NMR pen taa cet a teSolvent CD~OD Acetone-~ CD30D

C-1C-2C-3C-4C-5C-6C-7CN

G-1G-2G-3G-4G-5G-6OMeOHe

CDaOD166.4 s

70 7 d86.3 d76.7 d32.0 t76.5 d95.2 d

117.6 s104.1 d74.7 d78.1 d71.4 d78.1 d62.7 t58.5 q58.2 q

158.8 s69.3 d75.1 d69.4 d33.9 t77.7 d97.9 d

116.2 s102.1 d72.3 d73.7 d69.1 d73 d62.5 t

3-BenzoylCO, o 165 .6, 130.3m p 1 2 9 . 4 1 3 4 . 04-BenzoylCO, o 166.4, 13 0.7m p 1 2 9 . 4 1 3 4 . 0Ac 20. 5, 170.0 etc

165.0 s67.9 d79.0 d67.7 d34.3 t76.0 d95.6 d

116.9 s102.7 d75.0 d79.4 d71.4 d78.5 d62.7 t

Senecioyl166.0 s116.6 d156.9 s26.9 q

20.0 q

ll l . 1 s130.2 d110.4 d160.3 s104.8 d157.1 s

17.9 t119.5 s103.3 d74.8 d78.8 d71.0 d78.4 d62.2 t

1H NMRSo 1vent CDaOD Ace t one-d 6 CDaOD CDaODFreq. 400 l~ z 400 lifflz 400 MHz 400 MHz

H-2H-3H-4

H-5aH-5bH-6H-7a - lH-2H-3H-4H-5

H-6 aH-6 b

etc

4. 70 dd, 9, 23.15 dd, 9,33.91 ddd, 4, 4,41.79 dt, 15,42.50 dt, 15,44 . 8 7 t 45.70 d, 24. 38 d, 83.26 dd, 8,93.30 m3.36 m3.21 ddd, 8, 2,53.65 dd, 5, 123.83 rid, 12,2Me 3.44, sMe 3.47, s

5.50 dd, 1 0.3, 2.05.16 dd, 1 0.3,3 .35.77 m2.34 ddd, 15. 6,3. 7,3. 02.67 ddd, 15.6, 3.2, 2.95.09 ddd, 3.7, 3.2, 2.05.96 d, 2.04 .46d , 7 .8

3.21-3.45 (4H)3.66 dd, 11.7 ,5.93.89 dd, 1 1.7, 1.8Bz (o) 7.90 m, 8.14 mBz (m) 7.40 m, 7.51 mBz (p) 7.58 m, 7.65 m

5.68 dd, 10,25.18 dd, 10,34.6 6 ddd, 3, 3,32.69 dt, 15,31.82 dt, 15,35.52 t, 36.25 d, 25. O3 d, 83.97 dd, 8,94.21 dd, 9,84.21 dd, 9,83.91 ddd, 9, 2,54.4 4 dd, 12,24.2 8 dd, 12,5Sell 5.56, sep t, 1.3Sen 1.56, d, 1.3Sell 2.07, d, 1.3

7.33 d, 86.83 dd, 8,27.37 d, 2

4. O0 d, 183.90 d, 185.46 d, 73.92 dd, 7,84.26 m4.28 m3.89 ddd, 2, 5,94.3 8 dd, 12,24.31 dd, 12,5

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B e h a v i o u r o n h y d r o l y s i sT h e c y a n o me th y l e n e c y c lo h e x y l g lu c o s id e s ( 1 - 1 3 ) h a v e a c o mmo n s k e l e to n , 2 - 1 3 - D-g lu c o p y r a n o s y l c y c lo h e x y l id e n e me th y l c y a n id e, s o m e o f wh ic h h a v e a d o u b le b o n d in

the r ing . Di f fe r ing f rom the cyanogen ic g lucos ides , menisdaur in (1 ) d id no t l ibe ra te hydrogencyan ide on ac id hydro lys is , bu t cyc l ized to menisdaur i l ide ( la ) [8 ] . S imi la r cyc l iza t iono c c u r r e d f o r t h e c o mp o u n d s 2 - 6 o n a c id o r e n z y ma t i c h y d r o ly s i s t o a f fo r d t h e c o r r e sp o n d in glac tones [5 , 14 , 16] . In add i t ion to the cor respond ing lac tone , s im mo nds in (6 ) a f fo rdedthe a romat ized lac tone (6a) on ac id hydro lys is , whi le enzymat ic hydro lys is wi th 13-g lucos idase (E . C . 3 .2 .1 .21) gave m ix tu res o f a romat ic m ate r ia l s and g lucose [ 1 .

NC. NC.

i i ~or emulsin e ~ ,

OH OH OMe OMel a 6 6 a

S p e c t r a l c h a r a c t e r i s ti c sT h e s p e c t ra l d a t a o f t h e c y a n o me th y l e n e c y c lo h e x y l g lu c o s id e s a r e t a b u l a te d i n T a b l e s 2and 3 . In the IR spec t ra , the mos t c harac te r i s tic s igna l o f these co m poun ds i s the CN

st re tch ing band . S t rong absorp t ion appear ing a t abou t 2220 cm fo l lowed by absorp t ion o fthe con juga ted doub le bond a round 1620 cm l a re de f in i te in fo rmat ions abou t th i s g roup . Inadd i t ion , the 13C N M R resona nces o f CN a t 8 1 16-12 0 and the ad jacen t t r i subs t i tu tedd o u b le b o n d a t 1 5 5 - 1 6 6 ( s ) a n d 9 5 - 1 0 0 ( d ) a re c h a r a ct e r is t ic s i g na l s. E a c h c o mp o u n d s h o we ds ix ca rbon s igna ls a t t r ibu tab le to a 13-g lucopyranosy l g roup wi th an anomer ic p ro ton s igna la round 8 5 .0 hav ing a coup l ing cons tan t o f ca. 7 Hz . In add i t ion , an odd number molecu la rp e a k i n t h e M S s u g g e s t e d th e e x i s t en c e o f s o me t ime s u n e x p e c t e d n i t r o g e n a to m.S i m m o n d s i n 6 )His to r ica l ly , s imm onds in (6 ) i s the f i r st repor ted com pound of th i s se ries . I t wa s i so la tedf r o m S i m m o n d s i a c h i n en s is [syn. S i m m o n d s i a c a l i f o r n i c a ] ( B u x a c e a e [ o r S immo n d s i a c e a e ] )a n d c h a r a c t e r iz e d i n 1 9 7 3 b y me a n s o f c h e mic a l d eg r a d a t io n a n d p r o to n N M R m e a s u r e d a t100 M H z [ 1 . The geom etry o f the doub le b ond and the re la t ive conf igura t ion w as es tab l i shedo n th e b a s i s o f t h e c o u p l in g ma g n i tu d e. Ho we v e rthe abso lu te conf igura t ion was no t dec ided . Af te r two OMe OGleidecades , s immonds in was s te reose lec t ive ly syn thes ized 4 6 ~ e ~J~6f rom L-quebrach i to l , conf i rming the geometry andthe abso lute config urat ion [4] . I t is note w orth y that MeO ,,,CNthe conformat ions shown here i s s tab le fo rm in sp i te o fthe p resence o f 1 ,3 -d iax ia l in te rac t ion o f hyd roxy func t ions H[1 , 4 ] . F ro m the sam e p lan t , 2 ' - fe ru la te o f s imm onds in , 3 - S t a b l e c o n f o r m a t i o n o f 6 [ 1 , 4 ]O- d e s me th y l s immo n d s in a n d 4 - O- d e s me th y l s immo n d s inwere a l so repor ted [2 ] .G r i f f o n i n l it h o s p e r m o s i d e ) 3 ) a n d d a s y c a r p o n i n 5 )Chro nolog ica l ly , g r i f fon in (3 ) i s p robab ly the second com poun d i so la ted (1976) wh ichbe longs to th is g roup . I t was ob ta ined f rom the roo ts o f G r i f f o n i a s i m p l i c i f o l i a Bail l . (syn.

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Bandeiraea s impl i s i fo l ia Benth . ) of the Legu minosa e Caesa lp inaceae) fami ly .The s t ruc ture of 3 , wi th i t s cor responding lac tone , gr if fonil ide , w as dec ided by IH N M R 250M Hz ) and conf i rmed by X -ray ana lys is of the c rys ta l line lac tone , bu tthe absolute stereochemistry was not solved [5,6] . In 1977, 3 was claimed to have beeniso la ted f rom Li thosperum purpureo-caeruleum way back in 1955, and was namedli thospermoside, al though at that t ime the structure could not be ful ly elucidated. In the 1977report , the structure and relat ive configurat ion were clar if ied using the sample isolated from L.purpureo-caeruleum and f rom L. officinalis [7] . In 1979, 3 and i ts diastereomer, dasycarponin5) were i so la ted f rom the tw o p lan ts , Thalictrum rugosum Ait. syn. Z glaucum Desf.) and T.dasycarpum Fisch. and Lall . Ranu nculaceae) . T heir s tructures we re elucidated andthe absolute configurat ions were determined by ut i l izat ion of dibenzoate chiral i ty rule in CDspec tra [ 14].M enisdaur in 1) an d purshianin 2)

Ab out the same t ime, in 1978, me nisdaurin 1) wa s isolated from Menisperm daur icumDC M enispermaceae) wi th the cor responding lac tone , menisdaur i lide la ) , and the s t ruc tureswere dec ided through 13C and IH NMR. The geometry and re la t ive conf igura t ion were a l sodetermined , but in spi te of the CD data, the absolute co nfigurat ion w as tentat ive [8] .These compounds were la te r i so la ted f rom hol ly , I lex aqui fol ium Aquifol l iaceae) , butthe wrong structures were proposed for the lactone [9] and the glucoside [10]. Later on,the structure in l i t . 10 was corrected as 1 [ 11 ] , and a new plant origin, I . warburgi i Loesn . wasreported [ 15]. The absolute structure of 1 was clar ified using ano ther plant origin, Purshiatridentata DC Rosaceae) , f rom which , a d ias tereomer ic g lucos ide , pursh ian in 2) was a l soisolated [20]. From Sinomennium acutum Rehder e t W i lson Men ispermaceae) ,we have i so la ted 1 , l a and a lac tone 2a) cor responding to 2 and two more s imi la r lac tones[13] . The absolu te conf igura t ion of la was de te rmined b y X-ray c rys ta l ana lys is of p-b romobenzoa t e o f l a . Compound 2a was p r ev ious ly i so l a t ed f rom Aqui legia a t rata var.atroviolacea Ranunculaceae) and named aquilegiol ide [21], and later from Phyl lanthusanisolobus Euphorbiaceae) a long wi th la [ 12].Bauhinin 4)

Bauhin in 4) was iso la ted in 19 85 f rom Bauhinia championi i Benth . Legum inosae) ofTaiwan or ig in , and the s t ruc ture was unambiguous ly dec ided by the resu l t s of s ingle-crys ta lX-ray ana lys is of i t s d ihydra te , and the absolu te s te reochemis t ry was based f rom the knownabs olute con figu ratio n o f 13-D-glucose [ 16].Lop hirosides 7-1 9)

Loph i ros ides 7-1 0) a re b i t te r g lucos ides f rom the Afr ican Ocnaceae p lant , Lophiraalata. The geo m etry of the double bond w as dec ided by the observa t ion o f a s ignif icant NO Ebetween H-7 and H-2 a f te rassigning al l the proton signals ,and the absolu te s te reochemis t rywas clar if ied by the applicat ionof dibenzoate chiral i ty rule inthe CD spec t ra of lophor is ide A17) itself, since it is one of

the rare natural d ibenzo ate [ 17].

O z OGIc4 [ H . u 6 1I l l i l l I

H ~ HCN

0 2C-5 ~ H

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Ehretiosides 11-14)Recently , we have isolated simmondsin (6) and four ehretiosides (11-14) fromthe Phil ippine endemic medicinal p lant, Ehretia philippinensis (Borag inaceae) [ 18] . Am ongthem, only ehretioside B (14) is an aromatic com pound, OH OGle

suggesting the biogenesis o f these comp ounds.Three a l icycl ic compounds, eh ret ios ides A1-A3 (11-13) hadthe same molecu lar fo rmula , CI9H27OIoN and showed HO . ,CNthe characterist ic CN band at 2230 cm 1 in the IR spectra. The 1 la H~H and ~3C N M R data suggested the p resence of J3- glucopyranosy l andsene cioyl moieties,and the s t ructu res o f the ag lycones were es tab l ished th rough H-H CO SY and HS QC NM Rdata . Methano lysis o f 11 wi th KOH in MeOH affo rded the deacy la ted compound ( l la) whichwa s identical with the comp ound obtained from the methanolysis of lophoriside A1 [17].Com parison o f the NM R spect ra o f 11 wi th those o f l la led the posi tion o f the senecioy lgroup to be 3- 0. In the same m anner, structures of 12 and 13 we re readily decided (Figure 1).

Ehretioside B (14) is the only aromatic compound, and the aglycone, 2 ,4-dihydroxyphenyl acetonitri le was previously isolated from Erica scoparia (Erica cea e) [ 19].Isopentenyl glucosides 15 -20

Recently , sutherlandin (15), an unusual non-cyanogenic cyanoglucoside which has anisopentane skeleton was isolated from Acacia sutherlandii (Leguminosae) [22] . Fo l lowingthis, sim ilar glucosides w ere reported [23-28 ] (Table 1 and Figure 1). Interestingly, allcompounds have the same carbon skeleton.

iogenesisThe b iogenesis o f cyanogen ic g lycosides , which have the cyano g roup a lpha tothe glyc osy l bond, wa s established. It starts from or-am ino acid as follow s [29]

H I~1"OOC (~--R2

+NH3Ha m i n o a c i d

00 2 + H + H I~1 H2 0[ O ] H O O ~ C: ~1 ~ N ~ ~ ~ _ _ RR 2 ~

OH a l d o x i m e7 1 [ O ]N ~ C '- -R 2IH

"n i t r i le "

N ~ 7 1 U D P G I c I~ 1C R 2 - ~I N ~ C '- -R 2IOH UD P OGIcc y a n o h y d r i n

R1 = R2 = OH3 9R I = H R 2 = p h e n y l :R1 = H, R2 = p - O H - p h e n y l 9

va l i ne to l i namar inp h e n y l a l a n i n e t o p r u n a s i nty ros ine to dhu r r i n

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NC O ] NC_ , NCb O H U D P - G I c O G Ic

U D P~ ni tri le I 14OH OH OHOn the o ther hand, non-cyanogenic cyanoglycos ides which possess cyano groups notadjacent to a g lycosyl bond ma y be genera ted v ia a d i f fe ren t pa thway, but ve ry probably f rom

or-amino acid. Since 1-14 have the same main carbon skeleton, they might be generated froma comm on precursor , ty ros ine . The co-exis tence o f ehre t ios ide B (14) wi th cyano methy lene-cyc lohexyl g lucos ides in the same p lan t sugges ted th is hypothes i s. Ins tead of hydroxy la t ion a tthe or-posit ion (a) of the cya no grou p of ni t r i le , i f i t occurs at the arom atic ortho po si t ion (b)fo l lowed by g lucosyla t ion , the ta rge t cyano g lucos ide (14) would be formed. Some ofthe isopentane glucosides would be derived from leucine.

Biological ct ivityM ost o f the non-cyan ogenic cy anoglucos ides were i so la ted f rom plants used as medic ina l,or know n to have spec i fic phys io logica l ac tiv it ies . H owev er , v ery few o f the i so la tedpure compounds were repor ted to have b io logica l ac t iv i t i es (Table 1) . Amongthese a re the lophi ros ides (7-10), sa rm entos in (19) and rhodiocyanos ide A (17). S imm onds in(6) was also one o f the exce ptional ly well s tudied com pou nds an d wil l be discussed in detai l.

Lophi ros ides (7-10) have weak an t i -bac te r ia l ac t iv i ty aga ins t iVficrococcus luteus(minimum inhib i tory amount = 100 ~g each) , bu t they may ac t as defens ive subs tancesaga ins t preda tory mam mals on acco unt of the ir b i t te rness [ 17].

Sarmentosin (19) , f i rs t isolated from Sedum sarmentosum [27] , was accumulated inmagpie moth . The h igh concent ra t ion of 19 in the imago (650 g per insec t ) sugges ts adefensive ro le for this substan ce [26].Rhodiocyanos ide A (17) , i so la ted f rom R b o d io la q u a d r~ d a , was found to inhibi t

the histam ine release b y 10 5 to 10 4 in a concentrat ion-de pend ent mann er. I t a lso s ignif icant lyinhibi ted the PCA (passive cutaneous anaphylaxis) react ion, suggest ing the ant i-al lergicact ivi ty of the plant [25].Simmondsin (6) exhibi ted unique inhibi tory act ivi ty on feeding. I t was f i rs t isolated from

j o j o b a Simmond sia ca l i forn ica) which is a dioecious desert shrub that grows wild mainly inthe south -wes tern United States . I ts seeds furnish high content of a l iquid wax com prisingma inly of C40, C42 and C wax esters , as well as a meal co ntaining 32% protein aider rem ovalof the o il which i s a po ten tia l rep lacement for spermaceti . Incorpora t ion of the jo job a mealinto the diet of wean ling rats caused extrem e weigh t loss , and this ref lected fai lure ofthe an imals to consume food. From the ac t ive e thyl ace ta te f rac t ion obta ined f romsuccessive solv ent extract ion (heptane, benzene, ethyl acetate and me thanol) o f the jojo baseed, s immondsin (6) was obtained as an act ive substance and the chemical s t ructure wasdetermined. I t exhibi ted inhibi tory act ivi ty on feeding, al though the oral acute toxici ty (LDs0>4 g /kg) w as e xtrem ely low [1 ] .

Recent ly , the pharmacologica l e f fec t s of s imm onds in was ex tens ive ly s tudied byCokelaere et al. us ing ra ts . The ex t rac ted and pur i f ied s imm onds in f rom jo joba meal caused afood intake reduct ion in adult rats . Taste was apparent ly not involvedbecause the same response was seen with intragastr ic intubat ion as oral administrat ion.

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The foo d in take reduc t ion w as p roba b ly due to an inh ib it ion o f hunger , ra ther than to anenh ance m ent o f sa ti s fac tion . S im m onds in t rea ted w i th 13-g lucosidase and taken in togas t ro in tes t ina l t rac t seemed to be more ac t ive than s immonds in i t se l f [30] .Poss ib le tox ico log ica l in f luences o f s immonds in a f te r subacu te admin is t ra t ion in the ra t wass tu di e d , a n d a 5 - d a y a d m in i st r a ti o n o f 2 5 0 m g o f s immo n d s in /k g o f b o d y w e ig h t d id n o thave any tox ico log ica l in f luences on l ive r , pancreas and k idneys us ing severa l b io log ica lp a r a me te r s . T h e n o n c y a n o g e n e c i t y o f s imm o n d s in i n r a ts wa s a l so c o n f i r me d [ 31 ].T h e i n f lu e n c e o f jo jo b a me a l s u p p le me n ta t i o n o n g r o wth a n d o r g a n f u n c t i o n i n r a t s wa s a l s os tud ied , and a lower food e f f ic iency was due to an inc rease in T3 concen t ra t ion , which canbe exp la ined by a re la t ive p ro te in shor tage [32] .

The app l ica t ion o f s imm onds in to regu la te the feed ing o f l ives tock , espec ia l ly domes t icfowl , a s we l l a s the app l ica t ion to human d ie t food i s in p rogress . So fa r , s immonds in seemsto be sa fe , bu t an t i fe rt i l ity e f fec ts in ra t s a fte r long- te rm jo joba mea l su pp lem enta t ion hasbeen repor ted [33] . I t may no t be due to s immonds in , however , fu r the r s tudy i s needed toc o n f i rm th e s a f e ty o f th i s n o n - c y a n o g e n ic c y a n o g lu c o sid e .

e ferences1. Ell ige r , A. C. W aiss , Jr. and R. E. Lun din, J . Chem . Soc . Perk in I 2209 1973) .2 . Ell iger , A. C. W aiss , Jr . and R. E. Lun din, Phytochemistry 13, 2313 1974).3 . V erb isca r and T . F . Ban igan , J . Agric. Foo d Chem. 26, 1456 1978).4 . Ch ida , K. Ya m ada and S . Oga wa, J . C hem . Soc . Perk i n / 1131 1992) .5 . D .D . Badu , W . H. W atson , E . M. Gopa lakr i shna , T . U. Okar te r , J . E . Kna pp , P . L . Sh i f tand D. S. Slatkin , Lloydia 39, 385 1976).6 . E .M . Go pa lakr i shn a W. H. Watson , D. D. Badu , T . U. Okar te r , J . E . Knap p , P . L . Sh if f,

Jr . and D. S. Slatkin , Crys t . S t ruc t . Comm . 5, 779 1976).7 . A. Sosa , F . W in te rn i ts , R . W ylde and A. A. Pav ia , Phytochemistry 16, 707 1977 ).8 . K. Taka hash i , S . M atsuz aw a and M. Takan i , Chem . Pharm. Bul l . 26, 1677 1978).9 . H . T h o m a s a n d H . B u d z ik i e wic z , Phytochemistry 19, 1866 1980).10 . M . W il lems , Phytochemistry 27, 1852 1988).11 . A. N ahrs ted t and V. W ray , Phytochemistry 29 , 3934 1990) .1 2. T . B a c h m a n n , F . Gh ia a nd K .B .G . T o r s se l l, Phytochemistry 33, 189 1993).13 . H. Otsuka , A. I to , N. Fu j ioka K. Kawamata , T . Kasa i , K. Yamasak i and T . Sa toh ,Phytochemistry 33 , 389 1993) .14 . J . Wu, E . H. Fa i rch i ld , J . L . Bea l , T . Tomimatsu and R . W. Dosko tch , J . N a t . P r o d 42,500 1979) .15 . K. Ueda , K. Yasu tomi and I . Mo r i , Chemistry Letters 149 1983).16 . C-C . C hen , Y-P . Chen , H -Y. H su , K-H. Lee , S . Tan i and A. T . M cPha i l , J . N a t . P r o d 48,933 1985) .17. A. Murak am i , H. Ohigash i , S . Tanaka , M. Hiro ta , R . I r ie , N. Takeda , A. Ta tematsu and K.Ko s h imiz u , Phytochemistry 32 , 1461 1993) .18 . L . R . S impol , H. Otsuka , K. Ohtan i , R . Kasa i and K. Yamasak i , Phytochemistry 36, 911994) .19 . A. Ba l les te r , A. Verw ay and J . C . Overeem, Phytochemistry 14, 1667 1975).20 . T . Nak an ish i , M. Nish i , M . Some kaw a, H. M ura ta , M. M izuno , M. I inuma, T . Tanaka , J .

Mura ta , F . A. Lang and A. Inada , Chem . Pharm . Bul l. 42, 2251 1994).21 . A. Guerr ie ro and F . P ie t ra , Phytochemistry 23 , 2394 1984) .22 . W . K. Swen son , J . E . Dunn and E . E . Conn , Phytochemistry 26, 1835 1987).23 . M . Lec h ten berg and A. Nahrs ted t , Pl an ta M ed i ca 59 , A616 1993) .24 . M. Lech tenberg , A. Nahrs ted t , V. Wray and F . F . F ronczek , Phytochemistry 37, 10391994) .

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25. M. Yoshikawa, H. Shimada, H. Shimoda, N. Murakami, J . Yamahara and H. Matsuda,Chem. Ph arm . Bull. 44, 2086 1996).26. R. Nishida, M. Rothschild and R. M um me ry, Phytochemistry 36, 37 1994).27 S. D . F ang, X. Q. Yan, C. F. Li, Z. Y.Fan, X. Y. Xu and J. S. Xu, A cta Chim. Sinica, 40,273 1982).28 Pourm ohseni, W .-D. Ibenthal , R. M achinek, G. Rem berg and V. W ray, Phytochemistry33, 295 1993).

29. T. W. Goodwin and E. I . Mercer, Introduction to Pla nt Biochem istry seco nd editionPerg am on Press, Oxford, p . 356 1983).30. M. M. Cokelaere, H. D. Dangreau, S. Arnouts, E. R. K0hn and E. M.-P. Decuypere, jr .Agr . Food Chem . 40, 1839 1992).31 M. M . Cokelaere, H. D. Dangreau, P. Daenens, N. Bruneel , S . Arnouts, E. M.-P.Decuypere and E. K. Kiahn, J. Agr . Food Chem. 40, 2443 1992).32. M. M. Cokelaere, J . Buyse, P. Daenens, N. Bruneel , S . Arnouts, E. Decuypere, E. K0hnand M. Van Boven , J. Agr . Food Chem. 41, 1444 1993).33 M .M . Cokelaere, J . Buyse, P. Daenens, E. Dec uypere, E. Kiahn and M. Van Boven, jr.Agr . Food Chem. 41, 1449 1993).

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