Some Fundamental Aspects of the Chemistry of Sucrose - American

4 Some Fundamental Aspects of the Chemistry of Sucrose

Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on October 14, 2014 | http://pubs.acs.org Publication Date: June 1, 1977 | doi: 10.1021/bk-1977-0041.ch004

RIAZ KHAN Tate & Lyle Ltd., Group R & D, P.O. Box 68, Reading, RG6 2BX, Berks, England

Sucrose represents a regenerable chemical resource of undetermined commercial p o t e n t i a l . I t s value has been l o n g r e c o g n i z e d as a c h e m i c a l raw m a t e r i a l f o r food a d d i t i v e s , s u r f a c t a n t s , p l a s t i c s and polymers, a g r i c u l t u r a l chemicals and pharmaceuticals. However, a c t u a l commercial s u c c e s s , so f a r , has been l i m i t e d . D u r i n g t h e p a s t f e w y e a r s , i t h a s become e v i d e n t t h a t no s i g n i f i c a n t p r o g r e s s i n t h i s d i r e c t i o n c a n b e made w i t h o u t a profound knowledge o f t h e fundamental chemistry o f sucrose. Our o b j e c t i v e , t h e r e f o r e , h a s been to study t h e b a s i c chemistry o f t h i s molecule. This p a p e r r e v i e w s some r e c e n t w o r k o n c h e m i c a l m o d i f i c a t i o n s o f s u c r o s e w i t h t h e hope t h a t i t w i l l form a b a s i s f o r commercial e x p l o i t a t i o n o f such d e r i v a t i v e s . Structure Sucrose i s a non-reducing d i s a c c h a r i d e which i s s y s t e m a t i c a l l y named 3 -JD-f r u c t o f u r a n o s y l a - D - g l u c o p y r a n o s i d e (A),and t h e numbering o f t h e carbon p o s i t i o n s i n t h e m o l e c u l e i s a s s h o w n i n F i g u r e 1. S u c r o s e c o n t a i n s e i g h t hydroxyl groups,three o f which a r e primary (C-l , C-6, a n d C - 6 ) a n d t h e r e m a i n i n g f i v e a r e s e c o n d a r y (C-2, C-3, C-3', C-4, a n d C - 4 ) . The s t r u c t u r e o f s u c r o s e h a s b e e n e s t a b l i s h e d 'both b y c h e m i c a l ( 1 - 4 ) a n d enzymic (5-7) s y n t h e s e s . I t s s t r u c t u r e a l s o h a s been c o n f i r m e d b y p h y s i c a l methods such a s , X-ray c r y s t a l l o graphy (8,9), neutron d i f f r a c t i o n (10), and n u c l e a r magnetic resonance spectroscopy (11-12). 1

1

1

Tritylation

Reaction

The t r i t y l g r o u p h a s b e e n u s e d w i d e l y f o r t h e b l o c k i n g o f primary h y d r o x y l groups i n carbohydrate chemistry (13). T r i t y l a t i o n o f sucrose u s u a l l y i s 40

In Sucrochemistry; Hickson, J.; ACS Symposium Series; American Chemical Society: Washington, DC, 1977.

4.

Fundamental Aspects

KHAN

41 6

CH OH


2

A_

Sucrose Figure 1

performed by r e a c t i o n w i t h an a p p r o x i m a t e l y s t o i c h i o m e t r i c amount o f c h l o r o t r i p h e n y l m e t h a n e i n p y r i d i n e a t room t e m p e r a t u r e o r a b o v e . T r i t y l a t i o n a t C-6 a n d C-6 h y d r o x y l groups h a s been found t o undergo complet i o n i n t h e o r d e r o f 1 h o u r a t 100°, w h e r e a s t h e m o r e hindered primary hydroxyl group a t C - l p o s i t i o n r e a c t s more s l o w l y . Sucrose, on treatment with four molar equivalents o f chlorotriphenylmethane i n pyridine for 48 h o u r s a t r o o m t e m p e r a t u r e , a f t e r c h r o m a t o g r a p h y o n s i l i c a gel, afforded 6,6 -di-O-tritylsucrose (B) a n d l , 6 , 6 ' - t r i - O - t r i t y l s u c r o s e (C) i n 30 a n d 5 8 % y i e l d , r e s p e c t i v e l y (14). The p r e f e r e n t i a l r e a c t i v i t i e s o f t h e p r i m a r y h y d r o x y l g r o u p s a t C-6 a n d C - 6 p o s i t i o n s i n sucrose a l s o has been observed i n the t r a n s e s t e r i f i c a t i o n r e a c t i o n (15). The t r i t y l a t i o n r e a c t i o n o f 3 , 3 , 4 , 6 ' - t e t r a - O - a c e t y l s u c r o s e (D) h a s b e e n d e s c r i b e d (16). T r e a t m e n t o f c o m p o u n d (D) w i t h c h l o r o t r i p h e n y l m e t h a n e a n d p y r i d i n e f o r 4 h o u r s a t 85°, g a v e 3 , 3 ' , 4 ' , ö'-tetra-O-acetyl-ö-O-tritylsucrose (E) a n d 3 3 4 6 t e t r a - O - a c e t y l - 1 * , 6 - d i - O - t r i t y l s u c r o s e (F) i n y i e l d s o f 67.7 a n d 1 4 . 8 % , r e s p e c t i v e l y . When t h e r e a c t i o n w a s p e r f o r m e d f o r 24 h o u r s a t 90°,the y i e l d o f compound ( F ) i n c r e a s e d t o 85%. (See F i g u r e 2 ) . T r i t y l ethers o f sucrose are o f t e n c r y s t a l l i n e s o l i d s which are s t a b l e under b a s i c and o t h e r n u c l e o philic conditions. The t r i t y l p r o t e c t i n g group c a n be removed under m i l d a c i d i c c o n d i t i o n s a s , f o r example, hydrogen bromide i n g l a c i a l a c e t i c a c i d o r b o i l i n g aqueous a c e t i c a c i d . 1

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OH BR=H C R = Tr

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F

Figure 2

Methylation

Reaction

Methylation of carbohydrates containing b a s e - l a b i l e s u b s t i t u e n t s using a combination o f diazomethane, d i c h l o r o m e t h a n e , a n d b o r o n t r i f l u o r i d e e t h e r a t e i s known to proceed without concomitant m i g r a t i o n o f a c y l groups (17, 1 8 ) . C o n s e q u e n t l y , t h i s method was c h o s e n f o r methylation of various, p a r t i a l l y acylated derivatives o f s u c r o s e (19») . M e t h y l a t i o n o f 1' , 2,3 3 ', 4 ,6 ' - h e x a O-acetylsucrose (G) w i t h a f r e s h l y p r e p a r e d s o l u t i o n o f diazomethane i n dTchloromethane and b o r o n t r i f l u o r i d e e t h e r a t e f o r 0.5 h r a t - 5 ° a f t e r c h r o m a t o g r a p h i c s e p a r 1

f



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KHAN

Fundamental Aspects

43

H R = AC I R= H Figure S

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a t i o n on s i l i c a g e l , g a v e 1 2,3,3 ,4 ,6•-hexa-O-acetyl4 , 6 - d i - O - m e t h y l s u c r o s e (H) i n 9 5 . 5 % y i e l d (19). T h e s t r u c t u r e o f (H) w a s s u p p o r t e d b y i t s 100 MHz p r o t o n n u c l e a r m a g n e t i c r e s o n a n c e (-^H n.m.r.) s p e c t r u m a n d b y mass s p e c t r o m e t r y . The p r e s e n c e o f a m e t h y l group a t C-4 i n (H) w a s i n d i c a t e d b y t h e a b s e n c e o f a n H-4 s i g n a l i n t h e r e g i o n o f T 4 . 5 - 5 . 4 o f t h e ! H m.m.r. s p e c trum where i t u s u a l l y o c c u r s i n a c e t y l a t e d d e r i v a t i v e s o f s u c r o s e , t h e m a s s s p e c t r u m o f ( H ) s h o w e d p e a k s a t m/e 3 3 1 a n d 275 d u e t o k e t o f u r a n o s y l a n d h e x o p y r a n o s y l c a t ions, respectively. The f r e e m e t h y l e t h e r ( I ) was o b t a i n e d i n 6 7 % y i e l d , b y t r e a t m e n t o f (H) w i t h a c a t a l y t i c amount o f s o d i u m m e t h o x i d e i n m e t h a n o l . ( S e e Figure 3 ) . f

Acylation Reaction A c y l a t i o n o f sucrose g e n e r a l l y i s performed w i t h the appropriate a c i d anhydride o r a c y l h a l i d e i n p y r i d i n e a t o r below room t e m p e r a t u r e . T h e m o s t common a c y l d e r i v a t i v e s o f sucrose used a r e a c e t a t e s and ben-


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zoates. Their value i s w e l l recognized i n protecting the h y d r o x y l groups of the sucrose molecule a g a i n s t r e a c t i o n s w h i c h p r o c e e d u n d e r a c i d i c and n e u t r a l c o n d i tions. The c l e a v a g e o f c a r b o x y l a t e e s t e r p r o t e c t i n g g r o u p s c a n be e f f e c t e d u n d e r m i l d l y b a s i c c o n d i t i o n s s u c h as c a t a l y t i c s o d i u m m e t h o x i d e i n m e t h a n o l o r m e t h a n o l i c ammonia. 6 , 6 - D i - 0 - t r i t y l s u c r o s e ( B ) , on t r e a t m e n t w i t h a c e t i c a n h y d r i d e and p y r i d i n e a t room t e m p e r a t u r e , gave the expected hexa-acetate(J) (ljO . D e t r i t y l a t i o n of 2,3,3',4,4'-penta-O-acetyl-1 ,6,6 -tri-O-tritylsucrose w i t h h y d r o b r o m i c a c i d i n g l a c i a l a c e t i c a c i d and c h l o r o f o r m a t 0° , h a s b e e n r e p o r t e d t o g i v e 2 , 3 , 3 ' , 4 , 4 ' penta-O-acetylsucrose i n 74% y i e l d (20). The p o s s i b i l i t y o f a c y l m i g r a t i o n m u s t be t a k e n i n t o a c c o u n t i n the s e l e c t i v e p r o t e c t i o n of sucrose. When c o m p o u n d ( J ) was t r e a t e d w i t h b o i l i n g a q u e o u s a c e t i c a c i d , d e t r i t y l a t i o n a c c u r r e d w i t h c o n c o m i t a n t m i g r a t i o n o f an a c e t y l g r o u p f r o m 0-4 — • 0-6, p r o b a b l y v i a t h e 4 , 6 - o r t h o e s t e r , t o g i v e 1 ' , 2 , 3 , 3 ' , 4 ' , 6 - h e x a - 0 - a c e t y l s u c r o s e (K) (21). In c o n t r a s t , however, s i m i l a r treatment of hexaO - b e n z o y l - 6 , 6 ' - d i - O - t r i t y l s u c r o s e and o f 2,3,3',4,4'penta-O-benzoyl-1',6,6'-tri-O-tritylsucrose brought about the expected l o s s e s of t r i t y l groups but caused l i t t l e o r no m i g r a t i o n o f e s t e r g r o u p s (1_4, 22) . (See F i g u r e 4 ) .


f

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Fundamental Aspects

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CH OTs 2

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M Figure 5

Sulfonylation

Reaction

The s e l e c t i v e p - t o l u e n e s u l f o n y l a t i o n o f s u c r o s e has been i n v e s t i g a t e d w i d e l y ( 2 2 - 2 7 ) . Treatment o f s u c r o s e w i t h a b o u t t w o m o l a r e q u i v a l e n t s o f £-toluenes u l f o n y l c h l o r i d e i n p y r i d i n e f o r 6 days a t 0 ° a f t e r chromatography on s i l i c a g e l , gave c r y s t a l l i n e 6 , 6 ' - d i O - p - t o l y l s u l f o n y l s u c r o s e ( L ) i n 1 8 % y i e l d (26). A s i m i l a r r e a c t i o n o f sucrose w i t h t h r e e moles o f p - t o l u e n e s u l f o n y l c h l o r i d e a n d p y r i d i n e g a v e 1',6,6 -tri-0-£t o l y l s u l f o n y l s u c r o s e (M) i n 2 3 % y i e l d (22) . T e t r a m o l a r P - t o l u e n e s u l f o n y l a t i o n o f s u c r o s e h a s been r e p o r t e d t o g i v e , i n a d d i t i o n t o compound ( M ) , 1 ' , 2 , 6 , 6 ' - t e t r a - O - p t o l y l s u l f o n y l s u c r o s e (N) i n 4 0 % y i e l d (2V) ( S e e F i g u r e 5). T h e o r d e r o f r e a c t i v i t y f o r s u c r o s e i s t h u s 0-6= 0-6 ' > 0 - l ' > 0 - 2 . Methanesulf o n y l a t i o n r e a c t i o n s o f s u c r o s e and i t s d e r i v a t i v e s a l s o h a s been s t u d i e d . T r e a t m e n t o f l , 2 , 3 , 3 ' ,4' , 6 , 6 ' - h e p t a - 0 - a c e t y l s u c r o s e a t 0° gave c r y s t a l l i n e 1 ' , 2 , 3 , 3 ' , 4 ' , 6 , 6 ' - h e p t a - 0 - a c e t y l - 4 - 0 ( m e t h y l s u l f o n y l ) s u c r o s e i n 8 8 % y i e l d (28). The l o c a t i o n o f the i s o l a t e d methanesulfonyloxy groups i n s u c r o s e c a n b e i d e n t i f i e d b y h i g h r e s o l u t i o n H n.m.r. spectroscopy. I n c o m p a r i s o n w i t h t h e H n.m.r. d a t a f o r o c t a - O - a c e t y l s u c r o s e , t h e s i g n a l d u e t o H-4, i n the above 4 - s u l f o n a t e d e r i v a t i v e , appeared a t a s l i g h t l y h i g h e r f i e l d , i . e . , a t x 5 . 2 (2_8) . S i m i l a r l y , i n t h e *H n.m.r. s p e c t r u m o f 1' ,3,3 ' ,4 ' ,6 ,6 ' - h e x a - 0 - a c e t y l 2 , 4 - d i - 0 - ( m e t h y l s u l f o n y l ) s u c r o s e , t h es i g n a l s due t o H-2 a n d H-4 a p p e a r e d a t r e l a t i v e l y h i g h e r f i e l d s , i . e . , a t T 5 . 3 5 a n d 5.2, r e s p e c t i v e l y ( 1 6 ) . f

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SUCROCHEMISTRY

46 Acetalation

Reaction

The v a l u e o f c y c l i c a c e t a l s f o r t h e p r o t e c t i o n o f h y d r o x y l g r o u p s i n c a r b o h y d r a t e c h e m i s t r y i s w e l l known. S e v e r a l c y c l i c a c e t a l s of s u c r o s e were s u c c e s s f u l l y s y n t h e s i z e d i n t h e l a s t two y e a r s . S u c r o s e , on t r e a t ment w i t h b e n z y l i d e n e b r o m i d e and p y r i d i n e f o r 0 . 5 h o u r a t 95° , a f t e r a c e t y l a t i o n a n d c h r o m a t o g r a p h i c separat i o n , gave 1 ,2,3,3',4 ,6 -hexa-O-acetyl-4,6-O-benzylidenesucrose (0) i n 35% y i e l d ( 2 9 7 " . The m e t h o d i n v o l v i n g the use o f 2 , 2 - d i m e t h o x y p r o p a n e , N , N - d i m e t h y l f o r m a m i d e , and p - t o l u e n e s u l f o n i c a c i d has been a p p l i e d t o m o n o s a c c h a r i d e s t o a f f o r d s t r a i n e d and o t h e r w i s e i n a c cessible c y c l i c acetals (30-33). Use o f t h i s c o m b i n a t i o n o f r e a g e n t s w i t h s u c r o s e and 6 , 6 ' - d i c h l o r o - 6 , 6 ' d i d e o x y s u c r o s e (P) g a v e s e v e r a l a c e t a l s . S u c r o s e , on treatment w i t h 2,2-dimethoxypropane i n N,N-dimethylformamide i n t h e p r e s e n c e o f a c a t a l y t i c p r o p o r t i o n o f £t o l u e n e s u l f o n i c a c i d , g a v e 4 , 6 - 0 - i s o p r o p y l i d e n e - and 1', 2:4,6-di-0-isopropylidenesucrose i n 55 and 15% y i e l d , respectively (16,34). The l a t t e r p r o d u c t , a p p a r e n t l y , c o n s t i t u t e s the f i r s t example i n c a r b o h y d r a t e c h e m i s t r y o f a compound w i t h an e i g h t - m e m b e r e d , c y c l i c a c e t a l r i n g (l',2-0-). The r e a c t i o n o f c o m p o u n d (P) w i t h t h e a b o v e c o m b i n a t i o n o f r e a g e n t s , a f t e r a c e t y l a t i o n and chromat o g r a p h y on s i l i c a g e l , a f f o r d e d 3 , 3 ' , 4 , 4 ' - t e t r a - O - a c e tyl-6,6 -dichloro-6,6'-dideoxy-1',2-O-isopropylidenes u c r o s e (Q) a n d 3 , 4 ' - d i - 0 - a c e t y l - 6 , 6 - d i c h l o r o - 6 , 6 dideoxy-l ,2:3,4-di-0-isopropylidenesucrose(R)in yields o f 37 and 3 9 % , r e s p e c t i v e l y (35) (See F i g u r e 6 ) . The r e a c t i o n o f 1, 6 , 6 ' - t r i - O - t r i t y T s u c r o s e w i t h 2 , 2 - d i m e t h oxypropane—N,N-dimethylformamide—j>-toluene s u l f o n i c a c i d a t room t e m p e r a t u r e , a f t e r a c e t y l a t i o n and c h r o m a t o g r a p h y on s i l i c a g e l , gave 2 , 3 - 0 - i s o p r o p y l i d e n e - l , 6 , 6 ' - t r i - O - t r i t y l s u c r o s e t r i - a c e t a t e and 3 , 4 - 0 - i s o p r o pylidene-T' ,6 , 6 ' - t r i t y l s u c r o s e t r i - a c e t a t e i n y i e l d s of 24% a n d 2 0 % , r e s p e c t i v e l y ( 3 5 ) .


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These r e s u l t s i n d i c a t e t h a t the o r d e r o f p r e f e r e n c e the formation of a c e t a l s i n sucrose i s 4,6>2,1'>2,3

>3,4.

Bimolecular Nucleophilic

Displacement

Reaction

Bimolecular n u c l e o p h i l i c displacement reactions of s u c r o s e s u l f o n a t e s and d e o x y h a l i d e s have been s t u d i e d . T r e a t m e n t o f o c t a - O - ( m e t h y l s u l f o n y l ) s u c r o s e (S) w i t h sodium i o d i d e i n butanone under r e f l u x gave 6 , 6 ' - d i deoxy-6,6'-dideoxy-6,6 -diiodo-1',2,3,3',4,4'-hexa-O( m e t h y l s u l f o n y l ) s u c r o s e (T) i n 75% y i e l d (26). The 1



4.

Fundamental Aspects

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Q Figure 6

i n a c t i v i t y o f t h e s u l f o n y l o x y g r o u p a t C - l ' i n (S) p r o b a b l y i s due t o u n f a v o r a b l e s t e r i c and p o l a r f a c t o r s . A difference i n the r e a c t i v i t i e s of the sulfonyloxy g r o u p s a t C-6 a n d C - 6 w a s n o t e d d u r i n g t h e r e a c t i o n o f 6,6'-di-0-£-tolysulfonyl s u c r o s e , benzoyl chloride, and p y r i d i n e a t room t e m p e r a t u r e (26). Subsequent i n v e s t i g a t i o n o f t h e r e a c t i o n o f 1 T 2 , 3 ,3 ,4 ,4 - h e x a - O acetyl-6,6 -di-0-£-tolysulfonyl s u c r o s e w i t h s o d i u m c h l o r i d e i n hexamethylphosphoric t r i a m i d e , gave l ' , 2 , 3,3 ,4,4'-hexa-0-acetyl-6, 6'-dichloro-6,6 -dideoxysuc r o s e a n d 1*2,3,3 4,4'-hexa-O-acetyl-ö-chloro-ö-deoxy6'-0-£-tolylsulfonylsucrose i n y i e l d s o f 51 a n d 3 4 % , r e s p e c t i v e l y (3£) . This suggested t h a t t h e s u l f o n y l 1

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American Chemical Society Library

1155 16th st. N. w. In Sucrochemistry; Hickson, J.; Washington, D.Chemical C. 20031 ACS Symposium Series; American Society: Washington, DC, 1977.

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o x y g r o u p a t C-6 i s m o r e r e a c t i v e t h a n t h e s u l f o n y l o x y g r o u p C-6'. A similar difference i n the r e a c t i v i t i e s o f t h e s u l f o n y l o x y g r o u p s a t C - l a n d C-4 i n (S) a l s o h a s b e e n e s t a b l i s h e d (37). Compound ( S ) , o n r e a c t i n g w i t h s o d i u m a z i d e i n hexamethylphosphorTc t r i a m i d e f o r 16 h r s . a t 85°,gave 6 - a z i d o - 6 - d e o x y - l , 3 , 4 - t r i - 0 - ( m e t h y l s u l f onylhß-]>-f r u c t o f u r a n o s y l 4 , 6 - d i a z i d o - 4 , 6 - d i d e o x y 2 , 3 - d i - 0 - ( m e t h y l s u l f o n y l ) - a - D - g a l a c t o p y r a n o s i d e (U) i n 80% y i e l d . When t h e a b o v e r e a c t i o n was p e r f o r m e d f o r 48 h o u r s a t 90° i t g a v e , i n a d d i t i o n t o t h e t r i a z i d e ( U ) (60%),1,6-diazido-l 6-dideoxy-3,4-di-O- (methylsulf onyl) ß-D-fructofuranosyl 4 6 - d i a z i d o - 4 , 6 - d i d e o x y - 2 , 3 - d i - O ( m e t h y l s u l f o n y l ) - a - D - g a l a c t o p y r a n o s i d e ( V ) i n 10% y i e l d . The s e c o n d a r y s u l f o n y l o x y g r o u p a t C-4 t h u s i s m o r e r e a c t i v e t h a n t h a t a t t h e p r i m a r y C - l p o s i t i o n i n (S) (See F i g u r e 7 ) .


1

f

f

1

I n t e r n a l Displacement

Reaction

Sucrose s u l f o n a t e s and d e o x y h a l i d e s , under b a s i c c o n d i t i o n s , h a v e b e e n shown t o u n d e r g o i n t e r n a l d i s placement r e a c t i o n s t o g i v e anhydro d e r i v a t i v e s (22,24, 26,38-42). T h e c o n v e r s i o n o f 6,6'-di-0-£-tolylsulf o n y l s u c r o s e ( L ) i n t o 3,6: 3 ' , 6 ' - d i a n h y d r o s u c r o s e (W) has been a c h i e v e d u s i n g sodium methoxide i n methanol (26). The d i a n h y d r i d e (W) a l s o h a s b e e n s y n t h e s i z e d from 6,6'-dichloro-6,6'-dideoxysucrose (P) i n 8 0 % y i e l d ( 4 3 ) , b y means o f s o d i u m m e t h o x i d e i n m e t h a n o l . A sTïnilar t r e a t m e n t o f 1 ' , 2 , 3 , 3 ' , 4 , 4 ' , 6 ' - h e p t a - O - a c e t y 16-chloro-6-deoxysucrose (X) w i t h M s o d i u m m e t h o x i d e i n methanol under r e f l u x , a f t e r c o n v e n t i o n a l a c e t y l a t i o n w i t h a c e t i c a n h y d r i d e and p y r i d i n e , gave c r y s t a l l i n e 1 ' , 2 , 3 ' , 4 , 4 ' , 6 ' - h e x a - O - a c e t y l - 3 , 6 - a n h y d r o s u c r o s e (Y) i n 83% y i e l d (42_) . (See F i g u r e 8 ) . Elimination

Reaction

Dehydrohalogenation o f 1',2,3,3',4,4'-hexa-O-benz o y l - 6 , 6 ' - d i d e o x y - 6 , 6 ' - d i i o d o s u c r o s e , 1',2,3,3',4,4'hexa-O-benzoyl-6,6'-dibromo-6,6'-dideoxysucrose, a n d öjö'-dideoxy-öjö'-diiodo-l ,2,3,3',4,4'h e x a - O - ( m e t h y l s u l f o n y l ) s u c r o s e , b y means o f s i l v e r f l u o r i d e a n d p y r i d i n e g i v e s t h e c o r r e s p o n d i n g 5,5'diene d e r i v a t i v e (26,36). 1 ,2,3,3',4,4',6'-Hepta-Oacetyl-6-deoxy-6-iodosucrose (Z^) o n t r e a t m e n t w i t h a n h y d r o u s s i l v e r f l u o r i d e i n p y r i d i n e f o r 24 h o u r s a t room t e m p e r a t u r e , a f t e r p u r i f y i n g f r o m a column o f s i l i ca g e l , gave 1 , 3 , 4 , 6 - t e t r a - 0 - a c e t y l - 3 - D - f r u c t o f u r a n o s y l 2,3,4-tri-0-acetyl-6-deoxy-a-D-xylo-hex-5-enopyranoside (AA) i n 6 0 % y i e l d (4£) . The h i g h r e s o l u t i o n n.m.r. s p e c t r u m o f (AA) s h o w e d t h e w e l l - k n o w n (45) a l l y l i c 1

1


Fundamental Aspects


4. KHAN

49

Figure 7

c o u p l i n g between t h e p r o t o n s ( S e e F i g u r e 9) Reduction

a t C-4 a n d C-6

(44).

Reaction

Deoxy d e r i v a t i v e s o f s u c r o s e have been p r e p a r e d b y c a t a l y t i c reduction o f the corresponding deoxyhalides o r e x o c y c l i c v i n y l e t h e r s (2£,2j5,3J7' ) • Reduction o f c o m p o u n d (Z)in m e t h a n o l w i t h R a n e y n i c k e l a n d h y d r a z i n e 44



SUCROCHEMISTRY

Figure 9


4.

KHAN

51

Fundamental Aspects 1

1

h y d r a t e gave t h e e x p e c t e d 1',2,3,3 ,4,4 6»-hepta-Oa c e t y l - 6 - d e o x y s u c r o s e (BB) i n 7 5 % y i e l d ( 4 4 ) . Reduction of theexocyclic vinyl ether ß-D-fructofuranosyl g - D - x y l o - h e x - 5 - e n o p y r a n o s i d e b y means o f p a l l a d i u m - o n c h a r c o a l i n methanol, a f t e r a c e t y l a t i o n and chromatography on s i l i c a g e l g a v e (BB) a n d l , 3 4 , 6 - t e t r a - 0 acetyl-ß-D-fructofuranosyl 2 , 3 , 4 - t r i - 0 - a c e t y l - 6 - d e o x y ß-L-idopyranoside (CC) i n 10 & 4 6 % y i e l d s r e s p e c t i v e l y . When s i m i l a r r e d u c t i o n w a s p e r f o r m e d w i t h (AA) i t g a v e t h e L - i d o i s o m e r (CC) a s t h e o n l y i s o l a b l e p r o d u c t i n 46% y i e l d . L i t t l e o r no f o r m a t i o n o f t h e D - g l u c o i s o m e r (BB) w a s o b s e r v e d . T h e s t r u c t u r e o f (CC) w a s s u p p o r t e d b y i t s 100 MHz H n.m.r. s p e c t r u m . The d e r i v e d f i r s t o r d e r c o u p l i n g c o n s t a n t s (Ji,2 *°'îl2 3 ' 'îZ.3 4 * and J / c 2 . 5 H * ) , w e r e i n a g r e e m e n t w i t h tließ-L-ido c o n f i g u atiön a n d ^ 4 c o n f o r m a t i o n f o r t h e h e x o p y r a n o s y l r e s i d u e i n (CC) (44_) . ( S e e F i g u r e 1 0 ) . f

f


f

f

2

Methanesulfonyl chloride plex Reaction

—

3

5

3

5

N, E j - D i m e t h y l f o r m a m i d e

Com-

The m e t h a n e s u l f o n y l c h l o r i d e a n d N , N - d i m e t h y I f o r mamide c o m p l e x [ M e 2 N = C H O M s ] C 1 " has been used f o r t h e s e l e c t i v e r e p l a c e m e n t b y c h l o r i n e (46>) o f p r i m a r y h y d r o x y l groups o f hexopyranosides. Subsequent investigat i o n o f t h i s r e a c t i o n with methyl glucopyranosides, m e t h y l ß-maltoside and s u c r o s e , r e v e a l e d t h a t s u b s t i t u t i o n also occurs o f secondary p o s i t i o n s (42,47,48).The s u b s t i t u t i o n o f t h eh y d r o x y l group a t a c h i r a l c e n t r e has b e e n shown t o p r o c e e d with inversion of configurat i o n (£7). T r e a t m e n t o f 1 , 2 , 3 , 3 , 4 , 6 - h e x a - O - a c e t y l s u c r o s e (DD) w i t h m e t h a n e s u l f o n y l c h l o r i d e a n d N N - d i methyIformamide, i n i t i a l l y f o r 2 hours a t 0° and t h e n f o r 24 h r a t 98 , g a v e t w o p r o d u c t s w h i c h w e r e s e p a r a ted on s i l i c a g e l and c h a r a c t e r i z e d as 1 , 3 , 4 , 6 - t e t r a O - a c e t y l - ß-D-fructofuranosyl 2 3 - d i - 0 - a c e t y l - 4 , 6 - d i c h l o r o - 4 , 6 - d i d e o x y - a - D - g a l a c t o p y r a n o s i d e (EE) a n d 1 , 2 , 3 , 3',4* 6 -hexa-0-acetyl-6-chloro-6-deoxy-4-0-formylsuc r o s e ( F F ) (4_2) . The f o r m a t i o n o f f o r m i c e s t e r s h a s b e e n r e c o g n i z e d (46) d u r i n g t h e r e a c t i o n o f h e x o p y r a n o sides w/methanesulfonyl c h l o r i d e — N N - d i m e t h y I f o r m i d e c o m p l e x v i a h y d r o l y s i s o f [Me2N=CHO"ÏÏ]~*Cl" O u r a t t e m p t s to i s o l a t e such i n t e r m e d i a t e s r e c e n t l y have been succ e s s f u l (4_2) . T h e f o r m y l g r o u p i n ( F F ) w a s s e l e c t i v e l y c l e a v e d b y t r e a t m e n t w i t h IRA-94S (HO ) r e s i n i n methanol t o a f f o r d 1',2,3,3 4 ,6 -hexa-0-acetyl-6-chloro-6d e o x y s u c r o s e (GG) . ( S e e F i g u r e 111". +

r

1

1

1

1

f

f

1

r

f

f

-

1

1

1

f



SUCROCHEMISTRY

Figure 11


4.

Fundamental Aspects

KHAN


Chlorosulfonylation

53

Reaction

The r e a c t i o n o f s u l f u r y l c h l o r i d e w i t h s u g a r s h a s been i n v e s t i g a t e d t o g i v e p r o d u c t s i n which t h e p r i m a r y h y d r o x y l groups were r e p l a c e d by c h l o r i n e and second a r y h y d r o x y l groups e i t h e r were e s t e r i f i e d b y c y c l i c s u l f a t e o r substituted by chlorine with inversion o f c o n f i g u r a t i o n (49-57). The r e a c t i o n o f methylß-D-glucopyranoside w i t h s u l f u r y l c h l o r i d e and p y r i d i n e has b e e n r e p o r t e d t o p r o c e e d v i a m e t h y l ß-D-glucopyranoside t e t r a k i s ( c h l o r o s u l f a t e ) t o give methyl 4,6-dichloro-4,6dideoxy-ß - D - g a l a c t o p y r a n o s i d e 2 , 3 - s u l f a t e (154) . The assumed S ^ c h a r a c t e r o f t h e d i s p l a c e m e n t r e a c t i o n h a s been q u e s t i o n e d r e c e n t l y b y Khan ( 5 5 ) . Treatment o f 2 , 3 , 3 ' , 4 , 4 ' - p e n t a - 0 - b e n z o y l s u c r o s e (HH) w i t h s u l f u r y l c h l o r i d e a n d p y r i d i n e i n c h l o r o f o r m a t -75° gave t h e corresponding 1 ' , 6 , 6 ' - t r i s ( c h l o r o s u l f a t e ) (II) i n 78% yield. Compound (11) o n t r e a t m e n t w i t h p y r T d i n i u m c h l o r i d e i n c h l o r o f o r m f o r 4 h o u r s a t 50° a f f o r d e d 2,3, 3',4,4'-penta-O-benzoyl-6,6'-dichloro-6,6'-dideoxysucrose 1'-chlorosulfate ( J J ) i n 76% y i e l d . The v a l u e of c h l o r o s u l f a t e r e s i d u e as a l e a v i n g group has been e m p h a s i z e d (5£) . H o w e v e r , when ( I I ) a n d 1 ' , 2 , 3 , 3 ' , 4 , 4 ' hexa-O-benzoylsucrose 6,6'-bis(chlorosulfate)was treated w i t h s o d i u m a z i d e i n b u t a n o n e , t h e o n l y i s o l a b l e p r o d u c t s were ( J J ) ( 8 3 % ) and 1',2,3,3',4,4'-hexa-O-benzoyl6,6'-dichloro-6,6'-dideoxysucrose (69%), r e s p e c t i v e l y . The a b o v e r e a c t i o n s u g g e s t e d a n e f f e c t i v e c o m p e t i t i o n by t h e c h l o r i d e i o n w h i c h c o u l d h a v e a r i s e n o n l y f r o m t h e c h l o r o s u l f a t e g r o u p s o f ( I I ) a n d 1',2,3,3',4,4'hexa-O-bensoylsucrose 6 , 6 ' - b i s ( c h l o r o s u l f a t e ) . Hence, t h e d i s p l a c e m e n t o f t h e c h l o r o s u l f a t e groups i n (II) and 1',2,3,3',4,4'-hexa-O-benzoylsucrose 6,6'-bis (cïïlorosulfate) b y c h l o r i d e i o n , p r o b a b l y i n v o l v e d a n intramolecular process, s i m i l a r t o theS 1 reaction o f a l k y l c h l o r o s u l f i t e s o r a l k y l chloroformâtes. (See Figure 12). N

N

Selective

D e - e s t e r i f i c a t i o n o f Sucrose

Derivatives

Selective d e - e s t e r i f i c a t i o n o f sucrose octa-acet a t e , u s i n g a column o f a l u m i n a ( L a p o r t e Type H ) , h a s been r e p o r t e d t o g i v e 2,3,4,6,1',3',4'-hepta-O-acetylsucrose, 2,3,6,1',3',4',6'-hepta-O-acetylsucrose, and 2 , 3 , 4 , 6 , 1 ' , 3 ' , 6 ' - h e p t a - O - a c e t y l s u c r o s e i n y i e l d s o f 9, 2.7 a n d 6% r e s p e c t i v e l y (58). We h a v e i n v e s t i g a t e d t h e u s e o f ammonia i n m e t h a n o l t o a c h i e v e s e l e c t i v e d e e s t e r i f i c a t i o n o f 2,1':4,6-di-O-isopropylidenesucrose tetra-acetate (KK). T r e a t m e n t o f t h e d i a c e t a l (KK) w i t h ammonia i n m e t h a n o l a t 0 ° , a f t e r c h r o m a t o g r a p E y o n



54

SUCROCHEMISTRY

a column o f s i l i c a g e l , gave S ^ ' - d i - O - a c e t y l - ^ , ! ' :4,6d i - O - i s o p r o p y l i d e n e s u c r o s e (LL) and 3 - 0 - a c e t y l - 2 , 1 : 4 6-dï"-0-isopropylidenesucrose (MM) i n y T e l d s o f 7 1 % a n d 22%, r e s p e c t i v e l y ( 5 7 ) . These r e s u l t s suggested t h a t the l a b i l i t y o f t h e a c e t y l groups i n t h e furanose r i n g o f (KK) w e r e i n t h e o r d e r o f 0-3=O-4>0-6. Lack o f r e a c t i v i t y o f t h e a c e t y l g r o u p a t 0-3 i n (KK) p r o b a b l y i s due t o t h e s t e r i c e f f e c t o f t h e n e i g h b o u r i n g a c e t a l (2,1':4,6-di-0-) groups. (See F i g u r e 1 3 ) . 1

f

Sucrose

Epoxides

The v a l u e o f s u g a r e p o x i d e s a s s y n t h e t i c i n t e r m e d i a t e s i s well-known i n carbohydrate chemistry. Synt h e s i s o f s u c r o s e epoxides h i t h e r t o has n o t been r e p o r -


4.

KHAN

Fundamental Aspects

55

ted. H o w e v e r , a n e p o x i d e d e r i v a t i v e o f s u c r o s e , 4,6dichloro-4,6-dideoxy-2,3-0-sulfo-a-D-galactopyranosyl 3,4-anhydro-l,6-dichloro-l,6-dideoxy-ß-D-ribo-hexulof u r a n o s i d e formed d u r i n g t h e r e a c t i o n o f sucrose and s u l f u r y l c h l o r i d e a t room t e m p e r a t u r e (57). T h e s t r u c t u r e o f t h e above epoxide h a s n o t y e t been c o n f i r m e d . I n t r a m o l e c u l a r Sßj2_ r e a c t i o n s o f 3 ,4 ' - d i - O - p - t o l u enesulfonylsucrose hexa-acetate(NN),3 -O-p-toluenesulfonylsucrose hepta-acetate(RR) and 4'-0-p-toluenesulp h o n y l s u c r o s e hepta-acetateTQQ) have been i n v e s t i g a t e d (59). T r e a t m e n t o f (NN) w i t h M s o d i u m m e t h o x i d e i n m e t h a n o l u n d e r r e f l e x f o r 1-2 m i n , a f t e r c o n v e n t i o n a l a c e t y l a t i o n and chromatography on s i l i c a g e l , gave 2,3, 4,6-tetra-O-acetyl-a-D-glucopyranosyl 1,6-di-0-acetyl3,4-anhydro-ß-D-lyxo-hexulofuranoside (00) a n d 2 , 3 , 4 , 6-tetra-O-acetyl-a-D-glucopyranosyl 1,6-di-0-acetyl-3, 4-anhydro-B-D-ribo-hexulofuranoside (PP) i n y i e l d s o f 76% a n d 1 2 % , r e s p e c t i v e l y . T h e s t r u c t u r e s o f (00) a n d (PP) h a v e b e e n c o n f i r m e d b y u n a m b i g u o u s s y n t h e s e s . R e a c t i o n o f t h e 3'-tosylate(RR) w i t h M sodium methoxide i n m e t h a n o l f o r 1-2 m i n , a f t e r a c e t y l a t i o n a n d c h r o m a t o g r a p h i c f r a c t i o n a t i o n , gave t h e r i b o - e p o x i d e (PP) i n 1


1

H 0 MM

Figure 13


56

SUCROCHEMISTRY

r i s e to a r i n g opening reaction e x c l u s i v e l y at C-4' i n each case (59). Consequently, reaction of the 3 ' , 4 ribo-epoxide (PP) with sodium azide followed by acetyl a t i o n gave a-D-glucopyranosyl 4 - a z i d o - 4 - d e o x y - £ - D - x y l o hexulofuranoside hepta-acetate (SS) i n 82% y i e l d . Similarly,treatment of the 3 ' , 4 - l y x o - e p o x i d e (00) with sodium azide followed by acetylation gave, 4 - a z T d o - 4 ' deoxysucrose hepta-acetate(TT) i n 63% y i e l d , as the only product. The d i r e c t i o n of cleavage of these epoxides, presumably, were governed by a combination of 96% y i e l d . The short time required for the formation of the epoxide indicated that the reacting groups (C-4',OTs and C - 3 ' , - 0 A c ) i n (RR) had coplanar configurations. Synthesis of the lyxo-epoxide (00)was achieved i n 82% y i e l d by treatment of the 4 ' - t o s y l a t e (QQ) with M s o d i um methoxide i n methanol under reflux for 1-2 m i n , f o l lowed by a c e t y l a t i o n with a c e t i c anhydride and p y r i d i n e . (See Figure 14). f

1


,

Ring Opening Reactions of Sucrose Epoxides Treatment of the ribo-(PP) and lyxo-(00) epoxides with sodium azide i n aqueous ethanol was found to give s t e r i c and polar f a c t o r s . In p a r t i c u l a r , the lack of r e a c t i v i t y at C - 3 i n each of these cases i s i n d i c a t i v e of the polar interactions which would occur between the permanent dipoles of the two C-2'-0 bonds and the d i pole which would be set up i n the t r a n s i t i o n state. This can be considered to be analogous to the low react i v i t y of a 2-sulphonyloxy group, i n n reactions, i n hexopyranosides. (Figure 15). 1

s

2

Acknowledgment I thank Professor A . J . V l i t o s , Chief Executive of the Tate & Lyle Research Centre, for his i n t e r e s t and support, and K . S . Mufti and M.R. Jenner who have p a r t i cipated during the past few years i n the program of work reviewed i n t h i s paper.My thanks are also extended to Professor L . Hough, Drs. K . J . Parker and H . F . Jones for h e l p f u l discussions. Abstract During the past six years, the objectives of our research have been to develop new applications of sucrose, by studying the fundamental chemistry of sucrose and i t s d e r i v a t i v e s . The value of c y c l i c acetal groups is well recognised for the protection of hydroxyl functions i n carbohydrate chemistry. The first synthesis of



4. khan

Fundamental Aspects

57

Figure 14 a c y c l i c a c e t a l d e r i v a t i v e of sucrose, 4,6-O-benzylidene sucrose, was achieved i n t h i s laboratory i n 1974. Since then progress i n t h i s f i e l d has been rapid and various c y c l i c acetals of sucrose and its d e r i v a t i v e s have been prepared. Sucrose on treatment with 2,2-dimethoxypropane-N, N-dimethylformamide-toluene-p-sulfonic acid (reagent A) gave 4,6-0-isopropylidene (55%) and 1 ' , 2 : 4 , 6 - d i - 0 - i s o propylidene d e r i v a t i v e (15%). When 6 , 6 ' - d i c h l o r o - 6 , 6'-dideoxysucrose was treated with reagent A , the corresponding mono-(1',2-) and di-(1',2:3,4-) acetals were


SUCROCHEMISTRY


58

TT SS

— Figure 15

isolated in yields of 40% and 37%, respectively. On the basis of these results, i t has been concluded that the order of preference for the formation of acetal l i n kage in the sucrose skeleton is 4,6>1',2>2,3>3,4. These cyclic acetals of sucrose and their derivatives allow selective reactions with previously inaccessible hydroxyl groups, in particular C-2, C-3, C-3', and C-4 . Some of these selective reactions also will be discussed. '

Literature Cited 1. Lemieux, R.U., Huber, G., J.Amer.Chem.Soc., (1953) 75, 4118. 2. Tushida, H., Komoto, M., Agr. Biol. Chem. (Tokyo), (1963), 29, 239--242. 3. Ness, R.K., Fletcher, Jr., H.G., Carbohyd. Res., (1971), 17, 465--470. 4. Reid, B.F., Intern. Symp. Carbohyd. Chem. VII in, Bratislava, (1974). 5. Hassid, W.Z., Dondoroff, M., Barker, H.A., J . Amer. Chem. Soc., (1944), 66, 1416--1419. 6. Hassid, W.Z., Dondoroff, M., Advan. Enzymol., (1950) 10, 123--143. 7. Kauss, H., Z. Naturforsch., (1962), 176, 698--699. 8. Beevers, C.A., Cochran, W., Proc. Roy. Soc. (London) Ser. A., (1947), 190, 257--272. 9. Beevers, C.A., McDonald, T.R.R., Robertson, J.H., Stern, F., Act. Crystallogr., (1952), 5, 689-690.



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KHAN

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10. Brown, G.M., Levy, H . A . , Science, (1963), 141, 921— 923. 11. Binkley, W.W., Horton, D . , Bhacca, N . S . , Carbohyd. Res., (1969), 10, 245—258. 12. De Bruyn, A., Anteunis, M . , Verhegge, G . , Carbohyd. Res. (1975), 42, 157--161. 13. Helferich, B . , Advan. Carbohyd. Chem., (1948), 3, 79--106. 14. Hough, L., Mufti, K . S . , Khan, R., Carbohyd. Res. (1972), 21, 144--147. 15. Reinfeld, E . , Klaudianos, S., Zucker, (1968), 21, 330--338. 16. Khan, R., Mufti, K . S . , Carbohyd. Res., (1975), 43, 247--253. 17. Gros, E . G . , Flematti, S.M., Chem. Ind. (1966), (London) 1556-1557. 18. Deferrari, J . O . , Gros, E . G . , Mastronardi, I . O . , Carbohyd. Res., (1967), 4, 432--434. 19. Lindley, M . G . , B i r c h , G.G., Khan, R., Carbohyd.Res., 43, 360--365 (1975). 20.Suami, T., Kato, N., Kawamura, M . , Nishimura, T., Carbohyd. Res., (1971), 19, 407--411. 21. Khan, R., Carbohyd. Res., (1972), 25, 232--236. 22. Khan, R., Carbohyd. Res., (1972), 22, 441--445. 23. Bragg, P . B . , Jones, J.K.N., Can. J. Chem., (1959), 37, 575--578. 24. Lemieux, R . U . , Barrette, J . P . , Can. J. Chem., (1959) 37, 1964--1969. 25. Neuman, R., Ibara, J.A., J. prakt. Chem., (1972), 314, 365--366. 26. Bolton, C.H., Hough, L., Khan, R., Carbohyd. Res., (1972), 21, 133--143. 27. Ballard, J . M . , Hough, L., Richardson, A.C., (Unpublished Data). 28. Khan, R., Unpublished data. 29. Khan, R., Carbohyd. Res., (1974), 32, 375--379. 30. Evans, M . E . , Parrish, F.W., Tetrahedron L e t t . , (1966) 3805--3807. 31. Evans, M . E . , Parrish, F.W., Long, Jr., L., Carbohyd. Res., (1967), 3, 453--462. 32. Hasegawa, A . , Fletcher, Jr., G . H . , Carbohyd. Res., (1973), 29, 209--222. 33. Hasegawa, A. and Nakajima, M . , Carbohyd. Res., (1973), 29, 239--245. 34. Khan R., Mufti, K . S . , Brit. Pat. 1,437,048. 35. Khan R., Jenner, M.R. and Jones, H . F . , Carbohydrate Research, 49, 259--265 (1976); Khan R., and Jenner, M.R., (Unpublished data). 36. Hough, L., Mufti, K . S . , Carbohyd. Res., (1972), 25, 497--503.


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37. Hough,L., Mufti, K . S . , Carbohyd. Res., (1973), 27, 47--54. 38. Lemieux, R . U . , Barrette, J.P., J. Amer. Chem. Soc., (1958), 80, 2243--2246. 38a.Lemieux, R . U . , Barrette, J.P., Can. J. Chem., (1960), 38, 656--662. 39. Buchanan, J.G., Cummerson, D . A . , Turner, D . H . , Carbohyd. Res., (1972), 21, 283--292. 40. Buchanan, J.G., Cummerson, D . A . , Carbohyd. Res. (1972), 21, 293--296. 41.Isaacs, N.W., Kennard, C . H . L . , O'Donnell, A.W., Richards, G . N . , Chem. Commun., (1970), 360. 42. Khan, R . , Jenner, M.R., Mufti, K . S . , Carbohyd. Res., (1975), 39, 253--262. 43. Khan, R., (unpublished data). 44. Khan, R . , Jenner, M.R., Carb. Res.,48,306-311(1976). 45.Sternhell, S . , Rev. Pure Appl. Chem., (1964), 14, 15--46. 46. Evans, M . E . , Long, Jr., L., Parrish, F.W., J. Org. Chem., (1968), 33, 1074--1076. 47. Edwards, R . G . , Hough, L., Richardson, A . C . , Tarelli, E., Tetrahedron L e t t . , (1973), 26, 2369--2370. 48. Khan, R . , Mufti,K.S.,Parker K.J.,Brit.Pat. 1,430,288 49. Helferich, B., B e r . , (1921), 54, 1082--1084. 49a.Helferich, B., Lowa, A., Nippe, W., Riedel, H . , Ber., (1923), 56, 1083--1087. 50. Helferich, B . , Sprock, G . , Bester, E., B e r . , (1925), 58, 886--891. 51. Jennings, H.J., Jones, J.K.N., Can. J. Chem.,(1962), 40, 1408--1414. 52. Jennings, H.J., Jones, J.K.N., Can J. Chem., (1963), 41, 1151--1159. 53. Jennings, H.J., Jones, J.K.N., Can J. Chem., (1965), 43, 2372--2386, 3018--3025. 54. Cottrell, A . G . , Buncell, E., Jones, J.K.N., Chem. Ind., (London), (1966), 552; Can. J. Chem., (1966), 44, 1483--1491. 55. Khan, R . , Carbohyd. Res., (1972), 25, 504--510. 56. Ballard, J . M . , Hough, L., Richardson, A . C . , Chem. Commun., (1972), 1097--1098. 57. B a l l a r d , J . M . , Hough, L., Richardson, A . C . , F a i r clough, P . H . , J. Chem. Soc., Perkin 1, (1973), 1524--1528. 58. Ballard, J . M . , Hough, L . and Richardson, A.C., Carbohyd.Res., (1974), 34, 184--188. 59. Khan, R., and Jenner, M.R., (Unpublished r e s u l t s ) .


4. KHAN

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Biographic Notes Riaz Khan, Ph.D., Industrial research chemist. Education at Bristol Univ. Joined staff of Tate & Lyle, Ltd., in 1968. Many papers on carbohydrate reactions and analyses. Philip Lyle Memorial Research Laboratory, Tate & Lyle, Ltd., P.O. Box 68, Reading, Berkshire RG6 2BX, England.


Some Fundamental Aspects of the Chemistry of Sucrose - American

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