Optical resolution of epoxy derivative of butyric acid with brucine and configuration determination by treatment with ammoni

Harada, K.

Oh-Hashi, J.-I.

English

NASA Technical Reports Server

# 
c 
. K  
I O  
1 0  
- 1 -  
F 
3 
K 
I -  
t: 
Tho d i r e a t  opoxidr t ion  o f  t ho  (loublo bond of  a ,  0 
unsa tu ra t ed  acid8 by p o r o q  .aid or by Q d r o a o n  poroxido ha8 
boer bown t o  bo (onoral ly  rory slow. 
butyrio  a c i d  ( o p o q  a c i d  I )  wu muccorrfully mynthorleod 
(~)-tra~-2,3-Bpoq- 
L 
from a r o t o a l c  r a i d  ( t r a m )  by opoxidr t ion  with hydrogon 
roa nu01 #.iiiiava - poroxido and 80dilU t w 8 t r t O  .i / LAw8ohits o t  g . i l / r o p o r t d  
tho m i r u t i o n  of I by t r o a t i n g  with berzyluino or ammonia 
in whiah thoy roportod tho myathorir of (*) r l l o t h r o o a i a ~ .  
In the promoat r tudy ,  tho o p o q  m i d  (I) w a 8  roso l rod  
by brucino. 
(-1 t r ra8-2 ,3-0poqbutyr ia  r a i d  ((-) o p o q  a c i d ]  (111) , It 
w a 8  t r o a t o d  with b o n t y l u i a o  o r  amoPia. a82 was done by 
Liwrohl tz  fi a. Tho r e 8 u l t l a g  I-bonzyl r l l o f h r o o n i n e  (IV) 
To d o t o m i n o  t h o  ooafigurrtion of the r e s o l r o d  
L’Storoochomi8try of  Olycidlc Aoid 11, P a r t  I of tu8 sor ior ,  
K. H l r d a ,  - J .  a. - Chom. 00, 000 (1966). 
2’Aid.d by G r a n t  no. SmG-689 of t h o  I a t i o a a l  h r O M U t i a 8  ud 
Sproo Admiai r t ra t ion .  Coa t r ibu t ioa  lo. 061 of  tho  
I n m t l t u t o  of I loloaular  Bvolut lon,  UnirorriQ of  Mlul. 
https://ntrs.nasa.gov/search.jsp?R=19660021324 2020-03-16T20:47:55+00:00Z
c 
. 
- 2 -  
was hydrogenolyced by the uae of pallrdilu on uhuaoal. The 
isolated cuino acid was found to be optically pur. (+)- 
allothreonine (V) and it did not contain any throonine or 
other amino acid, even in the reaction mixture This wa8 
exaained paper chromatographioally 2/ and nlmo by the automatic 
amino acid analyzer. This fact suggerte that the cuination 
proceed0 with a typical SN2 mechanism and no racemization 
occurs during the reaation. The configuration of the 
resulting (+)-allothreonine (v) is known as: 2(S), 3(S). 
Therefore the configuration of (-) trsn0-2,3-epoxybutyric 
acid would bo 2 ( B ) ,  3 ( S ) .  Tho reaction products of epoxy 
ncid and amaonia ahowed a l u g e  allothreonine peak and a 
little penk at about the rlmino .rea in the automatic amino 
acid ulalyeer, (ratio al1o:unknown = 99.4:0.6). The lattor 
peak might be a-hydroq 8-amino butyric acid (irothreonine) 
which is a possible ammonolyrio product. Attempts to obtain 
optically active a-hydroxybutyric acid by reduction 03 (-) 
epoxy acid (111) with sodium borohydride and by catalytic 
hydrogenation were unaucoermful. In each case, mainly 
8-hydroxybutyric acid war isolnted by column chromatography.- 6/ 
- 38 3421 >'K. N. F Shaw nnd S. W .  box, L. &. Chom (1953). n-but.nOl:.ooton.:oon8. m Z E T E : H F  0~12.5: 
12.5 :75. 
i'E. F. Phnres - et - * '  a1 A@. Chem. 3, 660 (1952). 
-._ . .-. 
I . 
r 
I 
- 3 -  
COOH 
brucine 
1 
CH' 
?Is. 1 
- 4 -  
(+) - trs~r-2 ,3- lEpo~butyric  w i d  ( I )  - T h e  opory ac id  
was prepared by tho  mothod of P y n o  a d  W i l l i a m .  21 
r.p. 83'.  
Brucine malt of (~)-traas-2,3-0poxybutyric  a c i d  (11) - 
Epoxy a c i d  ( I ) ,  20.4 g. ( 0 . 2  mol.), and bruc lne ,  78.8 g. 
(0.2 r o l e ) ,  woro d i r so lvod  In 200 m l .  of  ho t  methanol. T h o  
s o l u t i o n  war f i l t e r o d  19d t he  ro lvont  w a r  ovaporatod & 
- vacuo. 
of r o t h a n o l  ( 2 0  m l . )  d aootone (180 ml.) .  After e o o l l l y ,  
c r y s t r l l l t a t i o n  of  bruoino malt bogm by roodlag with m n  
r u t h o n t i c  r p o c h o n  whhh warn obt r inod  in m o t h o r  c r y s t a l l i e a -  
t i o n  o x p o r h o n t .  Aftor  rtaading o v o m h t  at room tempore- 
t u r o ,  t ho  orystals woro f i l t o r o d  .ILd woro warhod with oold 
acotone.  Tho c r y r t a l r ,  35.0 6 .  (73$), woro r o c r y r t r l l l e o d  
from a h o t  mixturo of mothmol ( 5  ml.) .pd aootono (95 ml.). 
Y i e l d ,  52 .0  g. ,  mop.  173.0, [el2' = -26.0. (2 2.1, E,O). 
Tho roe1du.l ryrup waa d i r r o l r o d  in a h o t  mlxturo 
B 
' (-) - t r m r - 2 , 3 = S p o q b u t y r i c  aoid (111) - B N C i D .  B d t  
(11). 14.3 g. (0 .05 mol.), war dimrolvod in 100 m 1 .  of 
wator .  To t h i o  r o l u t i o n ,  1 g  IaOB molutlon, 3 3  m l . ,  vu 
addod. The p r o o i p i t a t o d  b N o i n n  war rop r ra tod  by filtra- 
t i o n .  T h o  f i l t ra to  n m  oxt rac tod  with bontoao throo tima 
t o  remove tho rosldual bruaino . Conoontratod bJdroohlorIo 
I 
8 . 
- 5 -  
a c i d  w a 8  u8.d t o  bring t h o  pH of  tho  aquoour r o l u t l o n  t o  2.5. 
Aftor  r ra turat lon o f  tho  r o l u t l o n  w i t h  rodlum ohlorid., t h o  
opoxy a c i d  war o x t r r c t o d  wi th  o thor  fir0 t lrom (100 rl. x 
5 ) .  Tho o t h e r  r o l u t l o n  w u  dr iod  with w d r o u r  r o d i u  
rulfato.  Af tor  o rapora t ion  of othor, 1.80 (. (6M) of crud. 
I11 w u  obtaiaod.  T h i s  n m  r o o r y r t r l l l c o d  from boncono. 
1.20 6 .  (40$), B o p .  61'C, tal2' I: -82.5. ( a  - 0 . 5 9 ,  boncone). 
a 
h u t .  oqulr. Bound: 102. Celod. f o r  C4H6O3= 
I+) I-Bontyl-allothrooPino ( I V Y  - A mixture of 111, 
1.53 g. ,  wator ,  5 rl., and bonsyluino, 2 rl., wad rof luxod 
for 2 hr. Afto r  o o o l i w ,  t h o  oxuorr boney lu ino  w a r  rororod 
by o t h o r  oxtraotioa .ad tho pH of t h o  aquoour r o l u t i o n  w a r  
brought t o  5 .5  by tho  rd(1t lon of  oonuontratod w d r o o h l o r l c  
a c i d .  P r o c l p l t a t o d  IV v u  warhod with aaotono and thon with 
o ther .  Tho orudo produot ,  2.2 I .  (70$), w a r  r o c r y ~ t a l l l r o d  
from E , I ~ - d i . o t h y l f o r r u l d o .  T i o l d ,  2.0 6 .  (67s ) .  r . p .  
245.C (decorp . ) ,  = +12.2. (2 1.9,  5 L ' H C 1 ) .  Found: 
C ,  63.42; E, 7.20; I, 6.68. 
€I, 7.23; I, 6.69s.  
B 
Calod. f o r  Cl1Hl5O31t C ,  63.14; 
1.) Allothroonino (V) - (+) 1-Boneyl-a.llothroonino (IV), 
( 2 . 0 9  g o ) ,  w a r  d i r r o l r o d  In 50 m 1 .  o f  50$ o thaao l .  To th i r  
r o l u t l o n ,  1.0 8 .  of 5s palladium on charaoal rrr  d d o d  and 
t h o  hydrogonolyr i r  w a r  c u r i o d  o u t  at r00r tOrpOrrtW0. 
Vhoa the hydroam uptrlco aorrod, t ho  oa t r ly r t  war rororod  by 
I 
4 
I 
flltrrtloa. Tho flltrrto n a  aorooatrato4 g fac110. Tho 
aryetallino rorlduo n r  rooryrtrllisod from -tar aad 
ethanol. Tlold, 1.13 6.  (95s ) .  T h i s  n r  ropurlfiod f r o m  
wator (1) aad o t h u o l  (9). Yield, 0.95 g. (80$).  a - p .  
285.C, = +32.9. (2 1.9, I RC1).1’ Found: C, 40.09; 
H, 7.48; 19, 11.57. 
H, 11.76$. 
@ 
Calod. for C4H9103r C, 40.33; E, 7.62; 
L+] Allothroonlno (V) by auoaoly8i8 of (111) - 
A mixture of 1.53 8 .  (0.015 mole) of 111 and 50 m1. o f  
conc. .uoala (mp. gr. 0.90) ww kopt at room tomporrturo. 
After 4 d y r  tho rarctlon rlxturo wab oonoontrrtod & vacuo. 
A roi&ht of 1.43 6 .  (M) of ONde V w r 8  obtrinod.2’ T h i m  
w m  recryrtalli~od from wrtor .  T i o l d ,  0.50 g. (28$), 
r . p .  285.C (dooomp.), [a]** = +33.5. (c - 2.0, HCl).l’ 
B 
Snmtltute of PIoloculu Evolution 
- 6 -  
and Doputront of C h o i l r t r y  
Univormity of 131ui 
Coral Oablom, Florida 
~-~ - ~~ 
I’D. F .  Elliot, - -  J. Ch8i. =., 1950, 62. 
bI2’ - +32.5. (c - 8.2, E HC1). 
S’The orudo V ooatrina memo Impurity whloh 18 ninhydrin 
nogatfve. I t  d o o o ~ p o r o r  rt 238. aad rhowr rpocrifla 
rotation [uJ25 II +27.2. (2 2.1, 1 
(+)-Allothrooaine, 
m 
HC1). 
m 


Optical Resolution and Configuration of Trans-2,3-epoxybutyric Acid

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