3iOS wld water immediately before use), acidified with 1 cc. of 80% trichloroacetic acid and extracted with chloroform (10 cc.) The color density 17.1s measured in a photoelectric coloriincter (Klctt) with 640 nip filter The results are given in Table I A cdlibrdtion curve for the dye from 2~ ~ 2-naphthyl @-D-glUC0naphthol is given e b e ~ . h e r e . The fururoiiolactone was not hydrolyzed a t all by tissue homogengtes or by purified @-glucuronidase. 2-Naphthyl 8-0glucopyruronoside was readily hydrolyzed. The toluidine salt was ieiq readilv hvdrolvied than either the acid or bru-
11s drolysi5 bY Hydrolysis supernataiit rat spleen by purified glvcuroeidase homogenate in 4 hours in 4 hours Color Color density density
bubstratr
2- Saphthyl 8-D-glucopyr~iroiiosidc Brucine talt of 2-naphthyl
[COY1R I B U r I O S
,515
900
FROM 7 HE NOYFS
CIIFMICAI
raAROR.41 ORY, l - \ I \ F R S I T l OF TLI,IVOIS]
The Structure of Monocrotaline. XIV. B Y ROGER . b A & I S , H . L.
Synthesis of Monocrotalic Acid
~ 7 . % N n U U R E NA N D
KCCFIVEDTvr
1
F3 H. RRAYN
18, 1952
l-bfonocrotalic acid, obtained by the hydrogenolysis of the alkaloid monocrotaline, has been synthesized by the pertungstic acid oxidation of a,&r-trimethylglutaconic acid. The levo-isomer of a diastereoisomer of monocrotalic acid was also obtained during resolution of the oxidation product with brucine. The stereochemical configuration of monocrotalic acid was synthesized by two methods. acid is discussed. The previously undescribed 2,3-dimethyl-2,3-dihydroxybutyric
I n a previous paper' the synthesis of dihydroanhydromonocrotalic acid (I) was described. The structure of monocrotalic acid (11) as deduced by COOH
COOH
OH
I
cr-I c -c
e-0
CHs-CH
ciir
c 1%3--c 11-e-0
I
I1
degradation reactions2 was thus confirmed. Attempts to synthesize monocrotalic acid have now been successfully concluded. The double bond in a$,y-trimethylglutaconic acid (111) could not be hydroxylated by means of neutral potassium permanganate; the use of osmium tetroxide and hydrogen peroxide also failed. 'CVith pertungstic acid3 which favors trans addition, however, an oily acidic product resulted. This product, which could not be crystallized, proved to be a mixture of diastereoisomers of a,P-dimet hyl-P-hydroxy-y-carboxy- y-valerolactone (11), formed by lactonization of the a,P,y-trimethyla,@-dihydroxyglutaricacids (IV). CHJ CHI CH?
'
1
HOOC-CH-C-C--COOH I11 CHI OH
I
1
CH,
l l TIOOC-CH--C~C-COOH 1 1 CH3 OH
I1'
--+ OII
cooFr I
monocrotalic acid. Xn insoluble brucine salt separated which was readily purified and proved to be identical in melting point and rotation with the brucine salt of the authentic natural acid. Hydrolysis of the salt with hydrochloric acid yielded monocrotalic ;md, identical in melting point and rotation with monocrotalic acid from monocrotaline.4 'Thc product gave no depression in melting point on admixture with an authentic specitnen of monocrotalic acid. From the mother liquors of the crystallization of the first brucine salt, a second salt was obtained. This salt on hydrolysis yielded an acid, m.p. 180-lhl"", which gave a depression in melting point on admixture with monocrotalic acid. In a subsequent oxidation and resolution, the salt was not seeded with authentic brucine salt from rnonocrotalic acid. The brucine salt of the -60.8" acid crystallized out first and the brucine salt of monocrotalic acid was obtained from the mother liquors. From the mother liquors of the crystallization o f the first two brucine salts, a third fraction was obtained. This j)roduct proved to be a mixture of the salts of the two d-rotatory acids and could not bcx 5epdrated by fractional crystallization. The preparation of trimethylglutaconic acid presented unforeseen difficulties: Diethyl y-cyanoa,$,y-trimethylglutaconate (V) was prepared by the previously described method .> This ester on (I
+CH~--C-C-CAI
I
CHa-CHI1
>O CO
The oil from the pertungstic acid oxidation was treated with a mole equivalent of brucine in ethanol qolution and seeded with the brucine salt of natural ( 1 ) R. Adams and F B Hauserman, THISJ O U R N A L 74, 694 (1'352) ( 2 ) K Adams and T R Govindqchari, $bad, Z2, 158 fi'?joJ 1 7 ) hl Mugdan aud D P Young, J C h ~ mCOG 2'188 ( I S l S l
CII
CFI -C-C-
COOClH,
I
Cs
v
1-1
( 4 ) I
