S Y N T H E S I S O F 6 - A M I N O L E V U L I N I C

A C I D H Y D R O C H L O R I D E

S. I . Z a v ' y a l o v , N. I . A r o n o v a , N . N . M a k h o v a , a n d Y u . B . V o l ' k e n s h t e i n

UDC 542.91:547.484.451:547.466

6-Aminolevulinic acid (I) is a b i o p r e c u r s o r of the porphyr ins and has a s t imulat ing effect on the b io- synthes is of v i tamin BI2 [1]. F o r a fur ther study of the b iochemica l p rope r t i e s of (I), in the p r e sen t pape r we accompl i shed the d i rec t synthes is of hydrocblor ide (II) by the reac t ion of hippuric acid (III) with C1CO �9 (CH2)2COOCH3(IV) in 7-picol ine and the subsequent acid hydro lys i s of the in te rmedia te 2 - p h e n y l - 4 - ( f l - c a r - bomethoxypr opionyl)-5-oxaz olinone (V)

C0(CH~)~COOCH3

CsH~CONHGH2COOH(III) (iV} '1 oI=O H,oHC------]-* HC1 .H2NCH~CO(CH2)2COOH(II)

- - ~ ( v )

The p repa ra t ion of (V) f rom (III) and (IV) r e p r e s e n t s the f i r s t case of using (HI) in the D a k i n - W e s t reac t ion with an acid chloride. The chemical synthes is of (II) accompl ished by us is s im i l a r to the biogenesis of (I) f rom ~ycoco l l and succinic acid [1].

E X P E R I M E N T A L M E T H O D

p r e p a r a t i o n of (II). With s t i r r ing , to a solution of 40 g of (III) in 200 ml of T-p ico l ine was added 56 ml of (IV) a t such a r a t e that the t e m p e r a t u r e r emained a t 5-0~ (~ 2 h), a f t e r which the mix tu re was s t i r r e d a t this t e m p e r a t u r e for another 5 h. With s t i r r i ng , the reac t ion m a s s was poured into a mix tu re of 1 kg of ice and 160 ml of conc. HC1, and the obtained p rec ip i t a te was washed in success ion with wa te r and ethyl a c e - tale. We obtained 41 g (65%) of (V), mp 176-178 ~ , which did not depress the mixed mel t ing point with an authentic spec imen [2].

The obtained (V) was mixed with 1 l i t e r of dilute HC1 solution (1 : 1), ref luxed for 10 h, and cooled to ~20 ~ The obtained benzoic acid was f i l te red, while the mothe r l iquor was ref luxed for 30 min in the p r e s - ence of ac t ive carbon, which was r emoved by f i l t ra t ion and the f i l t ra te was evapora ted in vacuo to d ryness . The res idue was dissolved in 20 ml of conc. HC1 a t ~100 ~ a f t e r which 200 ml of acetone was added with s t i r r i ng , and the mix tu re was kept a t ~20 ~ for 3 h. The obtained c ry s t a l s were f i l te red , washed with a c e - tone, and dr ied in a v a c u u m - d e s i c c a t o r over KOH. We obtained 19 g (51%) of (II), mp 148-151 ~ , which did not dep re s s the mixed mel t ing point with an authentic spec imen.

CONCLUSIONS

A method was developed for the synthesis of 6-aminolevul inic acid by the reac t ion of the acid chlor ide of monomethyl succinate with hippuric acid in 7 -p i c~ and subsequent acid hydro lys i s of the in te rmedia te 2-phenyl-4-( f i - ca rbomethoxypr opionyl) -5-oxazol inone.

LITERATURE CITED

i. V. Ya. Bykhovskii, N. I. Zaitseva, and V. N. Bukin, Progress in Biological Chemistry, Vol. i0, Nauka (1969), p. 199.

2. W.R. Hearnand M. E. Wfldfeuer, Anal. Biochem., 2, 140 (1961).

N. D. Zel inski i Inst i tute of Organic Chemis t ry , Academy of Sciences of the USSR. Izves t iya A k a d e m i i N a u k SSSR, Seriya Khimicheskaya , No. 3, pp. 657-658, March , 1973. submit ted May 17, 1972.

Translated from Original article

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