ELMERE. JONES
2408
[CONTRIBUTION FROM
THE
AND
DAVIDLIPKIN
Vol. 78
DEPARTMENT O F CHEMISTRY, WASHINGTON UXIVERSITY]
Serine and Ethanolamine Diesters of Orthophosphoric Acid BY ELMER E.
JONES AND
DAVIDLIPKIN
RECEIVED NOVEMBER 25, 1955 (2-Aminoethyl)-(~-2’-amin0-2’-carboxyethyl)-pho~phoric acid ( I ) , the corresponding DL-serine derivative 11, bis-(o~-2amino-2-carboxyethpl)-phosphoricacid (111), bis-(2-aminoethyl)-phosphoric acid ( I V ) and the L-serine derivative corresponding to I11 ( V ) were prepared by techniques which lead to unequivocal structures for the products. Compound I, which was isolated as a formamide solvate, was shown to be identical in its paper chromatographic behavior with the phosphorus-containing compound recently isolated from turtle muscle by Roberts and Lowe. Furthermore compound I was hydrolyzed by snake venom in the same manner as the naturally-occurring compound.
Roberts and Lowe’ recently described the isola- the amino groups of both the ethanolamine and sertion from turtle muscle of a new phosphorus-con- ine were blocked by means of carbobenzoxy groups, taining compound. This compound ( I ) was found while the carboxyl group of the serine was proby these authors to be a diester of orthophosphoric tected by conversion to the benzyl ester. Phenyl acid in which one of the ester groups is derived from phosphorodichloridate was used as the blocked L-serine and the other from ethanolamine. Using a phosphorylating ager~t.~,b All of the blocking series of reactions which have been successfully ap- groups were removed from the intermediate neutral plied by Baer and his co-workers2t o the preparation phosphate esters (VI) by hydrogenolysis, first in of similarly constituted compounds, we have suc- the presence of a palladium catalyst and then a ceeded in synthesizing I as well as the DL-serine de- platinum catalyst. The products ( I to V) were puririvative (11) , bis-(DL-Z-amino-2-carboxyethyl)-phos-fied by cellulose column chromatography and were phoric acid (111) and bis-(2-aminoethyl)-phos- isolated in satisfactory over-all yields, with one exphoric acid (IV) . In addition, bis-(~-2-amino-2-car- ception. boxyethy1)-phosphoric acid (V) and I11 were isoThe bis-ethanolamine ester I V was isolated in lated as by-products in the preparation of I and 11, good crude yield (65YGbased on ethanolamine) , b u t respectively. The I and I1 prepared synthetically the final yield of the product was poor. This apparwere found to be identical in their behavior on pa- ently was due to the ease with which I V underwent per chromatography with a sample of the naturally- rearrangement and decomposition on attempting to occurring material isolated by Roberts and Lowe.’B3 purify it by recrystallization or cellulose column I t also was found t h a t I was hydrolyzed by snake chromatography. I t was demonstrated by paper venom in the same manner as the naturally-occur- chromatography t h a t when I V was allowed to stand ring c ~ m p o u n d . ~ a t room temperature in sulfuric acid solution a In order t h a t the syntheses of the compounds product of different R f was formed than when it was mentioned above be unequivocal, i t was necessary allowed to stand in sodium hydroxide solution. to use reactants t h a t were suitably protected by The fact t h a t IV contains two basic groups and blocking groups which eventually could be removed only one acidic group per molecule, whereas the readily by a mild procedure. As shown in the dia- other compounds (I, 11, I11 and V) do not contain grammatic representation of the reaction scheme more basic than acidic groups, may be related to the ease with which I V is converted t o other substances. Nitrogen-oxygen migrations of diisopropylphosphory16 or acyl groups’ in 1,2-aminoalcohols have been observed by other investigators. I t is probable that the instability of IV is due to this quinoline type of migration. Both of the products isolated in the preparation of I V (see Experimental section) are believed to be OH OC&6 pure ethanolamine diesters of orthophosphoric I Pt + HP Pd Hz I R”0-P *-OR”’ RO-P+-OR’ acid, even though they each give two spots on paHClOa I I per chromatography in one of the solvent systems CrHnOH 0\‘I 0used. The multiple spots are believed to be due to R and R’: CsH5CH20CONHCH~CHz-,DL- or different species, such as IV itself and the correL-CsHsCHzOOCCH( SHCOOCHzCsH5)CHzsponding positive ion formed by the addition of I : R”, L-HOOCCH(NH2)CHz-; R”’, HzVCH2CHzI1 : R ” , DL-HOOCCH(NHZ)CH~T;R”’, HzSCHL!Hza proton to IT’. The formation of multiple spots 111: R ” and R”’, DL-HOOCCH(~H*)CHZon paper chromatography of pure amino acids IT‘: R ” and R”’, HzKCHZCHZhas been observed.8,g V: R” and R”’,L-HOOCCH(N€IZ)CH~I
-+
(1) E. Roberts a n d I. P Lowe, J . B i d Chem., 211, 1 (1934). ( 2 ) E. Baer and hl. Kates, THIS JOURIAL, 70, 1394 (1948); E. Baer a n d M . K a t e s , Science, 109,31 (1949); E. Baer and hZ. Kates, THIS J O U R X A L , 72, 942 (1950); E. Baer, J. M a u r u k a s a n d M . Russell, Science, 113, 12 (1951); E. Baer, J. hfaurukas and hl. Russell, THIS J O U R N A L74, , 152 (1952); E. Baer and J. hfaurukas, ibid., 74, 158 (1952); E. Baer and €I. C. Stnnrer, i b i L 75, 4510 (1953). (31 !Ye wish t o thank rlr. 1Liii.etie l3, 11 7 8 [!I1 I,‘ I.i-
