DE2034784A1 - Adenosine 5 carboxylic acid ester - Google Patents

Description

BOEHRINGER MANNHEIM GMBH

I7IO

Adenosine-5'-carboxylic acid ester

The present invention relates to adenoein-S ¹ -carboxylic acid esters of the general formula I

B — 0 -

(D,

0 0

in which R is an aliphatic or araliphatic group

and Z is two hydrogen atoms or the divalent radical of one lower alkyl group means »

as well as processes for the production of the same

The new compounds of general formula I are valuable intermediate products and are used for the production of substances with strong circular

running effect, especially that in our patent application int · Kr * 1702 » ι File number F described connections

The process for the preparation of the compounds of the general Formula I is characterized by the fact that adenosine-5'-carboxylic acids of the general formula II

JH ₁

HOO

0 0

in Veloher Z has the meaning given above ', with compounds of the general formula III

E-OH (III).

in which R has the meaning given above,

converts in the presence of strong mineral acids and the Pfο obtained products I, if desired, umsatert in a manner known per se.

109884/1 85Λ

It is extraordinarily surprising that the Bioh Esterification method using strong intrinsic acids, especially concentrated ones Sulfuric acid, in this special case, can be carried out, “Since it is known that the glyoosidic bond in adenosine is extreme easily attackedj it was above all not foreseeable that the reactions almost quantitative or in excellent yields get lost.

₍ It has proven particularly advantageous for the further processing of the intermediate products I to use those compounds of the general formula III in which the radical R is a lower alkyl radical or an araliphatic radical with a lower alkylene group.

The esterification of the adenosine-5 ¹ -carboxylic acid is best carried out at a low temperature in a large excess of the alcohol component of the formula III in the presence of a catalytic amount of mineral acid; the same applies in the event that an ester of the general formula I is to be transesterified.

The eosine-5 "-carboxylic acid used as the starting product is in Soo. 1963, p. 1152 and reports 101, p. 590 (1968).

In the following examples, the process according to the invention is used explained in more detail «

109884/1854

game 1

One gives <0 S Adesesin-fj ^ easebon & aur © in © in ßomiseh of 1 "4 absolute methaaol and 15 parts of concentrated sulfuric acid © - wnd or = heats 45 Minatea sra Si © d © n _e Di © sohuash © solution is filtered and Bit © in®s? Solution r®n 27 g KfatriOThydrogsnoarbonat in 1 liter water v © rs © tsto Ea d®s3 aautr © lisi © rt © n Reaktioasgemisoh. there is "l next © 500 Express / ater ₉ can üb®s laaht in the refrigerator to crystallize _s sa ^ gt @b wad troelmet di © Torbiadting ia iakura = trookeneciiraako Man rhält © 47 S (92 fo A ₀ ¹ ₀ Sh) Adonosin = 5 ^! = oarfeon = acid methyl ester? voa Sotop ₀ 215 ° 217 Co

In an analogous way, by converting the free adenosine = 5 '= carboxylic acid jait itanol d © adenosine ^ i'"Cagbj m @ aure ~ ät] grlester (mp. 204-205 0) ia aiB © ^ Ausbettt © voa 78 fa & ₀ Κι ° and the adenosine = · ^

C) in © in © r yield © of 54 '^ doTh

© i s ρ i © 1

10 g 2 ' _t 5'-0-IaopEOpjlid®a = 5'"© © rfeonssur® are dissolved in 400 ml M © ethanol uud ial'ö 6 al toassSisfeisiPteX ¹ SOhWSfSIsMIiS ¹ Q v®r @ © tsto The reaction is left 4 sti »fi © a fe®! Ziaaisrteaperatus '© t®h © n neutralizes düiaa ait © lass *' LSnaag from 17 in 200 ml ¥ as @ ®r ₀ The @ms | _

naoheinaader ait 5 S ^ ig © r "wlss ^ ig ©?

Water and essential methaaol

10.4 B 2 ·, J '^ O ^ IsogPopjlis

(Pp. 239-24O ⁰ G) in oiaes ¹ ABstomto of 74 fs

Example 3

Adenosine-5'-carboxylic acid-n- "buty! Ester

5 g of adenosine-5'-carboxylic acid methyl ester are dissolved in 200 ml of n-butanol and refluxed for 3 hours together with 3 g of D-amphetamine. The reaction mixture is filtered and the filtrate is evaporated in vacuo. The residue is triturated with ether, filtered off with suction, washed again with ether and dried. 5 »6 g of adenosine-5'-carboxylic acid n-butyl ester (melting point 166467 C-) are obtained in a yield of 87 io of theory. The crude product can be recrystallized from water.

example Adenosine-5'-carboxylic acid n-hexyl ester

5 g of adenosine-5'-carboxylic acid are dissolved in 2 ml of concentrated sulfuric acid and heated to 100 ° C. for 3 hours. While it is cooling, the reaction mixture is neutralized with triethylamine and left to stand overnight, the n-hexyl ester and sulfuric acid triethylamine crystallizing out. The latter is washed out with water after suction and the remaining ester is recrystallized from methanol. 3 g (48 ^ of theory) of adenosine-5'-carboxylic acid n-hexyl ester with a melting point of 145-147 ° C are obtained -

109884/1854

example Adenosine-3'-carboxylic acid benzyl ester

5 g of adenosine-5'-carboxylic acid inethylester are suspended in 200 ml benzyl alcohol under the addition of 7 8 triethylamine and heated for 5 hours at 10O ⁰ C, wherein the ester goes into solution,! Times the reaction is complete pulls the base and excess alcohol in the vacuo, the residue is triturated with ether to remove amine and solvent residues and crystallized after the suction from water. 5.3 g (53 % of theory) of adenosine 5'-carboxylic acid benzyl ester with a melting point of 144-145 C- are obtained.

109884/1854

Claims (1)

Pa t e η t a η β ρ ri o-h β Adenosine-5 ^l -o®r "bona acid ester of the general, ΡογιηθΙ Ι ffl, ■ ι (D, O O aliphatic or araliphatic group in almost all cases uad two hydrogen atoms or the "bivaleatea Rm% lower " Alky! group 2 · Process for the production of AdiBnoBia-J'-oartoaeättreeetera. the general formula 1 .- —0 - 0 On. 0 0 109884/1854 (D ¹ in which R is an aliphatic or araliphatic group and Z is two hydrogen atoms or the bivalent radical of a lower alkylene group! means _t characterized in that adenosine-5'-carboxylic acids of the general Formula II Ξ00 oo in other words, Z has the abovementioned meaning ait compounds of the general formula III R- OH in which R has the meaning given above, Reacts in the presence of strong mineral acids and the products obtained I, if desired, transesterified in a manner known per se. 109884/1854 BAO ORIGINAL