DE703400C - Process for the preparation of adenosine polyphosphoric acids or their salts - Google Patents

Process for the preparation of adenosine polyphosphoric acids or their salts

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Publication number
DE703400C
DE703400C DE1939H0160350 DEH0160350D DE703400C DE 703400 C DE703400 C DE 703400C DE 1939H0160350 DE1939H0160350 DE 1939H0160350 DE H0160350 D DEH0160350 D DE H0160350D DE 703400 C DE703400 C DE 703400C
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adenosine
salts
polyphosphoric acids
preparation
yeast
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DR GEORG HENNING CHEM PHARM WERK GmbH
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DR GEORG HENNING CHEM PHARM WERK GmbH
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • C07H1/02Phosphorylation

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Description

Verfahren zur Herstellung von Adenosinpolyphosphorsäuren oder ihren Salzen Aus der Arbeit von N e e d h a m und v a n I I e y n i n g e n in der Zeitschrift »Nature«. London, Bd. 135 (1)35)e S.585, 586, ist es bekannt, daß durch Zugabe von Phospho- glycc#rinsäure und Adenylsäure zu welcher Allcali enthält, Adenosintri- hhosphorsäure gebildet wird. Das Arbeiten mit Muskelextrakt ist jedoch in der Praxis zu umständlich und kostspielig, zumal die hier- hei erzielten Ausbeuten nicht befriedigen. Aus der Arbeit von O s t c r n und T e r - szakotve@ in Hoppe-Sevlers Zeitschrift für ph@:ioloriischc Chemie, Bd. 250 (t937), 5. 155 bis 157, ist es weiterhin bekannt, (1a13 Adcnosin in Gegenwart von anorganischem I'ltosphat unter der Einwirkung von Ilefe teeben Adcn0siti-5-mottopltosphorsäurc auch .\<lcnosintriphosphors#iurc bildet. Gemäß der vorlie-enden 1'srfitlcttttt" gelingt cs nun, statt des erwähnten Gemisches prak- tisch nur Adenosintripltosphorsäure und -poly- pltosphorsäuren in 75- bis loot?.oI;;cr Reitt- licit frei von Adenosinntonophosphorsättre ztt ;et#:itinet@. . Dies ist deswegen von besonderer Iledeututlg, weil nach neueren physiologischen Untersuchungen gerade die Adenosintriphos- pltorsäure und -polvphosphorsäuren für die Beeinflussung des Kreislaufs von viel grü13e- rer Bedeutung sind als die Adenosinmono- phosphorsäure. Als Ausgangsmaterial kann bei dem neuen `'erfahren ebenso wie bei der bekannten Ar- beitsweise Adenosin als solches oder irgend- eine Verbindung verwendet werden, die sich, wie z. B. Iietettucleittsäure, ixt Adenosin spalten läl3t. Als Phosphat können ehensowohl an- organische Phospltatpulierlösungen als auch die bekannten Zuckerphosphorsäurcester, wie z. B. die sog. Neuberg-, Robison-, Cori-, Ktnb- den-, Ilardcn- und Young-Ester, verwendet werden, ebenso auch I'hosphoglyccrinsäiurc ; att<@Ii Mischun-en von organischem und an- orgattiscltcnt Phosphat sind verwendbar. Diese Ausgangsstolle »erden nun durch Einwirkung von friscltcr IIcfe, Trockenhefe bzw. Ilefc- cxtrakt oder IIefeplasrnolysat in Adenosintri- bzw. -polyphosphorsäure übergeführt. Dahui ist es von besonderer Bedeutung, (1a13 die Hefe in vorge-orenetn Zustande, und zwar zweck- tn:il:@i@ poY;tionsweise, dein Rc#ahtionsgcntisch i#- Iluie unthau =I11'1 . :.-t :.. r11 __ nanu. v #n real dah t_.. . tie t' .-..dVI:.-#-G-a_ 1-. .- -.!_- 11:I 1a,: :I. I. (1i, .a11-;<_ :t': i::u und . -.4r 1:1 .-. --;-?- . - aIn ::11 .Gt!t'la-taa Vllt- . isAc _.:.i ... _ ... , .:I! :i._- . z". ;he iszein taxe Phojllt>r. 1-.ur -#1@ @.Llt" 1:11)::(>1n((0-:- ::ol'Salt:re . @#t:.;_'@:1 ,,I@ utt tter @c.*.it::lSelItC'll ow:ar'_ket. Die @-tt=.Irr_st-i:@@:t ,_?,__.=lus: at-tr -:it°rer.de:l immyms . .. .. .!t:@01:ilür@ ...Ittttrt_:ie@IC!le: _ 4:71a _..all ttlie kr;itti;:i.-c:.@:\@ I-It@ie 1>t t"Iiola«-tti=e .i;'1- L@t-ahtir-tl7emi@rill:l: °usetzt, nm so ein :11lf- :a3:Iin:c=1 <er i-#.`. st@har.1=e si<-aer ::u I7illtler::. Sc,i@ai<I tlie zeit, date die Phllslthat- <ufnahnie e_:tsprechend weit fu.Tzl;acli.itte:. ist, .:irtl <i. _\Iist'..:It et"r@ntiull@_;en@ül-t :ascii <,_tire_coi: .,:n _ic@~LL:i=.:e@el:de `i''t#)@=>.ata=c I"<'stlt,s a!@n:tirtu::. Dieses Aufbot (1'n :11a1.` :Iller':iil:@_, _;:11l uinu Hydrolyse der ;gebil'!enn I't!!=.-1)ilol)11'=tl"@att'."e Hydrolyse verhirderr. ?17t1 eichst _u AII-ameL. '_11"1t-# neu. .-juus 1'n1 !UM c @ru:uie sui, die _1>Cherhiute Miacltun'g ,such .-" h .:iet:e: " -@ ;111t endet da andunfalls alle EIIT 1'.p1(1: - k. , durch I-i#:drrayse Wreten ka:at IMe -1x @-#:o;l:;er.t- 1_;;t@u:r@ d@c pr.lkti;ch leas gesamte .@tlc;:t@sitl in Form der I'ol-phos. la1'rsliuren elahale `:11-t1 1:11I: !u:te'hniäblg nie l 1e ::>1i1 @ .:lü-'ievee t'.urch Iviltrwimn llc#- ir#'i r@ ir:ü;@i@;cit '::ird r111? t-i11er kltlizelarier- t"I1 I_t".@l1Il@. ill('@ la't!ali@all@al/e#. \('(l 7.. 11i. li:ll"lt;ln:l@ta;::, ttl--t'tlT, n:il die ge-aIntell .We- tlt:sinj,,@i:.-I,ll@)@hlmrs;iurtel i:2 Irlrm ihrer I3:t- r@ulllsai@a ;u f;iI1cI1. 1)1<,e I):7riums:ll-re 1\crdul .i:-:SC.=...'l.t'a: .271I :et'(lu.-:I1W 1' @t't;l`:(.'?C'L@<lllt"e. 1 ü,.. W .a2"1 :-#O;:,l::i.el;, 11;1L.: tja yt'WLI17tC' 1>,("111I11 als riit' die truic .lclenasir:u-i=;:."spllt3r.aiurc 13zv. :@tlcn@sinpulu_ I@hct.;pllc)rs:iure u:.tll:ilt,.': i11-'1 durch zctiti-itii- _jerell schne!: tont \ierlt@r>c 111a t#eti-eriiii, da- Init 111e ialerst'iiti==i;e S:iurt' 11:'1n< scll:it@li<-lu' u:id :11-1(,1((l in t'.ic@üt:f- i@i, llit-..tei 1,13h t:i'.lt.(`.:tl'i:@t:-tl .. @I#:alr ;111(-e als _ IW'_'r war v- 1-1 pnltiwh 1r1'1 1t)7( 1 :1.@@11'..:Ilü"-lleltl 1'nt@@lht:li und 1:11t- ((11("t-12 etwas 1r171 teer kann. tilela- 1-"-a::#t"1 :11e:. ':e, @tlt:.t.@121- a11.17; 111t. I_@J_:::::, .::tch l£t'iii .@u1h.,chun u2111 hihrit-Ie'n Ilüt , i' . h"!!, c ui: it'i-tt l1 ljisunl; lcr r-t>t/t 111((l .\Ilcohul zu;iht. llil'rliti t;:!@t i1 di,' : alchunsalzu der \tlrt:t,@in!nll@-I)!!@_!rll ,,-_,,ulr'Il ;I111. 11i1' 11lllnit- tt'lll;lr vt'!".\t':Itlll;ll" @1nd. (!h, in it 1-ll:lltcll \\'ertlcil, hü;il:el..:ur II@ r<11 (:1l it#r Baliuni-, \mriuni-< \Ia;;ne@ium-. \Iall@,@lli<;ll@t' u,\\. diellcn. die als hruis'a1111llinel 11i' eletltun'; 1,11c(!. Linigc' Bei- -ollen ((,i, V@ rf;lllrt #I 111:i1(1': <#rl:iurc'nt. Iit'i:i3it i I rusclü,ullg verrührt. Init ,; 1-i'.' -\atriumphus- ;#hallll>un und ; 1 1 t' hli;gel- .\dello#.in- - Wur', versetzt und irei i, " ;111g1"y)1'l'll. Nach i Stu:a!'_' setz( :11.:7: 1 '.:,.; !i1#11(. die illit 1 1 ist. und ;ao r1 (n I'oluoi zu utd,wi duriltit dic Zugabe der Hefe nach K nur Wtrla 11 Stunde. W:ill- rel:d des _anzeli \Wui hcs \1 iO geruhrt. Die .lufrt;llune lies in,ganist-licn Phosphors wird I;lil!t'lltl i@t@llll-Illllel-L 1111(L 111'r V ursuch altge- ;-trt i,( (l, nenn kri1) 1'lt@t.!rli<sr nu'hr auftc_ 17,;1:n `.:irtl @::Inc:l a11fge'kocht, ,.t rt let ::üh't ..:!11 UMt. 11ß' , lyslmg Und niit \autlaLm;lt' skau>1mrmacht und 11111 1);ll-IL:Illallt.lt @c@@111. 11a5 rollt' Iiar111177- .ldcl;t,_illh\rl\pllr,,l@l:at '\1:-1l ;Il>icl:trifu@icrc und nlit und .@Il;t@!u@l ;`t\\:I@t'lleil. @-t rrul:rt n(.(:: a@ ,,11c I'lo,@!,i1;1t ullccr Lvüh- Il:: ::n .. @ti@c1: Mull.;e verdünnter und Üil'L5t dic' Losung 'u:au:- 1<üllrt'li i:i 1'11l inchrtadles @@@Illf:lell .-'@Ilitrllt@l. <.t 1<111t t in «t`il:@t#:, 11u1-ki- ;@c> Produkt .111s. '.\-t'It'lll'@ 1111 \ve,#t`Iltlichen <ILI@ 1111'1l rohu:1 .@llt'litt@lilpl)I\'p@lll@pllol'@al@l'l'11 he'lchl. l>it.e '.,-<r<11'1( -)toll .th,rr;augt ulld 1)11t :1i;;olltsl und Sie sind will- umpilndllch Il I',ellt'llll@hl'IL 111(d :;(1:,s1'11 sutti;-t im I:@#ihl::lttrr@trul'kllct ller- rlt (l. 1 (1t' .\usl)t'n;r lit 4t '\\ i@t'llt`II -lt> ulld ;o g. I>1'iapicI _ 1 h@; (111'r1<11 viril luit 1 1 Iull,J;Uer 1J11- rrl Inll ; 1\;1;1"Itlllll)lltl@- I:I::lr:ti.-III:. l,1'11 ; u11(1 = ! 1 ""i;;t'r _111ellosill- lt-111i#.I \-t`I#el/L 11((1l 1,1'I ';7 .Ill,.@l':@t)1'(`11. \;11'l1 .u \Iilllnell #t'.t@t ((lall ' S @; ! I tlt'Ii\@etlll>llt»l)lit)1'_ @,Illlt'@ \.il1IIIII1 1 I I.tl@llll@l 11111L ,jUOI'('111111- '.Ittl l(11.1 n:1(11 \lllll'1-t'll : 1l @Illlllll'll nochmals I 11;g 1L1:!1', 111t' Inh 1 I 1 t"' @tl;',L'I- ( .llll't3@('llr@llll ltt:;a'@,t.lt:t in, ,':1. @::ltt 1,1 tl,'!@t@t'tli!riltl,ltilnl"- ,.tLll-c o.11(1( 111w .':lt-Ilrt-lait'I:tlt' \letlnt' 1'1W i- pllt,;;iyt'ri;l \@'viu'r- \t r;1111 11u1: \\iu in l@t:i-I»el 1. Beispiel 3 i kg Bierhefe wird mit 1 1 i o %iger G1 ucoselösung verrührt; nach Beginn der stürmischen Gärung werden 5 1 i o,'oiger Adenosinlösung, i5o g fructosediphosphorsaures Natrium in 3 1 Wasser oder die entsprechende Menge phosphoglycerinsautes Natrium und 3oo ccm Toluol zugesetzt. Es wird gerührt und die Temperatur auf 37° gehalten. Nach 30 Minuten wird nochmals i kg Bierhefe, die mit 11 1oofoiger Glucoselösung angegoren ist, zugegeben. W eiterverarbeitung wie in Beispiel 1. Beispiel i oo g Hefenucleinsäure werden bis zur vollständigen Spaltung mit Emulsin behandelt. Man entfernt das Guanosin, kocht das Reaktionsgemisch kurz auf, klärt die Lösung und unterwirft sie, wie im Beispiel i angegeben, der Gärung. Nach Beendigung der Phosphorylierung wird schnell kurz aufgekocht und die gebildete Adenosinpolyphosphorsäure in der Lösung durch Ermittlung der leicht abspaltbaren Phosphorsäure bestimmt. Will man die Adenosinpolyphosphorsäure isolieren, so fällt man sie als Bariumsalz, zentrifugiert ab und wäscht mit destilliertem Wasser aus. Zur weiteren Reinigung löst man in verdünnter Salpetersäure, klärt die Lösung u:-.d neutralisiert bis zu einem pH-Wert von 6. Die ausfallenden Bariumsalze werden, wie in Beispiel i angegeben,' weiterbehandelt. Die Bildung der Adenosinpolyphosphorsäure ist praktisch quantitativ. Die gleichzeitige Anwesenheit von Cytidin und Uridin beeinflußt die Phosphorylierung nicht. Beispiel 5 Man spaltet ioo g Hefenucleinsäure mit Pyridin, vertreibt das Pyridin durch Destillation mit Wasserdampf und verarbeitet die verbleibende Lösung, wie in Beispiel q. angegeben.Process for the preparation of adenosine polyphosphoric acids or their salts From the work of Needham and van II eyningen in the journal "Nature". London, vol. 135 (1) 35) e p. 585, 586, it is known that by adding phospho- glyc # ric acid and adenylic acid which contains Allcali, adenosine tri- phosphoric acid is formed. The work however, using muscle extract is in practice too cumbersome and expensive, especially since the hot yields are not satisfactory. From the work of O stcrn and T er - szakotve @ in Hoppe-Sevler's magazine for ph @: ioloriischc Chemie, Vol. 250 (t937), 5. 155 to 157, it is also known (1A13 Adcnosine in the presence of inorganic I'ltosphate under the action of Ilefe Teeben adcnositi-5-mottophosphoric acid too . \ <lcnosine triphosphorus # iurc forms. According to the present 1'srfitlcttttt "succeeds cs now, instead of the mentioned mixture practically table only adenosine triphosphoric acid and poly phosphoric acids in 75- to loot? .oI ;; cr Reitt- licit free from adenosine monophosphorus saturation ztt ; et #: itinet @. . That is why this is special Iledeututlg, because according to recent physiological Investigations especially the adenosine triphosphere Fluoric acid and polyphosphoric acids for the Influencing the circulation of much greener are of greater importance than the adenosine mono- phosphoric acid. The starting material for the new '' experience as well as the well-known art sometimes adenosine as such or any- a connection can be used that is such as B. Iietettucleittäure, ixt cleave adenosine laps. Both phosphate can be used organic phosphor powder solutions as well the known sugar phosphoric acid esters, such as z. B. the so-called Neuberg-, Robison-, Cori-, Ktnb- den, Ilardcn and Young esters are used be, as well as phosphoglyccric acid; att <@Ii Mixtures of organic and other orgattiscltcnt phosphates are usable. These Exit tunnels »are now grounded by action of friscltcr IIcfe, dry yeast or Ilefc- extract or plasma plasmolysate in adenosine tri- or polyphosphoric acid converted. Dahui it is of particular importance (1a13 the yeast in pre-established condition, specifically tn: il: @ i @ poY; tion mode, your rc # ahtionsgcntisch i # - Iluie unthau = I11'1 . : .- t: .. r11 __ well. v #n real dah t_ ... tie t ' .- .. dVI: .- # - G-a_ 1-. .- -.! _- 11: I 1a ,:: II (1i, .a11 -; <_: t ': i :: u and . -.4r 1: 1 .-. -; -? -. - a In :: 11 .Gt! t'la-taa Vllt- . isAc _.:.i ... _ ...,.: I! : i ._-. z ".; he iszein taxe Phojllt> r. 1-.ur - # 1 @ @ .Llt " 1:11) :: (> 1n ((0 -: - :: ol'Salt: right. @ # t:.; _ '@: 1 ,, I @ utt tter @c. *. it :: lSelItC'll ow: ar'_ket. the @ -tt = .Irr_st-i: @@: t, _?, __. = lus: at-tr -: it ° rer.de: l immyms . .. ...! t: @ 01: ilür @ ... Ittttrt_: ie @ IC! le: _ 4: 71a _ .. all ttlie kr; itti;: i.-c:. @: \ @ I-It @ ie 1> tt "Iiola« -tti = e .i; '1- L @ t-ahtir-tl7emi @ rill: l: ° usetzt, nm like this: 11lf- : a3: Iin: c = 1 <er i - #. `. st@har.1=e si <-aer :: u I7illtler ::. Sc, i @ ai <I tlie time, date the Phllslthat- <ufnahnie e_: correspondingly far fu.Tzl; acli.itte :. is,.: irtl <i. _ \ Iist '..: It et "r @ ntiull @_; en @ ül-t: ascii <, _ tire_coi:.,: n _ic @ ~ LL: i = .: e @ el: de `i''t #) @ =>. ata = c I "<'stlt, sa! @N: tirtu ::. This mobilization (1'n: 11a1.` : Iller ': iil: @_, _ ;: 11l uinu hydrolysis of the; gebil'! Enn I't !! = .- 1) ilol) 11 '= tl "@att'." E Prevents hydrolysis. ? 17t1 calibrates _u AII-ameL. '_11 "1t- # new ..-Juus 1'n1! UM c @ru: uie sui, die _1> Cherhiute Miacltun'g, such .- "h.: iet: e:" - @; 111t ends there otherwise all EIIT 1'.p1 (1: - k., through Ii #: drrayse Wreten ka: at IMe -1x @ - #: o; l:; er.t- 1 _ ;; t @ u: r @ d @ c pr.lkti; ch leas entire. @ tlc;: t @ sitl in the form of I'ol-phos. la1 ' r sliuren elahale `: 11-t1 1: 11I:! u: te'hniäblg never l 1e ::> 1i1 @.: lü-'ievee t'.urch Iviltrwimn llc # - ir # 'ir @ ir: ü; @ i @; cit' :: ird r111? t-i11er kltlizelarian- t "I1 I_t". @ l1Il @. ill ('@ la't! ali @ all @ al / e #. \ (' (l 7 .. 11i. li: ll "lt; ln: l @ ta; ::, ttl - t'tlT, n: il die ge-aIntell .We- tlt: sinj ,, @ i: .- I, ll @) @ hlmrs; iurtel i: 2 Irlrm their I3: t- r @ ulllsai @ a; uf; iI1cI1. 1) 1 <, e I): 7riums: ll-re 1 \ crdul .i: -: SC. = ... 'l.t'a: .271I: et' (lu .-: I1W 1 '@ t't; l` :(.'? C'L @ <lllt " e. 1 ü, .. W .a2 "1: - # O;:, l :: i.el ;, 11; 1L .: well yt'WLI17tC '1>, (" 111I11 as riit 'die truic .lclenasir: ui =;:. "spllt3r.aiurc 13zv.: @ tlcn @ sinpulu_ I @ hct.; Pllc) rs: iure u: .tll: ilt ,. ': i11-'1 by zctiti-itii- _jerell schne !: tont \ ierlt @ r> c 111a t # eti-eriiii, that- Init 111e ialerst'iiti == i; e S: iurt '11:' 1n <scll: it @ li <-lu ' u: id: 11-1 (, 1 ((l in t'.ic@üt: f- i @ i, llit - .. tei 1,13h t: i ' .lt. (`.: tl'i: @t: -tl .. @ I #: alr; 111 (-e as _ IW '_' r war v - 1-1 pnltiwh 1r1'1 1t) 7 ( 1 : 1. @@ 11 '..: Ilü "-lleltl 1'nt @@ lht: li and 1: 11t- ((11 (" t-12 something 1r171 tar can. tilela- 1 - "- a :: # t" 1: 11e :. ': e, @tlt: .t. @ 121- a11.17; 111t. I_ @ J _ :::::,. :: tch l £ t'iii. @ U1h., Chun u2111 hihrit-Ie'n Ilüt, i '. h "!!, c ui: it'i-tt l1 ljisunl; lcr rt> t / t 111 ((l. \ Ilcohul to; iht. llil'rliti t;:! @ t i1 di, ': alchunsalzu der \ tlrt: t, @ in! nll @ -I) !! @_! rll ,, -_ ,, ulr'Il; I111. 11i1 '11lllnit- tt'lll; lr vt '! ". \ t': Itlll; ll" @ 1nd. (!there it 1-ll: lltcll \\ 'ertlcil, hü; il: el ..: ur II @ r <11 (: 1l it # r Baliuni-, \ mriuni- < \ Ia ;; ne @ ium-. \ Iall @, @ lli <; ll @ t 'u, \\. light. as hruis'a1111llinel 11i 'eletltun'; 1,11c (!. Linigc 'Bei- -ollen ((, i, V @ rf; lllrt #I 111: i1 (1 ': <#rl: iurc'nt. Iit'i: i3it i I rusclü, ullg stirred. Init,; 1-i '.' - \ atriumphus- ; #hallll> un and; 1 1 t 'hli; gel-. \ Dello # .in- - Wur ', offset and irei i, ";111g1" y) 1'l'll. To i Stu: a! '_' set (: 11.: 7: 1 '.:,.;! i1 # 11 (. die illit 1 1 is. and ; ao r1 (n I'oluoi zu utd, wi duriltit dic addition the yeast after K only Wtrla 11 hours. Want- rel: d des _anzeli \ Wui hcs \ 1 iO stirred. the .lufrt; llune lies in, ganist-licn phosphorus will I; lil! T'lltl i @ t @ llll-Illllel-L 1111 (L 111'r V ursuch old- ; -trt i, ((l, nenn kri1) 1'lt@t.!rli <sr nu'hr auftc_ 17,; 1: n `.: Irtl @ :: Inc: l a11fge'kocht, , .t rt let :: üh't ..:! 11 UMt. 11ß ', lyslmg And not \ autlaLm; lt 'skau> 1mrmacht and 11111 1); ll-IL: Illallt.lt @ c @@ 111. 11a5 rolls' Iiar111177- .ldcl; t, _illh \ rl \ pllr ,, l @ l: at '\ 1: -1l; Il> icl: trifu @ icrc and nlit and. @ Il; t @! u @ l; `t \\: I @ t'lleil. @ -t rrul: rt n (. (:: a @ ,, 11c I'lo, @ !, i1; 1t ullccr Lvüh- Il :: :: n .. @ ti @ c1: Mull .; E thinned and Üil'L5t dic 'solution' u: au: - 1 <üllrt'li i: i 1'11l inchrtadles @@@ Illf: lell .- '@ Ilitrllt @ l. <.t 1 <111t t in «t`il: @ t # :, 11u1-ki- ; @c> product .111s. '. \ - t'It'lll' @ 1111 \ ve , # t`Illichen <ILI @ 1111'1l rohu: 1. @ Llt'litt @ lilpl) I \ 'p @ lll @ pllol' @ al @ l'l'11 he'lchl. l> it.e '., - <r <11'1 ( -) toll .th, rr; augt ulld 1) 11t: 1i ;; olltsl and you are will- umpilndllch Il I ', ellt'llll @ hl'IL 111 (d :; (1:, s1'11 sutti; -t im I: @ # ihl :: lttrr @ trul'kllct ller- rlt (l. 1 (1t '. \ usl) t'n; r lit 4t' \\ i @ t'llt`II -lt>ulld; o g. I>1'iapicI _ 1 h @; (111'r1 <11 viril luit 1 1 Iull, J; Uer 1J11- rrl Inll; 1 \; 1; 1 "Itlllll) lltl @ - I: I :: lr: ti.-III :. l, 1'11; u11 (1 =! 1 ""i;;t'r _111ellosill- lt-111i # .I \ -t`I # el / L 11 ((1l 1,1'I '; 7 .Ill,. @ l': @ t) 1 '(`11. \; 11'l1 .u \ Iilllnell #t'.t@t ((lall 'S @;! I tlt'Ii \ @etlll> falls »l) lit) 1'_ @, Illlt '@ \ .il1IIIII1 1 I I.tl @ llll @ l 11111L, jUOI'('111111- '.Ittl l (11.1 n: 1 (11 \ lllll'1-t'll: 1l @ Illlllll'll again I 11; g 1L1:! 1 ', 111t' Inh 1 I 1 t "'@tl;', L'I- (.llll't3 @ ('llr @ llll ltt:; a '@, t.lt:t in,,': 1. @ :: ltt 1.1 tl, '! @ t @ t'tli! riltl, ltilnl "- , .tLll-c o.11 (1 (111w. ': lt-Ilrt-lait'I: tlt' \ letlnt '1'1W i- pllt, ;; iyt'ri; l \ @ 'viu'r- \ tr; 1111 11u1: \\ iu in l @ t: iI »el 1. EXAMPLE 3 1 kg of brewer's yeast is stirred with 1 1 10% strength glucose solution; After the start of the stormy fermentation, 5 liters of 10% adenosine solution, 150 g of fructose diphosphoric acid sodium in 3 liters of water or the corresponding amount of phosphoglycerol sodium and 300 cc of toluene are added. It is stirred and the temperature is kept at 37 °. After 30 minutes, another 1 kg of brewer's yeast, which has been fermented with 11 100% glucose solution, is added. Further processing as in Example 1. Example 100 g of yeast nucleic acid are treated with emulsin until the cleavage is complete. The guanosine is removed, the reaction mixture is briefly boiled, the solution is clarified and subjected to fermentation, as indicated in Example i. After the end of the phosphorylation, the mixture is quickly boiled for a short time and the adenosine polyphosphoric acid formed in the solution is determined by determining the easily split off phosphoric acid. If the adenosine polyphosphoric acid is to be isolated, it is precipitated as a barium salt, centrifuged and washed out with distilled water. For further purification, the solution is dissolved in dilute nitric acid, the solution is clarified and neutralized up to a pH value of 6. The barium salts which precipitate are treated further as indicated in Example i. The formation of adenosine polyphosphoric acid is practically quantitative. The simultaneous presence of cytidine and uridine does not affect the phosphorylation. Example 5 100 g of yeast nucleic acid are cleaved with pyridine, the pyridine is driven off by distillation with steam and the remaining solution is processed as in Example q. specified.

Claims (1)

PATENTANSPRÜCHE: i. Verfahren zum Herstellen von Adenosinpolyphosphorsäuren oder ihren Salzen durch Anlagerung von Phosphorsäureresten an Adenosin unter der Einwirkung von Hefe, gegebenenfalls in Gej#enwart von vergärbaren Zuckern, dadurch gekennzeichnet, daß man die Hefe in bereits vorgegorenem Zustande, zweckmäßig portions,-weise, mit der Adenosin und Phosphorsäurereste enthaltenden Reaktionsmischung zusammenbringt, das Gemisch nach erfolgter Phosphorylierung rasch zum Kochen bringt, rasch wieder abkühlt und die nach dem Versetzen der Lösung mit einer Erdalkaliverbindung erhaltenen Salze abtrennt. z. Verfahren nach Anspruch i, dadurch gekennzeichnet, daß man die nach Anspruch i erhaltenen Salze der Adenosinpolyphosphorsäuren mit Mineralsäure zersetzt und aus der erhaltenen Lösung die Adenosinpolyphosphorsäuren mit Hilfe von Alkohol fällt.PATENT CLAIMS: i. Process for the preparation of adenosine polyphosphoric acids or their salts by the addition of phosphoric acid residues to adenosine under the Effect of yeast, possibly in the presence of fermentable sugars, thereby characterized in that the yeast is already pre-fermented, expediently in portions, with the reaction mixture containing adenosine and phosphoric acid residues, quickly bring the mixture to a boil after phosphorylation has taken place, quickly again cools and obtained after the addition of an alkaline earth compound to the solution Separates salts. z. Process according to claim i, characterized in that the according to claim i obtained salts of adenosine polyphosphoric acids with mineral acid decomposed and from the resulting solution the adenosine polyphosphoric acids with the help drops of alcohol.
DE1939H0160350 1939-08-05 1939-08-05 Process for the preparation of adenosine polyphosphoric acids or their salts Expired DE703400C (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1283845B (en) * 1961-10-05 1968-11-28 Schwarz Bio Res Inc Process for the preparation of 5'-di- and / or 5'-triphosphates of adenosine, guanosine, cytidine, uridine or deoxyadenosine

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1283845B (en) * 1961-10-05 1968-11-28 Schwarz Bio Res Inc Process for the preparation of 5'-di- and / or 5'-triphosphates of adenosine, guanosine, cytidine, uridine or deoxyadenosine

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