LT4663B - N-formyl-o-acyl-threo- and erythro-dl-beta-phenylserine ethyl esters and process for preparing thereof - Google Patents

N-formyl-o-acyl-threo- and erythro-dl-beta-phenylserine ethyl esters and process for preparing thereof Download PDF

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LT4663B
LT4663B LT99-087A LT99087A LT4663B LT 4663 B LT4663 B LT 4663B LT 99087 A LT99087 A LT 99087A LT 4663 B LT4663 B LT 4663B
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acyl
beta
formyl
erythro
phenylserine
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LT99087A (en
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Juozapas Straukas
Nijole Dirvianskyte
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Biochemijos Institutas
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Abstract

This invention presents a convenient preparatory method allowing synthesis of N,O-diacyline beta-phenyl serine structures with different acyl groups. In the system formic acid - hydrogen fluoride in the on-going migration of N-acyl beta-phenyl serine combinations of the acylic N > O is accompanied by N-formyl. Using this method, new N-formyl-O-acyl-threo- and erythro-DL-beta-phenylserine ethyl esters are synthesised from N-acyl-threo and erythro-DL-beta-phenyl serine ethyl esters in good yield after affecting them with 1.5% hydrogen fluoride solution in formic acid.

Description

Išradimas yra iš nebaltyminių aromatinių aminorūgščių chemijos ir yra skirtas naujiems N-formil-O-acilinių β-fenilserino dariniams ir jų preparatyviniam gavimo būdui.The present invention relates to non-protein aromatic amino acid chemistry and is directed to novel N-formyl-O-acylic β-phenylserine derivatives and their preparative process.

Žinoma, kad kai kurie N-aciliniai, O-aciliniai bei N,O-diaciliniai β-fenilserino dariniai pasižymi gana plačiu biologinio veikimo spektru, būtent, priešuždegiminiu (SU a.l. 689139, 1979; 757522, 1980; 961297, 1982 ir 1078844, 1983), antivinisiniu (SU a.l. 1135150, 1984; 1140423, 1984; 1363764, 1987 ir 1405269, 1988), fungicidiniu (SU a.l. 936608, 1982; 1048698, 1983 ir 1197394, 1985), imunosupresiniu (SU a.l. 790622, 1980).Some N-acylic, O-acylic and N, O-diacyl derivatives of β-phenylserine are known to exhibit a relatively broad spectrum of biological activity, namely anti-inflammatory (SU al 689139, 1979; 757522, 1980; 961297, 1982 and 1078844, 1983). ), antiviniscent (SU al 1135150, 1984; 1140423, 1984; 1363764, 1987 and 1405269, 1988), fungicidal (SU al 936608, 1982; 1048698, 1983 and 1197394, 1985), immunosuppressive (SU al 790622, 1980).

Aukščiau nurodytos Ν,Ο-acilinių fenilserino darinių biologinės savybes sudaro prielaidas šio tipo junginių tolimesnėms paieškoms ir sąlygoja poreikį surasti patogų jų gavimo būdą. Lig šiol nesusintetinta N-formil-O-acilinių fenilserino junginių ir nežinomas patogus jų gavimo būdas. Todėl šio išradimo tikslas yra gauti N-formil-O-acilinius fenilserino darinius, kurie yra potencialūs antivirusinio. priešuždegiminio, kancerolitinio veikimo požiūriu.The biological properties of the Ν, Ο-acylphenylserine derivatives referred to above provide the basis for further search for this type of compound and the need to find a convenient way to obtain it. So far, N-formyl-O-acyl phenylserine compounds have not been synthesized and a convenient method for their preparation is not known. It is therefore an object of the present invention to provide N-formyl-O-acyl phenylserine derivatives which are potent antiviral. in terms of anti-inflammatory, carcinolytic action.

Šio išradimo esmė - sistemoje skruzdžių rūgštis-vandenilio fluoridas pravedama Nacilinių β-fenilserino darinių acilinės grupės N—>0 migracija, tuo pačiu metu vykstant Nformilinimui. Tokiu būdu, šis patogus preparatyvinis metodas leidžia gauti su skirtingomis acilinėmis grupėmis N.O-diacilinius β-fenilserino darinius (1 b-7b).SUMMARY OF THE INVENTION The present invention is directed to the systemic migration of formic acid-hydrofluoric acid to the acyl group N → O of the acyl group of N-acyl β-phenylserine derivatives, with simultaneous N-formylation. Thus, this convenient preparative method allows the preparation of N.O-diacylic β-phenylserine derivatives (1b-7b) with different acyl groups.

Junginių lb-7b sintezė vykdyta pagal žemiau pateiktą schemą 1:The synthesis of compounds lb-7b was carried out according to the following scheme 1:

Schema 1Scheme 1

C6H5CH(OH)CHCOOC,H5 C 6 H 5 CH (OH) CHCOOC, H 5 HF/HCOOH χΟ -> C6H5CH(OCZ RjCHCOOC’TLHF / HCOOH χ Ο -> C 6 H 5 CH {OC Z RjCHCOOC'TL i /P i / P i i HNC-R HNC-R HNC-H HNC-H DL, la-7a DL, la-7a DL, lb-7b DL, lb-7b

Junginiai Compounds la, b la, b 2a, b 2a, b 3a, b 3a, b 4a, b 4a, b 5a, b 5a, b 6a, b 6a, b 7a, b 7a, b Diastere- omerai Diastere- omerai treo treo eritro erythro treo treo treo treo treo treo treo treo eritro erythro R R ch3 ch 3 ch3 ch 3 ch3ch; ch 3 ch ; BrCH,CH, BrCH, CH, c6h5ch.c 6 h 5 ch. F1 F1 F1 F1

čiaFl =C6H4^hereFl = C 6 H 4 ^

I CH-CFT.I CH-CFT.

csh/c s h /

N—>0 acetilinės grupės migracijai naudoti N-acetil-treo-DL-P-fenilserino etilo esteris la ir N-acetil-eritro-DL-P-fenilserino etilo esteris 2a buvo resintezuoti literatūroje aprašytu būdu [\V.S. Fones. J. Org. Chem., Vol. 17, p.p. 1734-1739 (1952)]. Kondensuojant propionilo, 3-bromopropionilo, fenilacetilo ir 9-fluorenacetilo chloridus atitinkamai su treo bei eritro DL-P-fenilserinų etilo esterių hidrochloridais [K.N.F. Shavv, S.W. Fox. J.Amer. Chem. Soc., Vol. 75, p.p. 3417-34 (1953)] chloroforme dalyvaujant trietilaminui buvo sintezuoti N-propionil-treo-DL-P-fenilserino etilo esteris 3a, N-(3-bromopropionil)-treoDL-P-fenilserino etilo esteris 4a, N-fenilacetil-treo-DL-P-fenilserino etilo esteris 5a, N-(9fluoreneacetil)-treo-DL-P-fenilserino etilo esteris 6a ir N-(9-fluoreneacetil)-eritro-DL-Pfenilserino etilo esteris 7a. N-Acil-treo- bei eritro-DL-P-fenilserinų esterius (la-7a) paveikus 1,5 % vandenilio fluorido tirpalu skruzdžių rūgštyje buvo gauti N-formil-O-aciltreo- bei eritro-DL-P-fenilserinų etilo esterių dariniai (lb-7b). Sintezuotų β-fenilserino darinių 3a-7a ir lb-7b išeigos, lydymosi temperatūros, kristalinimo tirpikliai, empirinės formulės ir elementinė analizė pateikta 1 lentelėje. Šių junginių IR spektrai užrašyti Perkin Elmer Spectrum BX FT-IR spektrometru vazelino aliejuje. Junginių la-7a IR spektrų duomenys pateikti 2 lentelėje, o junginių lb-7b IR spektrų duomenys - 3 lentelėje. Ή BMR spektrai užrašyti spektrometru Hitachi R-22 (Japonija) su darbiniu 90 MHz dažniu, vidinis etalonas - heksametildisiloksanas, temperatūra 35 °C. Junginių 3a-7a ‘H BMR spektrų duomenys pateikti 4 lentelėje, o junginių lb-7b ‘H BMR spektrų duomenys - 5 lentelėje.N-acetyl-threo-DL-P-phenylserine ethyl ester la and N-acetyl-erythro-DL-P-phenylserine ethyl ester 2a were used to synthesize the N-> 0 acetyl group, and were synthesized as described in the literature. Fones. J. Org. Chem., Vol. 17, p.p. 1734-1739 (1952)]. By condensation of propionyl, 3-bromopropionyl, phenylacetyl, and 9-fluorenacetyl chlorides with hydrochlorides of ethyl esters of threo and erythro DL-P-phenylserines, respectively [K.N.F. Shavv, S.W. Fox. J.Amer. Chem. Soc., Vol. 75, p.p. 3417-34 (1953)] in the presence of triethylamine in chloroform, N-propionyl-threo-DL-P-phenylserine ethyl ester 3a, N- (3-bromopropionyl) -threoDL-P-phenylserine ethyl ester 4a, N-phenylacetyl-threo- DL-P-phenylserine ethyl ester 5a, N- (9-fluoreneacetyl) -treo-DL-P-phenylserine ethyl ester 6a and N- (9-fluoreneacetyl) -erythro-DL-Pphenylserine ethyl ester 7a. Esters of N-Acyl-threo- and erythro-DL-P-phenylserines (la-7a) were treated with 1.5% hydrogen fluoride in formic acid to give ethyl esters of N-formyl-O-acyltreo and erythro-DL-P-phenylserines. derivatives (lb-7b). The yields, melting points, crystallization solvents, empirical formulas, and elemental analysis of the synthesized β-phenylserine derivatives 3a-7a and lb-7b are shown in Table 1. The IR spectra of these compounds were recorded on a Perkin Elmer Spectrum BX FT-IR spectrometer in petroleum jelly. The IR spectra of the compounds la-7a are shown in Table 2 and the IR spectra of the compounds lb-7b are shown in Table 3. Ή NMR spectra recorded on a Hitachi R-22 spectrometer operating at 90 MHz, internal standard - hexamethyldisiloxane, temperature 35 ° C. The H NMR spectra of the compounds 3a-7a 'are shown in Table 4 and the 1 H-7b' H NMR spectra are shown in Table 5.

Sekantys pavyzdžiai iliustruoja šį išradimą.The following examples illustrate the present invention.

Pavyzdys. N-Aciliniai β-fenilserinų etilo esterių dariniai 3a-7a.An example. N-Acylic derivatives of the ethyl esters of β-phenylserines 3a-7a.

Į 2,46 g (10 mM) β-fenilserino etilo esterio hidrochlorido ir 20 ml chloroformo mišinį 0 °C temperatūroje maišant pridedama 3 ml (22 mM) trietilamino, o po to 10 mM atitinkamos rūgšties chloranhidrido. Reakcijos turinys 1 vai. virinamas, po to atvėsinamas iki kambario temperatūros, paeiliui praplaunamas vandeniu, IN druskos rūgštimi, 5 % natrio bikarbonato tirpalu, vandeniu. Chloroforminis ekstraktas džiovinamas bevandeniu natrio sulfatu. Chloroformą pašalinus vakuume, gautas produktas perkristalinamas iš atitinkamo tirpiklio (žr. 1 lentelę).To a stirred mixture of 2.46 g (10 mM) of β-phenylserine ethyl ester hydrochloride and 20 ml of chloroform at 0 ° C was added 3 ml (22 mM) of triethylamine followed by 10 mM of the corresponding acid anhydride. Reaction contents for 1 h. Boil, then cool to room temperature, wash successively with water, IN hydrochloric acid, 5% sodium bicarbonate solution, water. The chloroform extract was dried over anhydrous sodium sulfate. After removal of chloroform in vacuo, the resulting product is recrystallized from the appropriate solvent (see Table 1).

Pavyzdys. N-Formil-O-aciliniai β-fenilserinų esterių dariniai lb-7b.An example. N-Formyl-O-Acylic Derivatives of β-Phenylserine Esters lb-7b.

g N-acilinto β-fenilserino etilo esterio (la-7a atitinkamai) ir 10 ml 1,5 % vandenilio fluorido tirpalo skruzdžių rūgštyje (paruošto iš 48 % vandenilio fluorido vandeninio tirpalo ir >99,7 %-skruzdžių rūgšties) 1 vai. šildoma 50 °C temperatūroje. Po to atvėsintas reakcijos turinys išpilamas ant ledo. Junginiai lb-5b išsiskiria alyvos pavidalu, kurie ekstrahuojami chloroformu. Chloroforminis ekstraktas džiovinamas bevandeniu natrio sulfatu. Tirpiklį pašalinus vakuume, produktas perkristalinamas iš atitinkamo tirpiklio (žr. 1 lentelę). Kietame pavidale išsiskyrę junginiai 6b ir 7b atskiriami filtravimu, kurie po to perkristalinami iš praskiesto etilo alkoholio.g of N-acylated β-phenylserine ethyl ester (la-7a, respectively) and 10 mL of 1.5% hydrogen fluoride in formic acid (prepared from 48% aqueous hydrogen fluoride and> 99.7% formic acid) for 1 h. heated at 50 ° C. The cooled reaction contents are then poured onto ice. The compounds lb-5b are isolated in the form of an oil which is extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the product is recrystallized from the appropriate solvent (see Table 1). The compounds 6b and 7b which are liberated in solid form are separated by filtration, which is then recrystallized from dilute ethyl alcohol.

Lentelė. Junginių 3a-7a ir lb-7b išeigos, lydymosi temperatūros, kristalinimo tirpikliai, empirinės formulės ir elementinė analizėTable. Yields, melting points, crystallization solvents, empirical formulas and elemental analysis of compounds 3a-7a and lb-7b

Jung Jung Išeiga3’ (%)Yield 3 '(%) Lyd.t. (°O Melting point (° O Kristalinimo tirpiklis Crystallization solvent Empirinė formulė Empirical formula Rasta'Apskaičiuota, % % Found C C H H N N 3a 3a 59 59 129-131 129-131 Et,0 heksanas Et, 0 hexane c14h19no4 c 14 h 19 no 4 63,51/63,38 63.51 / 63.38 7,18/7,22 7.18 / 7.22 5,34/5,28 5.34 / 5.28 4aa) b) 4a a) b) 68 68 118,5-119 118.5-119 EtOH/H,O EtOH / H, O CI4H18BrNO4 C I4 H 18 BrNO 4 48,08/48,85 48.08 / 48.85 5,31/5,27 5.31 / 5.27 3,91/4,07 3.91 / 4.07 5a 5a 79 79 151-153 151-153 MeOH MeOH C,9H2INO4 C, 9 H 2I NO 4 70.00 69 71 70.00 69 71 6,31/6,47 6.31 / 6.47 4,36 4,28 4.36 4.28 6a 6a 84 84 162-163 162-163 EtOH EtOH c26h25no4 c 26 h 25 no 4 75,03/75,16 75.03 / 75.16 5,93/6,07 5.93 / 6.07 3,39/3,37 3.39 / 3.37 7a 7a 53 53 132-133 132-133 MeOH MeOH c26h25no4 c 26 h 25 no 4 75,40/75,16 75.40 / 75.16 6,16/6,07 6.16 / 6.07 3,21/3,37 3.21 / 3.37 lb lb 74 74 103-105 103-105 EkO EkO C14H17NOįC 14 H 17 NO 60,47/60,20 60.47 / 60.20 6,33/6,13 6.33 / 6.13 5,30 5,02 5.30 5.02 2b 2b 52 52 152-154 152-154 EtOHTLO EtOHTLO CI4HrNO5 C I4 H r NO 5 60,21/60,20 60.21 / 60.20 6,11/6,13 6.11 / 6.13 5,09.5,02 5,09.5,02 3b 3b 90 90 92-94 92-94 Et,0 No, 0 C,3H19NO5 C, 3 H 19 NO 5 61,51 '61,42 61.51 '61, 42 6,46/6,52 6.46 / 6.52 4,5 L4,77 4.5 L4.77 4b b> 4b b > 63 63 91,5-92 91.5-92 EtOH/H,O EtOH / H, O C15H13BrNO5 C 15 H 13 BrNO 5 48,40/48,40 48.40 / 48.40 4,99/4,87 4.99 / 4.87 3,55/3,76 3.55 / 3.76 5b 5b 68 68 121-122 121-122 EtOH/H2OEtOH / H 2 O C20H2INO3 C 20 H 2I NO 3 67,60/67,59 67.60 / 67.59 5,89/5,95 5.89 / 5.95 4,10/3,94 4.10 / 3.94 6b 6b 80 80 129-130 129-130 EtOHH.O EtOHH.O c27h25no5 c 27 h 25 no 5 73,44/73,12 73.44 / 73.12 5,64/5,68 5.64 / 5.68 3,18/3,16 3.18 / 3.16 7b 7b 73 73 143-145 143-145 EtOH/H.O EtOH / H.O. C2-H25NO3 C 2 -H 25 NO 3 73,35 73,12 73.35 73.12 5,55 '5,68 5.55 '5.68 3.04 3,16 3.04 3.16

a) Išeigos po kristalinimo iš atitinkamo tirpiklio(a) Yields after crystallization from an appropriate solvent

b) Junginiams 4a ir 4b Br rasta/apskaičiuota, %: 24,07/23,21, 20,98'21,47 atitinkamaib) For compounds 4a and 4b Br found / calculated,%: 24.07 / 23.21, 20.98'21.47 respectively

Lentelė. Junginių la-7a IR spektrai (υ cm1)Table. IR spectra of compounds la-7a (υ cm 1 )

Jung. Jung. CMO (COOCH,) CMO (COOCH,) c = o (HNCOR) c = o (HNCOR) ΝΗ,ΟΗ ΝΗ, ΟΗ la la 1742 1742 1662 1662 3224, 3269, 3353 3224, 3269, 3353 2a 2a 1711,1726 1711.1726 1665 1665 3306 3306 3a 3a 1737 1737 1649 1649 325S, 3356 325S, 3356 4a 4a 1736 1736 1646 1646 3249, 3329 3249, 3329 5a 5a 1729 1729 1651 1651 3230 3355 3230 3355 6a 6a 1743 1743 1653 1653 3348 3348 7a 7a 1740 1740 1647 1647 3289 3289

Lentelė. Junginių lb-7b IR spektrai (υ cm'1)Table. IR spectra of compounds lb-7b (υ cm -1 )

Jung. Jung. C = O (COOC2H5)C = O (COOC 2 H 5 ) c = o 0 (OC - R) c = o 0 (OC - R) c = o (HNCOH) c = o (HNCOH) NH NH lb lb 1732 1732 1746 1746 1659 1659 3198 3198 2b 2b 1724 1724 1745 1745 1657 1657 3265 3265 3b 3b 1732 1732 1756 1756 1647 1647 3268 3268 4b 4b 1730 1730 1744 1744 1658 1658 3292 3292 5b 5b 1731- 1731- 1731 1731 1647 1664 1647 1664 3247 3247 6b 6b 1727 1727 1740 1740 1665 1665 3345 3345 7b 7b 1727 1727 1727 1727 1680 1680 3390 3390

Lentelė. Junginių 3a-7a ’lI-BMR spektrai (δ skalė, cheminiai poslinkiai m.d., multipletiškuinas, sukinio-sukinio sąveikos konstanta J)Table. IR NMR spectra of compounds 3a-7a '(δ scale, chemical shifts in da., multipletine, spin-spin interaction constant J)

m O m O 0,73 t, 0.73 t, G II G II 0,91 t, 0.91 t, ro r-' II —i ro r- ' II —I co co J = 7,0 J = 7.0 Ό >»/ Ό > »/ c7 II c7 II J=7,0 J = 7.0 _r cy oo - II — _r cy oo - II - J = 7,0 J = 7.0 '“į '' To ^2 ^ 2 o o '—į, - to, u u r- r- r- r- ’Tt 'Etc r- r- e- e- r- r- o o r- r- oo oo A A co co e- e- o o II II II II II II cy cy II II II II —- —- II II II II U U r, U U r, re re r, r, •—J • —J m m i—5 i-5 re re r, r, e e - - — - E E r- c r- c c c o o U U U U s s o o LO) LO) o o yr yr c c o o θ' θ ' ri -r ri -r o o e e 00 N -e 00 N -e C- Jl C- Jl Ό II Ό II (f II (f II ? ? c ’Z', c 'Z', r- Ij r- Ij r·'·' r · '·' U U co fl co fl oc II oc II G G ii ii G II G II o o LT' LT ' J* J * r- r- c c cc' cc ' u u -T -T T T *-T * -T E E 11 — - c c ’čf 'Chf e-i e r*-, r * -, r-j r-j r*~, r * ~, n n C-J C-J ru ru Tt Etc. . r . r C) C) re re A, A, r. 7 r . 7th — - T“ T " M M T- T - M M >—1 > —1 M M C) C) ΓΤ ΓΤ M M (M (M _J_J _J_J HM HM zc zc M M >-* > - * r- r- C ) C) U U u υ u υ U u U u U U rJ rJ u u U U G' G ' u u U U t-4 t-4 U U u u G G O O U U s«_✓ s «_✓ 1 1 1 1 1 1 <0 <0 oc oc ei no — - cc cc o o re re r*“, r * ", rt-1:rt -1 : r^, r ^, c c Γ Γ Ό Ό — - C· C · —* - * ue ue re re O O Le, Le, ca ca O O te, you, e“, e ", s s Le Le re re ei no — - CM CM re re re re r r ei no N N ei no r- r- ei no N N r-’ r- ' — - oc oc 1 1 T3 T3 zc zc o o , , *T * T oc oc •o • o cc cc r-7 r-7 r r O O C' C ' o o u2 u2 r- r- II II r- r- II II — - II II z z 00 00 II II ca ca II II sC sC II II o o o o ra ra ra ra a_M a_M r- r- *—5 * —5 r- r- ·—5 · —5 C- C- o o te, you, *“5 * "5 -—r -—R O O 1-* 1- * o o •Ό • Ό CM CM Ό Ό Ό Ό o o O O s»> s »> re re re re Ό Ό re re ue ue ;J ; J rd’ rd ' re re ee ee ’rt 'Rt r- r- 00 00 — - II II oc oc II II ’rt 'Rt X X II II II II Ό Ό II II te, you, II II r- r- O O II II u u e- e - rj- rj- —> -> e- e- e- e- ^7 ^ 7 Tf Tf *“> * "> N“ N " e e — - ;*e ; * e ue, ue, te, you, r- r- oc oc o o II II —r - r II II <x <x Ό Ό *“5 * "5 o o re re ie, ie, ra ra s s u u . o . o » » r- r- <— <- r r C— C— • e • e ’-ς '-Σ re re -> -> e*, e *, sj sj re re c c L> L> r^, r ^, —y —Y e| e | LT) LT) ei no 11 11th e· e · r^, r ^, ii ii o o II II ΓΊ ΓΊ II II — - II II o o v v A- A- II II u u ΕΠ ΕΠ —Ϊ —Ϊ Le, Le, -e -e LT) LT) •—5 • —5 Le, Le, te, you, LO LO •—i • —i 1— 1— cz cz r* r * c c zz zz ei no n n e- e- re re — - CM CM r- r- co co r-F r- F r- r- (Z, (Z, e- e- r- r- U' U ' A A -JT' -JT ' ei no \C \ C re o re o O- O- —. -. CM CM o o o o o o u u r- r- l> l> e- e- e- e- ^e ^ e J·. J ·. Ό Ό r“. r ". o ra o ra ' sj> 'sj> r··, r ··, ΣΣ ΣΣ r-s r-s ~ ~ □ □ C- C- ΖΛ ΖΛ re' U re ' U c*-, c * -, sc sc re re u* u * Σ r\ Σ r \ U U Q 5 Q. 5 Σ Σ u u u u ώ ώ c c 2 2 s s *3 * 3 c: c: ίζ ίζ s s re re n n m m '-C '-C 'i i r- r-

a) R - radikalai atitinkamai tie patys kaip ir schemoje 1(a) R is the same as in Scheme 1

Lentelė. Junginių lb-7b ’lI-BMR spektrai (δ skalė, cheminiai poslinkiai m.d., multiplctiškiimas, sukinio-sukinio sąveikos konstanta J)Table. IR-NMR spectra of compounds lb-7b '(δ scale, chemical shifts in da, multiplicity, spin-spin interaction constant J)

u u o, O oh, O o Ί o Ί 0,91 t 0.91t r-'' II r- '' II 0,87 t, 0.87 t, Γ-' II Γ- ' II 0,90 t, 0.90 t, G II ·—> G II · -> Q\ Q \ c-” II c- " II Ό Ό G 3 G 3 ^t- ^ t- r-’ II r- ' II si si -J -J l> l> |A A (A (A Si Si r- r- Si Si * * Si Si Γ- Γ- n n r- r- Oi Oops II II X X LO LO G G II II o o ii ii o o II II o o o. o. II II c^\ c ^ \ II II 0 0 II II 0, 0, U U O, Oh, tT tT R-J R-J O O Oi Oops 0 0 ’tT 'TT o o o o u u X X X X X X X X X X X X X X — - — - O O o. o. o o 0 0 ΧΊ ΧΊ 1 1 O-) O-) ·—« · - « 1— 1— — - O υ Oh oc oc OC OC X* X * X* X * x x co co X X o o 3- 3- J J OI Oops u Oi u Oops o. o. x x '5b 5b o X o X X II X II II II d 0 d 0 Ck Ck 1 X 1 X Te c You c OC OC II II \O IO \ O IO II II u. o C- u. o C- 5 Ό 5 Ό kO o kO o Ό O Ό O sOr O-sO r O- JI JI 0 c* 0 c * JJ JJ s s ,—, , -, 0 0 Q\ Q \ oc oc _— _ - '—T '—T C\ C \ . #·. . # ·. . <-. . <-. — - Ό Ό Ό Ό c~c c ~ c CT CT . r- . r- O O o o LT? LT? Έ Έ o ir? o is? Έ X Έ X of of 04 04 iri II iri II Ό Ό X X kO kO 0 0 cy cy II II -η -η II II II II o_ o_ o o II II II II Cį Here II II u u ιΧ ιΧ O? O? M* M * Oi Oops F F F F _ _ KO, KO, o l> II o l> II Γ-” Γ- " lo sO lo SO kO J!_ kO J! _ Έ' Έ ' x x U CM U CM x x zc zc U CM U CM II II II II - - tr, tr, II II oc 3 oc 3 ii ii II II 7 7th | | Cl X Cl X *-5 cc * -5 cc Cl I Cl I uT cc CM uT cc CM X -r' X -r ' \C CJ 0 \ C CJ 0 δ2 δ2 d oč Tf d oh Tf -- - ,_ , _ d F7 c- d F7 c- 1 1 X X u, u, U U u u U U u u 0 0 u u 0 0 G' G ' kj kj U U G' G ' 1 1 0 0 u o u o OI Oops OI Oops 1- 1- O O 04 04 04 04 oc oc %o % o Ό Ό 04 04 0 0 0 0 ’d- 'd - kO kO Ό Ό o o O O t-' t- ' xh xh Ck Ck 0, 0, O O — - c, c, — - — - OI Oops —- —- OI Oops O. O O O kO kO 04 04 O O 04 04 0 0 S S '—y '—Y O, Oh, 1 L· 1 L · O, Oh, m m c· c · ΧΊ ΧΊ LT) LT) O O II II O O II II Oi Oops — - II II Cl Cl II II OI Oops II II Cl Cl Cl Cl Cl Cl Cl Cl II II u u sO SO Ό Ό T-5 T-5 kO kO %o % o \O \ O O) O) sO SO \O \ O 0 0 E E E E E E ι- Ε ι- Ε r r oc oc O, Oh, tT tT o o c- c- X X s. s. I> I> o o ę· · · c- c- c- c- X X kO kO oc oc 04 04 — - H H — - — - Q\ Q \ — - 777 777 o o Γ-' Γ- ' r- r- Γ-' Γ- ' o· o · \0 \ 0 0' 0 ' G G M M ** ** ** ** W- W- Cl Cl o o rr rr LG LG kO kO —5 —5

OO

Claims (5)

APIBRĖŽTISDEFINITION 1. Junginiai N-formil-O-acil-DL-P-fenilserinų etilo esteriai bendros struktūrinės formules:1. Compounds of the ethyl ester of N-formyl-O-acyl-DL-P-phenylserines in the general structural formula: C6H5CH(OC - R)CHCOOC,HJ; I /zOC 6 H 5 CH (OC - R) CHCOOC, H J; I / zO HNC-H kurioje R reiškia acetilo, propionilo, 3-bromopropionilo, fenilacetilo ir 9-fluorenacetilo radikalus.HNC-H wherein R represents acetyl, propionyl, 3-bromopropionyl, phenylacetyl and 9-fluorenacetyl radicals. 2. Junginiai pagal 1 punktą, besiskiriantys tuo. kad jų gavimo būdas paremtas N-acilinių β-fenilserino darinių acilinės grupės N—»0 migracija skruzdžių rūgšties - vandenilio fluorido sistemoje.Compounds according to claim 1, other than that. that their preparation is based on the migration of the N-»0 acyl group of N-acylic β-phenylserine derivatives in the formic acid-hydrogen fluoride system. 3. Junginiai pagal 1 punktą, besiskiriantys tuo, kad juos sintezuojant N-»O acilinę migraciją lydi N-formilinimas.3. Compounds according to claim 1, characterized in that their synthesis is accompanied by N-formylation during the synthesis of N-O. 4. Junginių pagal 1 punktą gavimo būdas, besiskiriantis tuo, kad apima N-acilinių β-fenilserinų darinių reakcijas su HF skruzdžių rūgštyje.4. A process for the preparation of compounds according to claim 1, which comprises reacting N-acylic β-phenylserine derivatives with HF in formic acid. 5. Gavimo būdas pagal 4 punktą, besiskiriantis tuo, kad naudoja 1.5 % HF tirpalą skruzdžių rūgštyje, o reakciją vykdo 50 °C temperatūroje.5. A process according to claim 4, wherein the solution is 1.5% HF in formic acid and the reaction is carried out at 50 ° C.
LT99-087A 1999-07-20 1999-07-20 N-formyl-o-acyl-threo- and erythro-dl-beta-phenylserine ethyl esters and process for preparing thereof LT4663B (en)

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SU757522A1 (en) 1978-05-31 1980-08-23 Inst Biokhim An Litovskoj Ssr Sodium salt of n-phenylacetyl-n-m-salisylidene-treo-dl-serine possessing antiinflammating activity
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SU936608A1 (en) 1980-09-08 1990-12-07 Институт биохимии АН ЛитССР Chlorohydrate of ethyl ester of o-myristoyl-treo-dl-phenylserine as fungicide
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SU757522A1 (en) 1978-05-31 1980-08-23 Inst Biokhim An Litovskoj Ssr Sodium salt of n-phenylacetyl-n-m-salisylidene-treo-dl-serine possessing antiinflammating activity
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SU936608A1 (en) 1980-09-08 1990-12-07 Институт биохимии АН ЛитССР Chlorohydrate of ethyl ester of o-myristoyl-treo-dl-phenylserine as fungicide
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SU1140423A1 (en) 1983-05-20 1990-12-07 Институт биохимии АН ЛитССР N-acyl derivatives of treo-dl-phenylserine against virus of a2 influenza
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RU1363764C (en) 1986-01-31 1993-12-30 Институт биохимии АН ЛитССР N-2-fluorenesulfonyl-o-propionyl-threo-d,l-phenylserine ethyl ester showing antiviral activity with respect to echo 11 virus

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