Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB888808475Aexternal-prioritypatent/GB8808475D0/en
Application filed by Farmitalia Carlo Erba S.R.L.filedCriticalFarmitalia Carlo Erba S.R.L.
Publication of SI8910718ApublicationCriticalpatent/SI8910718A/en
Publication of SI8910718BpublicationCriticalpatent/SI8910718B/en
Pharmaceuticals Containing Other Organic And Inorganic Compounds
(AREA)
Saccharide Compounds
(AREA)
Claims (3)
1 v prisotnosti Ν,Ν-diizopropiletilamina in katalitske količine 4-dimetilamino-piridina s sulfonilno spojino s formulo II: R-S02X (II) v kateri X predstavlja atom halogena, skupino 0S02R, imidazolilno skupino, skupino NH(C6H5)(RS02) ali drugo skupino, ki je sposobna, da reagira s fenolom ob nastanku sulfonata, in R predstavlja alkilno skupino z 1 do 10 atomi ogljika, ki je po izbiri substituirana z enim ali več atomi halogena, ali arilno skupino, ki je po izbiri sub-stituirana s halogenom, alkilom, alkoksi ali nitro; (ii) presnovimo nastali sulfonirani 4-demetil-13-dioksolanil-davnomicinon s formulo (4): 2 R1 in the presence of N, N-diisopropylethylamine and a catalytic amount of 4-dimethylamino-pyridine with a sulphonyl compound of formula II: R-SO2X (II) in which X represents a halogen atom, a 0SO2R group, an imidazolyl group, an NH group (C6H5) (RS02) or another group capable of reacting with phenol to form a sulphonate, and R represents an alkyl group of 1 to 10 carbon atoms which is optionally substituted by one or more halogen atoms, or an aryl group which is optionally substituted by substituted with halogen, alkyl, alkoxy or nitro; (ii) metabolizing the resulting sulfonated 4-demethyl-13-dioxolanyl-davnomycinone of formula (4): 2 RΛ”' v kateri je R definiran kot zgoraj, v reduktivnem okolju ustvarjenim s tri-alkilamonijevim formiatom, s katalitsko količino spojine s formuloR ”'in which R is as defined above, in a reductive medium formed with a tri-alkylammonium formate, with a catalytic amount of a compound of formula(III) v kateri M predstavlja paladij ali nikelj, L in L’, ki sta lahko enaka ali različna, predstavljata vsak anion, molekulo topila, mono- ali di-fosfm, fosfit ali diamin, in lahko n in m variirata od 0 do 4; in (iii) odstranimo zaščitno skupino 13-okso iz nastalega 4-demetoksi-13-dioksolanil-davnomicinona (5):(III) in which M represents palladium or nickel, L and L ', which may be the same or different, represent each anion, solvent molecule, mono- or di-phosphine, phosphite or diamine, and n and m may vary from 0 to 4; and (iii) removing the 13-oxo protecting group from the resulting 4-demethoxy-13-dioxolanyl-davnomycinone (5):111 PATENTNI ZAHTEVKI 1. Postopek za pripravo 4-demetoksi-davnomicinona s formulo (I):A process for the preparation of 4-demethoxy-davnomycinone of formula (I):označen s tem, da (i) presnovimo 4-demetil-13-dioksolanil-davnomicinon s formulo (3):characterized in that (i) metabolize 4-demethyl-13-dioxolanyl-davnomycinone of formula (3):2. Postopek za pripravo 4-demetoksi-davnorubicina s formulo (IV) o OH oA process for the preparation of 4-demethoxy-davnorubicin of formula (IV) o OH o3 v kateri R1 predstavlja o CH3 in which R1 represents o CHHO ali njegove farmacevtsko sprejemljive soli, označen s tem, da presnovimo 4-demetoksi-davnomicinon s formulo (I), ki smo ga pripravili po postopku v skladu z zahtevkom 1, s primernim derivatom sladkorja in po želji pretvorimo tako dobljeni 4-demetoksi-davnorubicin v njegovo farmacevtsko sprejemljivo sol.HO or a pharmaceutically acceptable salt thereof, characterized in that the 4-demethoxy-davnomycinone of formula (I), prepared according to the process according to claim 1, is reacted with a suitable sugar derivative and, if desired, the 4-demethoxy- davnorubicin into a pharmaceutically acceptable salt thereof.3. Postopek po zahtevku 2, označen s tem, da ima derivat sladkorja formulo (V) HalProcess according to Claim 2, characterized in that the sugar derivative has the formula (V) Halv kateri Hal predstavlja atom halogena, R2 predstavlja zaščiteno hidroksi skupino in R3 predstavlja zaščiteno amino skupino, in po reakciji s 4-demetoksi-davnomicinonom odstranimo zaščitne skupine. Za FARMITALIA CARLO ERBA S.r.l.in which Hal represents a halogen atom, R2 represents a protected hydroxy group and R3 represents a protected amino group, and after reaction with 4-demethoxy-daunomycinone the protecting groups are removed. For FARMITALIA CARLO ERBA S.r.l.
SI8910718A1988-04-111989-04-10Process for preparing 4-demethoxy-daunomycinone
SI8910718B
(en)