ORGANIC COMPOUNDS AND PROCESSES

摘要

1322136 Ara-cytidine esters UPJOHN CO 21 Dec 1971 [27 Jan 1971] 59368/71 Heading C2C Novel 21-O-, 31-O-monoesters and 21,51-O-, 31,51-O- and 21,31-O-diesters of aracytidine, wherein the acyl radicals are RCO, where R is a C 1-20 aliphatic, C 6-10 aromatic, C 7-20 cage-type hydrocarbon, C 4-10 monocyclic aliphatic, C 7-12 araliphatic or monocyclic heterocyclic (containing 4 to 10 carbon atoms) radical including such radicals substituted by halogen, hydroxy, carboxyl, nitro, alkoxy or mercapto or where R1 is a C 1-20 aliphatic, C 6-10 aromatic or C 7-12 araliphatic radical, and acid addition salts thereof, are prepared by one of the following methods: (a) 21-O-, 31-O-monoesters and 21-31- diesters may be prepared by O-acylation of a compound of Formula VII wherein X is Cl or Br, followed by separation of the mixed esters and hydrolysis of the 51-O- and N-protecting groups in either order; (b) 21,51-O- and 31,51-O-diesters may be prepared by O- acylation of a compound of Formula XIa wherein w is the anion of a strong acid, followed by neutralization and separation of the products; (c) 31,51-diO-esters may be prepared by acylation of a compound of Formula XIIa or a salt thereof with a strong acid then, where the free base is used, selective hydrolysis of the N-acyl group and in both cases hydrolysing the 2,21-anhydro linkage; and (d) 31-O-mono esters may be prepared by O-acylating a compound of Formula XVII hydrolysing the compound of formula wherein Y is RCO or R1OCO at the 51-O-position to give a compound of formula in which the 2,21-anhydro bond is hydrolysed using a base. Intermediates prepared in the above processes are isolated. Compounds of Formula XVII above are prepared by reaction of triphenylmethyl halide with the salt of a compound of Formula XIIa above with a strong acid. Compounds of Formula VII above are prepared by reaction of a compound of formula CX 3 .CR 2 .O.CO.X where X = Cl or Br with a compound of Formula VI: Pharmaceutical compositions in conventional forms for oral or parenteral administration and having immunosuppressant, anti-neoplastio and antiphage activity comprise an above novel compound and a carrier or diluent.