Neue phosphorylierte Phosphoniumylide und Verfahren zu deren Herstellung

摘要

1,243,213. Phosphonium ylids. SYNTEX CORP. 11 July, 1968 [18 July, 1967; 29 Feb., 1968]; No. 33243/68. Heading C2C. - Novel phosphonium ylids of the general Formula A in which R1, R2 and R3 are independently alkyl having 1 to, 6 carbon atoms, aryl, substituted aryl, aralkyl, or substituted aralkyl, or R1, R2 and R3 are all three N-piperidyl, N-morpholinyl or cyclohexyl, R4 is hydrogen, alkyl having 1 to 6 carbon atoms, cyclohexyl, optionally substituted aryl or. optionally substituted aralkyl, Y is oxygen or sulphur, Z1and Z2 are independently N-piperidyl, N-morpholinyl or the group OR5, SB6 or NR7R8 where R5 and R6 are alkyl having 1 to, 6 carbon atoms, alkenyl, optionally, substituted aryl or optionally substituted aralkyl, and R7 and, R8 are alkyL having 1 to 6 carbon atoms, aryl or aralkyl or Z1 and Z2 together are the group -0-R9-O-, -O-R9-S-,or-S-R9-S- in which R9 is alkylene or arylene, are prepared by one of the following methods: (1) A monosubstituted phosphonium ylid of the Formula (I) is condensed under substantially anhydrous conditions with an appropriately disubstituted phosphonyl or thionophosphonyl halide of the Formula (11) in which X is chloro or bromo, in an inert solvent, at a temperature from 0‹ C. to the reflux temperature of the solvent, optionally in the presence of an inert atmosphere. (2) A trisubstituted phosphine of the Formula III is reacted under the same conditions as above with an appropriately disubstituted halomethylphosphonic , acid of halpmethylthioi.iophosphonic acid of the Formula IV in which Z1' and. Z2' are N-piperidyl, N-morpholinyl, NR7R8 or OR5', where R5' is optionally substituted aryl or aralkyl to give a salt, which is treated with an aqueous solution, of a base to. give an ylid of Formula A in which R,4 is hydrogen, Z1 is'Z1'' and Z2 is Z2'. This may he, reacted with an alkyl or cyclohexyl halide to obtain the ylids in which R4 is alkyl or cyclohexyl. (3) To give ylids of the Formula A in which Y is oxygen, a monosubstituted phosphonium ylid of the Formula (I) is reacted with an appropriately tetrasubstituted pyrophosphate of the formula VII. The novel phosphonium ylids (A) can be reacted with a wide variety of aldehydes and ketones to give unsaturated phosphonate and thiophosphonate derivatives which can be converted into the corresponding saturated phosphonic and thiophosphonic acids. In particular nucleoside.-61-phosphonic acids, are, prepared by the steps of (a) reacting a phosphonium ylid of Formula A with a nucleoside'- 51-aldehyde to give, a nuclepside-51 -61unsaturated 61-phosphonate; (b) catalytic hydrogenation or di-imide reduction to give the corresponding saturated nucleoside 61-phosphonate; and (c) removing the ester groups (i.e. Z1 and Z2) by hydrolysis, hydrogenolysis, anionic dealkylation, enzymatic action, or combinations thereof to give the corresponding nucleoside-61- phosphonic acid. Examples are given of the preparation of phenyl [1 - (5,6 - dideoxy - (3- D - ribo hexofuranosyl)uracil] 61 - phosphonic acid from 21,31 - 0 - anisylidene uridine - 51 - aldehyde.; of a salt of [9 - (5,6- dideoxy - # - D - ribo - hexofuranosyl) adenine] 61-phosphonic acid from 21,31-0-isopropyl idene adenosine-51-aldehyde, and of the acids from 31-O-acetylthymidine 51-aldehyde, 1-(N4, O2',3'-tribenzoyl-#-D-arabinofuranosyl-): [ cytosine 51 aldehyde; and others.