| 摘要 |
<p>Enrichment of a salt of amino compound (I) in isomer (Z), comprises adding benzyl alcohol to a suspension of a mixture of salts of (Z)- and (E)- amino compounds in acetonitrile, and mechanically separating the salt of the amino compound enriched in isomer (Z). Enrichment of salt of amino compound of formula (I) in isomer (Z), comprises adding benzyl alcohol to a suspension of a mixture of salts of (Z)- and (E)- amino compounds in acetonitrile, and mechanically separating the salt of the amino compound enriched in isomer (Z).B 1>= counter-anion, preferably Cl ->or SO 4 2> ->. Independent claims are included for: (1) a process for the preparation of a combretastatin of formula (Z)-(Ic) comprising: coupling the salt of (Z)- amino compound (I) with doubly protected L-serine derivative of formula (II) to obtain the combretastatin compound of formula (Z)-(Ib), then deprotecting and opening the (Z)-(Ib) cycle; or enriching (I), coupling the enriched salt with (II) in the presence of propane phosphonic acid anhydride (T3P) of formula (III) to obtain (Z)-(Ib), and then deprotecting and opening the cycle (Z)-(lb); or coupling salt of (Z)-amino compound of formula (IV) with (II) in the presence of (III) to obtain (Z)-(Ib) and then deprotecting and opening the (Z)-(lb) cycle; and (2) use of (III) for carrying out the coupling of (IV) with the double protected L-serine derivative (II). PG : protective group of the amino function, preferably tert-butoxycarbonyl, benzyloxycarbonyl or 9-fluorenylmethyloxycarbonyl. [Image] [Image] [Image] [Image] [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given.</p> |
