Patent ID: 6252094
Filing Date: 2001-06-26
Classification: C07D,C07F

Abstract:
A cyclic method employing chemical switching for solubilizing and desolubilizing a taxo-diterpenoid with respect to an aqueous solvent, an underivatized form of the taxo-diterpenoid having a low solubility and including a reactive C.sup.n -hydroxyl, the method comprising the following steps:Step A: converting the underivatized form of the taxo-diterpenoid from low solubility to high solubility by derivatizing the reactive C.sup.n -hydroxyl with an onium salt of a 2-halogenated aza-arene to form an onium salt of a taxo-diterpenoid-C.sup.n,2-O-aza-arene derivative having high solubility, wherein the onium salt of the 2-halogenated aza-arene is represented bv the following structures I and II: ##STR46##wherein:R.sup.0 is a halogen selected from the group consisting of Cl, Br, F, and I;Z.sup.1 and Z.sup.2 are each selected from the group consisting of C and N;Z.sup.3 is selected from the group consisting of S and O;R.sup.1 is selected from the goup consisting of C.sub.1 -C.sub.6 alkyl, allyl, arenxyl, propargyl, and fused aryl;R.sup.2 and R.sup.6 are each selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, allyl, arenxyl, propargyl, and fused aryl;if Z.sup.1 is C, then R.sup.3 is selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, allyl, arenxyl, proparyl, C.sub.1 -C.sub.6 O-alkyl, OH, halogen, and fused aryl;if Z.sup.1 is N, then R.sup.3 is absent;R.sup.4 and R.sup.8 are each selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, allyl, arenxyl, propargyl, C.sub.1 -C.sub.6 O-alkyl, OH, halogen, and fused aryl; andif Z.sup.2 is C, then R.sup.5 is selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, allyl, arenxyl, propargyl, C.sub.1 -C.sub.6 O-alkyl, OH, halogen, and fused aryl;if Z.sup.2 is N, then R.sup.5 is absent, andS.sup.- is a counter ion; and thenStep B: converting the onium salt of the taxo-diterpenoid-C.sup.n,2-O-aza-arene derivative produced in said Step A from high solubility by contacting the taxo-diterpenoid-C.sup.n,2-O-aza-arene derivative with a serum protein for displacing the 2-O-aza-arene and forming a protein:taxo-diterpenoid intermediate, the protein:taxo-diterpenoid intermediate then dissociating to produce the underviatized form of the taxo-diterpenoid employed in said Step A.