Multi‐Step Application of Immobilized Reagents and Scavengers: A Total Synthesis of Epothilone C

Abstract

The total synthesis of the cytotoxic antitumour natural product epothilone C has provided a stage for the exploitation and further development of immobilized reagent methods. A stereoselective convergent synthetic strategy was applied, incorporating polymer-supported reagents, catalysts, scavengers and catch-and-release techniques to avoid frequent aqueous work-up and chromatographic purification.

Synthesis of Alkaloid Natural Products Using Solid-Supported Reagents and Scavengers

“…For example, in our laboratories we have used immobilised reagents to prepare 1,2,3,4-tetrasubstituted pyrroles [42], isoxazolidines [43], aminothiazoles [44], benzodioxanes [45], pyrazoles [46], piperidinothiomorpholines [47], benzofurans [48], bicyclo(2,2,2)octane derivatives [49], and the pharmaceuticals Sildenafil [50], Salmeterol [51] and various HDAc [52] and MMP inhibitors [53]. The most complex natural product synthesised by these methods is the potential anticancer agent epothilone C, achieved in no less than 29 steps [54].…”

Oxidation of Alcohols, Carbohydrates and Diols

“…PSP/ THF [69] and PSP/CH 2 Cl 2 [116] which were used for part of a synthesis of the analgesic (±)-epibatidine [117] and the alkaloid (±)-oxomaritidine [69]; stoich. PSP/CH 2 Cl 2 for the alkaloid (±)-epimaritidine [116] and, as PSP/O 2 /toluene/110°C, for the cytotoxic antitumour epothilone C [118].…”

Polymer‐Supported Organosuperbases

“…As a related work, the utility of mesoporous silicasupported TBD catalysts was demonstrated in the reaction of propylene oxide with carbon dioxide to prepare the corresponding carbonate derivative under the ultrasonic activation [79]. In general, polymer-supported superbases are quite convenient as scavengers for removing acidic by-products by simple filtration [80][81][82][83]. Storer et al are actively working in this field, and in their own multi-step organic synthesis they introduced a catch and release technique that required neither aqueous work-up nor chromatographic purification [82] It was found that the use of a triflate salt of PS-PAPT (0.1 equiv.)…”

“…In general, polymer-supported superbases are quite convenient as scavengers for removing acidic by-products by simple filtration [80][81][82][83]. Storer et al are actively working in this field, and in their own multi-step organic synthesis they introduced a catch and release technique that required neither aqueous work-up nor chromatographic purification [82] It was found that the use of a triflate salt of PS-PAPT (0.1 equiv.) in conjunction with sodium hydride (2.5 equiv.)…”