Enantiospecific Total Synthesis of Natural (+)-Taxusin. 2. Functionalization of the A-Ring and Arrival at the Target

Abstract

A total synthesis of (+)-taxusin (1) has been realized by virtue of the development of a practical route for complete functionalization of the A ring. To achieve this goal, it proved necessary to devise a strategy that would enable chemical transformations to proceed in a very congested environment. The successful pathway from 2 required 19 steps consisting principally of chemoselective oxidation and reduction maneuvers of various types. The requisite methyl substituent was introduced by 1,2-addition of the methylcerate reagent to a C(12) ketone intermediate. Several tactics that ultimately proved unsatisfactory are also discussed in an effort to set important boundary limits on chemical reactivity. The pivotal roles played by samarium diiodide and tetrapropylammonium perruthenate in permitting the deployment of appropriate chemical changes are noteworthy.

23‐Oxa‐Analogues of OSW‐1: Efficient Synthesis and Extremely Potent Antitumor Activity

“…[5] The results are shown in Scheme 4. Oxidation of the 16a-OH group of 8 b by treatment with TPAP/NMO [16] gave the 16-keto compound 10 b in 91 % yield. Reduction of the resulting 16-ketone with NaBH 4 in the presence of CeCl 3 afforded 16b-ol 11 b stereoselectively in 81 % yield.…”

Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes

“…As illustrated in Figure 1, Taxol™ can be viewed as a "level 11" taxane due to the presence of 9 oxidized carbon atoms and two degrees of unsaturation; over 100 natural products at this oxidation state have been isolated. Similarly, decinnamoyltaxinine E ( 2 ) 29 , taxabaccatin III ( 3 ) 30 , taxusin ( 4 ) 31–36 , taxuyunnanine D ( 5 ) 37,38 , and taxadiene ( 6 ) 39–41 can be viewed as level 3–5 taxanes and represent over 100 additional natural products. In this report, the first enantioselective total syntheses of decinnamoyltaxinine E ( 2 ) and taxabaccatin III ( 3 ) are presented.…”

Synthetic Studies on Taxoids: Enantioselective Total Synthesis of (+)-Taxusin and (-)-Taxol

“…5 Thus, increased interest both in synthetic chemistry as well as the clinical aspects have prompted studies on taxanes and their analogs by many research groups. 8 Further, total synthesis of the more complex and biologically important taxol has been accomplished by six groups, including us. The first total synthesis of its antipode was accomplished by Holton and his colleagues 6 using a (-)-patchino derivative.…”