Synthesis camptothecin

The camptothecin synthesis of Comins (Scheme 2) commences with the or/Ao-directed... 

The camptothecin synthesis of Shen/Dani-shefsky [16] (Scheme 8) starts with the construction of the D ring reaction of 46 with 47 affords 48. The next step (48 49) introduces the C20 ethyl group. Hydroxymethylation of 49 delivers lactone SO. The B ring of the camptothecin precursor 52 should be accomplished by a Friedlander condensation of 10 with 11. For this purpose, a keto group at C2 of the C,D,E ring building block had to be installed. Shen and Danishefsky solved this problem by combination of an aldol condensation (50 —> 51) and a subsequent ozonolysis (51 11). Important for... 

There has recently been another crop of publications devoted to camptothecin synthesis. Corey s synthesis includes a resolution at an early stage, and is the first synthesis of optically active 205-camptothecin (237) (Scheme 33) unfortunately the yield in the vital coupling-cyclization step (xxi—xxii) is very low indeed (6.5%). 

After the almost frenetic activity in camptothecin synthesis during the last two years there is little to report during the year under review. Full details of the synthesis by Tang and Rapoport "" are now available. 

Radical reactions have developed into indispensable methods in organic synthesis [1] and are often used as key steps in the construction of complex natural products. Impressive demonstrations are found in the following examples taken from the current literature the dactomelyne synthesis by Lee et al [2] the camptothecin synthesis by Curran et al., [3] and of (7)-deoxypancratistatin by Keck et al.,... 

Intermolecular radical bond formations with companally high yields and stereoselectivities are still very rare in the total synthesis of bioactive compounds. One exception is Curran s camptothecin synthesis. However, progress in acyclic stereoselection of radical reactions [11] should soon help to formulate new solutions for these synthetic challenges. 

Scheme 13.33 Bond-sets of Danishefsky s and Curran s camptothecin synthesis...

Scheme 1-162. Two consecutive metalations followed by electrophilic substitutions as a crucial part of a Camptothecin synthesis.

---