Epothilones retrosynthetic analysis

Figure 13 outlines our retrosynthetic analysis of epothilone D (49). Since epoxidation of epothilone D to give epothilone B (3) is the last step in all total syntheses of the latter, this is considered to be trivial. Furthermore, epothilone D shows a lower non-specific toxicity relative to its antimitotic properties. 

In comparison to other aldolases, DERA has a rather broad substrate range. DERA-catalyzed aldol reactions were used to get an access to key intermediates for epothilones (Fig. 36) [194]. According to retrosynthetic analysis, both fragments of the molecule could be obtained from aldol building blocks, and two out of seven stereocenters were established enzymatically. For the southern part of epothilone A,... 

Scheme I. Epothilone A and B and the retrosynthetic analysis followed in this highlight. (PG = Protecting Group, TBS = fm-butyldimethylsilyl, Hal = Cl, Br, I).

Epothilones A and B [82] In 1997, Nicolaou and coworkers reported the total synthesis of epothilones A (90) and B (91), two natural products isolated from myxobacteria Sorangium cellulosum [82]. These molecules exhibit impressive antitumor activities due to important microtubule binding affinities. Their retrosynthetic analysis relied on a late-stage epoxidation and a macrolactonization (Scheme 2.60). The synthesis of the two macrolactone... 

---