Chapter 2 Maytansinoids

Publisher Summary The maytansinoids are a relatively new and rare class of natural products that have generated a great deal of interest since their initial discovery in 1972. The novel structures of the maytansinoids are of interest also. Mayfansinoids are ansa macrolides, that is, they are macrocycles containing an aromatic nucleus connected in nonadjacent positions by an aliphatic bridge, structures similar to the ansamycin antibiotics. All representatives are 19-membered lactam rings and are the first ansa compounds to exhibit tumor inhibiting properties. Most maytansinoids contain an aryl chloride and a C-4, C-5 epoxide. All contain a 4-hydro-2-oxo-2,3-dihydro[6H]-l,3-oxazine fused to C-7 and C-9. The biologically potent compounds contain an ester moiety at C-3. This chapter deals with the isolation and structural variation of maytansinoids and its physical properties. In attempting a total synthesis of any of the maytansinoids one undertakes a formidable task. A brief look at the general structure shows seven chiral centers, a conjugated diene, a trisubstituted epoxide, a tetrasubstituted aromatic ring, and a cyclic carbamate. Putting all these pieces together has provided a challenge that many organic chemists have answered.