Synthesis of Novel Aromatic C Ring Taxol Analogs Toward a Synthesis of a Brevetoxin B Analog New Methods for the Construction of Cyclic Ethers PDF Download

Author: Christopher Fairman Claiborne
Publisher:
ISBN: 9780591099461
Category : Aromatic compounds
Languages : en
Pages : 886

Get Book Here

Book Description
Model studies were carried out on key steps directed toward a synthesis of taxol. A model aromatic taxol C ring was coupled to taxol A ring via the Shapiro reaction. Selective functionalization of the A ring was carried out by epoxidation of the allylic alcohol derived from Shapiro coupling. Compatible protecting groups were found to rigidity the model AC framework in preparation for cyclization of the B ring. The McMurry reaction was established as an effective method for the formation of the eight membered B ring. Selective functionalization of the C-13 position of the A ring by PCC oxidation was accomplished. Controlled reduction of the C-13 ketone was carried out and subsequent coupling to the taxol side chain was achieve by the Oijima-Holton method. A biologically active analog of taxol was synthesized. Toward a synthesis of a brevetoxin B analog, a model ABC ring fragment was synthesized by established 6 -endo hydroxy-epoxide cyclizations. A model EF ring system was also synthesized by similar methods. Variations on the ABC fragment were independently coupled to the FG fragment and in a novel titanium mediated metathesis, the D ring was formed. Functionalization of the resulting D ring enol ether set the stage for the formation of the E ring via a hydroxy-ketone condensation. A hexacyclic (B - G) and heptacyclic (A - G) fused polyether ring systems were synthesized during our efforts to prepare a brevetoxin B analog.