Taxane diterpenes 2: Synthesis of the 7-deoxy ABC taxane skeleton, and reactions of the A-ring

Article abstract of DOI:10.1016/0040-4020(96)00866-6

The bicyclo[5.4.0]undecenones 5, 6 and 7 are converted through a four step sequence involving activation, gem-methylcyclopropanation and reductive cleavage into the B/C rings of the taxanes, 18 and 19. The A-ring has been attached to the B/C ring system by cyclization of the sulfone-ester 28 to give 29, and also at a higher oxidation level; 33 gives 34. The same type of anionic cyclization is successful in the presence of the C-1 hydroxyl group; 39 gives 40. The A-ring can also be made using the classical aldol reaction; 43 to give 45. A third A-ring closure method using the nitro-aldol reaction (Henry reaction) was also successful; 47 gives 48. The A-ring has been elaborated by conversion into the tax-12,13-enes 53 and 58. Hydroxyl directed epoxidation of 60 results in completely stereospecific oxidation to give 61. Autoxidation of 41 gave the 12,13-dioxotaxane 67 which was further elaborated into the exomethylene ketone 70. The α,β-unsaturated nitro alkene 74 has been converted into the 13-ketotaxane 76 using a reductive Nef reaction. Subsequent reduction of the C-13 carbonyl group with DIBAL-H gave the 13-α-alcohol 77 with the correct C-13 taxol stereochemistry. β-Elimination of the 3,10-oxido bridge via the dianion of the acid 81 results in transannular hydride shift to give the butenolide 83.