166534-10-7

Upstream product

• 185013-20-1 (1S,2R,6S,8R,9R,11S)-11-(2-Benzenesulfonyl-ethyl)-11-hydroxy-6,10,10-trimethyl-12-oxo-2-triisopropylsilanyloxymethyl-13-oxa-tricyclo[6.4.1.0^1,6]tridecane-9-carbonitrile 

Downstream Products

• 166534-11-8 methyl 1β-hydroxy-1α-(2'-phenylsulfonylethyl)-3α,10α-oxido-2α,13α-oxido-8β,12,12-trimethylbicyclo<6.4.0^3,8>dodec-11α-oate 
• 185013-21-2 1β-hydroxy-2,4Hβ-13-phenylsulfonyl-11,12-dihydro-3α,10α-oxido-2α,20α-oxido-12-nortaxane-12-one 

Relevant academic research and scientific papers

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

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.

New strategy for the synthesis of the taxane diterpenes: Formation of the A-ring and introduction of the C-1 hydroxyl group

The A-ring of the taxanes is conveniently made from an ester-sulfone condensation, and is compatible with the 1-hydroxyl group, thus completing the synthesis of the ABC-rings.