Progesterone, biomimetic synthesis

Here is one of Johnson s best examples which leads eventually to a biomimetic synthesis of the human hormone progesterone. The cydization occurs just on treatment of the tertiary alcohol with acid. 

In summary, the stereochemical course of cation-7t cyclizations is determined by stereoelectronic and conformational effects. Concerted cation-Ti cyclizations usually involve a stereospecific trans-addition (axial attack) of the carbocation to the double bond. This is exemplified by Johnson s biomimetic synthesis ( )-progesterone, which possesses a trans, anti, trans-fused ring system." - ... 

The synthesis of lanosterol (140) from epoxide 139 has an Lfo, =+4. The key multiple ring-closure step 141+142- [143] in Johnson s synthesis of progesterone has also an Lfoj =+4 (Lfor for [143]- 144 would depend on the by-products). Next, we see the three steps 145+146- 147- [148]- 149 in Vollhardts synthesis of estrone with Lfor is +3, -1, +2 respectively for the overall transformatiom L r =+3-l+2=+4. The next two transformations, ISO- 151 in Nicolaou s biomimetic synthesis of endiandric acid A, and Negishi s palladium-catalyzed tetracyclization 152- 153 are also characterized by Lfor =+4. Trost s one-step polyclization... 

Johnson, W.S. et al. 1977, Asymmetric total synthesis of 1 la-hydroxy progesterone via a biomimetic polyene cyclization , Journal of the American Chemical Society, 99, 8341-3. 

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