Editing Progesterone (section)

====Total synthesis====
[[File:Progesterone Synthesis.png|class=skin-invert-image|thumb|right|upright=2|The Johnson total synthesis of progesterone.<ref name="pmid5131151"/>]]

A [[total synthesis]] of progesterone was reported in 1971 by [[William Summer Johnson|W.S. Johnson]].<ref name="pmid5131151">{{cite journal | vauthors = Johnson WS, Gravestock MB, McCarry BE | title = Acetylenic bond participation in biogenetic-like olefinic cyclizations. II. Synthesis of dl-progesterone | journal = Journal of the American Chemical Society | volume = 93 | issue = 17 | pages = 4332–4334 | date = August 1971 | pmid = 5131151 | doi = 10.1021/ja00746a062 | bibcode = 1971JAChS..93.4332J }}</ref> The synthesis begins with reacting the [[phosphonium salt]] '''<u>7</u>''' with [[organolithium reagent|phenyl lithium]] to produce the [[phosphonium ylide]] '''<u>8</u>'''. The ylide '''<u>8</u>''' is reacted with an [[aldehyde]] to produce the [[alkene]] '''<u>9</u>'''. The [[ketal]] [[protecting group]]s of '''<u>9</u>''' are hydrolyzed to produce the diketone '''<u>10</u>''', which in turn is cyclized to form the cyclopentenone '''<u>11</u>'''. The ketone of '''<u>11</u>''' is reacted with methyl lithium to yield the tertiary alcohol '''<u>12</u>''', which in turn is treated with acid to produce the tertiary cation '''<u>13</u>'''. The key step of the synthesis is the π-cation cyclization of '''<u>13</u>''' in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce '''<u>14</u>'''. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as ''biomimetic''. In the next step the [[enol]] [[orthoester]] is hydrolyzed to produce the ketone '''<u>15</u>'''. The cyclopentene A-ring is then opened by oxidizing with ozone to produce '''<u>16</u>'''. Finally, the diketone '''<u>17</u>''' undergoes an intramolecular [[aldol condensation]] by treating with aqueous potassium hydroxide to produce progesterone.<ref name="pmid5131151"/>