In the last few decades, studies on the female pregnancy hormone progesterone demonstrated that it can be used as an efficient agent against brain contusions after traumatic brain injury[1]. However, progesterone may not be an attractive drug candidate, because treating males with female hormones can cause undesired side effects. More recently, the enantiomer of progesterone was demonstrated to have similar advantageous effects against brain trauma, but presumably it does not cause the same undesired hormonal effects as natural progesterone does.[2] Therefore, ent-progesterone could be a suitable drug candidate. However, there is currently no efficient source of ent-progesterone. The previously reported synthesis of ent-progesterone is long (18 steps LLS), and not efficient enough to produce the product on a large scale. Attempts to design and develop an efficient synthesis of ent-progesterone will be described. Two main strategies are being investigated: (1) resolution of late-stage intermediates from the classic Johnson synthesis of racemic progesterone[3]and (2) enantioselective synthesis using a novel stereospecific cation-p cascade reaction strategy.[1] � Ma J, Huang S, Quin S, You C. Progesterone for acute traumatic brain injury. Cochrane database of Systematic Reviews 2012, Issue 10. Art. No.:CD008409. DOI: 10.1002/1465185.CD008409.pub3.[2] � Stein D. G. et. al. Neuropharmacology Volume 51, Issue 6, November 2006, Pages 1078�1085[3] � Johnson, W. S. et. al. Acetylenic Bond Participation in Biogenic-Like OlefinicCyclizations. II. Synthesis of dl-Progesterone. JACS, 1971, 4332 � 4334

Synthetic efforts toward efficient synthesis of <i>ent-</i>?progesterone

247th National Meeting (2014)

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Synthetic efforts toward efficient synthesis of ent-?progesterone