30-08-2013, 02:27 PM
Total Synthesis of Progesterone
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What is progesterone?
• Human hormone – related to pregnancy and
menstruation
• Steroid hormone
• Additive to birth control pills
Syntheses of Progesterone
• Stork, G.; McMurry, J. E. Stereospecific Total Synthesis of Steroids via
Isoxazole Annelation. dl-D-Homotestosterone and dl-Progesterone.
J.A.C.S. 1967, 5464 – 5465
• Johnson, W. S.; Gravestock, M. B.; McCarry, B. E. Acetylenic Bond
Participation in Biogenic- Like Olefinic Cyclizations. II. Synthesis of dl-
Progesterone. J.A.C.S. 1971, 4332 – 4334
• Nemoto, H.; Nagai, M.; Fukumoto , K.; Kametani, T. A Stereoselective Total
Synthesis of ∆9-Progesterone via an Intermolecular Cycloaddition
Reaction. Tet. Lett. 1985, 4613 - 4616
Biomimetic polyene ring synthesis
• Method of synthesis utilizing a single reaction
to form several rings with a cation- pi
mechanism
• Contrasts the older method of synthesis which
uses sequential annulations in a stepwise
fashion
Historical overview of inquiry into the bioorganic
chemistry of polyolefin cyclization
• First link between squalene and steroid ring systems
proposed by Robinson in 1934 (!) utilizing cyclization
from a circular conformation.
• Work by Bloch led to the proposal of a serpent-like
intermediate for cyclization in the late 1940s
• Research culminating in stereochemical insight
largely credited to Stork, Eschenmoser in 1950s but
many others were involved at all steps