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Total Synthesis of Prostaglandins F2
and E2as the naturally occurring forms
Kirk W. ShimkinTotal Synthesis Spring 202
!orey" et al. JACS,1970"#2" $#%
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Elias &. !orey 'orn in (ethuen" () in #2% *age %$+ 'irth name is actually (atthe," mother
changed it to Elias to honor his father ,hodied shortly after his -irth.
'.). #/%" (T Ph1. #" (T *age 22+
(ade full professor at uni3ersity of llinois in #4 *at age 256+ ##present7 Professor of chemistry at 8ar3ard uni3ersity Focuses on synthetic organic chemistry -ecause of 9its intrinsic
-eauty and its great rele3ance to human health.:
;3er 000 pu-lications" in 2002 ,as recogni
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!orey" !ont. Kno,n For7
Pyridinium !hlorochromate *P!!" aka the !oreySuggs reagent+
t-utyldimethylsilyl *T'1(S+" triisopropylsilyl *TPS+"metho>yetho>ymethyl *(E(+ protecting groups
!orey'akshiShi-ata enantioselecti3e reduction
!oreyFuchs reaction !oreyKim reaction
!oreyWinter ole?n synthesis
!orey8ouse synthesis
!orey&ohnson!hayko3sky reaction
!oreySee-ach reaction Total synthesis of ginkolide ) and '" @actacystin" Ecteinascidin
5/$" Salinosporamide )" prostaglandins" among many others.
1e3elopment of retrosynthetic analysis
!laims to ha3e inspired the inception of the Wood,ard8oAman rules in a #4/ con3ersation ,ith Bo-ert Wood,ard.
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Prostaglandins
=aturally occurring hormones found in allanimal cells
@ipid compounds deri3ed from fatty acids
)ll contain 20 car-ons" mem-ered ring
First isolated from seminal Cuid in #$ *Dlf3on Euler+" -ut is actually produced -y 3arioustypes of cells
Begulate contraction and rela>ation of smoothmuscle tissues *one of many functions+
Sune K. 'ergstrom" &ohn B. ane" and 'engt .Samuelsson ,on no-el pri
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Prostaglandin F2
(arketed as dinoprost and en
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BetrosynthesisG strategy
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Synthesis
Product of ?rst reaction is unsta-le" isomeri
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Enantioselecti3ity7 ephedrine
resolution
Proof of !onformation
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Synthesis cont.
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!ompleting the synthesis
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!onclusion
First stereospeci?c synthesis of Prostaglandin F2
and E2completed
'icycloheptane strategy used to set relati3e
stereochemistry at $ stereogenic centers Ephedrine resolution pro3ides enantiopure
intermediate for enantiospeci?c synthesis
(ain precursor can -e made in roughly 0I yield
from enantiopure cyclopentene intermediate.
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Juestions