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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