J . Org. Chem., Vol. 43, No. 22, 1978 4377
Notes
Synthesis of Thio Analogues of Prostaglandin H2 and Prostaglandin Fx from Prostaglandin Azl Andrew E Greene, Antonio Padilla, and Pierre CrabbB* 1,obnratoire do ('himre' (Jrganique,C E R M 0 , Universite Sclentifi(,up et Mbdicale, d8041 Crenoble, France
R w e i i v d J u n e 19. 1978
The prostaglandin endoperoxides PGG2 ( l a ) and PGHz ( l b ) occupy a pivotal position in the biosynthesis of the primary prostaglandins, thromboxane A2, and prostacyclin (PG1.2)from arachidonic acid.' The interesting spectrum of independent hioiopical activity exhibited by the endoperoxides coupled with their lability has prompted the synthesis 0-
I --
0L
X
C
0
Z
H
I
bR
1 a)
R=OH
b) R = H
of several potentially more stable analogue^.^,^ A t the inception of a program in our laboratory aimed principally a t the synthesis of the endo-disulfide analogue (6) of PGH2, there was a surprising lack of C-9 and C-11 thio analogues of the prostaglandins in the literature. During the course of our work in this area, however, Hayashi et al.3 reported a somewhat lengthy total synthesis of the endo-disulfide 6, via the tetrahydropyranyl ether derivative of Sa,lla-dimercapto9,lLdideoxyprostaglandinF2 methyl ester (5b), and showed it to be a very effective biochemical mimic of PGH2. In this note we wish to present a short, stereoselective synthesis from (+)-PGA, (2a) of two endo-peroxide analogues, the novel endo-trithiocarbonate 4 and the endo-disulfide 6, as well as 1la-mercapto-11-deoxyprostaglandin F2
