Interest in the unique biological properties 2) of 8-iso-prostaglandin (PG)
El (1), which has been isolated by Daniels et al. in the biochemical transformation of 8,11,14-eicosatrienoic acid 3) , prompted us to synthesize a series of 8-iso-prostanoids.
As the reported syntheses 4-6) of 1. have not been stereochemically controlled, we have developed a new pathway to a-1 and a-8-iso-PGE2
(2) utilizing the bicyclic cis-lactone 2 obtained by the intramolecular cyclopropanation and subsequent ring cleavage 7) (,+&-,Z). Reaction of dibromoketene with cyclopentadiene in n-pentane gave the adduct 8) 5 (mp 23-24', 77%). Ring opening9) of 6 with NaOMe (-5 ester 1 [bp 87-900/2 mmHg; 83%; NMRl'), --10') yielded the trans o 5.85(1H, d., J=5 Hz, -CHBr2)). Isomeric cis ester fi [bp 59-61'/0.01 mmHg; 89%; NMR, o 6.30(1H, d., J=5 Hz, -CHBr2)] 0 was obtained by the similar reaction at -15 . Conversion of 2 to 1 by treatment with NaOMe at -5--10' confirmed the trans-configuration of 1. The dibromo ester 1 was partially reduced with Bu3SnH (neat, 5-15O, 16 hr) to the monobromide 2 11) (bp 104-106'/8 mmHg; 88%; NMR,a 3.52(2H, m., -CH2Br)). The partial reduction of the dichloro ester corresponding to 1 was not successful. 12) K. Kojima and K. Sakai, Tetrahedron Letters, 3333 (1972). 13) Reported mp 101-103° (ref. 4). This discrepancy may be attributed to the polymorphism observed in natural 1. (ref. 3).