Prostaglandins PGA2, synthesis

Problem 24.20 One synthesis of prostaglandin PGA2 involved a Dieckmann reaction as a key step. What is the structure of X in the reactions drawn below ... 

Stork and Raucher described the first synthesis of a natural prostaglandin (PGA2) (66) from the simple sugar erythrose (60) which is distinguished because it avoids totally the need for separation of enantiomers. The route, outlined in Scheme 19, includes two Claisen rearrangements, one to produce the is-geometry of the (13,14-) double bond (61) -> (62), the other to transfer chirality of the C—O bond to that of a non-adjacent C—C bond, viz. (63) (64), and uses the Dieckman>, cyclization... 

The unexpected source of starting material for partial synthesis i)f these agents was the sea. The isolation of 15CR)-PGA2 and its iicetate (44) from the lowly sea whip, Plexura homomalla, one of I he so-called soft corals, made an approach to prostaglandins rrom natural products possible. 

Since several excellent recent reviews of prostaglandin chemistry are available (14.15.16), we will limit the chemical discussion to the development at Lederle and elsewhere of the synthesis of prostaglandin analogs by the convergent conjugate-addition approach and by the derivatization of I-PGA2, available 0-8412-0536-l/80/47-118-301 16.40/0 1980 American Chemical Society... 

E prostaglandins has prompted the synthesis of more stable analogues. Thus compounds e.g. 8-methyl-PGC2 [108], 12-methyl-PGA2 [109] and ( )-10, 10-dimethyl-PGEi [110] have been synthesized having methyl groups in key positions which block the normal transformation to the relatively inactive PGB products. 

Synthesis of natural prostaglandins and their analogs. Corey has disclosed three direct syntheses of PGA2. The first involves conversion of the key intermediate 3 to [R = S1(CH2)2C(CHt)2] and subsequent treatment by previously reported procedures to yield PGA2 as the primary product.35... 

The Roussel-Uclaf group has published full details of the synthesis of dihydro-10,11 -PGA2, and Trost and his co-workers have described an interesting chiral synthesis of the PG analogue (92). The application of conjugate addition of zirconium alkenyls to cyclopentenones leading to prostaglandin intermediates has been reported, and Kondo et a/. have extended their approach to... 

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