Prostaglandin 11-alkyl

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

This compound has not been previously reported in the literature. The compound is unusual In that the substitution pattern of alkyl and hydroxyl groups on the ring Is analogous to the prostaglandin F series. 

Studies on the biosynthesis of prostaglandins revealed that a strained bicyclic bis(secondary-alkyl) peroxide was not only a key intermediate, but could survive the biological conditions long enough to be isolated, albeit in minute amounts. This was a startling discovery in that no simple bicyclic peroxides of the same type were known, clearly for reasons of preparative difficulty. The prostaglandin connection focused attention upon this missing class of peroxides and stimulated... 

During the last decade, a substantial number of novel (sometimes even stereoselective) strategies for the preparation of allenic prostaglandins have been devised. The approach used by Patterson involves a three-component coupling via a 1,4-addi-tion of the organocopper compound 121 to the enone 120, followed by alkylation of the enolate formed with the bromide 122 (Scheme 18.40) [121]. However, due to the notoriously low reactivity in the alkylation of the mixed copper-lithium enolate formed during the Michael addition [122], the desired product 123 was obtained with only 28% chemical yield (the alkylation was not even stereoselective, giving 123 as a 1 1 mixture of diastereomers). 

In a synthesis of optically active allethrolone and prostaglandin intermediates, Yamada and co-workers (92) studied the reduction of certain 2-alkyl-1,3,4-cyclopentanetriones (82) with a reagent prepared by the reaction of LAH with 3 equivalents of (- )-A-methylephedrine in THF. Reduction of the cyclopen-tanetriones 82 with this reagent gave (/ )-83 in 55 to 58% e.e. (Scheme 12). Thus (/ )-83b (R2 = Ac, after acetylation) was obtained in 48% yield and 55% e.e. from 82b. The steric course and enantiomeric excess in the reduction were... 

Unsaturated carboxylic acids can be de-carboxylated to alkyl radicals that undergo an intramolecular addition. The S-exo-trig-cyclization of fi-allyloxy radicals, generated from an appropriate carboxylic acid, combined with a final heterocoupling has been applied to synthesize a precursor of prostaglandine PGF2q (Fig. 47) [246] and a branched carbohydrate (ratio of diastereo-mers 1.8 1) (Fig. 48) [247]. A radical tandem cyclization of a doubly unsaturated monocyclic carbocyclic acid provides a... 

A synthesis of the prostaglandin analogue TEI-9826 is presented in Scheme 9.40 as an example of the use of an Ir-catalyzed aUyUc alkylation [44]. The allylic alkylation with a malonic amide of the Weinreb type as pronucleophile gave the substi-... 

Scheme 9.40 Synthesis of the prostaglandin analogue TEI-9826 via Ir-catalyzed allylic alkylation.

Alkyl tosylates and mesylates are cleaved on the action of KOj in DMSO and give rise to the corresponding alcohols. This reaction also proceeds with inversion of configuration at carbon atoms (Morkovnik and Okhlobystin 1979). Such process may be of importance in prostaglandin chemistry. 

Application of the Pd-catalyzed alkylation of hydrogencarbonate to the meso-biscarbonate 29 gave the allylic alcohol 30 in 87% yield with 96% ee (Scheme 2.1.4.31). Alcohol 30 has been converted via the silyl ether 31 and alcohol 32 to ketone 33, the enantiomer of which is an important building block for the synthesis of prostaglandins [40]. Since both BPA and mt-BPA are readily available, access to ent-33 is also provided. 

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