Prostaglandins. IX. Synthesis of (+-)-prostaglandin E1, (+-)-11-deoxyprostaglandins E1,F1.alpha., and F1.beta., and (+-)-9-oxo-13-cis-prostenoic acid by conjugate addition of vinylcopper reagents

Abstract

The syntheses of (±)-PGEi and (±)-ll-deoxyprostaglandins in the E: and Fi series have been carried out by conjugate addition of bis(triethyl phosphite)copper(I) cyanide vinyllithium to the substituted cyclopentenones la and lb, and subsequent elaboration of vinylamylcarbinol side chain via the intermediate carboxaldehydes 3b and 3d. The intermediate 3d was also converted to (±)-9-oxo-13-czs-prostenoic acid (6c). These transformations are characterized by high yields and ease of operation. The synthesis of prostaglandins has been the subject of considerable synthetic effort during the past several years. In the course of this work a number of elegant syntheses of prostaglandins have been developed, but, in general, these approaches are lengthy and rather complex in nature.2

New Bioactive Oxylipins Formed by Non‐Enzymatic Free‐Radical‐Catalyzed Pathways: the Phytoprostanes

“…Spur and coworkers developed very efficient syntheses of the PPE 1 via a two components coupling process typically used for the synthesis of PG and analogs [47][48][49]. By simply modifying ''work-up'' conditions using chelating proton sources, a switch from PG trans-dialkyl stereochemistry to PP cis-dialkyl stereochemistry was accomplished.…”

Synthesis And Novel Stereochemical Results In The Lithium–Ammonia Reduction Of Some 4-Alkyl-Δ1(9)-2-octalones

“…Furthermore, the conformational analysis of substituted A1-octalines of the type 32 and 33 has not as yet been put on a quantitative basis and it is thus very difficult to accurately assess the magnitude of the various nonbonded interactions involved in the different conformations of possible intermediates and/or transition states. Therefore, it is difficult to offer, in quantitative terms, an explanation for the stereochemical results summarized in Table 1 (34,35,36),6 each of which could theoretically lead to protonation transition states to afford 32 and/or 33. However, considering angle and torsional strain, Robinson concluded that 36 would generally involve too high an energy (large angle strain, lack of planarity of the conjugated system) to be a likely conformation.…”

“…Considering now the stereochemical results obtained from the lithium-ammonia reduction of octalones 4 and 7-11, inclusive, it is reasonable to propose that the stability gained by changing the conformation of the reduction intermediate from 34 (axial C4-alkyl group) to 35 (equatoriallike C4-alkyl group) would at least partially off-set the angle and torsional strain inherent in conformation 35. If the protonation transition 5The reasoning which led to this conclusion will not be reproduced here.…”

“…able that the stabilization arising from changing the alkyl group from the axial orientation (34) to the equatorial-like orientation (35) would also increase somewhat. This would make the transition state resembling 35 increasingly more favored and could thus account for the observed fact that as the C,-alkyl group increases in size, the amount of cis-fused decalone obtained also increases.…”

“…It should be noted that recently, subsequent to the time at which the above-described work was carried out, there have appeared a number of reports concerning the use of lithium divinylcuprate (25)(26)(27)(28)(29) and related reagents (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) in conjugate addition to a variety of u,p-unsaturated ketones.…”