New stereocontrolled synthesis of prostaglandins via prostaglandin A2

Corey, E. J.; Mann, Jill

doi:10.1021/ja00801a053

Cited by 86 publications

(28 citation statements)

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“…The endoperoxides are also potent stimulants of vascular (rabbit aorta and umbilical artery) and air-way smooth muscle (6 Fig. 1 starting from PGA2 methyl ester acetate (IV) which is available either by total synthesis (8)(9)(10) or by extraction of the soft coral Plexaura homomalla (11). The methyl ester acetate IV was converted to a mixture of a-and ,B-10,11-epoxides (V) by reaction at -20°for 1.5 hr in methanol (18 ml/g of IV) with 0.5 eq of sodium hydroxide and 10 eq of 30% aqueous hydrogen peroxide, following a known method (12).…”

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confidence: 99%

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

Corey¹,

Nicolaou²,

Machida³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

116

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The 9,11-azo-prostanoid III [(5Z, 9a, Ila, 13E, has been obtained by synthesis and tested for biological activity in systems which are responsive to the prostaglandin endoperoxides PGH2 (I) and PGG2 (II). The azo analog III is a powerful mimic of these endoperoxides with reference to platelet aggregation and release of serotonin when added to human platelet-rich plasma. The analog III is substantially more active (about 7 fold) than PGG2 in stimulating muscle contraction in the isolated rabbit aorta strip. The very great stability of III relative to PGH2 and PGG2 and its potency as a mimic of these important substances suggest that this azo analog will be of considerable value in future studies of the prostaglandin endoperoxides. The two prostaglandin (PG) endoperoxides, PGH2 (I, Fig. 1) and PGG2 (II), derived in vio from arachidonic acid, are very potent in inducing rapid and irreversible aggregation of human platelets through release of ADP and serotonin (1-8). The endoperoxides are rapidly metabolized to a hemiacetal derivative 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD) in platelets, and this metabolite is released in large amounts during aggregation induced by various agents (4, 5). A physiological role of the endoperoxide system in human platelets has been established through studies demonstrating that a hemostatic defect involving an abnormal platelet release mechanism was due to deficiency of the cyclo-oxygenase responsible for endoperoxide synthesis (3). The endoperoxides are also potent stimulants of vascular (rabbit aorta and umbilical artery) and air-way smooth muscle (6).The endoperoxides PGH2 and PGG2 are intrinsically highly unstable substances (half-life, t1/2, about 5 min in aqueous solution at 370 and pH 7.4). Further, they are transformed with great rapidity enzymically [e.g., t1/2 about 10 sec in platelet-rich plasma (PRP)]. Because of the extraordinary lability of these endoperoxides and the consequent difficulties and limitations in experimental use, the design and synthesis of a stable and active analog was deemed important. The most interesting analog for initial study appeared to be the azo compound represented by formula III in Fig. 1. It was anticipated that this substance would possess very nearly the same molecular geometry as PGH2 (I), but would be indefinitely stable at pH 7 and 370. Although there was no assurance a priori that III would behave as a close mimic of PGH2 (or PGG2) rather than as an antagonist, the experimental resolution of this question itself seemed worthwhile as a step toward a better understanding of the biochemical mode of action of PGH2.MATERIALS AND METHODS The preparation of the endoperoxides PGG2 and PGH2 has been described previously (2). Blood from healthy donors, who had not taken any drugs for at least 1 week, was collected from the antecubital vein with 0.13 volume of 0.1 M trisodium citrate. After centrifugation at 200 X g for 15 min at room temperature, PRP was removed. Calcium chloride (10 ,ul 0.25 M solutio...

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confidence: 99%

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

Corey¹,

Nicolaou²,

Machida³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

116

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“…In the synthesis of prostaglandin derivatives, compound (I) (Pirkle et al, 1977) was reported as a suitable starting material (Corey & Mann, 1973;Collington et al, 1983), and also for the generation of the title compound, (IV), which has been used for the synthesis of strigol, a natural germination stimulant (Rö hrig et al, 1998;Johnson et al, 1981). Compound (IV) can exist in the tautomeric carbaldehyde, (III), or hydroxymethylene, (IV), forms, where E/Z isomers can occur.…”

Section: Commentmentioning

confidence: 99%

rac-(3E,3aR,6aR)-3-(Hydroxymethylene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one

et al. 2007

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The crystal structure of the title compound, C8H8O3, was determined in the course of our studies of the synthesis of cyclopenta[1,2‐b]furan‐4‐one derivatives. The title compound has two chiral C atoms and was obtained as a racemic mixture. It was found to possess a vinylogous acid group with an E configuration at the double bond. The compound exists in the hydroxymethylene and not in the tautomeric carbaldehyde form. The asymmetric unit consists of two molecules.

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“…In the synthesis of prostaglandin derivatives the compound 3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one [(I) and (Ia); Pirkle et al, 1977] was reported as a suitable starting material (Corey & Mann, 1973;Collington et al, 1983). In this study, we used alkaline iodolactonization of racemic (I) to generate (IVa) as enantiomers with defined stereochemistry (see schemes).…”

Section: Commentmentioning

confidence: 99%

(2aRS,3RS,4aSR,6aRS,6bSR)-3-Hydroxy-2a,3,4a,6,6a,6b-hexahydro-1,4-dioxacyclopenta[cd]pentalen-2(5H)-one

et al. 2007

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The molecular structure of the title compound [enantiomers (VIII) and (VIIIa)], C8H10O4, was determined in the course of our studies on the synthesis of cyclopenta[1,2‐b]furan‐4‐one derivatives. Tricyclic (VIIIa) consists of a planar bridged lactone unit and the two other ring systems in the envelope conformation. It contains five chiral C atoms and was obtained as a racemic mixture. The X‐ray analysis showed the compound to possess a half‐acetal unit with an endo orientation of the half‐acetal ether bridge with respect to the lactone unit.

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New stereocontrolled synthesis of prostaglandins via prostaglandin A2

Cited by 86 publications

References 0 publications

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

rac-(3E,3aR,6aR)-3-(Hydroxymethylene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one

(2aRS,3RS,4aSR,6aRS,6bSR)-3-Hydroxy-2a,3,4a,6,6a,6b-hexahydro-1,4-dioxacyclopenta[cd]pentalen-2(5H)-one

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