Synthesis of prostaglandins by conjugate addition and alkylation of a directed enolate ion. 4,5-allenyl prostaglandins

Journal Article · Fri Sep 28 00:00:00 EDT 1990 · Journal of Organic Chemistry; (United States)

DOI:https://doi.org/10.1021/jo00307a028· OSTI ID:5111951

Patterson, J W ^[1]

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1. Syntex Research, Palo Alto, CA (United States)

Over the previous two decades many elegant syntheses of prostaglandins, which in more sophisticated forms, allow the stereospecific introduction of the various asymmetric carbons have been accomplished. However, among these approaches the cuprate addition/enolate alkylation of suitable cyclopentenone {sup 2} stands out because of brevity and convergence. The recent reports by Noyori{sup 3} and Corey{sup 4} and their colleagues have reduced to practice the conversion of 4-alkoxycyclopentenones to prostaglandin E{sub 2} (PGE{sub 2}) by conjugate addition of an organocopper derivative of the lower side chain followed by alkylation of the resulting carbanion with methyl 7-halohept-2-enoate. The subject of this paper is application of the Tardella tin enolate alkylation developed by Noyori to the synthesis of 4, 5-allenic prostaglandins, a pharmacologically important class of compounds. The authors results demonstrate that the tandem alkylation of an enone precursor with a cuprate reagent followed by alkylation of the corresponding tin enolate with bromide reagent is a viable synthetic method for 4,5-didehydro-PGE{sub 2}. Because the optically active forms of 1 and the vinyl iodide precursor of the PGE{sub 2} lower side chain have been employed to produce a single enantiomer of PGE{sub 2}, the extension of the methodology described here to the synthesis of single enantiomers of 4a awaits only the preparation of the separate enantiomers of allene 14.

• OSTI ID: 5111951
• Journal Information: Journal of Organic Chemistry; (United States), Vol. 55:20; ISSN 0022-3263
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PROSTAGLANDINS
CHEMICAL PREPARATION
ACETIC ACID
ALCOHOLS
ALKENES
ALKYLATION
CARBANIONS
COPPER IODIDES
ENOLS
ETHERS
HYDROLYSIS
INFRARED SPECTRA
ISOMERS
LIQUID COLUMN CHROMATOGRAPHY
LITHIUM BROMIDES
NMR SPECTRA
ORGANIC SILICON COMPOUNDS
OXIDATION
RACEMATES
SILICA GEL
THIN-LAYER CHROMATOGRAPHY
ADSORBENTS
ALKALI METAL COMPOUNDS
ANIONS
BROMIDES
BROMINE COMPOUNDS
CARBOXYLIC ACIDS
CHARGED PARTICLES
CHEMICAL REACTIONS
CHROMATOGRAPHY
COPPER COMPOUNDS
COPPER HALIDES
DECOMPOSITION
HALIDES
HALOGEN COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
IODIDES
IODINE COMPOUNDS
IONS
LITHIUM COMPOUNDS
LITHIUM HALIDES
LYSIS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
SEPARATION PROCESSES
SOLVOLYSIS
SPECTRA
SYNTHESIS
TRANSITION ELEMENT COMPOUNDS
551000* - Physiological Systems