- Efficient asymmetric synthesis of prostaglandin E1
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A simple synthesis of prostaglandin E1 (PGE1) is described. The key steps are an asymmetric Michael addition to establish the desired (R)-configurations at C8 and C12 of the 2-(trimethylsilyl)ethoxymethyl- (SEM) protected PGE1 and its one-pot deprotection with magnesium bromide in high yield. This method is potentially useful for the preparation of other modified prostaglandins.
- Jung, Jae-Chul,Park, Oee-Sook
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- The Meyer-Schuster rearrangement: A new synthetic strategy leading to prostaglandins and their drug analogs, Bimatoprost and Latanoprost
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Gold(I) mediated Meyer-Schuster rearrangement for the installation of the 'lower' side chain of prostaglandins and their analogs has been developed. This Au-mediated rearrangement, featuring a low catalyst loading and mild reaction conditions, has been demonstrated to be an efficient alternative to the standard Horner-Wadsworth-Emmons reaction in prostaglandin chemistry. Moreover, the present results provide a new synthetic process leading to pharmacologically active prostanoids: Latanoprost and Bimatoprost, that continue to hold key positions in the anti-glaucoma drug market.
- Zanoni, Giuseppe,D'Alfonso, Alessandro,Porta, Alessio,Feliciani, Lazzaro,Nolan, Steven P.,Vidari, Giovanni
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experimental part
p. 7472 - 7478
(2010/12/25)
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- LOW-MOLECULE DRUG-CONTAINING NANOPARTICLE HAVING SUSTAINED RELEASE NEGATIVELY CHARGED GROUP
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A nanoparticle containing a low-molecular-weight drug having a negatively charged group is provided that is effectively targeted to an affected site, is capable of sufficiently sustained release of the drug, and has a reduced tendency to accumulate in the liver to cause reduced side effects. The nanoparticle containing a low-molecular-weight drug having a negatively charged group is obtained by hydrophobicizing the low-molecular-weight drug having a negatively charged group with a metal ion, and reacting the hydrophobicized drug with poly L-lactic acid or poly (L-lactic acid/glycolic acid) copolymer and poly DL- or L-lactic acid-polyethylene glycol block copolymer or poly(DL- or L-lactic acid/glycolic acid)-polyethylene glycol block copolymer.
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- Isoform-selective inhibitors and activators of PDE3 cyclic nucleotide phosphodiesterases
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The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments.
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- Drug preparations for treating sexual dysfunction
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Topical gelled compositions comprising a drug which causes vasodilation, and optionally prostaglandin E1, dispersed within a polymer matrix, and methods of treating sexual dysfunction, including both male and female sexual dysfunction, using said compositions.
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- An efficient asymmetric synthesis of prostaglandin E1
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An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (-)-PGE1 5 in high yield.
- Rodriguez, Ana,Nomen, Miguel,Spur, Bernd Werner,Godfroid, Jean-Jacques
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p. 2655 - 2662
(2007/10/03)
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- Process for preparing prostaglandin E1, E2 and analogs thereof using furylcopper reagents
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A process for synthesizing prostaglandin E 1, E 2 and derivatives thereof is provided. The process is a ""one-pot"" method in which 2-furyllithium, copper cyanide, a lower alkyllithium reagent and either an (E)-alkenylstannane or a halogenide are combined with cyclopentenone (II) STR1 in which A, R 6 and R 7 are as defined herein. The reaction gives rise to the desired prostaglandin product in yields of 80% or higher.
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- Method alleviating migraine headache with mast cell degranulation blocking agents
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A method of preventing or alleviating a migraine headache which comprises administering a pharmaceutically effective amount of a mast cell degranulation blocking agent just prior to or during the prodromal phase of the migraine in the absence of an analgesic. The agent can also be administered in combination with a central nervous system stimulant.
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- Prodrug derivatives of carboxylic acid drugs
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Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
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- Nitro-Olefin Trapping Reactions of Enolates In Situ Generated by Conjugate Addition Reaction: Short Syntheses of PGE1, 6-Oxo-PGE1, 6-Oxo-PGF1α, and PGI2
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The nitro-olefin trapping of the enolates in situ generated by conjugate addition of organocopper reagents to the chiral oxygenated cyclopentenone synthon, R-4, gives the three-component coupling products in a regiospecific manner.The intermediary nitronate anion 17 is further transformed into the nitro compound or 6-oxo-PGE1 (19) in a single pot.This coupling reaction is applicable to syntheses of naturally occurring prostaglandins such as PGE1, 6-oxo-PGF1α, and PGI2.
- Tanaka, Toshio,Hazato, Atsuo,Bannai, Kiyoshi,Okamura, Noriaki,Sugiura, Satoshi,et al.
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p. 813 - 824
(2007/10/02)
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- A SHORT SYNTHESIS OF (-)-PROSTAGLANDIN E1
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(-)-Prostaglandin E1 has been prepared from (R)-4-t-butyldimethylsiloxy-2-cyclopentenone by using as a key operation the tandem organocopper conjugate addition/nitroolefin Michael trapping of the resulting enolate intermediate.
- Tanaka, T.,Toru, T.,Okamura, N.,Hazato, A.,Sugiura, K.,et al.
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p. 4103 - 4104
(2007/10/02)
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- Method of inducing cytoprotection
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A method of inducing cytoprotection in mammals utilizing the prostaglandin derivative 16-methyl-1,11α,16RS-trihydroxyprost-13E-en-9-one is described.
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