- Alkyne cross metathesis reactions of extended scope
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equation presented A catalyst formed in situ from Mo[N(t-Bu)(Ar)]3 1 (Ar = 3,5-dimethylphenyl) and CH2Cl2 in toluene effects cross metathesis reactions of functionalized alkynes that are beyond reach of more traditional promotors. An application to the synthesis of prostaglandin E2 (PGE2) 19 and the acetylated PGE derivative 18b shows the compatibility of this method with sensitive substrates.
- Fuerstner, Alois,Mathes, Christian
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p. 221 - 223
(2007/10/03)
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- Novel and flexible entries into prostaglandins and analogues based on ring closing alkyne metathesis or alkyne cross metathesis
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The suitably functionalized cyclopentanone derivatives 12, 13, 19, and 37 serve as common precursors for the synthesis of various prostaglandins, prostaglandin-1,15-lactones, and unnatural analogues thereof. All of them contain a 2-butynyl entity which is
- Furstner,Grela,Mathes,Lehmann
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p. 11799 - 11805
(2007/10/03)
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- Soluble-polymer supported synthesis of a prostanoid library: identification of antiviral activity.
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[formula: see text] The prostaglandins are potent natural products taking part in many biological processes. The "convergent generation of diversity" from a "toolbox" of prostanoid components, augmented with additional polymer-supported transformations, c
- Lee,Angulo,Ghazal,Janda
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p. 1859 - 1862
(2008/02/11)
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- Enantioselective Rh-Mediated Synthesis of (-)-PGE2 Methyl Ester
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Intramolecular Rh(II) carboxylate catalyzed cyclization of an α-diazo β-methylene ketone to form a fused cyclopropane is shown to compete efficiently with β-hydride elimination, so long as a catalyst derived from an electron-donating carboxylate is used.C
- Taber, Douglass F.,Hoerrner, R. Scott
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p. 441 - 447
(2007/10/02)
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- PALLADIUM(0) CATALYZED REACTIONS OF 1,4-EPIPEROXIDES
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The Pd(PPh3)4 catalyzed reaction of 2,3-saturated and 2,3-unsaturated 1,4-epiperoxides proceeds by courses markedly different from those of the previously reported transition metal catalyses.The Pd(0)-promoted reaction of 2,3-saturated epiperoxides gives the corresponding 4-hydroxy ketones and 1,4-diols as the major products.From 2,3-dedihydroepiperoxides are formed the corresponding 4-hydroxy enones, syn-1,2;3,4-diepoxides, and 1,4-diols.The results are interpreted in terms of competing Pd(0)/Pd(II) exchange mechanisms.Exposure of prostaglandin (PG) H2 methyl esterto Pd(PPh3)4 produces a mixture of methyl esters of PGD2, PGE2, PGF2α, and (5Z,8E,10E,12S)-12-hydroxy-5,8,10-heptadecatrienoic acid.
- Suzuki, Masaaki,Oda, Yoshihisa,Hamanaka, Nobuyuki,Noyori, Ryoji
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p. 517 - 535
(2007/10/02)
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- The Three-Component Coupling Synthesis of Prostaglandins
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A convergent one-pot construction of the prostaglandin (PG) framework has been accomplished by the organocopper-mediated conjugate addition of the S configurated ω side-chain unit to a protected (R)-4-hydroxy-2-cyclopentenone followed by trapping of the enolate intermediate by α side-chain alkyl halides.Transmetalation with use of triphenyltin chloride at the enolate stage serves as key operation for the succesful three-component coupling synthesis.The use of methyl (Z)-7-iodo-5-heptenoate as the α side-chain component allows short synthesis of PGE2 and PGD2.Introduction of a triple bond at the C-5-C-6 positions with methyl 7-iodo-5-heptynoate as the α side-chain synthon has opened a general entry of PGs.The protected 5,6-didehydro-PGE2 derivatives are convertible to a variety of PGs of 1 and 2 series by the controlled hydrogenation of the C-5-C-6 unsaturated bonds and α-selective (100percent) reduction of the C-9 keto function, if necessary.Lithium aluminum hydride reagents modified by (R)- and (S)-2,2'-dihydroxy-1,1'-binaphthyl exhibit a unique kinetic discrimination in reduction of PGE type compounds.A protected 5,6-didehydro-PGF2α has been transformed stereoselectively to PGI2 by using intramolecular alkoxypalladation/depalladation as the key step.
- Suzuki, M.,Yanagisawa, A.,Noyori, R.
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p. 4718 - 4726
(2007/10/02)
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- A Triply Convergent Total Synthesis of L-(-)-Prostaglandin E2
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This paper details a versatile and efficient total synthesis of l-(-)-PGE2 (3).The key step is a triply convergent conjugate-addition/alkylation reaction involving the 1,4-addition of chiral vinyllithium reagent 7b to chiral vinyl sulfone D-47 to afford sulfone-stabilized anion , which is subsequently alkylated to produce the basic prostaglandin E2 skeleton 70.The synthesis of chiral vinyl sulfone D-47 involves a five step sequence with an enantioconvergent resolution process as one step and produces vinyl sulfone D-47 from readily available sulfide alcohol DL-11 in an overall yield of 36percent.The preparation of D-47 features two steps that utilize stereospecific SN2'reactions.The synthesis of l-(-)-PGE2 (3) involves a seven-step sequence from vinyl sulfone D-47 using mild conditions with an overall yield of 40percent and features an efficient peracetic acid oxidation of secondary amino acid 120 to oximino acid 121, which is, in turn, desulfonylated by 1,4-elimination of phenylsulfinic acid to generate a vinyl nitroso species that undergoes stereospecific 1,4-reduction by sodium borohydride to yield oxime 131.The hydrolysis of oxime 131 to l-(-)-PGE2 (3) using boron trifluoride and paraformaldehyde is the first reported high-yield method (84percent).This gives an overall yield for the synthesis of l-(-)-PGE2 (3) from racemic sulfide alcohol DL-11 of 14.5percent, including the resolution process.
- Donaldson, R. E.,Saddler, J. C.,Byrn, S.,McKenzie, A. T.,Fuchs, P. L.
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p. 2167 - 2188
(2007/10/02)
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- Total Synthesis of (+/-)-Prostaglandin E2 Methyl Ester from exo-2-Bromo-endo-3-hydroxybicycloheptan-6-one using Dimethyl-t-butylsilyl Protected Intermediates
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Peracetic acid oxidation at -78 deg C of the dihydroxybicyclohepten-6-one (23) afforded the dihydroxylactone (24) which was protected as its bisdimethyl-t-butylsilyl ether (26) and reduced to the corresponding lactol (27).A Wittig reaction on (27), carried out in benzene with a short reaction time, gave mainly the required 11α-silyl ether (28) together with a trace of the 9α-silyl ether (29) which results from 1,5-migration of the silyl group.Oxidation of (28) followed by quantitative deprotection using aqueous HF in acetonitrile afforded (+/-)-PGE2 methyl ester (20).This short stereo- and regioselective total synthesis proceeds in an overall yield of 10percent starting from cyclopentadiene.
- Howard, Colin,Newton, Roger F.,Reynolds, Derek P.,Roberts, Stanley M.
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p. 2049 - 2054
(2007/10/02)
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- 8β,12α,15β-PGF2 β Compounds
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This invention is a group of 8-beta, 12-alpha-PG2 (prostaglandin-type) analogs having variable chain length, or methyl or phenyl substitution in the hydroxy-substituted side-chain, and processes for making them. These compounds are useful for a variety of pharmacological purposes, including anti-ulcer, inhibition of platelet aggregation, increase of nasal patency, and labor inducement at term.
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- Enzymatic preparation and purification of prostaglandin E2.
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An enzymatic system has been developed for the production of prostaglandin E(2) (PGE(2)) from arachidonic acid by extracts of sheep seminal vesicular glands. The presence of glutathione insures high yields. A new procedure for the purification of PGE(2) was also developed, based on the dialysis of the biosynthesized product at pH 8 and extraction of the dialysate at pH 3 with chloroform. This procedure routinely gives yields of PGE(2) of 25-37% (from arachidonic acid) with a purity of 90-100%. Additional analytical proof of the identity of PGE(2) was provided by physicochemical characteristics of the crystalline thiosemicarbazide derivative, which can be readily prepared under mild conditions.
- Lapidus,Grant,Alburn
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p. 371 - 373
(2007/10/16)
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