Showing papers on "Epimer published in 1996"
TL;DR: In this article, a trimethylstannyl radical carbocyclization of a diene was used to obtain the 2,3-trans/3,4-cis and 2, 3-trans and 3-4-trans adducts in a 2.8:1 ratio and in high yield, respectively.
Abstract: (−)-α-Kainic acid (1) and its C4 epimer (+)-α-allokainic acid (2) have been prepared from l-serine. The requisite stereochemical array in (−)-α-kainic acid (1) was introduced using a trimethylstannyl radical carbocyclization of a diene, which gave the 2,3-trans/3,4-cis and 2,3-trans/3,4-trans compounds in a 2.8:1 ratio and in high yield. The destannylation of the trisubstituted pyrrolidine nucleus was achieved via an oxidative cleavage of the C−Sn bond with ceric ammonium nitrate. This provided a dimethyl acetal that was further transformed into the intended α-kainic acid. When the same radical carbocyclization was attempted on a triene, the 2,3-trans/3,4-trans and the 2,3-trans/3,4-cis adducts were obtained in a 2.5:1 ratio, respectively. This approach was used to synthesize (+)-α-allokainic acid.
73 citations
TL;DR: Sonogashira coupling reactions of highly functionalised cyclohexenyl halides have been developed and utilised to prepare the naturallyoccurring anti-cancer agent harveynone and its C-4 epimer.
57 citations
TL;DR: Mossambine (6) was obtained by a six-step reaction sequence from the indoloazepine ester 7 by selective pyrolysis of the resulting diastereomeric alcohols 18 and 19 or 20 and 21.
Abstract: Mossambine (6) was obtained by a six-step reaction sequence from the indoloazepine ester 7. Radical cyclization of the tetracyclic vinyl iodide 12a provided a racemic pentacyclic ketone 16E, which could be converted to either enantiomer by condensation with (S or R)-N,S-dimethyl-S-phenylsulfoximine and selective pyrolysis of the resulting diastereomeric alcohols 18 and 19 or 20 and 21. Selective reductions of the resolved (or racemic) ketone 16E provided mossambine (6) and its hydroxy epimer 17.
43 citations
TL;DR: The NIS-mediated cyclization of aminoheptenitols was used in the synthesis of a precursor of an aza-C-disacharide and its reaction with triethyl phosphite.
40 citations
TL;DR: In this paper, a new synthetic method providing both enantiomers by heteroconjugate addition strategy is described for stereocontrolled synthesis of optically active compounds from D-sugar chirons.
29 citations
TL;DR: In this article, three new proline-rich cyclic nonapeptides, cycloleonuripeptides A: cyclo (-Gly-pro-Pro-ProTyr-ProPro-Met-Ile-), B: cycloclo(Glypro-propro-Tyr)-pro-Met(O)-Ile-, and C: cyclocalo(C) were isolated from the fruits of Leonurus heterophyllus and their structures were elucidated by extensive 2D NMR methods.
25 citations
TL;DR: In this article, a C 2-symmetric macrocyclic alkaloid isolated from the sponge Xestospongia exigua and its C(9) epimer araguspongine E (2) have been synthesized.
Abstract: Xestospongin A [also known as araguspongine D (1)], a C2-symmetric macrocyclic alkaloid isolated from the sponge Xestospongia exigua (Xestospongia sp.), and its C(9) epimer xestospongin C [also known as araguspongine E (2)] have been synthesized. The route capitalizes on the facile condensation between 5-halovaleraldehydes and 1,3-aminoalcohols to produce an oxaquinolizidine ring system in which all proper relative stereochemical relationships are controlled by equilibration. A linchpin synthesis was used to construct one key monomeric precursora 2,5-disubstituted thiophene derivative 26 [N≡CCH2CH(OH)-2-Th-5-CH2CH2CH(CH(OMe)2)CH2CH2CH2Cl]. A second precursor lacking the thiophene ring 38 [N≡CCH2CH(OH)(CH2)6CH(CH(OMe)2)CH2CH2CH2Cl] was assembled in a similar fashion. The carbinol center in each of these precursors was efficiently resolved enzymatically; lipase (PS-30) hydrolysis of the racemic acetate derivative of the thiophenemethanol derivative 26 and SP-435-catalyzed esterification of the β-hydroxynitr...
23 citations
TL;DR: The first total synthesis of the novel β-adrenergic receptor antagonist MY336-a 1 and its epimer 2 has been achieved from 2,3-dimethoxytoluene by Jackson cyclisation of Nbenzyl-N-tosylamido acetals and base-catalysed epimerisation of 1-substituted hydroxytetrahydroisoquinolines.
Abstract: The first total synthesis of the novel β-adrenergic receptor antagonist MY336-a 1 and its epimer 2 has been achieved from 2,3-dimethoxytoluene, by Jackson cyclisation of Nbenzyl-N-tosylamido acetals, Lewis acid-mediated addition of silicon-based nucleophiles to p-tosyliminium ions and base-catalysed epimerisation of 1-substituted hydroxytetrahydroisoquinolines, being key steps.
18 citations
TL;DR: The first total synthesis of (±)-dienomycin C 1 and its C-4 epimer 9 was reported in this article, using an intramolecular Mannich-type cyclisation.
18 citations
TL;DR: In this article, aldol reactions with lithium alkyl acetates (LiCRR) with (RS)-2-(p-tolylsulfinyl)cyclohexanone (1) (as an epimeric mixture at C-2) take place with very efficient control of the configuration at the tertiary hydroxylic carbon (C-1).
Abstract: Aldol reactions lithium alkyl acetates (LiCRR‘‘CO2R‘) with (RS)-2-(p-tolylsulfinyl)cyclohexanone (1) (as an epimeric mixture at C-2) take place with very efficient control of the configuration at the tertiary hydroxylic carbon (C-1). Stereoselectivity becomes complete if R and/or R‘‘ are not hydrogen. Only carbinols derived from (S2,RS)-1 epimer were obtained, the major ones being those exhibiting S configuration (opposite to that of the sulfur) at the hydroxylic carbon. When LiCHRCO2R‘ is used, mixtures of the two epimers at the new stereogenic center C-1‘ are obtained (∼10−82% de), their proportion being dependent on the size of R. The use of lactone enolates avoids the formation of epimeric mixtures, affording only one diastereoisomer with an (R3‘,S1,S2,RS) configuration at the four adjacent chiral centers. Tricoordinated lithium species, which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates, are invoked to explain the stereoselectivity observed in these aldol reactions with...
17 citations
TL;DR: In this paper, the isomerization of rel-(2R,4S,5R)-4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolane 7 with titanium tetrachloride affords rel-(1R,3R, 4S)-4-hydroxy-6,8-dim-ethoxy-1-3-dimethylamino-isochromane 19 and its C-1 epimer 20 in high yield.
Abstract: Stereoselective isomerisation of rel-(2R,4S,5R)-4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolane 7 with titanium tetrachloride affords rel-(1R,3R,4S)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 19 and its C-1 epimer 20 in high yield. The former predominates at a reaction temperature of –78 °C and the latter at –30 °C. Similar isomerisation of the 1 : 1 mixture of rel-(2S,4R,5R)- and rel-(2S,4R,5R)-4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolanes 8 and 9 gives rel-(1R,3R,4R)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 29 and its C-1 epimer 31, with the latter predominating at both –78 and –30 °C. At 0 °C, dioxolane 7 is isomerised to rel-(1S,1′R,3R)-1-(1′-hydroxyethyl)-4,6-dimethoxy-3-methyl-1,3-dihydroisobenzofuran 25 and its C-3 epimer 26 as the sole reaction products in a 10 : 1 ratio. Dioxolanes 8 and 9 are similarly converted into rel-(1R,1′R,3S)-1-(1′-hydroxyethyl)-4,6-dimethoxy-3-methyl-1,3-dihydroisobenzofuran 32 and its C-3 epimer 33. These furans probably arise through further isomerisation of the intermediate isochromanes at the higher reaction temperatures.
TL;DR: C -6-Alkyl carbohydrates may provide a new range of sugar mimics that control enzymes associated with formation, hydrolysis and other fates of sugar-6-phosphates.
TL;DR: In this article, a new lignan, epithuriferic acid has been prepared from isopicropodophyllone using spectral, chemical and molecular modelling findings and compared to that of its 8′ epimer, isolated from the Juniperus thurifera leaves.
TL;DR: In this paper, the venturicidene C-15/C-27 segment was synthesized in 15 steps, containing 8 stereogenic centers with the proper absolute configuration.
Abstract: Chain extension of an aldehyde by two “propionate” units has been attained by stereoselective allylboration with the chiral 1-methylbutenyl boronate 3 to give, e.g., the homoallylic alcohol 6, followed by a regioselective hydroboration/carbonylation procedure to give, e.g., the epimeric aldehydes 8. The latter were converted into the lactols 10, which equilibrated to the desired epimer. The lactols could again be subjected to an allylboration reaction, initiating a second round of the chain extension protocol. This technique has been used to synthesize in 15 steps the venturicidene C-15/C-27 segment 23, containing 8 stereogenic centers with the proper absolute configuration.
TL;DR: 17-Phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester and its epimer were stereoselectively epoxidized to produce each of the four diastereomeric epoxides, and the attack of the sulfur nucleophile on the epoxide occurred at either C13 or C14 depending on the stereochemistry of theEpoxide and of C15.
Abstract: Novel prostaglandin F2α derivatives, functionalized at C13 and C14, have been prepared. 17-Phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester [(15S)-1] and its epimer [(15R)-1] were stereoselectively epoxidized, using Sharpless conditions, to produce each of the four diastereomeric epoxides (15S)-2, (15S)-3, (15R)-2, and (15R)-3. Treatment of the four epoxides with LiOH stereospecifically-produced the pentahydroxy substituted analogues 12 and 13. Alternatively, epoxides 2 and 3 were allowed to react with thiophenolate ion. The attack of the sulfur nucleophile on the epoxide occurred at either C13 or C14 depending on the stereochemistry of the epoxide and of C15.
TL;DR: In this article, a new general synthesis for (±)-dibenzocyclooctadiene lignans was established via the spiro-dienone ethers E- and T-11 as the key intermediates, using Weitz' aminium salt, tris(4-bromophenyl)aminium hexachloroantimonate.
Abstract: We have established a new general synthesis for (±)-dibenzocyclooctadiene lignans, including (±)-schizandrin (la), (±)-gomisin A (1b), (±)-isoschizandrin (3a), and (±)-isogomisin A (3b), via the spiro-dienone ethers E- and T-11 as the key intermediates, prepared from the corresponding bisarylbutanol derivatives E- and T-10 by the oxidation with Weitz' aminium salt, tris(4-bromophenyl)aminium hexachloroantimonate (BAHA). These syntheses consist of 13 steps from the phenylpropanone 5
TL;DR: Compounds 2 and 10 were found to be potent 5-HT3 receptor antagonists, like 1.
Abstract: In physicochemical and pharmacokinetic evaluations of (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole hydrochloride 1 (YM060 : ramosetron), which is a highly potent 5-hydroxytryptamine (5-HT3) receptor antagonist, 4-hydroxy-6-[(1-methyl-1H-indol-3-yl)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole 2 was identified as a degradation product and metabolite of 1. The (-)-(4R, 6S)-isomer 2 was synthesized from the diketone derivative 3, via the stereoselective reduction of 3 followed by the stereocontrolled epimerization of the (-)-(4S, 6S)-isomer 10, the epimer of 2. The stereochemistry of 2 and 10 was determined by NMR and HPLC studies. Compounds 2 and 10 were found to be potent 5-HT3 receptor antagonists, like 1. Among the other oxidation products, the diketone derivatives 3 and 7 and the dihydroxylated derivative 4 retained antagonistic activity similar to that of ondansetron. This is of interest, because they do not possess the amine group which is known to be necessary for high affinity to the 5-HT3 receptor.
TL;DR: The mechanism of conversion of 2 into 3, as well as the unusually facile interconversion of 2-S-ethyl-2-thio-D-mannose (6) and its D-gluco epimer 10, has been investigated.
TL;DR: The first synthesis of nitro-multideoxy-sugar containing nucleosides was achieved in this article, where 1-(4,6-O-Benzylidene-3,deoxy-3-nitro-β-D-arabinohexopyranosyl)uracil (S) was obtained in 87% yield.
Abstract: The first synthesis of nitro-multideoxy-sugar containing nucleosides was achieved. 1-(4,6-O-Benzylidene-3-deoxy-3-nitro-β-D-glucopyranosyl)uracil (3) was converted in 75% yield into 1-(4,6-O-benzylidene-2,3-dideoxy-3-nitro-arabinohexopyranosyl)uracil (7) by acetylation followed by NaBH4 reduction in methanol. De-O-benzylidenation with CF3CO2H afforded crystalline 1-(2,3-dideoxy-3-nitro-β-D-arabinohexopyranosyl)uracil (S) was obtained in 87% yield. Raney Ni reduction of 8 afforded the corresponding 3′-amino-nucleoside 9. Acetylation of 8 followed by NaBH4 treatment afforded an 8:1 mixture from which 1-(2,3,4-trideoxy-3-nitro-β-D-threohexopyranosyl)-uracil (14) was obtained in pure crystalline form. After Raney Ni reduction of the mixture, 1-(3-amino-2,3,4-trideoxy-β-d-threo-hexopyranosyl)uracil (16) and its erythro epimer 21 were isolated. 1-(4,6-O-Benzylidene-2,3-dideoxy-3-nitro-β-d-lyxohexopyranosyl)uracil (24) was prepared in 72% yield from 1-(4,6-O-benzylidene-3-deoxy-3-nitro-β-d-galactopyrano...
TL;DR: In all six compounds the observed overall conformation of the major conformer around the Pro-His amide bond, and the observed increase of the cis/trans ratio between the conformers when L-His is replaced by D-His, can be accommodated by assuming that a ten-membered ring is formed by hydrogen bonding between the N-H and N pi-atom of the His imidazole nucleus.
Abstract: NMR studies have been used to examine conformational effects in thyrotropin-releasing hormone (TRH), the epimer incorporating D-His, and their analogues where trans- and cis-4-hydroxy-L-proline replace L-proline (Pro). In all six compounds the observed overall conformation of the major conformer around the Pro-His amide bond, and the observed increase of the cis/trans ratio between the conformers when L-His is replaced by D-His, can be accommodated by assuming that a ten-membered ring is formed by hydrogen bonding between the N-H of the Pro carboxamide function and the N pi-atom of the His imidazole nucleus.
Journal Article•
TL;DR: In this article, the 2-deoxy-2-thio-myo-inositol 1-phosphate was used to prepare a partir du myo-INositol.
Abstract: Les 2-deoxy-2-thio-myo-inositol 1-phosphate 2 et, 2-deoxy-2-thio-scyllo-inositol 1-phosphate 3 ont ete prepares a partir du myo-inositol.
TL;DR: The NIS-mediated cyclization of aminoheptenitols was used in the synthesis of a precursor of an aza-C-disacharide and its reaction with triethyl phosphite as discussed by the authors.
Abstract: The NIS-mediated cyclization of aminoheptenitols 5–8 (prepared in three steps from tetra- O -benzyl- d -hexopyranoses ) provided 1,2,6-trideoxy-2,6-imino-liodoheptitol derivatives 9–12, respectively, highly stereoselectively and in high yield. The “ α- d - gluco ” epimer 9 was used in the synthesis of a precursor of an aza-C-disacharide and its reaction with triethyl phosphite was investigated.
TL;DR: In this article, the 17-Phenyl-18,19,20trinorprostaglandin F2α isopropyl ester and its epimer (15R)-1] were stereoselectively epoxidized, using Sharpless conditions, to produce each of the four diastereomeric epoxides (15S)-2, ( 15S)-3, (15 R)-2), and (15 S)-3).
Abstract: Novel prostaglandin F2α derivatives, functionalized at C13 and C14, have been prepared. 17-Phenyl-18,19,20-trinorprostaglandin F2α isopropyl ester [(15S)-1] and its epimer [(15R)-1] were stereoselectively epoxidized, using Sharpless conditions, to produce each of the four diastereomeric epoxides (15S)-2, (15S)-3, (15R)-2, and (15R)-3. Treatment of the four epoxides with LiOH stereospecifically-produced the pentahydroxy substituted analogues 12 and 13. Alternatively, epoxides 2 and 3 were allowed to react with thiophenolate ion. The attack of the sulfur nucleophile on the epoxide occurred at either C13 or C14 depending on the stereochemistry of the epoxide and of C15.
Patent•
03 Sep 1996
TL;DR: In this article, a process for epimer enrichment of compounds of formula (I) where R 1 and R 2 are defined in the description, by fractional crystallization is described.
Abstract: The invention describes a process for epimer enrichment of compounds of formula (I) where R 1 and R are as defined in the description, by fractional crystallization.
TL;DR: The addition of 2-(lithiomethyl)indole 2 to the enantiopure oxazolinylpyridine 18 followed by acidic treatment afforded a mixture of tetracyclic compounds 21a and 21b in a 3:2 ratio as mentioned in this paper.
Abstract: The addition of 2-(lithiomethyl)indole 2 to the enantiopure oxazolinylpyridine 18 followed by acidic treatment afforded a mixture of tetracyclic compounds 21a and 21b in a 3:2 ratio. The major epimer 21a was converted to tetracycle 25a , a tetracyclic ABDE substructure of Strychnos alkaloids
TL;DR: The first total synthesis of (±)-dienomycin C 1 and its C-4 epimer 9 was reported in this paper, using an intramolecular Mannich-type cyclisation.
Abstract: The diastereoselective formation of 2,3,4-substituted piperidines is achieved by condensation of the iron dienal complex 2 and the primary amine 3 via an intramolecular Mannich-type cyclisation. This method is illustrated by the first total synthesis of (±)-dienomycin C 1 and its C-4 epimer 9.