A concise approach to both enantiomers of phytoprostane B1 type II

The synthesis of enantiomeric phytoprostane B₁ type II methyl esters has been accomplished in approximately 30% overall yield via two basic transformations starting from 3-[(dimethoxyphosphoryl)methyl]cyclopentenone as a key reagent. They include ethylation of the ring C(2) carbon and a Horner olefination reaction using the phosphonate moiety at C(3). The novel components of the Horner reaction, the enantiomeric methyl 9-formyl-9-hydroxynanoates, were easily prepared from racemic methyl 9-hydroxy-10-undecenoate via asymmetric Sharpless epoxidation (kinetic resolution) followed by ozonolysis.     

3-氨基-2-羟基-4-苯基丁酸的合成

3-氨基-2-羟基-4-苯基丁酸的合成;乌苯美司;氨基羟基苯基丁酸;合成     

Total syntheses of the Securinega alkaloids (+)-14,15-dihydronorsecurinine, (-)-norsecurinine, and phyllanthine

A new strategy for enantiospecific construction of the Securinega alkaloids has been developed and applied in total syntheses of (+)-14,15-dihydronorsecurinine (8), (-)-norsecurinine (6), and phyllanthine (2). The B-ring and C7 absolute stereochemistry of these biologically active alkaloids originated from trans-4-hydroxy-L-proline (10), which was converted to ketonitrile 13 via a high-yielding eight-step sequence. Treatment of this ketonitrile with SmI2 afforded the 6-azabicyclo[3.2.1]octane B/C-ring system 14, which is a key advanced intermediate for all three synthetic targets. Annulation of the A-ring of (-)-norsecurinine (6) with the required C2 configuration via an N-acyliminium ion alkylation was accomplished using radical-based amide oxidation methodology developed in these laboratories as a key step, providing tricycle 33. Annulation of the D-ring onto alpha-hydroxyketone 33 with the Bestmann ylide 45 at 12 kbar gave (+)-14,15-dihydronorsecurinine (8). In the securinine series, the D-ring was incorporated using an intramolecular Wadsworth-Horner-Emmons olefination of phenylselenylated alpha-hydroxyketone 47. The C14,15 unsaturation was installed late in the synthesis by an oxidative elimination of the selenoxide derived from tetracyclic butenolide 50 to give (-)-norsecurinine (6). The A-ring of phyllanthine (2) was formed from hydroxyketone 14 using a stereoselective Yb(OTf)3-promoted hetero Diels-Alder reaction of the derived imine 34 with Danishefsky's diene, affording adduct 35. Conjugate reduction and stereoselective equatorial ketone reduction of vinylogous amide 35 provided tricyclic intermediate 36, which could then be elaborated in a few steps to stable hydroxyenone 53 via alpha-selenophenylenone intermediate 52. The D-ring was then constructed, again using an intramolecular Wadsworth-Horner-Emmons olefination reaction to give phyllanthine (2).     

Aqueous ethylation of organotin compounds in simple solution for speciation analysis by cryofocussing and detection by atomic absorption spectrometry — comparison with hydride generation

A 2³ factorial experimental design has been used to determine the optimum reaction conditions for organotin ethylation in simple aqueous solutions for speciation by Cryogenic Trapping/ Gas Chromatography/Atomic Absorption Spectrometry (CT/GC/AAS). The factors chosen and their levels of variation (? and +) were the pH of the solution (levels 3 and 5), the amount of NaBEt₄ added (levels 1 and 9 mg) to the organotins and the time of ethylation reaction (levels 10 and 20 min). Optimum conditions were investigated for monomethyltin (MMT), diethyltin (DET) and dibutyltin (DBT) in mixed solution at a concentration of 10 ng of each Sn compound in 50 ml of solution (200 ng·l^?1). The influence of the different factors on the yield of the ethylation reaction in the ranges investigated depends on the degree of substitution and the nature of the alkyl groups of the organotins. The ethylation reaction for DET and DBT is more efficient at high pH levels, MMT gives higher yields at lower pH. Both MMT and DET require a high amount of reagent, while reagent concentration has no real influence on the DBT signal. Comparison of hydride generation and ethylation as derivatisation procedures for organotin speciation has been performed in simple solutions. Under these analytical conditions, hydride generation is shown to be slightly more sensitive than ethylation by a factor of 1.4 for MMT and DET and 2 for DBT. However derivatisation using ethylation provides more reproducible results and is not affected by inorganic interferents.     

Synthesis of (+)-bullatacin via the highly diastereoselective [3+2] annulation reaction of a racemic aldehyde and a nonracemic allylsilane

[reaction: see text] A total synthesis of (+)-bullatacin has been accomplished via a diastereoselective [3+2] annulation reaction of the highly enantiomerically enriched allylsilane 3 and racemic aldehyde 4, which provides the key bis-tetrahydrofuran fragment 15 with > or = 20:1 ds.     

Selenium determination using ethylation and on-line trapping/detection by graphite furnace atomic absorption spectrometry

An on-line system for the continuous ethylation of selenium (IV) in combination with trapping and detection of the produced diethylselenide in the coated AAS graphite furnace was developed. Due to the slow kinetics of the ethylation the volume of the reaction coil and the reaction time had to be increased to 5.5 mL and 80 s, respectively. The sensitivity of the method was comparable with that of the hydride generation in the same system and the relative standard deviation was 6–10%. The determination of Se(IV) in real samples after the most widely used digestion with nitric acid could not be accomplished, because of the drastic signal depression caused by this acid.     

One-pot multicomponent synthesis of a new series of curcumin-derived 4H-pyrans under ambient conditions

Design and synthesis of a new series of pharmaceutically interesting curcumin-derived 4H-pyrans have been accomplished via a one-pot tandem reaction between curcumin, aromatic aldehydes, and malononitrile under the influence of sodium formate as a mild base in ethanol at ambient conditions. Operational simplicity, mild reaction conditions, use of a cheap and nontoxic organocatalyst and eco-friendly solvent, and easy isolation of target products are the key benefits associated with the process.     

Ethylation and disproportionation of ethylbenzene over substituted AFI type molecular sieves

The vapour and liquid phase ethylation of ethylbenzene was performed over AlPO₄-5 and its substituted counter parts. The results obtained for vapour phase reactions have shown a higher catalytic activity at 350 and 400 °C. The catalysts, however, exhibited a faster deactivation rate. The results obtained for liquid phase reaction have shown a higher selectivity for para-diethylbenzene (84.4%) than the vapour phase reaction (41.5%). MnAPO-5 was found to be active up to 240 h for the liquid phase reaction. para-Diethylbenzene, meta-diethylbenzene and polyalkylbenzene were the major products obtained for ethylation of ethylbenzene. When ethylbenzene passed over MnAPO-5 yielded products, such as benzaldehyde, acetophenone, styrene and 2,3-diphenylbutane. This showed a preference for oxidation rather than disproportionation followed by alkylation. Notwithstanding the better acid characteristics of ZSM-5, MnAPO-5 could be a better choice for this class of reaction essentially due to its higher para selectivity.     

Stereoselective total synthesis of ent-EI-1941-2 and Epi-ent-EI-1941-2

The first asymmetric total syntheses of ent-EI-1941-2 and epi-ent-EI-1941-2 have been accomplished, starting from a chiral epoxy iodoquinone 6, a key intermediate in our total syntheses of epoxyquinols A and B. A key step in the preparation of ent-EI-1941-2 is an intramolecular carboxypalladation via a 6-endo cyclization mode, followed by beta-hydride elimination, while carboxymercuration is a key step in the synthesis of epi-ent-EI-1941-2. [reaction: see text]     

Short,enantioselective total synthesis of okaramine N

The first enantioselective total synthesis of a member of the okaramine family of bis-indole alkaloids, okaramine N (1), has been accomplished via intermediates 2-7, as outlined. The N-prenylated derivative of (S)-tryptophan methyl ester (2) was coupled with Fmoc-protected N-tert-prenylated tryptophan (3) to form the amide 4 in 70% yield. Pd(II)-mediated cyclization/rearrangement, a key step in the synthesis, transformed 4 into the indoloazacine 5 (44%), which was deprotected and cyclized in a single step to give the hexacyclic diketopiperazine 6 (95%). In the following novel and key sequence, 6 was transformed into 1: (1) selective ene reaction with N-methyltriazolinedione, (2) photooxidation of the remaining tert-prenylated indole subunit to provide 7, and (3) thermal retroene reaction of 7 to afford okaramine N (70% from 6).     

A practical synthesis of (+)-biotin from L-cysteine

Alpha-amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded alpha-amino nitrile 5 with high diastereoselectivity (syn/anti=11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.     

An unusual synthetic way to 2-methyl-3-alkyl-6-ethoxy-heptan-2-ols from 2-ethoxy-5-alkyl-3,4-dihydro-2H-pyrans

A simple and swift preparation of 2-methyl-3-alkyl-6-ethoxyheptan-2-ols may be accomplished in two steps starting from 2-ethoxy-5-alkyl-3-,4-dihydro-2H-pyrans via chlorination of the heterocyclic compounds and subsequent reaction with MeMgBr.     

Selenium determination using ethylation and on-line trapping/detection by graphite furnace atomic absorption spectrometry

An on-line system for the continuous ethylation of selenium (IV) in combination with trapping and detection of the produced diethylselenide in the coated AAS graphite furnace was developed. Due to the slow kinetics of the ethylation the volume of the reaction coil and the reaction time had to be increased to 5.5 mL and 80 s, respectively. The sensitivity of the method was comparable with that of the hydride generation in the same system and the relative standard deviation was 6–10%. The determination of Se(IV) in real samples after the most widely used digestion with nitric acid could not be accomplished, because of the drastic signal depression caused by this acid. Received: 10 June 1997 / Revised: 27 October 1997 / Accepted: 1 November 1997     

Concise asymmetric total synthesis of 9-epi-sessilifoliamide J

A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with sessilifoliamide J (6), has been accomplished from the key chiral building block 11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)-mediated coupling lactonization. The absolute configuration of the natural sessilifoliamide J was established.     

Dihydroxylation of 2-vinylaziridine: efficient synthesis of D-ribo-phytosphingosine

An efficient and highly stereoselective synthesis of D-ribo-(2S,3S,4R)-phytosphingosine was accomplished in 62% overall yield starting from commercially available (2S)-hydroxymethylaziridine via osmium-catalyzed asymmetric dihydroxylation as a key step.     

Synthesis of 7-Ethyl-10-hydroxycamptothecin and Proposed Reaction Mechanism

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Synthesis and properties of a new member of the calixnaphthalene family: a C(2)-symmetrical endo-calix[4]naphthalene

The synthesis of a new endo-calix[4]naphthalene is described. The reaction sequence involves the cyclocondensation of a key bisnaphthylmethane intermediate (8) with formaldehyde. This key intermediate (8) is formed using a modified Suzuki-Miyaura Pd-catalyzed cross-coupling reaction between bromomethylnaphthyl (6) and naphthylboronic acid (7), both of which can be derived from 2-hydroxynaphthoic acid.     

Palladium-catalyzed cycloalkylations of 2-bromo-1,n-dienes with organoboronic acids

Cascade palladium-catalyzed cycloalkylations of 2-bromo-1,n-dienes were accomplished in good to excellent yields, where the alkylpalladium intermediates, formed via an intramolecular Heck reaction of 2-bromo-1,n-dienes (n = 6 or 7), were successfully cross-coupled with various organoboronic acids. The optimal yields were achieved by the use of cesium carbonate in ethanol with Pd(PPh(3))(4) as catalyst, with 2-bromo-1,n-dienes and organoboronic acids at concentrations of 0.2 and 0.3 M (1.5 equiv), respectively.     

7-乙基-10-羟基喜树碱制备工艺改进

对7-乙基-10-羟基喜树碱的制备进行了研究,优化了合成工艺,使总收率由19.7%提高到33.2%,并对该合成路线的反应机理进行了初步的探讨.