Syntheses of sphingomyelin methylene, aza, and sulfur analogues by the versatile olefin cross-metathesis method

The syntheses of optically homogeneous sphingomyelin analogues, which possess CH₂, NH, and S instead of the phosphate oxygen connecting the phosphocholine head group to the sphingosine backbone, were successfully achieved by employing the olefin cross-metathesis protocol between 1-pentadecene and the amino alcohol parts possessing the suitable building block or functional group for construction of the phosphocholine moiety. In addition, fluorescence-labeled sphingomyelin methylene analogue was also synthesized.     

Synthesis of borondipyrromethene (BODIPY)-labeled sphingosine derivatives by cross-metathesis reaction

A new efficient and flexible synthesis of fluorescently labeled sphingosine derivatives from commercially available Garner aldehyde (8) is described. For this, appropriate alkenylated borondipyrromethene (BODIPY) dyes were synthesized and used for the first time in a cross-metathesis reaction, the key step of the approach. The labeled sphingosines with appropriate chain length were accepted as substrates by sphingosine kinases (SPHKs), yielding the corresponding phosphorylated products. One of these derivatives (11d) was identified as the first reported selective substrate for SPHK-1.     

Solid-phase syntheses of olefin-containing inhibitors for HTLV-1 protease using the Horner-Emmons reaction

[reaction: see text] The solid-phase Horner-Emmons reaction was successfully applied for the convenient syntheses of olefin-containing protease inhibitors. The isomerization during the solid-phase Horner-Emmons reaction can be minimized simply by the use of an appropriate amount of the base. The synthesized olefin peptides, which have an olefin gamma-amino acid at the scissile site, were found to act as effective inhibitors for the HTLV-1 protease for the first time.     

Metal-free synthesis of 1,2-amino alcohols by one-pot olefin aziridination and acid ring-opening

A one-pot, two-step reaction comprising olefin aziridination and ring-opening of an aziridine intermediate to synthesize 1,2-amino alcohols has been developed. This reaction is suitable for several types of olefin. This methodology allows an efficient and highly stereoselective approach to various 1,2-amino alcohols, readily providing an alternative route to conventional vicinal amino alcohols.     

Ring-opening cross-metathesis (ROCM) as a novel tool for the ligation of peptides

The development of ring-opening cross-metathesis (ROCM) as a novel tool for the site-specific ligation of peptide units is reported. The resulting structural units at the site of ligation resulting from ROCM resemble proline as well as other known beta-turn stabilising structural units. ROCM under mild reaction conditions between a variety of peptides bearing a cyclic olefin with amino acids or peptides results in high yields. The peptidic cross-partners for metathesis are equipped with double bonds via the N and the C terminus and the side chain, respectively, to allow the synthesis of linear as well as non-linear and branched peptides. The ligation in this manner succeeds with low catalyst loadings, with no need for any excess of one reaction partner and with a high compatibility with a wide range of functional groups. Furthermore, the stereochemical outcome of the ROCM can easily be controlled by using a Hoveyda-type chiral catalyst. Fluorescence labelling of peptides is possible in the same manner when using a cyclic olefin equipped with a fluorescence marker.     

An efficient total synthesis of the anticancer agent (+)-spisulosine (ES-285) from Garner’s aldehyde

An efficient total synthesis of (+)-spisulosine (ES-285) was completed in nine steps from (S)-Garner’s aldehyde. The vicinal amino alcohol moiety with anti-configuration was achieved by a highly diastereoselective addition of vinyl magnesium bromide to Garner’s aldehyde. The long hydrocarbon chain of the antitumor natural product was installed via olefin cross metathesis of the benzyl-protected allylic alcohol with an appropriate olefin counterpart followed by hydrogenation.     

Quantitative determination of olefin oxide, chlorohydrin, and cyclocarbonate in the presence of each other

A procedure was developed for the quantitative determination of olefin oxide, chlorohydrin, and cyclocarbonate simultaneously present in the reaction mixture of the synthesis of cyclocarbonate from olefin oxide and CO₂. To determine olefin oxide, an acetone solution of hydrochloric acid was added to a portion of the reaction mixture, and the excess of hydrochloric acid was titrated with an aqueous solution of potassium hydroxide with visual detection. The concentrations of chlorohydrin and cyclocarbonate were calculated from the data of the potentiometric titration of the same solution to which excess potassium hydroxide was added. Deceased.     

Catalytic intermolecular allylic C-H alkylation

The first electrophilic Pd(II)-catalyzed allylic C H alkylation is reported, providing a novel method for formation of sp3-sp3 C C bonds directly from C H bonds. A wide range of aromatic and heteroaromatic linear (E)-alpha-nitro-arylpentenoates are obtained as single olefin isomers in excellent yields directly from terminal olefin substrates and methyl nitroacetate. The use of DMSO as a pi-acidic ligand was found to be crucial for promoting functionalization of the pi-allylPd intermediate. Products from this reaction are valuable synthetic intermediates and are readily transformed to amino esters via selective reduction and optically enriched alpha,alpha-disubstituted amino acid precursors via asymmetric conjugate addition.     

Total synthesis of AI-77-B

A new stereoselective approach for the synthesis of AI-77-B has been described. Dihydroisocoumarin fragment was made in two routes using Heck reaction followed by oxidation of the olefin and LDA mediated reaction. The chiral amino acid moiety has been obtained from d-ribose involving Grignard reaction on ribosylimine. Finally, condensation of dihydroisocoumarin with acid fragment furnished the title target AI-77-B.     

Phosphine–Alkene Ligands as Mechanistic Probes in the Pauson–Khand Reaction

An alkyne tetracarbonyl dicobalt complex with a chelated phosphine–alkene ligand, in which the phosphorus atom and the alkene from the ligand are attached to the same cobalt atom has been prepared, isolated, and characterized by X‐ray crystallography. The complex serves as a mechanistic model for an intermediate of the Pauson–Khand (PK) reaction. Although the alkene fragment is located in an equatorial coordination site with an appropriate orientation, and, therefore, should undergo insertion, it failed to give the PK product upon either thermal or N‐methylmorpholine N‐oxide activation. However, a phosphine–alkene complex that contains a terminal alkene readily provided the corresponding PK product. We attribute this change in reactivity to the different ability of each olefin to undergo 1,2‐insertion. These results provide further insights into the factors that govern a crucial step in the PK reaction, the olefin insertion.     

Synthesis of dipeptide isosteres by cross-metathesis

This work describes the attachment of two amino acid derivatives by olefin cross-metathesis using Grubbs' second generation catalyst. They were connected at the carboxyl termini. In addition, a cyclic dilactam scaffold was used, which reacted with only a fraction of the amino acid derivatives. The remaining fraction coupled directly coupled with no scaffold. This highly trans-selective double attachment resulted in the cross-metathesis of a variety of amino acids in a single reaction.     

Microwave-accelerated cross-metathesis reactions of N-allyl amino acid substrates

Microwave heating has been utilised for the cross-metathesis reaction of N-allyl amino acid substrates to generate olefin homodimers. Remarkable acceleration of the cross-metathesis reaction (minutes compared to hours) over conventional reflux heating was observed. In addition, improved reaction yields and similar E/Z ratios for the cross-metathesis products were achieved.     

New and efficient synthesis of azabicyclo[4.4.0]alkane amino acids by Rh-catalyzed cyclohydrocarbonylation

[reaction: see text] Highly efficient syntheses of azabicyclo[4.4.0]alkane amino acids were achieved by Rh-catalyzed cyclohydrocarbonylation of dipeptides bearing a terminal olefin moiety and a heteroatom nucleophile.     

Preparation of optically pure fused polycyclic scaffolds by Ugi reaction followed by olefin and enyne metathesis

Optically pure fused polycyclic scaffolds containing up to eight stereocentres have been synthesised by olefin metathesis and tandem enyne metathesis/Diels-Alder addition of Ugi multicomponent reaction adducts generated from 7-oxa-[2.2.1]-bicyclic amino acid derivatives.     

直接共聚法制备功能化聚烯烃研究进展

从催化剂研究发展的角度概述了直接配位共聚法制备功能化聚烯烃的研究现状 ,重点讨论了催化剂的结构 ,主催化剂和助催化剂以及催化剂和极性基团之间的相互作用对直接功能化聚合反应的影响。     

Etudes sur le mecanisme de la metathese des olefines : IV. Echanges d'hydrure et carbenes

The possibility of exchanging hydrogen atoms between the catalyst and the substrate in olefin metathesis was examined. Exchange was observed at a high catalyst/olefin ratio, although virtually no exchange was observed at low ratio, Alkylidenetungsten, formed from WCl₆ and dimetallic derivatives of methane (i.e. CH₂M₂), proved to be efficient catalysts for olefin metathesis. It was concluded from these experiments and from those described earlier that olefin metathesis takes place by addition of an alkylidenetungsten to an olefin followed by fission of the resulting cyclobutane. A solution was proposed to the question raised by the Chauvin mechanism, namely the initiation, which was linked to the formation of alkyltungsten by addition of alkyl- or hydrido-tungten to olefins, followed by appropriate transformation to alkylidenetungsten compounds.     

Synthesis and Immunosuppressive Activity of Amino Alcohol Containing Coumarin and Benzothiophene

A series of amino alcohol derivatives containing coumarin and benzothiophene moieties was synthesized with 5-bromosalicylaldehyde and 5-bromo-2-thiophenecarboxaldehyde as starting materials, 6-substituted-3-chroma- none and 4,5-dihydrobenzo[b]-thiophen-5(4H)-one as intermediates and Suzuki reaction and spiro-hydantoin hydrolysis as key steps. The structures of key intermediate and target compounds were confirmed by ¹H NMR, ¹³C NMR, IR and HRMS. Their characterization as sphingosine 1-phosphate(S1P) receptor agonists was reported.     

Synthesis of some trifluoroethyl-substituted derivatives of aniline

A new procedure is presented for the preparation of N-trifluoroethylanilines by reaction of the appropriate aniline with ethyl trifluoroacetate or trifluoroacetic anhydride, followed by reduction with diborane in tetrahydrofuran. Yields are high unless the aniline carriers a carboyxl, carbonyl, olefin, or o-nitro substituent. several new N-substituted trifluoroacetamides and trifluoroethylanilines are reported.     

烯烃在催化裂化催化剂上反应机理的初步研究

在自制的微反-色谱装置上,进行了单体烯烃和催化裂化汽油在不同条件下的催化裂化反应实验。对单体烯烃的裂化反应规律和汽油中的烯烃在半再生催化剂和待生催化剂上的催化裂化反应规律进行对比分析。结果表明,单体烯烃反应中,C6及C6以下的烯烃主要发生骨架异构和双键异构反应,氢转移和直接裂化反应发生的较少。C7以上的烯烃95%以上发生转化,高温下直接裂化生成C3、C4,氢转移和异构化比率较大。汽油中的烯烃转化主要集中在C7以上,烯烃之间存在一定的交互作用,单体烯烃的催化裂化反应规律可以初步预测汽油中烯烃的转化。催化剂上的结焦类型对汽油中的烯烃的转化方式没有影响。     

Tetramic acids and indole derivatives from amino acid β-keto esters. Fine-tuning the conditions of the key Cu-catalyzed reaction

1,3,5-Trisubstituted tetramic acids and 2,3-disubstituted indole derivatives were prepared from β-keto esters derived from amino acids by their reaction with iodophenyl-2-trifluoroacetylamine under Cu-catalysis. Both heterocyclic systems were generated from the same starting materials by choice of the appropriate reaction conditions.