Synthesis and substrate-controlled reactions of 2,2′-unsaturated biquinazolinones

A series of BiQuinazolinones bearing either double or triple bonds in their lateral chains have been synthesized. These compounds were then subjected to substrate-controlled reactions such as Diels-Alder, epoxidation and Pauson-Khand reactions. The stereoselective outcome observed in these transformations is very promising for the future application of BiQuinazolinones as chiral auxiliaries.     

Sulfoxides as ‘traceless’ resolving agents for the synthesis of atropisomers by dynamic or classical resolution

Reacting (−)-menthyl sulfinate with an atropisomeric but racemic aryllithium gives two atropdiastereoisomeric sulfoxides. Separation (by chromatography or crystallisation) and sulfoxide-lithium exchange of each diastereoisomer regenerates the aryllithium in enantiomerically pure form which can be quenched with a range of electrophiles with retention of stereochemical integrity. Overall the reaction sequence is a resolution but without the need for an acidic or basic substituent—a ‘traceless’ method. In certain instances, for example when the nucleophile is an ortholithiated peri-substituted 1-naphthamide, the diastereoisomeric sulfoxides may be interconverted thermally. This allows a dynamic resolution, under thermodynamic control, and hence in principle can give yields of the final products of greater than 50%. The utility of the method is demonstrated by the synthesis of a known atropisomeric phosphine ligand.     

From chiral and prochiral N-allylpyrroles to stereodefined pyrrole fused architectures: A particular application of the rhodium-catalyzed hydroformylation

We review our recent results on the rhodium-catalyzed hydroformylation of chiral and prochiral N-allylpyrroles as a synthetic route to stereodefined 5,6-dihydro- and 5,6,7,8-tetrahydroindolizines. The indolizine nucleus at different degrees of unsaturation is a building block of natural and synthetic target compounds; thus new approaches, especially if stereoselective and/or stereospecific, are highly desirable. The construction of the indolizine architectures reported here occurs by formation of a C8-C9 bond through intramolecular cyclization of the 4-pyrrolylbutanal intermediate.     

Total synthesis and biological evaluation of marinopyrrole A and analogues

A five-step total synthesis of the antibiotic marinopyrrole A (1) is described. The developed synthetic technology enabled the synthesis of several marinopyrrole A analogs whose antibacterial properties against methicillin-resistant Staphylococcus aureus TCH1516 were evaluated.     

Introduction of a Novel Reaction of Triacetylmethane: One-Pot Synthesis of Dialkyl-2-(3,1-hydroxyethylidene-2,4-pentanedione-3-yl)-3-(triphenylphosphoranylidene)-butanedioate

Protonation of reactive 1:1 intermediates produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylate by 3-(1-hydroxyethylidene)-2,4-pentanedione leads to vinyl phosphonium salts, which undergo Michael addition with the conjugate base of CH-acid to produce the title compounds in high yield.     

Organocatalytic Enantioselective Synthesis of Axially Chiral N,N′-Bisindoles

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N′-bisindoles via chiral phosphoric acid-catalyzed formal (3+2) cycloadditions of indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various axially chiral N,N′-bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N,N′-bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiral N,N′-bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.     

Enantioenriched synthesis of Escitalopram using lithiation-borylation methodology

The asymmetric synthesis of Escitalopram has been completed using a lithiation-borylation reaction as the key step. Suitably functionalized enantioenriched carbamate (er 98:2) and boronic ester coupling partners were prepared and following deprotonation with s-BuLi and borylation, the tertiary alcohol was obtained in 42% yield and 93:7 er. The lithiation-borylation reaction was found to tolerate nitrile, benzylic alcohol and N-Boc functionalities. The tertiary alcohol was converted to Escitalopram in three further steps.     

Enantioselective recognition of amines with an atropisomeric 1,8-bisphenolnaphthalene

1,8-Bis[5′(2′-hydroxy-4′-methylbiphenyl)]naphthalene, 2, was prepared from 1,8-dibromonaphthalene and 4-methoxy-2-methylphenylboronic acid in four steps with 51% overall yield. The axially chiral anti-isomer of 2 is stable to racemization at room temperature and the free energy of activation for the conversion of the anti-isomer to the syn-form was determined as 110.0 kJ/mol at 77.1 °C. At submillimolar concentration, enantiopure 2 can be used as circular dichroism sensor to detect a wide range of chiral amines.     

Benzoxaboroles - Old compounds with new applications

This comprehensive review covers the structure, methods of synthesis, properties and fields of application of benzoxaboroles - derivatives of phenylboronic acids. Some of the title compounds were described over 50 years ago, however most of them have been investigated only recently due to their exceptional properties and wide applications. In addition to their usage as building blocks and protecting groups in organic synthesis, certain benzoxaboroles display biological activity and are under clinical trials. They also bind hydroxyl compounds and thus can be applied as molecular receptors for sugars and glycoconjugates.     

Concise total syntheses of heliannuols B and D

Concise and efficient enantioselective total syntheses of heliannuols B and D have been accomplished using chirality transfer through a Lewis acid-promoted Claisen rearrangement for the construction of the C7 tertiary stereogenic center and a relay ring-closing metathesis for assembling the dihydrobenzo[b]oxepine backbone of the natural products as the key steps.     

多氟烷氧基取代金属酞菁配合物的简便合成及其光谱特征

制备了一些氯酞菁金属配合物,研究了它们与多氟醇盐的反应.结果表明,该反应可以方便地在氯酞菁环上引入多氟烷氧基.借此合成了一些多氟烷氧基取代金属酞菁配合物.产物经分离提纯后,用元素分析、IR、UV-Vis及¹⁹FNMR谱进行了表征,并观测了多氟烷氧基的引入对其脂溶性、热稳定性及电子光谱性质的影响.     

Dipyridyl/pyridinium thieno[2,3-b]thiophenes as new atropisomeric systems. Synthesis, conformational analysis and energy minimization

Synthesis of a new class of cofacially oriented dipyridyl(pyridinium)lthieno[2,3-b]thiophenes with or without -CO₂Et and -COMe substituents at C2, and C5 positions of thieno[2,3-b]thiophene ring was readily accomplished using a double Dieckman cyclization protocol as the key step. While C2/C5 substituted dipyridylthieno[2,3-b]thiophenes exhibited syn/anti atropisomerism at least up to 70 °C with Arrhenius energy of activation (ΔG^≠) in the range of 17-18 kcal/mol, on the other hand unsubstituted dipyridylthieno[2,3-b]thiophene and its bis-N-quaternized salt were found to show free conformational rotation with an estimated ΔG^≠ of lower than 10 kcal/mol. Conformational energy minimization using AM1 protocol revealed a slight preference for the anti over syn isomers. Compared to the unsubstituted dipyridylthieno[2,3-b]thiophenes, higher energy barriers to rotation (3.7-5.1 kcal/mol) in substituted dipyridylthieno[2,3-b]thiophenes can be attributed to steric encumbrance resulting from -CO₂Et and -COMe substituents located on the non-rotating thienothiophene platform.     

全合成海南粗榧新碱类似物的研究

海南粗榧新碱具有一定的抗肿瘤活性，为了提高该类化合物抗肿瘤活性，研究其结构与活性的关系，以３，４－二甲氧基苯乙酸和脯氨醇为起始原料，经７步反应得到消旋的海南粗榧新碱类似物，并经酒石酸拆分得到ｅ．ｅ．值分别为９３％和９５％的一对对映体，经各种光谱及Ｘ－衍射证实其结构。     

Total synthesis of (±)-Scrodentoid A

An efficient total synthesis of scrodentoid A was accomplished starting from a Hagemann's ester and a substituted (2-bromoethyl)benzene. Key reactions in this synthesis include C-alkylation of the Hagemann's ester, 6-endo-Trig cationic cyclization of an enone and Lewis acid promoted isomerization of a cis-fused ketone.