Reactions of 4-oxo-1,3-benzoxazinium perchlorates with guanidines

Condensation of 2-methyl-4-oxo-1,3-benzoxazinium perchlorate with various aromatic and heterocyclic aldehydes provided previously unknown arylvinyl-and hetarylvinyl-substituted salts whose recyclization under treatment with guanidine resulted in formerly undescribed 1,3,5-triazines. The reaction of perchlorates obtained with guanidinebenzoxazole led to the formation of bishetarylamines, with guanidinebenzimidazole formed triazinebenzimidazoles, the cyanoguanidine reacted with 4-oxo-1,3-benzoxazinium perchlorates to give cyanamides.     

Iodocyclisation and rearrangement reactions of mono-protected allyl substituted guanidines

The iodocyclisation of a range N-allyl and N-homoallylguanidines using I₂/K₂CO₃ has been found to lead to a series of novel heterocycles which undergo selective rearrangements on variation of the reaction conditions, and predictable protecting group migration in the presence of trifluoroacetic acid in methanol.     

Phage display affords peptides that modulate beta-amyloid aggregation

As the population ages, the need to develop methods to understand and intercept the processes responsible for protein aggregation diseases is becoming more urgent. The aggregation of the protein beta-amyloid (Abeta) has been implicated in Alzheimer's Disease (AD); however, whether the toxic species is a large, insoluble aggregate or some lower order form is not yet known. Agents that can modulate the aggregation state of Abeta could resolve this controversy by facilitating our understanding of the consequences of aggregation and its underlying mechanism. To date, however, ligands that bind to specific forms of Abeta have not been identified. To address this deficiency, we tested whether phage display could yield such ligands by screening libraries against Abeta in two different states: monomeric or highly aggregated. Intriguingly, the peptides selected had different effects on Abeta aggregation. Peptides selected for binding to monomeric Abeta did not perturb aggregation, but those selected using highly aggregated Abeta increase the rate of aggregation drastically. The latter also alter the morphology of the resulting aggregate. The ability of a peptide to promote aggregation correlated with its affinity for the N-terminal 10 residues of Abeta. This result indicates that the mechanism by which the peptides influence aggregation is related to their affinity for the Abeta N-terminus. Thus, the identification of compounds that bind to this Abeta section can afford agents that affect aggregation. Moreover, the data suggest that endogenous ligands that interact with the N-terminal region can influence the propensity of Abeta to form aggregates and the morphology of those that form. Our data highlight the utility of phage display for identifying ligands that bind to target proteins in different states, and they indicate that such agents can be used to perturb protein aggregation.     

Copper-promoted rearrangement of 1,3-cyclohexadiene-acylnitroso cycloadducts

The ring opening of [2.2.2]-acylnitroso cycloadducts was obtained for the first time by means of a cationic rearrangement promoted by Cu(OTf)₂-PPh₃ under homogeneous and polymer-supported conditions.     

A nickel(0) catalyzed cycloaddition of alkynes and isocyanates that affords pyrimidine-diones

A Ni/N-heterocyclic carbene catalyzed cycloaddition of one alkyne and two isocyanates that affords pyrimidine-dione is described. The key to the success of this protocol is the use of unsymmetrically substituted alkynes that favors the formation of pyrimidine-diones over pyridones. A variety of pyrimidine-diones were prepared. A one-pot cycloaddition and Stille coupling were reported for tributyl(1-propynyl)tin. Competition studies also provide insights into the mechanism of the cycloaddition.     

Modified guanidines as potential chiral superbases. 1. Preparation Of 1,3-disubstituted 2-iminoimidazolidines and the related guanidines through chloroamidine derivatives

Modified guanidines were explored as potential chiral superbases. Thus, chiral 1,3-dimethyl-2-iminoimidazolidines with or without 4, 5-diphenyl groups, their guanidinium salts, and the 2-iminoimidazolidines with (S)-1-phenylethyl groups on the ring nitrogens were prepared by treatment of 2-chloroimidazolinium chlorides with appropriate amines. Bicyclic guanidines were also prepared from a prolinamide using a similar procedure.     

A simple one-pot synthesis of triflyl guanidines: access to highly substituted electron-poor guanidines

Unsymmetrical di- and trisubstituted triflyl guanidines are accessed through a simple, one-pot protocol from the corresponding isothiocyanate and amine. Furthermore, in the presence of base, trisubstituted triflyl guanidines are alkylated to obtain tetrasubstituted triflyl guanidines in high yields and complete regioselectivity.     

Nitrosation of amides involves a pseudopericyclic 1,3-sigmatropic rearrangement

Two possible pathways for the nitrosation of formamide and N-methyl formamide by nitrosonium ion (NO(+)) have been investigated at the B3LYP/6-31G(d,p) level. The key steps are pseudopericyclic 1,3-sigmatropic rearrangements to give the observed N-nitrosamides. The transition structures (8a and 8b) are close to planar on the amide moiety and have remarkably low barriers of only 6.6 and 4.8 kcal/mol from the lowest energy conformations of 6a and 6b, respectively. [reaction: see text]     

1,3-Phosphorotropic rearrangement of pyridyl phosphates to hydroxypyridyl phosphonates

The lithium diisopropylamide (LDA) induced regioselective 1,3-rearrangement of 3- and 2- pyridyl phosphates into the corresponding 3-hydroxy-4-pyridyl-and 2-hydroxy-3-pyridylphosphonates has been observed and investigated. The rearrangement is proposed as a useful method for a directed introduction of a phosphoryl group into a hydroxypyridine nucleus.     

A novel solid-phase synthesis of cyclic guanidines

We have developed a robust solid-phase approach to cyclic guanidines based on the Staudinger protocol. The synthetic sequence involves the reaction of the immobilized aza-Wittig reagents derived from the respective azidobenzoic acids with bifunctional amines. Convenient isolation and good yields of the desired products (34-84%) along with the diversity of the targeted molecules are distinctive features of the resultant library.     

Stereochemistry of the 1,2-Wittig rearrangement: A synthesis of syn-1,3-diol monoethers

The [1,2] Wittig rearrangement of β-alkoxyalkyl allyl ethers has been studied and found to provide syn-1,3-diol derivatives in 14–32% yield and with useful levels of diastereoselection.     

Regioselective Lewis acid-mediated [1,3] rearrangement of allylvinyl ethers

[reaction: see text]. Aluminum and copper Lewis acids were implemented to effect a regioselective [1,3] rearrangement of allylvinyl ethers in moderate to good yields. The use of trisubstituted alkenes leads to depressed levels of Claisen products.     

1,3-Polyol arrays via the stereoselective rearrangement of vinyl acetals

A series of 1,3-dioxanyl vinyl acetals were readily synthesized from the corresponding dioxanone by a reduction and in situ acylation followed by Petasis olefination. Treatment of these vinyl acetals with BF₃·OEt₂ results in an O to C rearrangement to form anti-3,5-dihydroxyketones while a mixture of Me₃Al and BF₃·OEt₂ provides the corresponding syn relationship via a stereoretentive rearrangement.     

Dialkylaluminum hydride-promoted cyclodimerization of silylated 1,3-enynes via skeletal rearrangement

The dialkylaluminum hydride-promoted reaction of 1-silylalk-3-en-1-ynes gave symmetrical 1,2,3,5-tetrasubstituted benzenes as single regioisomers. The novel cyclodimerization via skeletal rearrangement can be rationalized by an unprecedented mechanism involving sequential hydroalumination, alkene isomerization, carboalumination, carbon-carbon bond cleavage, and retro-hydroalumination.     

Photochemical synthesis of 1,3-dithiolane derivatives by Wolff rearrangement of 5-diazo-1,3-dithiane-4,6-dione

Russian Journal of Organic Chemistry -     

Semiconductor-catalyzed photocycloreversion,valence isomerization and [1,3]-sigmatropic rearrangement

The semiconductor-catalyzed photochemical [2+2]cycloreversion of n-methylquinolone dimer, valence isomerization of hexamethyl(Dewar)benzene, and [1,3]-sigmatropic rearrangement of 2,2-bis(4-methoxyphenyl)-1-dideuteriomethylenecyclopropane gave N-methylquinolone, hexamethylbenzene, and 2,2-bis(4- methoxyphenyl)-3,3-dideuterio-1-methylenecyclopropane, respectively.