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An efficient method for the synthesis of the thieno[2,3-c:4,5-c']dipyrrole ring system is described. Reaction of 13 with sodium azide followed by the treatment with triphenylphosphine and water gave parent compound 4. Reaction of 13 with benzylamine or aniline afforded N,N'-disubstituted derivatives 15 and 16 respectively. Diels-Alder reaction of 15 with DMAD gave cycloadducts 17 and 18. Oxidative removal of the imine bridge from 17 and 18 gave dibenzothiophene 19.

The synthesis and trapping of the parent compound and derivatives of the thieno[3,4-c]pyrrole ring system are reported. Intramolecular 1, 3-dipolar cycloaddition of the azides 9a–d and subsequent acid-catalysed 1,3-dipolar cycloreversion of the thienopyrrolotriazoles 10a–d afforded the parent compound 3a and its derivatives 3b–d. Trapping of 3a–d by 1,3-dipolar cycloaddition with N-phenylmaleimide via the azomethine ylide 2a–d gave cycloadducts 14a–d and 15a–d. Reactions of the halides 8a, c, d and g with benzylamine produced N-benzylazomethine glides 18a, c, d and g which were also trapped by N-phenylmaleimide to give the cycloadducts 19a, c, d and g.

A convergent strategy to construct the B-ring in an AC → ABC cyclization to the taxane framework was tested. The bicyclic bromomethyldimethylsilyl ether 2 was efficiently synthesized by a sequence proceeding through the alkylation of the C-ring malonate 4 by the hindered A-ring bromide 3 . The desired tandem 5-exo-trig/8-exo-dig cyclization of 2 to diol 1 was not observed. An alternative pathway was indicated by isolation of crystalline tetracyclic diastereomers 12a and 12b , derived by a diastereoselective sequence of three radical cyclizations.

A series of sulfonyl-N-hydroxyguanidine derivatives was designed and synthesized for cytotoxic evaluation as potential anticancer agents on the basis of the lead compound LY-181984. Replacement of the ureido moiety of the lead compound with hydroxyguanidine provided a stable cytotoxic agent. The conformation of sulfonyl-N-hydroxyguanidine derivatives, such as N-(4-chlorophenyl)-N‘-[(benzo[2,1,3]thiadiazol-4-yl)sulfonyl]-N‘‘-hydroxyguanidine (4g), investigated utilizing HMBC NMR, theoretical calculations, and X-ray crystallography, indicated stacking of the two aromatic rings. The derivatives were evaluated for in vitro cytoxicity against five human tumor cell lines, including HepG2, TSGH 8302, COLO 205, KB, and MOLT-4. The cytotoxic activities of the derived compounds against the human tumor cell lines were equal to or greater than that of the lead compound. N-(4-Chlorophenyl)-N‘-[[3,5-dichloro-4-(4-nitrophenoxy)phenyl]sulfonyl]-N‘‘-hydroxyguanidine (4n) and N-(4-chlorophenyl)-N‘-[[3,5-dichloro-4-(2-chlor...

A series of ampicillin and amoxicillin derivatives containing an N 1 -substituted-(6-fluoro-1,4-dihydro-4-oxoquinolin-3-yl) carbonyl moiety at the α-amino group were prepared and their antibacterial activities were evaluated. These derivatives displayed a broad spectrum of antibacterial activity against Gram-(+) and Gram-(–) bacteria. In comparison with the original antibiotics, some of the derivatives were more active against Pseudomonas aeruginosa strains. However, their antibacterial activities decrease when N-1 substitution was replaced with alkyl substituents. Interestingly, several products induced filamentation in three strains of P. aeruginosa .

A series of 2- and 3-indolylthio benzoic, phenylacetic and nicotinic acids or esters were cyclized under dehydrative conditions affording several tetracyclic indole-containing ketones, several of which constitute the first reported examples of novel ring systems, such as the [1]benzothiepino[2,3-b] and [3,2-b]indole and the pyrido[3′2′:5,6] and [3′4′:5,6]thiopyrano[2,3-b] and [3,2-b]indole as well as the [3′2′:5,6] and [3′4′:5,6][1,3]thiazino[3,2-a]indole ring systems.

An asymmetric synthesis of the dihydrobenzofuran segment of ephedradine C has been achieved. Key steps include a chiral oxazolidinone-mediated aldol reaction to form a β-hydroxy ester, followed by a novel debenzylation and concomitant intramolecular cyclisation with iodotrimethylsilane. An asymmetric Michael reaction with a homochiral lithium amide was used to form the third and final chiral centre. The absolute stereochemistry of these three centres was confirmed by X-ray crystal-structure determinations.

The reactions of chiral benzyl carbocations bearing α-phenyl substituents with N-sulfonylated indoles afford 1,1,2-triarylalkanes with anti-selectivities. This outcome is a reversal of facial diastereoselectivity relative to Bach’s α-alkyl-bearing benzyl cations. The reactions are promoted by either a Bronsted acid (TFA) or Lewis acid (BF3·OEt2), offering differential diastereoselectivities and reactivities. The electronic properties of both reacting partners strongly influence the reaction rates and the product diastereoselectivities and appear to operate under kinetic control. This chemistry provides an efficient access to sterically congested tetrasubstituted ethanes.

Palladium-catalyzed aminations of different ArBr with N , N -dialkylhydrazines are described. The reaction proceeded in moderate to excellent yield (up to 90%) with good functional groups compatibilities as cyano, ester, ketone and Boc-amine groups are all well tolerated. Several hydrazines were proved to be good coupling partners and this process provided a general method for the isosteric replacement of benzyl amines with arylhydrazines. Moreover, a method for the N–N bond cleavage of arylhydrazines was discovered, and this two-step sequence could be employed as an alternative synthesis of aniline derivatives.

Proteins in nature fold into native conformations in which combinations of peripherally projected aliphatic, aromatic and ionic functionalities direct a wide range of properties. Alpha-helices, one of the most common protein secondary structures, serve as important recognition regions on protein surfaces for numerous protein-protein, protein-DNA and protein-RNA interactions. These interactions are characterized by conserved structural features within the alpha-helical domain. Rational design of structural mimetics of these domains with synthetic small molecules has proven an effective means to modulate such protein functions. In this tutorial review we discuss strategies that utilize synthetic small-molecule antagonists to selectively target essential protein-protein interactions involved in certain diseases. We also evaluate some of the protein-protein interactions that have been or are potential targets for alpha-helix mimetics.

Various arylalkanes such as fluorenes, xanthene, anthrone, 9,10-dihydroanthracene, and diphenylmethane are effectively transformed into the corresponding aryl ketones, while amino and aldehyde functionalities remain intact, under air in the presence of cesium carbonate.

An asymmetric route to dihydroquinazolinones via the addition of ortho metalated substrates to tert-butanesulfinyl imines is reported. The scope of the nucleophile and electrophile components and the absolute stereochemical outcome are presented.

The reaction of 2-hydroxybenzaldehydes with alkanols in the presence of triphenylphosphine and di-tert-butyl azodicarboxylate (DBAD), under the Mitsunobu reaction conditions, gives rise to the formation of hydrazones as the major products rather than the expected alkyl aryl ethers.

Addition of the Reformatsky reagent derived from ethyl bromodifluoroacetate to alkyl- and aryl-substituted N-tert-butylsulfinimines furnishes beta-tert-butylsulfinamyl-beta-substituted alpha,alpha-difluoroproponiates in diastereomeric ratios ranging from 80:20 to 95:5. The diastereomers are easily separated and the enantiomerically pure, protected beta-amino esters are readily transformed to the corresponding acid, amide, and amine derivatives as useful synthons for medicinal chemistry targets.

The discovery, structure and absolute stereochemistry of coleophomones A and B are described, two structurally novel natural products that inhibit bacterial transglycosylase activity. Coleophomone A represents a new ring system, containing a highly condensed structure which undergoes a reversible retroaldol reaction to form coleophomone B.

5H-Thieno[2,3-c]pyrrole 1a and the N-substituted derivatives 1b-h and 11-13 were synthesized by the novel retro-malonate addition reaction. Thieno[2,3-c]pyrroles readily underwent the Diels-Alder reaction with reactive dienophiles. The free-energy barriers of inversion of the imine nitrogens of the cycloadducts 16 were investigated by variable-temperature 1 H NMR spectroscopy