Development and validation of a spectrophotometric method for quantification of residual cyclodextrin (DIMEB; Heptakis) in pertussis antigens.

Methylated derivatives of cyclodextrins such as DIMEB (2,6-di-O-methyl)-ß-cyclodextrin or Heptakis is commonly used as culture medium modifier in manufacturing of pertussis antigens for promoting the growth of bacteria. We report here development and validation of a spectrophotometric method for estimation of DIMEB in different product matrices of pertussis vaccine antigens i.e. Filamentous haemagglutinin (FHA), Pertactin (PRN) and Pertussis toxin (PT). The detection is based on characteristic reaction of hydrolyzed sugars derivatives from DIMEB i.e., furfural derivatives with anthrone reagent to form colored complexes which could be quantified at 625 nm. Method showed excellent linearity with correlation coefficient (R2) > 0.995 over the concentration of 5.0-80.0 µg. LOD and LOQ of 1.47 µg and 4.46 µg respectively was reported. The overall precision (repeatability and intermediate precision) showed % RSD for DIMEB content <10.0% for all the matrices. % Recoveries for DIMEB after three different spike levels (low, middle and high) were within 90%-113%. The method was successfully applied for determination of residual DIMEB in different product matrices of FHA, PRN and PT protein antigens. This can be used to monitor residual DIMEB levels during manufacturing of acellular pertussis antigens.

Functionalized 4-carboxy- and 4-keto-2,3-dihydropyrroles via Ni(II)-catalyzed nucleophilic amine ring-opening cyclizations of cyclopropanes.

A general synthetic approach to vinylogous 4-carboxy- and 4-keto-2,3-dihydropyrroles is reported using Ni(ClO4)2·6H2O as a Lewis acid catalyst for nucleophilic amine ring-opening cyclizations of donor-acceptor (D-A) cyclopropanes. This methodology provided good to excellent yields of functionalized 2,3-dihydropyrroles under milder reaction conditions than previously reported and is amenable to a variety of D-A cyclopropanes and primary amines.

A general intramolecular Friedel-Crafts approach to functionalized pyrrolo[3,2,1-ij]quinolin-4-ones.

An indium(III)-catalyzed intramolecular Friedel-Crafts annulation for the efficient synthesis of pyrrolo[3,2,1-ij]quinolin-4-ones is described. The products are formed in good to excellent yields (51-97%) with diastereoselectivities up to >99 : 1 dr.

Diastereoselective intramolecular Friedel-Crafts cyclizations of substituted methyl 2-(1H-indole-1-carbonyl)acrylates: efficient access to functionalized 1H-pyrrolo[1,2-a]indoles.

A general, catalytic method for the diastereoselective synthesis of functionalized 1H-pyrrolo[1,2-a]indoles via an intramolecular Friedel-Crafts alkylation of N-acyl indoles is reported. Products were obtained in excellent yields (up to 98%) with high diastereoselectivities (up to >25:1 dr).

An efficient synthesis of hydropyrido[1,2-a]indole-6(7H)-ones via an In(III)-catalyzed tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence.

An efficient Lewis acid-catalyzed cyclopropane ring-opening/Friedel-Crafts alkylation sequence of methyl 1-(1H-indole-carbonyl)-1-cyclopropanecarboxylates is reported. The protocol affords functionalized hydropyrido[1,2-a]indole-6(7H)-ones in up to 99% yield.

A catalytic homo-Nazarov cyclization protocol for the synthesis of heteroaromatic ring-fused cyclohexanones.

A general protocol for the catalytic homo-Nazarov cyclization of cyclopropyl heteroaryl ketones has been developed, which employs indium triflate as the promoter. A range of heteroaromatic ring-fused cyclohexanones was synthesized in 56-91% yield using this protocol. An example of a tandem cyclopropanation/homo-Nazarov cyclization is also reported in which the one-pot yield is greater than the overall yield of the two individual steps.

Indium-catalyzed homo-Nazarov cyclizations of alkenyl cyclopropyl ketones.

Herein, an efficient Lewis acid catalyzed protocol for the homo-Nazarov cyclizations of alkenyl cyclopropyl ketones is reported. Alkenes bearing ß-hydrogens (or silyl groups) provide 1.5:1 mixtures of methylene cyclohexenols and cyclohexenones. When no ß-hydrogens (or silyl groups) are present, only cyclohexenones are observed. Products are rapidly formed in good to high yields (up to 93%) under mild conditions and could be readily derivatized.