Latent class analysis of incomplete data via an entropy-based criterion

Latent class analysis is used to group categorical data into classes via a probability model. Model selection criteria then judge how well the model fits the data. When addressing incomplete data, the current methodology restricts the imputation to a single, pre-specified number of classes. We seek to develop an entropy-based model selection criterion that does not restrict the imputation to one number of clusters. Simulations show the new criterion performing well against the current standards of AIC and BIC, while a family studies application demonstrates how the criterion provides more detailed and useful results than AIC and BIC

Enantioselective synthesis of encecaline-derived potent antimalarial agents

The high antiplasmodial activity of racemic benzylamines rac-1 and rac-2 stimulated the synthesis of pure enantiomers. Ellman's chiral sulfinamides (S)-6 and (R)-6 were used as chiral auxiliaries. Condensation of prochiral ketone 5 with enantiomerically pure sulfinamides (S)-6 and (R)-6 and subsequent NaBH4 reduction provided predominantly unlike configured diastereomers (S,R)-8 and (R,S)-8 (ratio unlike-8:like-8 = 90:10). The same transformation of phenol 4 led to the diastereomeric sulfinamides (S,R)-12 and (S,S)-12 in the ratio 60:40. Acid hydrolysis of the diastereomerically pure sulfinamides followed by monobenzylation yielded the enantiomerically pure benzylamines (R)-1, (S)-1, (R)-2 and (S)-2. The enantiomeric purity of the products was proven by chiral HPLC and the absolute configuration by CD-spectroscopy. Generally, benzylamines with (R)-configuration show higher antiplasmodial activity than their corresponding (S)-configured enantiomers. Phenol (R)-2 represents a very potent lead against P. falciparum, with an IC50 value of only 0.026 μM against the NF54 strain. The very high eudismic ratio of 34 indicates the enantioselective interaction of phenol (R)-2 with a particular target protein of P. falciparum

Natural Product Derived Antiprotozoal Agents: Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Chromene and Chromane Derivatives

Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (<b>7</b>) served as key intermediate for the synthesis of different ethers <b>9</b>, amides <b>11</b>, and amines <b>12</b>. The chromane analogues <b>14</b> and the phenols <b>15</b> were obtained by reductive amination of ketones <b>13</b> and <b>6</b>, respectively. Angelate <b>3</b>, ethers <b>9</b>, and amides <b>11</b> did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines <b>12</b>, <b>14</b>, and <b>15</b> revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine <b>12a</b> and α-methylbenzylamine <b>12g</b> were active against <i>P. falciparum</i> with IC₅₀ values in the range of chloroquine, the analogous phenols <b>15a</b> and <b>15b</b> were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine <b>14d</b> based on the chromane scaffold has promising activity against <i>T. brucei rhodesiense</i> and <i>L. donovani</i>

Unprecedented “In Water” Imidazole Carbonylation: Paradigm Shift for Preparation of Urea and Carbamate

The first “In Water” imidazolecarbonylation of amine is described. A one pot reaction of carbonylimidazolide in water with a nucleophile provides an efficient and general method for the preparation of urea, carbamates and thiocarbamates. Use of an anhydrous solvent and an inert atmosphere could be avoided. Product precipitate out from the reaction mixture and can be obtained in high purity by filtration, resulting in a simple and scalable method

Natural product derived antiprotozoal agents : synthesis, biological evaluation, and structure-activity relationships of novel chromene and chromane derivatives

Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani