Research

Both diastereo- and enantioselective synthesis of organic compounds play a pivotal role in synthetic organic and medicinal chemistry. The development of an easily accessible synthetic methodology provides the essential synthetic tools for chemists in organic synthesis, as well as chemists in the field of drug discovery. Dr. Chanda’s current research is focused on the development of novel synthetic methodologies to obtain high diastero- and enantiomeric purity of synthetic molecules. We are also interested in applying these new methodologies for the diastereo- and enantioselective synthesis of small bioactive molecules.

Current Research Projects

1. Diasteroselective Aldol Reactions of Substituted Phenylacetates

Thomas; A.Y.; Walls III, T. L.; Nelson, B. N.; Primeaux, S. W.; and Chanda, P. B. “Temperature- and Reagent-Controlled Complementary Syn- and Anti-Selective Enolboration-Aldolization of Substituted Phenylacetates” J. Org. Chem. 2021, 86, 6184

2. Enantioselective Aldol Reactions of Substituted Phenylacetates

Boron-mediated enantioselective aldol reactions of ketones, thioesters, propanoates, 3,3,3-trifluoropropanoates, and phenylacetates have been well explored. However, such reactions of substituted phenyl acetates remain unexplored to date. We have recently reported syn- and anti-selective aldol reactions of substituted phenylacetates. 2,3-diaryl-3-hydroxy propanoates derived from substituted phenylacetates are important motifs for some bioactive compounds. In fact, 1,2,3-triazole analogs of 2,3-diaryl-3-hydroxy propanoates, which are prepared from substituted phenylacetates, exhibit higher potency than the corresponding compounds derived from unsubstituted phenylacetates. Diastereomerically pure analogs are required to inhibit aromatase enzyme complex (Cytochrome P450 19A1). Enantiomericaly pure analogs have never been examined for their inhibitory activities against aromatase enzymes probably due to the unavailability of enantiopure 2,3-diaryl-3-hydroxy propanoate synthons. Therefore, we are investigating enantioselective preparation of such compounds.

3. Diastereoselective Aldol Reactions of N,N-dialkylphenylacetamides

Boron-mediated stereo-selective aldol reactions of carbonyl compounds such as ketones and esters are well explored. However, those reactions of carboxylic acid amides are rarely reported. A combination of dicyclohexyliodoborane (Chx₂BI) and triethylamine was reported to provide syn-aldol products of N, N-dialkylphenylacetamide but anti-selective aldol reaction of N, N-dialkylphenylaceamide remains unexplored to date. We have used dialkylborontriflate (R₂BOTf) in the presence of trialkylamine (R₃N) to enolize N, N-dialkylphenylacetamide followed by reaction of a boron enolate with various aldehydes as electrophiles. The study of the effects of various factors such as bulk of a boron reagent, solvent used, reaction temperature, and steric of alkyl groups of tertiary amides provided the optimum conditions to get syn-and anti-aldols.

4. Diastereoselective Aldol Reactions of N,N-Dialkylsubstituted Phenylacetamides

5. Enantioselective Aldol Reactions of N,N-Dialkylphenylacetamides