Chitosan catalyzed synthesis and mechanistic study of steroidal 2H-pyran ring formation.

A simple and convenient method is reported for the preparation of steroidal 2H-pyran 2 by reacting 3ß-acetoxy cholest-5-ene-7-one 1 with N-benzyl-2-cyanoacetamide in presence of chitosan, a green and heterogeneous catalyst. The product 2 was characterized by using NMR (1H and 3C), IR, and mass spectroscopy. The mechanism of 2H-pyran ring formation is described by employing theoretical B3LYP/6-31G (d) density functional method. The reaction undergoes via formation of two intermediates A and B, and each intermediate undergoes through a transition state TS1 and TS2. The molecular properties like relative energy and FMO analysis were used to explain the mechanism of the reaction. The HOMOs and LUMOs were found in support of the present reaction mechanism. The stability of all the calculated structures which includes reactant (1a), intermediates (A and B), product (2a) as well as TS1 and TS2 transition states, was supported by calculating their energy minima and fundamental frequencies.

Formation of nitrogen-containing six-membered heterocycles on steroidal ring system: A review.

Steroidal heterocyclic compounds constitute interesting and promising scaffolds for drug discovery as they have displayed diverse chemical reactivity and several types of biological activities. This study is a concise report on the most recent advancements in the chemistry of the steroid skeleton, including reactions at the A, B, and D ring systems. The modern synthetic methods for the steroidal nitrogen-containing six-membered heterocyclic derivatives from 3-keto-, 6-keto-, 17-keto-, and 20-keto-steroids, as well as 2-Aldo-, 4-Aldo-, 6-Aldo-, and 16-Aldo-steroids, are discussed. However, some other methods for the synthesis of steroidal N-containing 6-membered heterocyclic derivatives are also included. These compounds have shown therapeutic potential as cytotoxic agents against various cell lines and have also shown antiproliferative, anti-inflammatory, and antioxidant activities. Therefore, they could be used as prospective candidates for the development of various medications. This paper not only describes synthetic details involved in creating N-containing 6-membered heterocyclic steroid derivatives, but also provides a brief overview of the medicinal applications of these compounds. This information will be highly useful for the medicinal chemists conducting research in this field.