Synthetic approaches towards cortistatins: evolution and progress through its ages.

Cortistatins are a family of steroidal alkaloids with a unique pentacyclic skeleton, having immensely potent anti-angiogenetic activities. Given the scarcity in the natural availability of these compounds, their syntheses became major attractions in organic chemistry. Along with total synthesis of the most potent congeners in the family: cortistatins A and J, the synthesis of two other members have been successfully completed, while various other analogues have also been designed with variable degrees of biological activities. This review is an exhaustive coverage of the significant attempts towards constructing this highly challenging molecule and also aims to highlight the deep understanding of the structure-activity relationships of these compounds, which have been garnered over time.

Construction of key building blocks towards the synthesis of cortistatins.

This work reports the construction of key building blocks towards the synthesis of cortistatins; a family of steroidal alkaloids. Cortistatin A, being a primary target due to its superior biological properties over other congeners, has been prepared by two different synthetic routes. Synthesis of the precursor to the heavily substituted A-ring starting from d-glucose and construction of the DE-ring junction employing a Hajos-Parrish ketone as a chiral pool have been demonstrated. Efforts are underway to assemble these key fragments and build towards the total synthesis of cortistatin A.

A new and informative [a,b,c,d] nomenclature for one-pot multistep transformations: a simple tool to measure synthetic efficiency.

Domino, cascade and tandem reactions constitute the most efficient and creative chemical transformations with a huge domain of synthetic utility and applications. A number of reactions may be achieved in a single pot, accompanied by the formation of new rings and new bonds, leading towards higher molecular complexity. A lack of one unified, yet informative descriptor often understates the synthetic ingenuity of certain highly creative transformations. In this review, we propose a new tetra-coordinated [a,b,c,d] nomenclature which takes into account and displays the basic parameters which generally indicate the level of efficiency of a chemical transformation. An almost exhaustive set of one-pot multistep reactions may be described by this system and this review is an attempt to display the one-pot multistep transformations reported from our group and to classify them based on our proposed descriptor.

A one-pot copper catalyzed biomimetic route to N-heterocyclic amides from methyl ketones via oxidative C-C bond cleavage.

A direct one-pot Cu-catalyzed biomimetic oxidation of methyl ketones to pharmaceutically important N-heterocyclic amides is reported. The scope of the method is broad, scalable, and mild, and the reaction is tolerant with various acid, base sensitive functionalities with multiple heteroatoms and aryl halides. The extensive mechanistic studies suggest that this reaction follows the Luciferin-Luciferase-like pathway.