From Glycals to Nitrogen Heterocycles and Carbocycles via “Cleavage‐Intramolecular Recombination Strategy”

Abstract

Glycals (carbohydrate enol‐ethers) have enjoyed profound applications in organic synthesis for more than a century. They not only serve as versatile glycosyl donors or as substrates for Ferrier rearrangement, but also find extensive synthetic applications especially as a “chiral pool” for accomplishing the synthesis of a variety of natural and biologically important compounds. As cyclic enol ethers, they demonstrate high reactivity and are among the most and variously transformable monosaccharide derivatives. The uniqueness of the reactivity of glycals is that they can be synthetically tuned to get a library of derivatives through stereo‐ and regioselective introduction of a variety of functional groups at C1, C2, C3 as well as C4 carbons of the sugar. We have developed a practical approach for stereoselective mono‐ and diamination of glycals and over the years utilized these scaffolds for the synthesis of a variety of biologically important nitrogen heterocycles and carbocycles through a “Diversity Oriented Approach”. Our synthetic strategy in this direction mainly relied on the cleavage of ring O−C bond of the sugar followed by an “intramolecular recombination” reaction. Utilizing this strategy, we have accomplished the synthesis of several biologically important natural products, their analogues and related unnatural derivatives. Examples of such compounds reported from our group include polyhydroxypyrrolidines, DMDP, anisomycin, steviamine, pochonicine, conduramines, bulgecinine, aminocyclitols, azepanes, 4‐hydroxy‐D‐proline, azanucleosides and their analogues. A personal account highlighting these syntheses is presented here.

Synthesis of densely functionalize pyrroles from unprotected carbohydrates

“…46,47 Based on these advantageous properties, many important compounds have been generated from carbohydrates, such as natural occurring polyhydroxypyrrolidine 7-9, therapeutic molecules 10-15, and N-heterocyclic acyclonucleosides 16-18. 48 (Figure 1-16) The improvement of present methodologies and the development of new synthesis routes have led to the accessibility of more N-heterocycle molecules from carbohydrates, such as pyrroles, pyridines, pyrazines, imidazoles, and pyrazoles.…”