Chemoenzymatic Synthesis of Hygromycin Aminocyclitol Moiety and its C2 Epimer

Abstract

This manuscript describes the enantioselective synthesis of the aminocyclitol moiety of the antibiotic hygromycin A in eight steps and 39 % overall yield from a non‐chiral starting material. The sequence made use of an initial enzymatic step to transfer chirality to an aromatic ring and was followed by selective organic chemistry transformations (oxidation, protection, azidation, hydrolysis) of the six‐membered ring in order to achieve the target. The approach is also amenable to the synthesis of other related unnatural analogues as exemplified by the synthesis of the C2 epimer of the natural aminocyclitol. All the intermediates were fully characterized, and the absolute stereochemistry assigned by spectrometric methods.

Bio-click chemistry: a bridge between biocatalysis and click chemistry

“…In this way, the cleavage of epoxides is generally achieved with high regio-and enantioselectivity, providing the corresponding products of the trans-1,2 addition efficiently. 86 Representative examples for the opening of monoepoxides 122 (obtained from biocatalytic enzymatic cis-dihydroxylation of benzene derivates 45) with different nucleophiles are ubiquitous (see Scheme 18, vitamin C, 87 codeine, 88 narseronine, 89 C2 epimer of aminocyclitol 90 ) and crucial in the synthesis of natural products.…”

“…Representative examples for the opening of monoepoxides 122 (obtained from biocatalytic enzymatic cis -dihydroxylation of benzene derivates 45) with different nucleophiles are ubiquitous (see Scheme 18 , vitamin C, 87 codeine, 88 narseronine, 89 C2 epimer of aminocyclitol 90 ) and crucial in the synthesis of natural products.…”

Achievements, Challenges, and Scope of Thirty Years of Work on the Biotransformation of Arenes and Their Synthetic Applications

“…After several unexpected results and necessary circumvents, the modified aminoinositol was prepared in seven steps from the known epoxide 3 (Scheme 24). This approach resulted in an efficient synthesis of the core, 98 , that allowed for the synthesis of a series of analogues [90] …”

“…This approach resulted in an efficient synthesis of the core, 98, that allowed for the synthesis of a series of analogues. [90]…”