Synthesis of D‐Desosamine and Analogs by Rapid Assembly of 3‐Amino Sugars

Abstract

D-Desosamine is synthesized in 4 steps from methyl vinyl ketone and sodium nitrite. The key step in this chromatography-free synthesis is the coupling of (R)-4-nitro-2-butanol and glyoxal (trimeric form) mediated by cesium carbonate, which affords in crystalline form 3-nitro-3,4,6-trideoxy-α-D-glucose, a nitro sugar stereochemically homologous to D-desosamine. This strategy has enabled the syntheses of an array of analogous 3-nitro sugars. In each case the 3-nitro sugars are obtained in pure form by crystallization.

State of the Art in Crystallization‐Induced Diastereomer Transformations

“…The recently witnessed renaissance in photochemistry provides an interesting general stimulus and the lately reported example of a photoinduced racemization combined with CIDT revealed just a single broad category of reversible reactions out of several other that have been possibly never linked with CIDT before [151] . In some cases, the decisive role of CIDT in the reaction outcome can only be surmised and CIDT itself might even remain unnamed, as was the case in Myers' captivatingly straightforward synthesis of D‐Desosamine [154] …”

“…[151] In some cases, the decisive role of CIDT in the reaction outcome can only be surmised and CIDT itself might even remain unnamed, as was the case in Myers' captivatingly straightforward synthesis of D-Desosamine. [154] Relatively less pronounced is the potential that CIDT has in green chemistry applications. Since the fundamental outcome of CIDT is a high purity product collected simply by filtration, both energy and resources consuming purification and waste production can be significantly minimized.…”

Resistance to Macrolide Antibiotics in Public Health Pathogens

“…Assays could be developed to ensure that the synthesis of certain vital proteins is impacted and/or to monitor the mechanism(s) of action, potentially enriching for compounds that promote frameshifting, for example. The route to total synthesis will allow the exploration of structure -activity relationships, overcoming any limitations of semisynthesis (see macrolide.com; Zhang et al 2016) and potentially extending spectrum beyond the community-acquired respiratory pathogens. With our present understanding, perhaps it is prime time to rethink macrolide drug discovery and use the existing and expanding tool sets to find molecules with more refined, targeted actions.…”

Avanços Recentes Na Química Dos Aminoaçúcares: Ocorrência, Biossíntese, Síntese E Aplicação

“…Os carboidratos e seus derivados são biomoléculas potencialmente úteis nos campos da química e da biologia, 1 de modo que modificações estruturais nestes compostos podem ocorrer por substituição com nitrogênio, enxofre, fosfato ou cloro, e outros grupos. 2 Os aminoaçúcares que são sem dúvida os mais importante açúcares modificados existentes, são os constituintes fundamentais 3,4 de muitos compostos biologicamente ativos, como antibióticos 5,6 e biopolímeros. 7 Aminoaçúcares são definidos como aldoses ou cetoses que têm seu grupo hidroxila substituído por grupo amino nos C2, C3 ou C4 do anel hexose ou pentose, exceto no carbono anomérico.…”