Synthesis of Methyl l-Kijanosides by Regio- and Stereoselective Ring Opening of 2-Oxazolidinone-Fused Aziridines

Abstract

Kijanose is one of the most highly functionalized deoxysugars found in nature and a challenging synthetic target. We found that the ring opening of trisubstituted, 2-oxazolidinone-fused aziridines is regio-and stereoselective, and the azide adduct has the same stereochemistry as that of kijanose after converting the azido to a nitro group. Therefore, both αand β-methyl Lkijanosides were prepared from ethyl L-lactate in 14% total yield. O riginally isolated from the acidic hydrolysis of an antibiotic kijanimicin (2), 1−3 D-methyl kijanosides (1) are one of the most highly functionalized sugars found in nature (Figure 1). 4 Kijanimicin and its related compounds, including tetrocarcins, 5−9 arisostatins, 10,11 lobophorins, 12−18 and microsporanates, 19 belong to the family of spirotetronate antibiotics, 20−23 in which kijanose is the common nitrosugar linked to the polycyclic aglycone (tetronolide). More than 60 spirotetronate antibiotics have been isolated, and most of these compounds also exhibit antitumor or other biological activities that have therapeutic potential. 24−31 However, the synthesis or modifications of the spirotetronates rely heavily on enzymatic synthesis or semisynthesis, as the preparations and linkages of the aglycone and the deoxysugars remain a challenging task. 32−37 All of the reported chemical syntheses of methyl α-D-kijanoside start from monosaccharides, require more than 10 steps, and often encounter regio-or stereoselectivity issues (Scheme 1). 38−42 On the contrary, the identified gene cluster for the biosynthesis of kijanimicin suggests that 10 enzymes are

Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines

“…We were pleased to nd that the oxazolidinone functional group could be efficiently removed with Ba(OH) 2 $8H 2 O to afford THIQ 2a in 81% yield. 16,17 Alternatively, reduction with DIBAL afforded Nmethyl THIQ 6a in 73% yield, providing a facile access of our hydrogenated products to N-methyl protected THIQs.…”

Rh2(II)-Catalyzed Intermolecular N-Aryl Aziridination of Olefins Using Nonactivated N Atom Precursors

“…To investigate the regioselectivity of nucleophilic addition, the reactivity of cyclohexene N -aryl aziridine 15d toward an array of nucleophiles was investigated (Scheme ). Indium-catalyzed addition of benzyl thiol to 15d produced the anti -thioether 27 as the only product.…”

Biocatalytic Synthesis of Metaxalone and Its Analogues

“…Additionally, oxazolidinones also serve as chiral auxiliaries and synthetic intermediates for a variety of organic transformations . Despite significant advancements in this field, organic chemists still face challenges in constructing oxazolidinone scaffolds due to the involvement of harsh reaction conditions or the necessity of expensive catalysts in many cases. In response to these challenges, there has been a growing effort to develop environmentally friendly methods for synthesizing oxazolidinones …”