A New Approach to Neuraminic Acid Analogues via 1,2-Oxazines

Abstract

A new stereoselective and potentially very flexible (C(5) + C(3) + C(1)) approach to neuraminic acid derivatives and analogues has been established using enantiopure nitrones and alkoxyallenes as C(3) and C(1) building blocks. Substituent OR(2) in position 4 of neuraminic acid analogues is defined by the alkoxyallene employed for the synthesis of the intermediate 1,2-oxazine. Side chain R(1) can be varied by using different precursor nitrones and introduction of different protection groups R(3) at the amino function is also possible.

Additions of Carbohydrate-Derived Alkoxyallenes to Imines and Subsequent Reactions to Enantiopure 2,5-Dihydropyrrole Derivatives

“…Two additional reactions were performed with lithiated alkoxyallene 2 to gain information for the planned synthesis of preussin. Given that a benzyl group has to be installed at C-2 of the pyrrolidine skeleton of this natural product, we studied additions of lithiated 2 to phenylethanal (11) and to its N-tosyl imine congener 14 (Scheme 4). From 2 and 11 we obtained the expected allenyl alcohol 12 in good yield as…”

“…10 This oxidative removal of two carbon atoms proves that lithiated alkoxyallenes are also synthetic equivalents of acyl anions and some years ago we used this capacity in a synthesis of neuraminic acid. 11 Under standard conditions of ozonolysis, the esters 8 and 9, still containing the carbohydrate-derived auxiliaries, were obtained in moderate yields, but with essentially unchanged diastereomeric ratios. An acid-catalyzed transesterification was then performed to convert the two intermediates into a compound with known absolute configuration.…”

Süße Versuchung: De‐novo‐Wege zu ungewöhnlichen Zuckern

“…Auch wenn der Siegeszug der Organokatalyse im letzten Jahrzehnt erstaunliche Synthesen von ungewöhnlichen Monosacchariden ermöglicht hat, trugen auch andere Gebiete der organischen Synthesechemie zu Fortschritten in der De‐novo‐Synthese bei. Mit dem Schlüsselschritt einer stereoselektiven [3+3]‐Cyclisierung eines Nitrons mit einem lithiierten elektronenreichen Allen synthetisierten Reißig et al eine Reihe von komplexen Monosacchariden und Monosaccharid‐Derivaten 7,8. In der Sialinsäuresynthese aus Abbildung 7 reagiert das von geschützter d‐Arabinose abgeleitete Nitron (29) als C5‐Baustein mit dem lithiierten Allen (30) als C3‐Baustein.…”

Samarium Diiodide Promoted Reduction of 3,6‐Dihydro‐2H‐1,2‐oxazines: Competition of 1,4‐Amino Alcohol Formation and Ring Contraction to Pyrrole Derivatives

“…These versatile heterocycles are easily available by [3+3] cyclization of lithiated alkoxyallenes with nitrones6 and can be subsequently modified. As disclosed in several reports, smooth SmI 2 ‐mediated ring opening of monocyclic 1,2‐oxazine derivatives4d,4f,7 and bicyclic compounds8 allow the efficient synthesis of various enantiopure cyclic or acyclic amino polyols. Whereas reactions of samarium diiodide with tetrahydro‐2 H ‐1,2‐oxazine derivatives of type 1 led, in almost all tested examples, exclusively to the desired amino alcohols 2 in excellent yields and purities, in the case of 3,6‐dihydro‐2 H ‐1,2‐oxazines 3 , which bear an enol ether moiety, in addition to the expected 1,4‐amino alcohols of type 4 , due to competing reactions, the formation of pyrroles 5 9 was also observed (Scheme ).…”