Aldonolactones as chiral templates in the synthesis of thiolactones, 1,3-polyols and hydroxy amino acids
The usefulness of aldonolactones as chiral templates is shown in the synthesis of varied asymmetric molecules. For example, enantiomerically pure 4-thio- D-ribono and 4-thio-L-lyxono- 1 ,Clactones have been respectively synthesized from D- gulono- and D-ribono- 1,4-lactones. Seven carbon 1,3-polyol chains have been enantioselectively obtained from D-glycero-D-gulo-heptono- 1 ,Clactone via chiral furanone derivatives. Also, furanones and pyranones derived from D-glucosaminic acid were employed as intermediates in the synthesis of hydroxy amino acids, such as cis-4-hydroxypipecolic acid and (2S,4S,5R)-4,5,6-trihydroxynorleucine. Aldonolactones are useful chiral templates in the synthesis of modified sugars and non-carbohydrate natural products (ref. 1). Many aldonolactones are commercially available products, or they can be readily obtained by oxidation of the respective monosaccharides. In our laboratory aldonolactones such as D-ribono-, D- gulono-, and D-glycero-D-gulo-heptono- 1,4-1actones, as well as unsaturated lactones derived from D- glucosaminic acid have been employed in the synthesis of sugar thiolactones, 1,3-polyol systems, and hydroxy amino acids. Particularly, D-ribono-1 ,Clactone has been considered a "chiral cornerstone" (ref. 2) because of its use as a chiral precursor of numerous naturally occurring, asymmetric molecules, and many derivatives have been prepared (ref. 3). However, no synthesis for its 4-thio analogue, 4-thio-D-ribono- 1,4- lactone, has been reported. This together with the fact that previous attempts to prepare sugar thiolactones from aldonic acids were not satisfactory, prompted us to develop a general procedure for the synthesis of aldopentono- 1 ,4-thiolactones. 4-Thio-D-ribono- 1P-lactone was our fist target, and L-lyxono-1 ,Clactone was selected as the chiral template, since the replacement of a HO group by thiol usually takes place with inversion of the configuration of the carbon involved. As this lactone is not commercial, D-gulono-1,4-lactone u), which has the same stereochemistry for all the ring stereocenters as lyxonolactone, was employed as starting material. Acetonation of 1 with acetone in the presence of sulfuric acid gave the diacetonide 2, which was selectively hydrolyzed with aqueous acetic acid to the 2,3-O-monoisopropylidene derivative 9. The glycol system was oxidized with sodium periodate to give the aldehyde 4, which was in equilibrium with the hydrated form, according to the NMR spectra. Chemoselective reduction of the aldehyde function with sodium cyanoborohydride (pH 4) led to the 2,3-O-isopropylidene-~-lyxono- 1,4-1actone (5) in 60% yield from 1. The free hydroxyl group of 5 reacted with p-tolylsulfonyl chloride affording the tosylate 4 in 78% yield.