Aldonolactone Synthesis

O. Varela, A. Fernandez Cirrelli, and R. M. de Lederkremer, P-Elimination in aldonolactones. Synthesis of 3,6-dideoxy-L-araWno-hexose (Ascarylose), Carbohydr. Res., 70 (1979) 27-35. 

Homeman, A.M. et al. Stereoselective Radical Induced Cyclisation of Unsaturated Aldonolactones Synthesis of Highly Functionalized, Enantiomerically Pure Cyclopentane Derivatives. 2.1 1995 [124]... 

Aldonolactones are useful starting materials for the synthesis of modified sugars. They have also been used as chiral templates in synthesis of natural products. Some of them are inexpensive, commercially available products or they may be obtained readily from the respective monosaccharides. The purpose of this chapter is to survey the main reactions of aldonolactones. Previous reviews on the subject include articles on gulono-1,4-lactones (1) and D-ribonolactone (2). Methods of synthesis, conformational analysis, and biological properties are not discussed in this chapter. 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

Carbene-mediated methylenation of aldonolactones provides a direct route to 1-methylene sugars, which may be used as intermediates for the preparation of furanoid or pyranoid C-glycosyl compounds, or chiral precursors for the synthesis of natural products. 

The cyanohydrin synthesis of higher sugars, which involves intermediate aldonolactones, allows the introduction of a 14C label in the sugar chain. Thus, for example, L-[5-l4C]arabinose was synthesized (12) from D-xylose, which was first converted, by addition of K14CN and hydrolysis, into D-[ 1-... 

The regio- and stereo-selective functionalization of aldonolactones yields optically active lactones, which are important precursors in natural product synthesis. Concepts such as chiral templates and chirons, derived from carbohydrates, have been ingeniously and widely applied in synthesis (233). Among the commercially available aldonolactones, D-ribono-1,4-lactone is... 

Synthesis of Nucleosides, Amino Acids, and Other N-Containing Products from Aldonolactones... 

Borchardt and coworkers (265) have employed the chiral cyclopenten-ones derived from aldonolactones for the synthesis of the analogue 302a of neplanocin A. Neplanocin A (302b) and aristeromycin (303), carbocyclic analogs of adenosine having antiviral and antitumor activities, have also been synthesized (277,278). 

Methyl oxetane-2-carboxylate derivatives (e.g., 284), obtained by ring contraction of aldonolactones, have been employed for the synthesis (279) of the nucleoside / -noroxetanocin [9-(/ -D-eryt/iro-oxetanosyl)adenine, 304] and its a-anomer via an a-chloride obtained by a modified Hunsdiecker reaction. Displacement of chloride by adenine and debenzylation gave 304. The threo isomer of304, /J-epinoroxetanocin (305), was likewise synthesized from D-lyxono-1,4-lactone. The oxetane nucleosides display potent antiviral activity against the human immunodeficiency virus (HIV). 

Although the use of abundant sugars as starting materials for chiral synthesis has received considerable attention, the ready availability of many aldonolactones is less well recognized by mainstream synthetic organic chemists. The chapter here contributed by de Lederkremer and Varela (Buenos Aires) provides a comprehensive overview of the practical potential of these cyclic esters and complements the more specialized contribution on gulonolactones by Crawford in Volume 38. 

As shown in chapter, Synthetic polymers from readily available monosaccharides by J, A, Galbis and M,G, Garcia-Martin, aldonolactones are useful monomeric materials for the synthesis of biodegradable polymers and bio-compatible polymers for medicinal applications. 

Among the aldonolactone-based surfactants are aldonolactone-linked fatty esters which have been prepared by selective acylation of unprotected aldono-1,4-lac-tones or aldono-1,5-lactones, One of the first reported examples of this type of surfactant was applied to the enzymatic synthesis of 6-0-aUcanoylgluconolactones [35], Thus, 6-0-decanoyl- and 6-0-dodecanoyl- derivatives (21a and 21b, respectively, Scheme 8) were obtained in 26-27% yield by esterification of glucono-1,5-lactone (1) at C-6 with the corresponding 2,2,2-trichloroethyl carboxylate in the presence of porcine pancreatic lipase (PPL) as catalyst. Compounds 21a,b are soluble in water at 90-96°C but precipitate when cooled to 30-37°C, NMR and GC-MS analysis after dissolution and precipitation indicated the presence in the mixture of compound 21b, the glucono-1,4-lactone-derived ester 22, and the... 

Scheme 23 Synthesis of di-hydroxylated 1,6-aldonolactams via aldonolactone-derived sulfites...

Selected examples of the synthesis of natural product starting from aldonolactones are presented in this section. 

The aim of this article is to focus on the diversity of aldonolactones as chiral synthons. The chemistry of aldonolactones was an almost unexplored area when, in 1979, we started our investigations on the reaction of aldonolactones with hydrogen bromide in acetic acid thereby obtaining bromodeoxyaldonolac-tones [1,2]. These compounds have over the years proven to be very versatile compounds for stereoselective synthesis, both in the carbohydrate field, giving access to otherwise less readily obtainable sugars, and as chiral, optically pure synthons in a broader sense within organic chemistry. 

Our work has mostly been focussed on the potential of selective transformation of aldonolactones, as will be described in this article, rather than on the synthesis of defined target molecules. Thus, the purpose of this paper is also to inspire researchers from the non-carbohydrate field to recognize these chiral synthons for further use in the synthesis of e.g.complex natural products. 

In planning the synthesis of biologically active compounds, strategies using aldonolactones or other compounds from the chiral pool should therefore continue to be considered, since they can provide attractive routes in comparison with alternative methods by asymmetric synthesis. 

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