As Chiral Starting Materials

The raw materials from which di-D-fructose dianhydrides can be obtained in appreciable yield are readily available from comparatively inexpensive agricultural feedstocks. Thus, these compounds are attractive as chiral-starting materials for chemical synthesis. Their stability to acid and heat, and their relative rigidity, because of the conformational constraints covered here, are also features that might be exploited during syntheses.119 A series of variously substituted di-D-fructose dianhydrides has been prepared,119 starting from 6,6 -dideoxy-6,6 -di-halosucroses. The properties of these and other derivatives of di-D-fructose dianhydrides are summarized in Tables XIV-XX. Two of these derivatives, 48 and 56, exhibit thermotropic liquid-crystal properties.119... 

A great number of natural compounds have been employed as chiral starting materials for asymmetric syntheses. Table 1-2 classifies such inexpensive reagents. 

In Part B, we analyse and discuss some recent enantiospecific natural product syntheses that have utilised monosaccharides as chiral starting materials. The coverage is not meant to be exhaustive or extensive but, rather, illustrative of the way in which monosaccharides are currently being used in asymmetric natural product synthesis. For more exhaustive coverage of this field, the reader is referred to several fine monographs and reviews.18... 

Quinic acid 13a has been chosen as chiral starting material, because its functionalisation is suitable for my synthetic strategy. In addition it is commercially available. 

A variety of complex natural compounds are synthesized by using monosaccharides as chiral starting materials. Exemplifying eight representative natural products, i. e., erythromycins, elaiophilin, herbimaycins, calbistrin A, lactacystin, tautomycin, FK-506, and halichondrin B, the methodology how monosaccharides are incorporated into natural product synthesis as chiral pools is described. 

Hydroxy acids, esters, and aidehydes as chiral starting materials... 

Kinoshita, Nakata, and coworkers synthesized erythronolide A (20) (O Fig. 4) [14,15,16,17]. Erythronolide A (20) was divided into three segments, 22 (C1-C6), 23 (C7-C9), and 24 (CIO-C13), of these fragments 22 and 24 were prepared from monosaccharides as chiral starting materials. 

Gordon and co-workers used A-4-pentenoyloxazolidinone 150 as chiral starting material in the asymmetric synthesis of (-)-sesaminone (159), Scheme (27) [90]. 

The total syntheses of (+)-muscarine chloride, its optically active or racemic diastereoisomers, and analogs have been carried out independently in several laboratories. In most cases carbohydrates or, rarely, amino acids were used as chiral starting materials, enabling stereoselective synthesis. The different synthetic approaches as well as other aspects of muscarine chemistry, occurrence, and pharmacology were discussed in an excellent review by Wang and Joullie (18) in this treatise and earlier by Wilkinson (23). 

The synthetic plan followed by the authors is presented in Scheme 24 which shows strategic bond formations in the retrosynthetic sense. For the construction of 181, a ketophosphonate aldehyde condensation was used as the macrocyclization step which led to compound 182, an ester derived from hydroxyaldehyde 183 and ketophosphonate acid 184. The remaining C-C bond formations are indicated on 183 and 184, which then conducted to the key building blocks 127,185-188. The authors took advantage of hidden symmetry elements which led them to select both enantiomers of xylose and tartaric acid as chiral starting materials and/or chiral auxiliaries. 

The first application involves an amino acid as chiral starting material in the synthesis of wnnatural amino acids, those never imagined by nature.t l 5-Serine (15) is converted into its N-protected analogue... 

See also section 7.1.1 for another application of terpenoids as chiral starting materials. 

A review on the synthesis of optically-active pheromones includes a section on the use of carbohydrates as chiral starting materials. ... 

Recently, Fraser-Reid and Tsang have extended their studies on the use of carbohydrates as chiral starting materials into the trichothecene field (47, 48). The triacetate (206), available from D-glucose, has been transformed into the modified trichothecene skeleton (208) as outlined in Scheme 21. The key ring-forming reaction in this sequence was an intramolecular alkylation of the amide (207). A number of transformations, including the transposition of the 8,9-olefin, still remain to convert product (208) into a naturally occurring trichothecene. 

The 1,2-amino acids 150, 153, and 156 are widely used as chiral starting materials for stereoselective synthesis of aziridines 152, 155, and 158. The A-activated amines 151, 154, and 157 undergo intramolecular C—N bond formation to afford chiral aziridines. The reactions can be conducted easily on a multigram scale with good overall yields (Scheme 40.30). 

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