Synthesis from L-arabinose

Aldono-1,5-lactones and free aldonic acids react with alcohols in the presence of hydrogen chloride to give the corresponding alkyl aldonates (84). The reaction is slower with 1,4-lactones. Because esterification takes place very slowly in the absence of an acidic catalyst, aldonic acids and their lactones may be recrystallized from boiling alcohols without appreciable esterification (85). However, in some instances, alkyl esters are formed under these conditions. For example, essentially pure ethyl L-mannonate was isolated (6.4% yield) from the mother liquors of crystallization L-man-nono-1,4-lactone, obtained by Kiliani synthesis from L-arabinose (86). Similarly, repeated recrystallization from ethanol of crude 2,3,4,6-tetra-O-acetyl-D-glucono- 1,5-lactone afforded the corresponding ethyl gluconate derivative (87). 

The second Merck Frosst synthesis (from L-arabinose) is discussed in detail in Section 2, Scheme 2.20. 

Isoaltholactone (119) has been obtained from G. malayanus, G. montanus and G. tapis and its relative stereochemistry assigned from NMR data and X-ray analysis. A synthesis from L-arabinose provided the absolute stereochemistry of (119). The biosynthetic pathway in Scheme 2 was proposed to account for the formation of altholactone (114) and isoaltholactone (119) from the same postulated precursor, 5-hydroxygoniothalamin (105) (124). 

Several rare amino sugars have been found in antibiotics. From puro-mycin (Achromycin), 3-amino-3-deoxy-D-ribose has been isolated by Waller and co-workers 260). The configuration of the amino sugar was confirmed by its synthesis from L-arabinose, with methyl 2,3-anhydro-i -L-ribopy-ranoside 261) as an intermediate (p. 392). Among the hydrolysis products of erythromycin, obtained from Streptomyces erythreus, is an amino sugar with the empirical formula CsHnNOs. Its structure has been partially determined as a 3-dimethylamino-3,4,6-trideoxyhexose 262). On hydrolysis... 

This reagent remains very useful, and it was recently used for an efficient synthesis of 2-deoxy-L-eryt/ ro-pentose (9), starting from L-arabinose (Scheme 2).16... 

Y. Chong and C. K. Chu, Efficient synthesis of 2-deoxy-L-eryt/fro-pentose (2-deoxy-L-ribose) from L-arabinose, Carbohydr. Res., 337 (2002) 397 102. 

However, it is rather difficult to search a library of natural sugars for an appropriate sugar derivative for the synthesis of 30. It is necessary to find either 5-deoxy-L-arabinose (61) or 5-deoxy-L-ribose (62), neither of which is available from natural resources [69]. Chemical derivation from easily available sugars is the only way to obtain 61 and 62,however, simple deoxygenation of the terminal alcohol group from L-arabinose (63) and L-ribose (64) generally requires a multi-step process. For example, the deoxygenative transformation... 

Baker s original work concerned the synthesis of 3-amino-3-deoxy-D-ribose, a component residue of the antibiotic puromycin.29 Two independent syntheses were achieved, starting from L-arabinose and D-xylose, respectively. The main steps in the reaction schemes are outlined in the following reaction sequences. 

Although developments in the chemistry of L-arabinose that use modem reagents as tools in organic synthesis produce only few universal functionalized building blocks, their potential value is enormous for further application as chiral organic material. An example is 3,4-O-isopropylidene acetal, which can be prepared simply and in very high yield from L-arabinose (30). 

The starting material in this synthesis was L-arabinonic acid y-lactone 33, which was readily derived from L-arabinose by tritylation and bromine oxidation (77, 75). Conversion of 33 to 34 was carried out by the similar procedures with the preparation of 17 and 21. 

Besides the investigations treated so far concerning the synthesis of the taxane skeleton, some groups have also reported on the synthesis of particular building blocks. Synthesis of the taxol side chain 30 (57) has already been introduced in Section V,B. A Swedish group presented an enantiospecific synthesis of a functionalized ring A derivative 105,106). Starting from L-arabinose, 136 (Scheme 33) was made in 20 steps and could be transformed by three further steps into 137. 

Starting with the acetonide of L—glyceraldehyde, readily obtained from L-arabinose, Rokach and co-workers have reported another type of synthesis of LTA4 methyl ester, as outlined in Section 2, Scheme 2.14, and Scheme 3.30. ... 

Scheme 3.30. Synthesis of LTA4 from L-arabinose via D-mannitol via D-Glyceraldehyde.

The Merck Frosst synthesis (Scheme 4.9) is quite efficient and straightforward, starting from the masked dialdehyde synthon 25, which is derived from D-arabinose (see Scheme 2.20)." Homologation of aldehyde 26 with formylmethylenetriphenylphosphorane followed by a second Wittig reaction led to protected (12S)-HETC, 27. The same sequence, starting from L-arabinose, provided the recently discovered (12/ )-HETE. ... 

L-Nucleosides represent a class of nucleoside analogs with an excellent profile for antiviral activity combined with minimal host toxicity [105]. Synthesis of new L-nucleosides can use L-ribose and 2-deoxy-L-ribose as starting materials. Synthetic preparations of L-ribose from natural epimeric L-aldopentoses such as L-arabinose or L-xylose has recently been reviewed [106]. The simpler approach used an oxidation-reduction at C-2 from L-arabinose as depicted in Scheme 18 [107, 108]. 

Despite a considerable amount of recent work on reactions of vinyl silanes with various kinds of imines [48,49], scant attention has been paid to N-sulfonyl imi-nes in this area. A single study of a vinyl silane/N-sulfonyl imine reaction has been published by McIntosh and Weinreb in the context of an approach to the total synthesis of [1, 3]-dioxolophenanthrene structural types of Amaryllida-ceae alkaloids such as narciclasine (137), lycoricidine (138) and pancratistatin (139) [50]. The substrate used in this approach was vinyl silane aldehyde 140, prepared enantiomerically pure in a straightforward manner from L-arabinose (Scheme 26). The N-tosyl imine derived from this aldehyde could be generated in two different ways. The first involved combination of 140 with N-sulfinyl-p-toluenesulfonamide at 80 °C, followed by exposure of the imine to BF3 etherate at 0°C, leading to a single cyclization product 142 in 36% yield. The second procedure was to simply react aldehyde 140 with p-toluenesulfonamide and BF3 etherate (-78°C -rt) to afford a 9.5 1 mixture of 142 144 in -80% yield. It was pro-... 

Preparation. L-Mannose can be prepared by chain elongation methods, starting from L-arabinose. Both L-glucose and L-mannose are obtained. The nitromethane synthesis leads to a mixture of the nitroalditols that are separated by fractional crystallization and converted individually into the L-monosaccharides.130... 

Synthesis from i-arabinose Synthesis of l,4-dideoxy-l,4-imino-L-arabinitol (2) from methyl 3-L-arabinopyranoside has been reported (Scheme 4). The double inversion involving the introduction of the azide function at CA has been effected in... 

Synthesis from i-arabinose (-)-Anisomycin (1) was prepared from 2,3,5-tri-O-benzyl-(3-L-arabinofuranose (9) (Scheme 2). Compound 9 was treated with benzylamine... 

Synthesis from D-arabinose The lactams (35, 41 ,55 )-l-benzoyl- and 1-benzyl-oxycarbonyl-5-benzyloxymethyl-3,4-dibenzyloxypyrrolidin-2-ones (34 and 35), important intermediates for fragment 36, have been synthesized from D-arabinose (Scheme 4). Treatment of D-arabinose with methanol-HCl afforded the methyl arabinofuranoside. 

The key-step in the synthesis of the 4-thio-oc,P-D-ery/Aro-pentofuranose derivative 31 from L-arabinose was the well-established ring-closure 29 ->30 (see Vol. 29, Chapter 11, Ref. 14). A range of other 2-deoxy-D-ery/Aro-pentose dibenzyl-dithioacetals have been prepared and similarly cyclized to 2-deoxy-4-thio-D-eryt/jro-pentofuranose derivatives. A synthesis of 4-thio-l,4-anhydro-L-ribitol (32) from D-arabinitoI was based on the episulfonium ion rearrangement shown in Scheme The conformation of 4-thio-L-lyxono-1,4-lactone is referred to in Chapter 21. 

Routes have been developed for the synthesis of P-L-didehydrodideoxy-nucleosides in the purine series (60, B=Ade, Gua, Hypoxanthine), and the corresponding hydrogenated compounds, starting from either L-xylose or from D-glutamic acid. The L-nucleoside derivative 61 has been prepared by known methods from L-arabinose, and was converted to p-L-d4C (60, B=Cyt), via 62 as an intermediate. Transglycosylation of 61 with 5-fluorouracil was used to make the L-enantiomer of 5-fluoro-d4C (60, B=5-fluoro-Ura). Some of these L-enantiomers have potent anti-HIV and anti-HBV activity. 

A formal total synthesis of canadensolide 33 has been achieved starting from l-arabinose-derived epoxide 30, converted to lactone 31 by known methods (Vol. 26, p. 159). Conversion of 31 to known canadensolide intermediate 32 involved debenzylation then Wittig reaction (Scheme 5). ... 

Reaction of the conventional 3-ulose prepared from di-O-isopropyl-idene-D-glucofuranose with nitromethane provided both the alio- and gluco- isomers of the corresponding 3-G-nitromethyl sugars, which were then converted by standard procedures to 3-C-hydroxymethyl pentoses with D-ribo, D-xylo, and D-lyxo configurations the last of these proved to be enantiomeric with the monosaccharide isolated from Phase I Coxiella burnetii LPS, which was confirmed by a synthesis of the L-form (16) from L-arabinose using the 3-ulose (17) with lithio 1, 3-dithiane to introduce the required L-lyxo branch chain. 

The initial synthesis of Woodward and Singh was reported for patulin (348) in 1950 (297). However, the yield was low and the synthesis impractical. Two almost identical syntheses were reported independently by the groups of Stapleton in 1988 298, 299) and Riguera in 1989 300). Both commenced from L-arabinose, a readily available starting material from the chiral pool notwithstanding this, deprotection of a late-stage acetal intermediate to deliver the natural product was followed, perhaps unsurprisingly, by rapid racemization at the hemiacetal center. For details of these earlier syntheses, the reader is directed to our recent review (70) and the primary literature. 

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