Achmatowicz approach

In the original Achmatowicz approach, the (racemic) furfuryl carbinol is oxidized with bromine in the presence of methanol under weakly basic conditions to provide the Clauson-... 

The synthesis of higher carbon sugars by an Achmatowicz approach was realized by Indian scientists [96]. This example should have been presented in O Sect. 2 (describing general methods) however, since it illustrates a concise approach to the synthesis of unsaturated sugars using different methods it is included here. 

In contrast, using the Achmatowicz approach, only pyranoses were formed. This approach began with the Sharpless dihydroxylation of achiral vinylfuran 5.6 to install the C-5 D-absolute stereochemistry as in 5.7. The fiirfuryl alcohol 5.7 can be stereoselectively converted into the a-spiroketal 5.8 by Achmatowicz oxidation, spiroketalization, Luche reduction and TBS-protection. Upjohn dihydroxylation of 5.8 was used to prepare both the manno-S.9 and allo-SAl isomers, with the manno-isomer being formed as the major isomer (4 1) (14). 

The de novo Achmatowicz approach to hexoses has great potential for preparing various d- and t-sugars because the starting 6-t-butoxycarboxy-2H-pyran-3(6H)-ones (10 and 13) can easily be prepared from optically pure fiirfiiryl alcohols 12 (either R) or (S) enantiomer) [16] by a one or two step procedure (Scheme 1.3). Depending on the temperature of the second step, the t-butylcarbonate acylation... 

An important aspect of this approach is the ease with which fiiran alcohols can be prepared in enantiomerically pure form from achiral furans (e.g., 7 and 8). There are many asymmetric approaches to prepare furan alcohols. The two most prevalent approaches are (i) the Noyori reduction ofacylfurans (8 to 12) and (ii) the Sharpless dihydroxylation of vinyUurans (7 to 12) (Scheme 1.4) [17]. Both routes are readily adapted to 100 g scale synthesis and use readily available reagents. While the Sharpless route is most amenable to the synthesis of hexoses with a C-6 hydroxy group, the Noyori route distinguishes itself in its flexibility to virtually any substitution at the C-6 position. Herein, we review the development of the Achmatowicz approach to the de novo synthesis of carbohydrates, with apphcation to oligosaccharide assembly and medicinal chemistry studies. 

Scheme 1.5 De novo asymmetric Achmatowicz approach to t-monno-hexoses.

Our de novo asymmetric Achmatowicz approach was also applied to the synthesis of the glycosylated tyrosine portion of the antibiotic mannopeptimycin-s [36]. Specifically, we targeted a protected tyrosine with bis-manno-l,4-disaccharide with an isovalerate at the C-4 position. This approach was used to prepare the amino acid portion of the natural product 62 as well as the disaccharide portion in the unnatural L/L-configuration. The linear route involved the application of the iterative bis-glycosylation, acylation, and bis-dihydroxylation of protected tyrosine in only six steps (Scheme 1.11). 

The de novo Achmatowicz approach to the tris-rhamno portion of the anthrax tetrasaccharide began with the synthesis of disaccharide 115 from pyranone ent-44 and benzyl alcohol (Scheme 1.21). After glycosylation and postglycosylation transformations to install the rhamno-stereochemistry (ent-44 to 111), the 1,2-traus-diol of 111 was then protected with the Ley-spiroketal to provide monosaccharide 112 with a free C-2 hydroxyl group. After a similar three-step glycosylation (112 and 113) and postglycosylation sequence, 113 was converted into disaccharide 114, which in a one-pot ortho-ester protocol was protected to give disaccharide 115 with a free C-3 alcohol. 

O. Achmatowicz, An approach to the synthesis of higher-carbon sugars, in Organic Synthesis, Today and Tomorrow, B. M. Trost and C. R. Hutchinson, eds., Pergamon Press, Oxford, 1981, p. 307. 

Scheme 1.3 Schreiber s approach to pre-encoding skeletal information using the Achmatowicz reaction. Reagents and conditions. (1) A -bromosuccini-mide, NaHCOj, NaOAc, THF-HjO (4 1), rt, 1 h PPTS, CH2CI2, 40-45°C, 20h, 11a 33% (64%) 11b 35% (86%) 11c 81% (>90%). Numbers in parentheses are purities determined by LC-MS.

P-DL-er>t/iro-pentopyranosid-4-ulose and l-0-benzoyl-P-DL-er>t/iro-pentopyran-os-4-ulose, respectively, which were converted into DL-ribose derivatives by reduction of their isopropylidene derivatives. In further work on the total synthesis of monosaccharides, Achmatowicz s group has synthesized methyl a-L- and a-i> glucopyranosides from methyl (R)- and (S)-(2-furyl)glycolates, respectively, by the reactions outlined in Scheme 1 for the D-series. Related approaches were used... 

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