Trideoxy hexoses

To overcome problems of poor acceptor substrate acceptance, high concentrations of aldehyde substrates are required to obtain synthetically useful product yields. Unfortunately, DERA shows rather poor resistance to such high aldehyde concentrations, especially toward CIAA, resulting in rapid, irreversible inactivation of the enzyme. Therefore, the organic synthesis of (3R,5S)-6-chloro-2,4,6-trideoxy-hexapyranoside 1 requires very high amounts of DERA. Thus, despite the synthetic usefulness of DERA to produce chiral intermediates for statin side chains, the large-scale application is seriously hampered by its poor stability at industrially relevant aldehyde concentrations. The production capacity for such 2,4,6-trideoxy-hexoses of wild-type E. coli DERA is rather low [15]. 

Deoxygenation at C-2, C-3, and C-4 of 6-deoxyhexoses and substitution of one of the remaining OH-groups by amino, di-V-methyl, O-methyl, and C-methyl groups creates significant structural diversity. In secondary metabolites, such as the polyketide antibiotics, 2,6-dideoxy- and 2,3,6-trideoxy-hexoses, contribute to the antibiotic and antitumor activity. 

By analogy with the synthesis of /V-acetylneuraminic acid,63 di-A-acetyl derivatives of 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids could be obtained by condensation of 2,4-diacetamido-2,4,6-trideoxyhexoses with oxaloacetic acid under basic conditions. Four chiral centers in the C precursors, C-2 C-5, correspond to the centers C-5-C-8 in the target C9 products, and the fifth asymmetric center, C-4, is formed upon condensation. At present, derivatives of twelve 2,4-diamino-2,4,6-trideoxy-hexoses with the d-gluco, o-manno, L-allo, r>-galacto, D- and L-altro, D- and L-talo, D- and l-gulo, D- and L-ido configurations have been prepared by multistep chemical syntheses.11,17,18,64,65... 

Figure 9 Glycan structures that have been identified on pilin from different Neisseria species and strains. Nm, N. meningitidis-, Ng, N. gonorrhoeae-, DATDH, diacetamido-trideoxy-hexose.

There has been substantial activity in the synthesis of 3-amino-2,3,6-trideoxy-hexoses and their di-A-methyl derivatives as a result of their wide occurrence in antibiotics. In a paper of substantial proportions, Bartner et alP have synthesized by standard reactions all four possible methyl 2,3,6-dideoxy-3-dimethylamino-a-D-hexopyranosides (and some /3-anomers) as well as the corresponding L-ribo isomer (L-megosaminide). Syntheses have been reported for D-ristosamine (3-amino-2,3,6-trideoxy-D-rz7 o-hexose) from methyl 2-deoxy-D-amfcmo-hexo-pyranoside and of the isomeric 3-amino-2,3,6-trideoxy-L-Jcy/o-hexose (1) from methyl 2,6-dideoxy-L- mZ>mo-hexopyranoside, using standard sequences involving azidej displacement of sulphonate esters for introducing the nitrogen. 

Syntheses of 3-nltro-2,3,6-trideoxy-hexoses have been covered in a 27... 

There has been a continuing interest in syntheses of 3-amino-2,3,6-trideoxy-hexoses such as daunosamine (9), acosamine (10), etc. In an interesting paper by Fronza et the two sugars have been synthesized from the non-carbohydrate compound (11), which was obtained in 25-30% yield from the incubation of cinnamaldehyde v th acetaldehyde in the presence of bakers yeast (Scheme 2). The crucial amino-lactone (12) was also synthesized from L-threonine. The same authors have also completed their synthesis of A-benzoyl-L-ristosamine (3-benzamido-2,3,6-trideoxy-L /6o-hexose) from 3-benzamido-2,3,6-trideoxy-L-xy/o-hexono-1,5-lactone (Vol. 13, p. 79). An alternative synthesis of methyl A-acetyl-a-L-acosaminide (13) has been described by reduction of the appropriate acetylated oxime by diborane. The thioglycoside (14) was also prepared. ... 

The lactone (6), prepared by a stereocontrolled aldol condensation followed by resolution of the enantiomers, has been converted into methyl cladinoside (7). Some branched 5-amino-2,5,6-trideoxy-hexose derivatives (eg (8)) have been prepared from a l,5-dideo3ty-pent 2-ulose derivative. Treatment of levoglucosenone with a basic excess of nitromethane has afforded products (9) and (10), whereas... 

Amino-2,3,6-trideoxy-L-hexoses fA-D in Scheme 3 9 occur naturally, forming the gly-cone part of anthracychnone andbiodcs, important in and-tiimor treatment ... 

Evernitrose 2,3,6-Trideoxy-3-C-methyl-4-0-methyl- 3-nitro-L-aralb/no-hexose... 

C51H83IN2016-2 H20 2,3,6-Trideoxy-3-(dimethylamino)-4-0-(4-iodobenzoyl)-L-rtho-hexose, dihydrate [4-0-(4-iodobenzoyl)megalomicin A, dihydrate] IBMEGC10 43 273... 

Attempted direct extension of the two foregoing methodologies to synthesis of the 3-C-methyl analogs of 17, 18, 23 and 24 starting from the diastereoisomeric methyl ketones 10 and 12 was ineffective, as ammonia does not add across the triply substituted double bond of the 3-C-methyl analogs of the esters 19 and 20. However, the phenyl-sulfenimines 25 and 26 add allylmagnesium bromide and diallylzinc with different stereochemistry (8), so that it is possible to have eventual access to the four configurational isomers of 3-amino-2,3,6-trideoxy--3-C-methyl-3-L-hexose. 

D. Horton and W. Weckerle, Synthesis of 3-amino-2,3,6-trideoxy-D-r/ho-hexose hydrochloride, Carbohydr. Res., 46 (1976) 227-235. 

Dideoxy-3-C-methyl-4-(methylamino)-D-altrose (22) 3-Amino-2,3,6-trideoxy-3-C-methyl-L-/j/xo-hexose (23)... 

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