Amino sugars L-daunosamine

Many DOHs, such as L-daunosamine, L-epivancosamine or L-ristosamine, contain an amino group at C3, which is introduced by an aminotransferase. The substrate for this reaction is the 3-keto sugar intermediate that arises as a consequence of the action of a 2,3-dehydratase. This transaminahon reaction has been biochemically characterized in the biosynthesis of L-epivancosamine [10]. Using a coupled reaction with EvaB (2,3-dehydratase) and EvaC (aminotransferase), with pyridoxal-5-phosphate (PEP) as a coenzyme and L-glutamate as a cosubstrate, they were able to show conversion of TDP-4-keto-2,6-dideoxyglucose into thymidine-5 -diphospho-3-amino-2,3,6-trideoxy-D-threo-hexopyranos-4-ulose. 

THP-Protected lactamide 459 has been used to synthesize (2R, 3 S)-2,3-(cyclohex-ylidenedioxy)butanal (462), a key intermediate for the synthesis of L-daunosamine, the amino sugar component of natural anthracycline antibiotics [85] (Scheme 66). The crucial reaction in the sequence is the yw-selective hydrosilane/fluoride reduction of ketone 460, which... 

Addition of acetone cyanohydrin to 606 in the presence of a catalytic amount of triethyl-amine affords cyanohydrin 607 as a mixture of isomers. Ketalization with cyclohexanone dimethyl acetal gives a near statistical mixture (45 55) of (2S, 3 S)-608 and (2R, 3 S)-609, which is separable by column chromatography (96% overall yield). Each isomer, with an optical purity greater than 95%, is a versatile intermediate, and they have been used in the synthesis of amino sugars A-benzoyl-L-acosamine (614) [189] (Scheme 85) and A-benzoyl-L-daunosamine (615) [190]. 

Several amino-sugar syntheses have used 3- and 4-carbon chiral starting materials. N-Benzoyl-L-daunosamine (30) has been constructed from the L-lactaldehyde ether (31) and methyl propiolate, the key step being intramolecular Michael addition of the (Z)-... 

Synthetic approaches to anthracycline antibiotics have been reviewed. Several papers report syntheses of daunorubicin analogues by the glycosidation of daunomycinone derivatives with amino-sugars glycosides of daunomycinone have been prepared from 3-epf-L-daunosamine, D-acosamine, D-daunosamine, D-ristosamine, and 3-ep(-D-daunosamine, and 4-demethoxy-9-deoxy-9-methyl... 

From chiral non-carbohydrates. - Several syntheses of amino-sugars from chiral non-carbohydrate starting materials have been reported. The a-L-daunosamine derivative 48 was obtained from L-aspartic acid via the known lactone 47, which was prepared in 2 steps. Key reactions were the anri-selective Grignard addition and syn-selective epoxidation (steps i and ii,... 

The preparations of C-3 branched amino-sugars of the 2,3,6-trideoxy-L-hexopyranose type related to daunosamine, for example 15 and 16, have been reported. (See Vol. 25, Chapter 14, ref. 16 and 49 and Vol. 24, Chapter 14, ref. 28 for related work). 

Similarly, 1,4-addition of azide to L-e yt/iro-hex-2-enopyranose provided a stereoselective route to the methyl and benzyl glycosides of L-acosamine (3-amino-2,3,6-trideoxy-L-am6ino-hexose). Inversion at C-4 yielded the L-daunosamine analogues, in the same manner as detailed above (ref. 23). Sugar aldehydes have been chain extended to unsaturated N-methylthiazolium salts such as (39) and (41), which were converted through Michael addition of benzylamine, to the 3-amino-2,3-dideoxy-0(-D-t/irco-pentopyranoside (40) and the 7-deoxy-6-e/7i-lincosamine derivative (42) as shown in Schemes 8 and 9, respectively. 3-epi-... 

The four isomeric methyl 2,4,6-trideoxy-4-C-methyl-4-trifluoroacetamido-L-hexopyranosides (L-ribo-. L-arabino. L-xylo. and L-lyxo-) have been synthesised from L-threonine. The synthesis of some branched-chain derivatives of daunosamine is discussed in Chapter 10. A new naturally occurring branched amino-sugar eremosamine is covered in Chapters 9 and 19. 

A number of synthesis of amino-sugars from chiral non-carbohydrate starting materials have been reported. A reaction sequence used previously to synthesize 2-amino-2-deoxy-D-ribose from 2,3-0-isopropylidene-D-glyceraldehyde (V0I.I6, p.92-3) has been improved K) achieve better stereoselectivity in the initial aldol condensation used to extend the chain by two carbon atoms. The synthesis of a 6,6,6-trifluoro-L-daunosamine derivative from 2,3-0-cyclohexylidene-D-glyceraldehyde is covered in Chapter 8, and of 2,5-dideoxy-2,5-imino-pentonic acids from tartaric acid in Chapter 16. 

All four diastereomeric 2-acetamido-2,4-dideoxy-D-hexopyranoses have been synthesized from the (5)-malic acid derived four-carbon aldehyde (37) (Scheme 11) as potential inhibitors of A/-acetylneuraminic acid synthase. The intermediates involved in the synthesis of the v-arabino-isomer (38) are shown in Scheme 11. The two vinyl Grignard addition reactions provided separable equimolar mixtures of C-3 epimers the analogous reactions applied to these yielded the three other isomeric amino-sugars. iV-Acyl-derivative (40) of L-daunosamine has been synthesized from the C-4-carboxy-branched intermediate (39), obtained by a stereoselective enolate-imine condensation (Scheme 12). The C-4-epimeric L-acosamine derivative was obtained by a similar sequence when compound (39) was first epimerized at C-4 (LiOH-HjO-MeOH). ... 

Following their recent synthesis of daunosamine (3-amino-2,3,6-trideoxy-L-/yxo-hexose) from methyl a-D-mannopyranoside (see Vol. 9, p. 62), Horton and Weckerle have described a related and high-yielding route to 3-amino-2,3,6-trideoxy-D-r/6o-hexose (110), the 5-epimer of daunosamine and the enantiomer of the naturally occurring amino-sugar ristosamine. " A closely related synthesis has afforded the ristosamine derivative (111), which is a key... 

Amino-sugar Derivatives.—3-Amino-2,3,6-trideoxy-L-/yxo-hexose (daunosamine, in a structural investigation of carminomycin), 4-amino-4-deoxy-D-glucose, 2-deoxystreptamine, and a 2,7-diamino-2,3,7-trideoxyoctadialdose (all components of apramycin), 5-0-benzoyl-a-D-arabinofuranosyIcarboxamide, ... 

In all cases, the sugar residues are attached to the 7-hydroxy group and this is the point of interest to carbohydrate chemistry. Until present, only the 3-amino-2,3,6-trideoxy sugars daunosamine (62) and rhodosamine (63) were found to be a-glycosi-dically linked to this position. The other saccharides 2-deoxy-L-fucose (64), L-cineru-... 

Anthracyclines isolated from stieptomyces show a 2,3,6-trideoxy-3-amino-L-/yxo-configurated sugar oc-attached to the aglycon. Therefore, the first interest centered on the synthesis of aminodeoxy sugars in the l-lyxo series, e.g., daunosamine [46-50]. Several new glycosides were prepared [51] in order to evaluate structure-activity relationships. 

Despite the high synthetic value of 1,2-amino alcohols, which are precursors of several therapeutically important sugar fragments, such as daunosamine, vancosamine and ristosamine, the osmylation of allylic amines or their derivatives often occurs with disappointing stereochemical results40 41. (Z)-Substituted allylic carbamates, however, show moderate syn selectivity105. A successful example is illustrated in the synthesis of l-benzyl-3,4-bis(benzyloxy)-5-(l,2-dihy-droxyethyl)pyrrolidine42. 

Deoxy functions in the sugar ring also increase the acid lability of the glycoside. Thus, was the methyl glycoside of daunosamine (2,3,6-trideoxy-3-amino-L-/yjt o-hexopyranose) efficiently transformed into the corresponding aryl thioglycoside by treatment with a thiol and BF3-etherate (O Scheme 23) [96]. The reaction was highly a-selective. 

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