A-Benzoyl-L-daunosamine

Another route to A-benzoyl-L-daunosamine is the 1,3-addition of silyl ketene acetal 4 to the chiral nitrone 5, accompanied by a silyl group transfer in acetonitrile under mild conditions. This reaction provides high stereoselectivity in favor of the tw -product 621. 

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]. 

An identical series of reactions using the minor isomer 608 furnishes A-benzoyl-L-daunosamine (615) in comparable yield. 

TiCU-mediated additions of silyl ketene acetal (98) to chiral imines (99) and (100) (R = Et, Pr", Bu", Bu ) are described in equations (33) and (34) good diastereoisomeric ratios were obtained using imines (100), derived from (S)-valine methyl ester, which form with TiCU the chelated complex (101). Znh-catalyzed additions of acetate-derived silyl ketene acetals to chiral a. -dialkoxy nitrones (102 R = H) were reported to proceed with good yield (86-100%) and high diastereofacial selectivity ca, 90 10) in favor of the anti isomer (103 R = H, R = CHPh , R = Bu ) or of the syn isomer (104 R = H, R = CH2Ph, R- = Me) depending on the steric hindrance of R and (Scheme 8). Addition to nitrone (102 R = Me) gave the anti isomer (103 R Me, R = CHMePh, R = Me) in quantitative yield and 100% diastereofacial selectivity. This material was further elaborated to A/-benzoyl-L-daunosamine (Scheme S). ... 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

In the synthesis of V-benzoyl-L-daunosamine (615) (Scheme 95), addition proceeds according to the Felkin model to give a 5 1 mixture of the anti-712 and syn-713 isomers. Since the minor product 713 possesses the desired stereochemistry, the mixture is oxidized to ketone 714 and the carbonyl is then reduced with L- Selectride to regenerate the syn isomer 713 (syn anti ratio >12 1). 

Lactaldehyde 929 has been used in a synthesis of JV-benzoyl L-daunosamine (615), a derivative of the carbohydrate component of adriamycin [175] (Scheme 125). Two important reactions in the synthetic pathway are the conversions 929—> 930 and 933 935. The nitroaldol reaction of 929 with methyl 3-nitropropionate leads to a mixture of three isomeric adducts from which the major diastereomer 930 is separated by crystallization and chromatography. After lactonization and functional group adjustment, the hydroxyl stereocenter of the D-ribo lactone 933 must be inverted to match the correct configuration of the target sugar. This is accomplished by conversion to the mesylate 934 and subsequent treatment with sodium benzoate. The resulting h4yxo lactone 935 is then carried on to 615 as shown in Scheme 95 (Section 1.5.6.1). 

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. ... 

Reduction of the nitro group and benzoylation affords a mixture of benzamides 558 and 719 that is separable by column chromatography. These benzamides serve as precursors to L-ristosamine and L-daunosamine respectively. 

Although most synthetic approaches to L-daunosamine start from carbohydrate precursors, some routes employ chiral synthons derived from other sources. The aldehydes 213 obtained through reaction of cinnamaldehyde with acetaldehyde in the presence of Baker s yeast followed by ozonolysis [157], and 214 obtained from L-tartaric acid [158-160] have been utilised in the synthesis of daunosamine derivatives, and protected daunosamines and acosamines have been synthesised from (synthetic approaches have employed lactic acid as a chiral starting material [162, 163] and the (S)-amine 215 obtained by resolution has been converted to V-benzoyl daunosamine together with its 3-epimer [164]. Wovkulich and Uskokovic have... 

As an alternative to the above approach, intramolecular Michael additions of -carbamates occupying allylic and homoallyllc positions relative to a,B-unsaturated esters as a means of diastereo-selective amination of acyclic systems appears to have much potential1, 2-syn-Cyclisations of both erythro- and threo-y -carbamoyloxy-a,B-unsaturated ester derivatives afforded trans-isoxazolidines which could be transformed into N-acetyl-D,L-acosa-mine" and N-benzoyl-D,L-3-epl-daunosamine respectively. However, although the expected 1,3-syn cyclisation was observed for the erythro-6-0-carbamoyloxy-a,B-ester, this leading to the synthe-sis of N -benzoyl-D, -ristosamine, the corresponding threo-... 

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, ... 

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