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. 

The conversion of azidoformates to fused-ring aziridines via the thermal generation of a nitrene has previously been reported. More recently, the photolytic conversion of a sugar-derived azidoformate has been used to prepare fused-ring aziridines <06JOC8059>. Photolysis of azidoformate 66 at 254 nm provides aziridine 67 in excellent yield. The resulting bicyclic aziridine was reduced to provide oxazolidinone 68 in 95% yield. Oxazolidinone 68 was subsequently converted to L-daunosamine. 

The legioselectivity of electrophilic additions of the C=C double bond in 7-oxabicyclo[2.2.1]hept-5-en-2-yl (7-oxanorbom-5-en-2-yl) derivatives depends on the nature of the substituents at C(2). The adducts so-obtained can be transformed into the corresponding 5,6-disubstituted 7-oxanorboman-2-ones, which can be mono-substituted at C(3) stereoselectively, giving products with the same stereochemical information as hexoses. Thus, optically pure 7-oxanorbom-5-en-2-yl derivatives can be viewed as "naked sugars" Applications to the total, asymmetric syntheses of L-daunosamine, 2-deoxy-L-fucose, D- and L-aUose, D- and L-talose, D- and L-ribose,... 

Hoping to improve or to shorten our total synthesis of L-daunosamine, we explored the following reactions with 112 and 113, the adducts of the racemic 7-oxanorbomene derivative 47 + 48 to PhSeCl and PhSCl, respectively. Saponification of 112 and 113, followed by treatment with formalin, afforded ketones 114 and 115, respectively. Treatment of with tributyltin hydride in toluene/benzene (AIBN 1 - 2%, 80 °C) gave the key intermediate ( )-I03 in 69 % yield. Under the same conditions, 115 was reduced to ( )-I03 in 40 - 45 % yield. Raney nickel reduction of 115 afforded ( )-103 in 50 % yield together with 40 % of ( )-7-oxabicyclo[2.2.1]heptan-2-one. However, we found the multistep procedure 32 100 101 102 103 easier to scale up. Several intermediates in our synthesis do not have to be isolated. For instance, transfomation of 32 into 102 can be carried out in the same pot in 94 % yield. 

The (2S,3R) methyldiols (4), generated in a multlenzymatlc process in fermenting baker s yeast from a-position unsaturated aromatic aldehydes, are used as starting materials in the synthesis of deoxy- and deoxy aminosugars of the L-series, including the L-daunosamine and L--vancosamine derivatives 17 and 34. 

Products 15 and 16 contain all of the chiral centers and the required functionalities for direct conversion into N-protected L— daunosamine (17) and L-ristosamine (18). This is achieved by N-pro-... 

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. 

An intramolecular [3 + 2] nitrone cycloaddition reaction has been employed in the chiral assembly of L-acosamine and L-daunosamine (81JA3956). Heating the masked aldehyde (503) with the oxalate salt of (-)-(S)-7V-hydroxy-a-methylbenzenemethanamine generated a nitrone which underwent intramolecular cycloaddition to give an 82 18 mixture of diastereomers (504) and (505). The N—O bond of the major isomer was cleaved with zinc... 

Loway et al. have prepared an aziridine by the application of photoinduced intramolecular aziridination the aziridine was subsequently converted to L-daunosamine glycoside (Scheme 4.65) [98]. 

Mendlik, M.T., Tao, P., Hadad, C.M., Coleman, R.S., and Lowary, T.L. (2006) Synthesis of L-daunosamine and L-ristosamine glycosides via photo-induced aziridination. Conversion to thioglycosides for use in glycosylation reactions. Journal of Organic Chemistry, 71 (21), 8059-8070. 

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