L-Daunosamine synthesis

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. 

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. 

The synthesis of L-daunosamine began with the condensation of trans-crotonaldehyde (56) with dibenzylhydrazine (Scheme 17). Sharpless asymmetric dihydroxylation of the resulting ( )-a, (3-unsaturated hydrazone 57 afforded the syn-diol 58 (70% yield, 89% ee by HPLC), and silylation with chlorodimethyl-vinylsilane then provided the radical cyclization precursor 59 in 98% yield. In the key step, exposure to thiyl radicals generated from PhSH and AIBN led to radical cyclization of dibenzylhydrazone 59. The unstable cyclic intermediate was then directly treated with fluoride to afford vinyl adduct 60 in 77% yield (dr 91 9, H NMR). In control experiments with corresponding monosilyl derivatives, the (3-O-silyl... 

Because it is often possible to control the stereochemical orientation of substituents on a cyclic array, Baeyer-Villiger cleavages of substituted cyclic ketones have been used extensively in the stereocon-trolled syntheses of substituted carbon chains. An asymmetric synthesis of L-daunosamine intermediate (30) from a noncarbohydrate precursor employed the cyclopentenol (28), prepared in optically pure form (95% ee) from 2-methylcyclopentadiene using asymmetric hydroboration (Scheme 8). Stereoselective epoxidation, conversion to Ae ketone and regioselective Baeyer-Villiger oxidation afforded lactone (29). 

Ethyl (5 )-lactate has been the primary source of chirality in several syntheses of aminodeoxycarbohydrates. The derivative 91 of 2-amino-2-deoxy-L-lyxonic acid is the major product of condensation of 2-0-benzyl L-lactaldehyde with the silyl ketene acetal 90. The derived ester 91 can be converted into lactone 92 (Scheme 13.38) [79], an intermediate for the synthesis of L-daunosamine and L-vancosamine. 

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]. 

Banfi, L, Cardani, S, Potenza, D, Scholastico, C, Stereoselective synthesis of t-butyl 2-amino-2,5-dideoxy-L-/yxo-pentanoate formal synthesis of L-daunosamine, Tetrahedron, 43, 2317-2322, 1987. 

Danishefsky diene, 619 L-Daunosamine, 597 total synthesis, 601 Deoxy sugars, 151 Deoxygenation, 151... 

A. Synthesis of L-daunosamine B. Synthesis of a-methyl mannofuranoside and p-methyl 601... 

In the presence of ZnBr2, nonchelation controlled addition of lithiated MN-dimethylacetamide to 2,3-O-cyclohexylidene-4-deoxy-i.-threose benzylimine proceeds in high stereoselectivity. The absence of the Lewis acid results in a slight preference for the other isomer. The product is used in the synthesis of l-daunosamine (equation 49). ... 

The most efficient synthesis of L-daunosamine is that of Horton and Weckerle it provides (as its hydrochloride) in 40% yield from readily available methyl a-D-mannopyranoslde (95). Thus butyllithium-induced cleavage of the dibenzylidene acetal 9 affords (91%), the oxime... 

In other work, methoxymercuration has been applied in the first stage of the synthesis of L-daunosamine (14). Methoxymercuration of L-rhamnal (15), followed by reduction of the carbon-mercury bond with potassium borohydride, afforded30 a route to methyl 2,6-dideoxy-a-L-arafcmo-hexopyranoside (16), the enantiomorph of methyl chromoside C. 

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