Daunosamine synthesis

A number of papers have described routes from carbohydrates to hydroxyl-ated aminoacids. The azide (78), derived from L-arabinose, was converted, via the 4,5-azirldine. into polyoxamlc acid (79), a constituent of the polyoxin class of antibiotics.The aminosugar derivative (80), an intermediate in Horton s daunosamine synthesis, can be transformed (Scheme 19) into (81), and hence into the lactone (82), which is a protected form of the hydrojqrlated 3-amino-acid found in the antiulcerogenic compound AI-77-B the regiochemistry in the reductive opening of the acetal is unexpected. 72 o-Glucose has been converted... 

Rather early it became evident that the NIS glycosy-lation of an axial 4-OH group, even in a blociced 3-amino sugar li)ce daunosamine or rhodosamine, could not be effected efficiently 6 ). Consequently, a trisaccharide synthesis was required that allowed facile inversion of a precursor structure subsequent to the advantageous use of NIS glycosylation steps. 

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. 

A. C. Richardson, The synthesis of D-daunosamine N-benzoate, /. Chem. Soc. Chem. Commun. (1965)... 

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. 

H. W. Pauls and B. Fraser-Reid, Stereocontrolled routes to cis-hydroxyamino sugars, Part VII synthesis of daunosamine and ristosamine, Carbohydr. Res., 150 (1986) 111-119. 

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... 

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