Ristosamine

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. 

Heyns et al. [53] started with di-O-acetyl-L-rhamnal (28) which after reaction with sodium azide in the presence of boron trifluoride etherate as Lewis catalyst gave again the four products 79-82 (R=Ac). Subsequent quenching with NIS and the aglycone led to ristosamine and acosamine glycosides 86 and 87. 

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. 

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. 

Ethyl lactate has also been used as a chiral fragment for numerous other studies. Included are synthetic efforts relating to salenomycin, (-)-biopterin, (+)-polyoxamic acid, jaspamide, the enantiomeric 2-pentanols, pumilitoxin B, D-ristosamine, protomycinolide IV, and tirandamycin. ... 

Ono, M, Saotome, C, Akita, H, Total syntheses of A-fluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine, and A-benzoyl-D-ristosamine from an achiral precursor, methyl sorbate. Heterocycles, 45, 1257-1261, 1997. 

Actaplanins, A-4696 Kamoran. Complex of glycopeptide antibiotics produced by Actinoplanes missouri-ensis. Six actaplanins (A, B, B2. Uv C,. G) have been isolated and characterized as having a central peptide core with the amino sugar ristosamine and up to four neutral sugars attached. Isoln R. L. Hamil) ei at.. Get. pat. 2,209,018... 

In the synthesis of D-ristosamine (388), all that is required is inversion of the 5-methyl group of lactone 393. This is readily accomplished by opening the lactone ring with potassium superoxide, acidification to pH 4, and a Mitsunobu reaction. Once again, reduction of the lactone to lactol (71% yield) followed by Wittig reaction and acid hydrolysis (HCl, methanol) affords the desired sugar 388, isolated as the diacetate in 23% yield [124]. 

Derivatives of three related amino sugars, daunosamine (386), the carbohydrate component of adriamycin and daunorubicin, acosamine, a C-4 epimer of daunosamine, and ristosamine, the carbohydrate component of ristomycin, have been prepared from lactaldehyde 689. All three syntheses begin with the same first step, the addition of methyl propiolate to 689. 

The synthesis of A-benzoyl L-ristosamine (729) parallels that of 615 (Scheme 95) on the basis of anti-111 instead of syn-113 [209]. 

The butyrolactone skeleton of precursors for the sugar component of the glycoside antibiotics L-ristosamine and L-daunosamine can be readily assembled by a nitroaldol reaction of 3-nitropropionate (553) with 831, followed by lactonization [229] (Scheme 111). The initial condensation gives 832 in only moderate yield, probably due to the reversible nature of the nitroaldol reaction. If the crude product is treated with pyridinium tosylate, a mixture of lactones 833 and 834 is produced with concomitant loss of the THP group. The ratio of lactones is dependent on the base used in the nitroaldol condensation. Use of potassium tert-butoxide affords a 2 1 mixture of 833 and 834. The ratio can be increased to 5 1 with KF 2H20/tetrabutylammonium chloride, but the overall yield decreases. 

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. 

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