Ristosamine synthesis

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. 

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]. 

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]. 

Oxidation of alcohol 100 to aldehyde 103 with PCC followed by treatment of the unpurified aldehyde with (carbethoxyethylidene)triphenylphosphorane affords a poor yield of a mixture of diastereomeric olefins 104 together with substantial amounts of unreacted 100. This may suggest that PCC oxidation is not the preferred method for optimal oxidation of 100 to 103. Nevertheless, the diastereomeric mixture 104 has been exploited in the synthesis of A -ben-zoyl-2,3,6-trideoxy-3-amino-L-x> /o-hexapyranose (105) [42]. In three steps, 105 is converted to AAbenzoyl-L-ristosamine (106), the aminodeoxy sugar component of the antibiotic risto-mycin [43] (Scheme 24). 

H. H. Baer and A. Jaworska-Sobiesiak, Synthesis of (S)-2-fluoro-L-daunosamine and (5)-2-fiuoro-D-ristosamine, Carbohydr. Res., 140 (1985) 201-214. 

There has been substantial activity in the synthesis of 3-amino-2,3,6-trideoxy-hexoses and their di-A-methyl derivatives as a result of their wide occurrence in antibiotics. In a paper of substantial proportions, Bartner et alP have synthesized by standard reactions all four possible methyl 2,3,6-dideoxy-3-dimethylamino-a-D-hexopyranosides (and some /3-anomers) as well as the corresponding L-ribo isomer (L-megosaminide). Syntheses have been reported for D-ristosamine (3-amino-2,3,6-trideoxy-D-rz7 o-hexose) from methyl 2-deoxy-D-amfcmo-hexo-pyranoside and of the isomeric 3-amino-2,3,6-trideoxy-L-Jcy/o-hexose (1) from methyl 2,6-dideoxy-L- mZ>mo-hexopyranoside, using standard sequences involving azidej displacement of sulphonate esters for introducing the nitrogen. 

From Chiral Non-carbohydrates - A section on amino-sugars has been included in a review of the synthesis of monosaccharides from non-carbohydrate sources. L-Ristosamine 42 was synthesized by addition of the Cs-synthon 40 (which contains a masked aldehyde function that can be readily demasked by mild acid hydrolysis) to the L-lactaldehyde derivative 41 (Scheme 11). The TBSOP adduct 43 (Vol.27, p.ll4), derived from 2,3-< -isopropylidene-D-glycer-aldehyde, has been converted into 3-amino-3-deoxy-D-altrose 46 by a route involving cis-hydroxylation of its unsaturated lactam moiety and periodate cleavage between C-6 and C-7 of the derived heptitol derivative 45 as key steps (Scheme 12). 3-Amino-3-deoxy-L-allose was obtained by converting 43 to its C-3... 

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. ... 

The full paper on the synthesis of D-forosamine(4-dimethylamino-2,3,4,6-tetradeoxy-D- ryz/rro-hexose) from (2) has also appeared. Standard transformations have been used in a synthesis of derivatives of L-ristosamine (3-amino-2,3,6-trideoxy-L-ara6i/ >-hexose), and its C-4 epimer, from l-rhamnal. Non-carbohydrate precursors have been utilized for the synthesis of the derivative (3) of racemic daunosamine (3-amino-2,3,6-trideoxy-/j xo-hexose), in a sequence involving allylic amination of a hexenal derivative using a selenium-chloramine T reagent, followed by m-hydroxylation which led to a crystalline product with the required lyxo configuration (Scheme 2). ... 

Molecular orbital calculations have been carried out on 2-fluoro- and 2-chloro-tetrahydropyrans as models for examining the anomeric effect in gtycosyl halides. The calculated population of the axial conformer decreased as the solvent polarity increased, which indicated a consequent decrease in the anomeric effect.The synthesis of a series of 2-(perfluoroall yl) ethyl glycosides is mentioned in Chapter 3, and some 3 -fluorinated ribonucleosides are covered in Chapter 20. The syntheses of 2-fluoro-L-daunosaniine and 2-fluoro-D-ristosamine are discussed in Chapter 9, while 2 -fluorocarminontydn is described in Chapter 19, and some fluorinated 2-deoxy KDO analogues are covered in Chapter 16. 

Following their recent synthesis of daunosamine (3-amino-2,3,6-trideoxy-L-/yxo-hexose) from methyl a-D-mannopyranoside (see Vol. 9, p. 62), Horton and Weckerle have described a related and high-yielding route to 3-amino-2,3,6-trideoxy-D-r/6o-hexose (110), the 5-epimer of daunosamine and the enantiomer of the naturally occurring amino-sugar ristosamine. " A closely related synthesis has afforded the ristosamine derivative (111), which is a key... 

Syntheses of amino-sugar glycosides and disaccharides, including chromogenic substrates for A -acetyl-p-D-glucosaminidase, are covered in Chapter 3. Synthesis of protected 2-amino-2-deoxy-glycosyl azides is covered in Chapter 10. 2,3,6-Trideoxy-5-0-(4-nitrobenzoyl)-3-trifluoroacetamido-L-riho-hexofuranosyl bromide, a furanoid ristosamine derivative, was synthesized from L-rhamnal via intermediates reported previously (Vol.25, p.253) to effect glycosylations. ... 

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