Isopropylidene derivatives utilization

These compounds are rather rare. One of the first examples was presented by Helferich who prepared 3,5-anhydro-l,2-0-isopropylidene-Q -D-xylofuranose (82) from the appropriate 3,5-dimesyl derivative by treatment with ethanolic potassium hydroxide [1]. Another convenient approach to such derivatives utilized the reaction of l,2-0-isopropylidene-5-0-triflate-a-D-glucofuranos-S,6-lactone (79) with base (K2CO3) in methanol, which produced the corresponding L-ilactone ring with formation of the alcoholate at 3-OH, which substituted the triflate with inversion of the configuration at the C-5 atom (O Fig. 17). 

The model monosaccharides just listed were prepared from common precursor IV.l (Scheme 39), which was readily obtained by azidonitration of 3,4,6-tri-O-acetyl-D-galactal followed by deacetylation with sodium methoxide. Treatment of IV.l with acetone and toluene p-sulfonic acid monohydrate at room temperature led to predominant formation of the thermodynamically favored 3,4-O-isopropylidene (IV.2) in 61% yield while also producing 27% of the 4,6-O-isopropylidene derivative IV.3. The position of the isopropylidene IV.2 was verified by the use of NMR chemical shift analysis to confirm the position of the acetate group in the resultant acetylated adduct IV.4. Synthesis of the 4-O-sulfate derivative (IV.7) from IV.2 utilized a step that differentiated the 3-OH and 4-OH positions after benzylation and de-isopro-pylidination of IV.2, a selective methylation at the 3-OH of diol IV.5 was achieved via a tin procedure [91] to give methyl glycoside IV.6. Conversion of the azide into... 

The utility of these metallated 2-allyloxybenzimidazoles was demonstrated further through a synthesis of both d- and L-ribose (81CL1005). The allylcadmium derivative (551) reacted with 2,3-O-isopropylidene-D- and -L-glyceraldehyde to form the corresponding ribo-5-hexenitols (554) with high regio- and stereo-selectivity. Conversion of these products through their oxiranes to d- and L-ribose (557) required only a few additional manipulations as shown in Scheme 122. 

Another highly versatile building block derived from diacetone-glucose 54 is the 1,2-acetonide of 3-C-methyl-a-D-allose in its furanoid form 57, which has been utilized as the key compound in a convergent total synthesis of ACRL Toxin I (63). Its elaboration from 54 starts with a pyridinium dichromate / acetic anhydride oxidation (64), is followed by carbonyl olefination of the respective 3-ulose with methyl (triphenyl)phosphonium bromide and hydrogenation (— 55 56), and is completed by acid cleavage of the 5,6-isopropylidene group. This four-step process 54 -> 57, upon optimization of reaction conditions and workup procedure, allows an overall yield of 58 % (63), as compared to the 22 % obtained previously (65). 

Carbohydrates have a wide range of structural variations and these can be used to evaluate steric and stereoelectronic effects. This feature has been utilized in hetero-Diels-Alder cycloadditions. Thus, 2,3 5,6-di-0-isopropylidene-D-mannonolactone oxime, on reaction with tert-butyl hypochlorite, gives the corresponding 1-chloro-l-nitroso derivative 1 which is stable at 20°C for several days the configuration was assigned by X-ray analysis92-93. 

Synthesis by carbon-carbon bond formation between an acyclic sugar derivative and the benzothiazole ring system has also been utilized for the synthesis of these C-nucleosides. In one report, 2,3-O-isopropylidene-D-glyceraldehyde (61) was coupled with 2-trimethylsilylbenzothiazole to afford the A-nucleoside 185 as an intermediate, which underwent a 1,2-shift of the alditolyl chain to produce the C-nucleoside 186 (85TL5477) (Scheme 55). 

In most of the syntheses of ribonucleoside 5 -phosphates that we have described thus far, 2, 3 -0-isopropylidene or 2, 3 -0-benzylidene acetals of nucleosides have been employed as starting materials, to permit selective phosphorylation on 0-5. Such protecting groups, in common with acetals generally, are removable with dilute, aqueous, mineral acid. In some cases, however, the marked instability of the nucleotide derivative to acid precludes the use of these acetals, as the conditions required for removal of the acetal group are too strong. p-Substituted benzylidene derivatives (97) or (98)122.146,146 have shown utility, as deacetalation of these derivatives is readily accomplished under milder acidic conditions. A series of... 

Heterocyclic radicals with two ring heteroatoms, such as the reactions of tartaric acid derivatives, have been investigated39. Here, the isopropylidene-protected hydroxy groups define the cyclopentyl unit and one of the carboxy groups is utilized as the precursor functionality. Irradiation leads to a radical chain process, in which addition of alkenes to the intermediate radical occurs preferentially tram to the /Lcarboxy group. Only the /ram-isomer is observed in the H-NMR spectrum of the product in all cases and d.r. (trans/cis) 25 1 is estimated from HPLC measurements after degradation of the monoadducts to known compounds. 

Alternatively, methyl 6-0-benzoyl-2,3-0-isopropylidene-a-D-talopyranoside (57), derived from D-mannose, was utilized for the synthesis of swainsonine but in low yield (Scheme 6)P Mesylation of 57 followed by removal of the isopropylidene group with TEA, displacement of the mesylate group with azide ion, acetonation with DMP in acetone and... 

Cyclohexylidene and isopropylidene monoketals 47 and diketals 48, 49, and 50 are well-known protected myo-inositol derivatives (Scheme 3-1). Compounds 47 ketalized at the 1,2-cis-positions have been utilized conveniently for the synthesis of various inositol phosphates since 47 can be regioselectively functionalized and prepared in good yield by the conventional ketalization procedure and subsequent partial deprotection of the less stable trans-type ketals from the diketal mixture formed first in the reaction.22 Three diketals S have been also often employed for the synthesis of target inositol derivatives, because they have the following advantages (1) A trans vicinal hydroxyl moiety as well as the 1,2-... 

These reactions may be accompanied by unwanted side-reactions, such as oxidation of hypobromite to bromate or its reduction to bromide. The electro-oxidation of 2,3 4,6-di-0-isopropylidene- -L-sorbofuranose (14) is affected by a number of factors, and here the method of mathematical planning of so-called extreme experiments for obtaining the optimal conditions for electrolysis was utilized the conditions are concentration of sodium bromide, 107.7 g per liter concentration of nickel chloride, 0.71 g per liter concentration of 2,3 4,6-di-0-isopropylidene-L-sorbose, 86 g per liter the amount of electric current passed, 1.912 A-hr/g of the diisopropylidene acetal current density, 4.56 A.dm pH of the solution, 9.83 the expected yield, 91.9 0.7%. A more-detailed survey of the mechanism and kinetics of the electrochemical oxidation of monosaccharides and their derivatives, as well as of the effect of experimental conditions on the yields of aldonic acids and of the di-O-isopropylidene-xylo-hexulosonic acid (15) formed, has been given. ... 

A convenient synthesis of (— )- xo-brevicomin (87) utilizes a radical chain reaction of methyl vinyl ketone with (45, 5R)-4-benzyloxymethyl-5-iodomethyl-2,2-dimethyl-l,3-dioxo-lane (209), prepared by treating the (R,R)-tartaric acid derivative 141 with triphenylpho-sphonium iodide in the presence of imidazole. Adduct 215, after acidic hydrolysis of the isopropylidene protecting group, furnishes the bicyclic acetal 216. Subsequent debenzylation and tosylation followed by methylation with lithium dimethylcuprate provides 87 in an overall yield of 17% from (R,R)-tartaric acid. The optical purity of 87 corresponds to greater than 99% ee (Scheme 50). Carrying out a similar series of transformations with ( S,5)-tartaric acid leads to ( + )-exo-brevicomin (90) [78]. 

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