Isopropylidene derivatives

Pyrazolones show a great variety of reactions with carbonyl compounds (B-76MI40402). For instance, antipyrine is 4-hydroxymethylated by formaldehyde and it also undergoes the Mannich reaction. Tautomerizable 2-pyrazolin-5-ones react with aldehydes to yield compound (324) and with acetone to form 4-isopropylidene derivatives or dimers (Scheme 8 Section 4.02.1.4.10). 

Dithiols, like diols, have been protected as 5,5 -methylene, 5,5 -isopropylidene, and 5,5 -benzylidene derivatives, formed by reaction of the dithiol with formaldehyde, acetone, or benzaldehyde, respectively. The methylene and benzylidene derivatives are cleaved by reduction with sodium/ammonia. The isopropylidene and benzylidene derivatives are cleaved by mercury(II) chloride with sodium/ ammonia the isopropylidene derivative is converted to a monothio ether, HSCHR-CHRSCHMe2- ... 

Proceeding from 5 -0-acetylazauridine (80), a mixture of 2 - and 3 -monophosphates (81, 82) was prepared by phosphorylation with polyphosphoric acid, and these were converted into the 2, 3 -cyclic phosphate (83). From the 2, 3 -0-isopropylidene derivative of 3-methyl-6-azauridine the 5 -phosphate was prepared by treatment with cyanoethylphosphate and the corresponding diphosphate from its morpholidate through the action of phosphoric acid. ° Furthermore, a diribonucleoside phosphate (85) with a natural 3 -5 internucleotide linkage was prepared from 6-azauridine, The starting material for the preparation of such derivatives was 5 -0-acetyl-2 -0 -tetrahydro-pyranyluridine-3 -phosphate (84) which was condensed with di-G-acetylazauridine (86) or with 2b3 -0-isopropylidene-6-azauridine (76) with the aid of dicyclohexylcarbodiimide. ... 

Other substituents Alkjd of p-dialkylamino group Mp (°C) of isopropylidene derivative Mp C C) of benzylidene derivative... 

Substitution of a phenyl residue in the 4-position of the selenazole ring causes only a minor alteration in the position of the absorption maximum. By contrast, the benzylidene compounds are markedly bathochromically shifted compared to the isopropylidene derivatives. Thus the absorption is caused by the whole of the conjugated system, which can be compared to that found in amino derivatives of... 

Other substituents Bis-isopropylidene derivative, mp ( C) Bis-benzylidene derivative, mp ( C)... 

O-isopropylidene derivative (10) was then phosphorylated with phosphorous oxychloride to form the phosphate ester (11) from which the protecting groups were removed by mild acid hydrolysis. The 3-phos-phate (15) was obtained by phosphorylating the 4,6-benzylidene derivative (13) of the same glycoside with phosphorus oxychloride, followed by hydrolytic removal of the protecting groups, from the ester (14) thus obtained. 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

The mass spectra of methyl 3-deoxy-p-v-tkreo-pentopyrano-side, methyl 4-deoxy-j3-T>-thieo-pentopyranoside, and 5-deoxy-fi-D-xylo-furanoside are discussed and compared fragmentation paths are sufficiently different to allow identification on the basis of their mass spectra. On the other hand, the mass spectra of methyl 2- and 3-deoxy-5-O-methyl-f3-i>-erythro-pentofuranosides do not exhibit fragmentation differences. The mass spectra of 3-deoxy-l,2 5,6-di-O-isopropylidene -d-xylo - hexofuranose, 5- deoxy -1,2-0-isopropylidene-D-xy o-hexofuranose, and 6-deoxy-l,2-0-iso-propylidene-D-glucofuranose show prominent differences, even between the 5- and 6-deoxy isomers. The interpretation of the spectra was aided by metastable-ion peaks, mass spectra of DzO-exchanged analogs, and the mass spectrum of an O-isopropylidene derivative prepared with acetone-d6. 

O-Isopropylidene derivatives of carbohydrates form structural isomers from carbohydrates which themselves are epimers. Since structural isomers often fragment differently whereas epimers do not, mass spectra of these derivatives may permit interpretation in terms of stereochemistry. Although molecular-ion peaks are not observed, the molecular weight can be determined readily from a relatively intense M-CH/ peak, resulting from loss of a methyl radical from a 1, 3-dioxolane ring (12). 

Paulsen and his coworkers first synthesized (-f-)-203 from L-quebrachitol (286) by a 21-step reaction as follows. The di-O-isopropylidene derivative was oxidized to the ketone (287), and then epoxidized with dimethyl sulfox-onium-methylide to give 288, which was subjected to benzoylation, mesyla-tion, and demethylation, followed by benzylation, to afford 289. Introduction of unsaturation was accomplished by epoxidation of 289 with sodium methoxide to 290 and 291, and deoxygenation to 292. The azido group was introduced with azobis(dicarboxylate) to give 293, which was hydrogeno-lyzed, followed by deprotection to afford 203. 

The effect of lactone ring-size on the inhibition was studied, for N-acetyl-)3-D-glucosaminidase from bovine epididymis, with lactones and lactone derivatives unable to undeigo ring-isomerization, by Pokomy and co-workers. From a comparison of Kj values for 2-acetamido-2-deoxy-D-glu-cono-1,5-lactone (0.45 nM) with the 1,4-lactone (4.5 fiM) and of Kj for the methyl ) -furanoside with that for the pyranose (4 mM), it was concluded that the 1,4-lactone has an 10-fold lower inhibitory potency than the 1,5-lactone. The weak inhibition by the 5,6-O-isopropylidene derivative of the... 

Protective Groups for Diols. Diols represent a special case in terms of applicable protecting groups. 1,2- and 1,3-diols easily form cyclic acetals with aldehydes and ketones, unless cyclization is precluded by molecular geometry. The isopropylidene derivatives (also called acetonides) formed by reaction with acetone are a common example. 

Oxidation of Isopropylidene Derivatives of Ketose Sugars. Whenever isopropylidene derivatives can be obtained in which all groups except the primary alcoholic grouping at Cl are blocked this method is undoubtedly the best. It may be illustrated by reference to the preparation of 2-keto-D-gluconic acid from D-fructose.14... 

Selective removal of one isopropylidene group from a diacetal may be achieved by a variety of procedures, most of them involving protic or Lewis acids.100 Particularly common is the hydrolysis of the acetal engaging of the primary position of di-O-isopropylidene derivatives. Bhaskar et al,101 studied the selective deprotection of di-O-isopropylidene acetals derived from D-glucose, D-xylose, and D-mannose, using acid zeolites and montmorillonite K-10. When 102 was submitted to acid hydrolysis in aqueous methanol, the best yields (85—96%) for the monoacetal 105 were obtained when H-beta and HZSM-5 zeolites were employed as catalysts (Scheme 24, Table IV). HY zeolite proved to be ineffective, whereas the yield obtained for the montmorillonite K-10-catalyzed reaction was low (22%). The zeolites found most effective were then used for the hydrolysis of the diacetal 103 and 104, providing excellent yields for the desired corresponding monoacetals 106 and 107. 

The preparation of sirupy 1-methyl-D-glucosone and crystalline 1-phenyl-D-glucosone (XXII), via the corresponding 2,3 4,5-di-0-isopropylidene derivatives, by Ohle and his colleagues61 64 (by treatment of 2,3 4,5-di-O-isopropylidene-2-oxo-D-arabmo-hexonic acid (XXI) with the requisite... 

The crystalline tri-0-isopropylidene-(2-hydroxy-L-x2/Zo-hexose) prepared from L-gulosone closely resembles the corresponding o-arabino-hexose derivative7 (p. 73) and is believed to have a similar structure.193 On graded hydrolysis, it forms a di-O-isopropylidene derivative which may be characterized as the crystalline diacetate. 

These compounds are O-isopropylidene derivatives of apiose and of a postulated isosaccharinic acid, respectively. 

A strategy has been described for the synthesis of 2-ethyIthio-6-(3-hydroxy-1,2-0-isopropylidenepropyl)pteridin-4(3//)-one 90 which can be used as a useful intermediate for the conversion of neopterin to biopterin. Diaminopyrimidinone 86 reacts with D-arabinose phenylhydrazone 87, the obtained diastereomeric mixture 88 is converted into its isopropylidene derivative 89 which under oxidation conditions yields 90 <00H(53)1551>. 

A remarkably selective phosphorylation at HO-3 in L-ascorbic acid and its 5,6-O-isopropylidene derivative has been achieved with phosphoryl chloride in aqueous pyridine204 the use of acetone-pyridine as the solvent led to a much less selective reaction. 

Reaction of D-glucono-1,4-lactone with 2,2-dimethoxypropane-tin(II) chloride yields the 5,6-0-isopropylidene derivative 13, which on periodate oxidation afforded 2,3-0-isopropylidene-D-glyceraldehyde (21). However, the acid-catalyzed isopropylidenation of D-glucono-1,5-lactone with 2,2-dimethoxypropane afforded methyl 3,4 5,6-di-0-isopropylidene-D-gluco-nate (14) as the main product (22). Reduction of the ester function gave... 

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