Show how another enediol rearrangement can move the

Problem 3P (a) There is only one ketotriose, called dihydroxyacetone. Draw its structure. (b) There is only one aldotriose, called glyceraldehyde. Draw the two enantiomers of glyceraldehyde.

Problem 1P Draw the mirror images of glucose and fructose. Are glucose and fructose chiral? Do you expect them to be optically active?

Draw and name the enantiomers of the sugars shown in Figure 23-2. Give the relative config- uration (D or L) and the sign of the rotation in each case.

Problem 21P Draw and name the products of bromine water oxidation of (a) D-mannose (b) D-galactose (c) D-fructose

Problem 5P Which configuration (R or S) does the bottom asymmetric carbon have for the D series of sugars? Which configuration for the L series?

Problem 2P (a) How many asymmetric carbon atoms are there in an aldotetrose? Draw all the aldotetrose stereoisomers. (b) How many asymmetric carbons are there in a ketotetrose? Draw all the ketotetrose stereoisomers. (c) How many asymmetric carbons and stereoisomers are there for an aldohexose? For a ketohexose?

Draw Fischer projections for the enantiomers of threo-hexane-1,2,3-triol. \(H O C H_{2}-C H(O H)-C H(O H)-C H_{2} C H_{2} C H_{3}\) Equation transcription: Text transcription: H O C H_{2}-C H(O H)-C H(O H)-C H_{2} C H_{2} C H_{3}

Problem 7P The bronchodilator ephedrine is erythro -2-(methylamino)-1-phenylpropan-1-ol. The decongestant pseudoephedrine is threo -2-(methylamino)-1-phenylpropan-1-ol. (a) Draw the four stereoisomers of 2-(methylamino)-1-phenylpropan-1-ol, either as Fischer projections or as three-dimensional representations (dotted lines and wedges). (b) Label ephedrine and pseudoephedrine. What is the relationship between them? (c) Label the D and L isomers of ephedrine and pseudoephedrine using the Fischer–Rosanoff convention. (d) Both ephedrine and pseudoephedrine are commonly used as racemic mixtures. Ephedrine is also available as the pure levorotatory 1-2 isomer (Biophedrine®), and pseudoephedrine is also available as the more active 1+2 isomer (Sudafed®). Can you label the 1-2 isomer of ephedrine and the 1+2 isomer of pseudoephedrine?

Problem 10P Allose is the C3 epimer of glucose. Draw the cyclic hemiacetal form of D-allose, first in the chair conformation and then in the Haworth projection.

Problem 11P Talose is the C4 epimer of mannose. Draw the chair conformation of D-talopyranose.

Problem 9P Draw the Haworth projection for the cyclic structure of D-mannose by laying down the Fischer projection.

(a) Draw -allose, the C3 epimer of glucose. (b) Draw -talose, the C2 epimer of -galactose. (c) Draw -idose, the C3 epimer of -talose. Now compare your answers with Figure 23-3. (d) Draw the C4 “epimer” of -xylose. Notice that this “epimer” is actually an ?-series sugar, and we have seen its enantiomer. Give the correct name for this ?-series sugar.

Problem 13P The carbonyl group in D-galactose may be isomerized from C1 to C2 by brief treatment with dilute base (by the enediol rearrangement, Section 23-8). The product is the C4 epimer of fructose. Draw the furanose structure of the product.

(a) Figure 23-2 shows that the degradation of ?-glucose gives ?-arabinose, an aldopentose. Arabinose is most stable in its furanose form. Draw ?-arabinofuranose. (b) Ribose, the C2 epimer of arabinose, is most stable in its furanose form. Draw ?-ribofuranose.

Problem 14P Draw the following monosaccharides, using chair conformations for the pyranoses and Haworth projections for the furanoses. (a) ?-D-mannopyranose (C2 epimer of glucose) (b) ?-D-galactopyranose (C4 epimer of glucose) (c) ?-D-allopyranose (C3 epimer of glucose) (d) ?-D-arabinofuranose (e) ?-D-ribofuranose (C2 epimer of arabinose)

Problem 15P Like glucose, galactose mutarotates when it dissolves in water. The specific rotation of ?-D-galactopyranose is +150.7°, and that of the anomer is +52.8°.When either of the pure anomers dissolves in water, the specific rotation gradually changes to +80.2°. Determine the percentages of the two anomers present at equilibrium.

Problem 17P Show how C3 of fructose can epimerize under basic conditions.

Problem 18P Show how another enediol rearrangement can move the carbonyl group from C2 in fructose to C3.

Problem 16P Propose a mechanism for the base-catalyzed epimerization of erythrose to a mixture of erythrose and threose.

Problem 19P When D-glucose is reduced with sodium borohydride, optically active glucitol results. When optically active D-galactose is reduced, however, the product is optically inactive. Explain this loss of optical activity.

Problem 20P Emil Fischer synthesized L-gulose, an unusual aldohexose that reduces to give D-glucitol. Suggest a structure for this L sugar, and show how L-gulose gives the same alditol as D-glucose. (Hint: D-Glucitol has –CH2OH groups at both ends. Either of these primary alcohol groups might have come from reduction of an aldehyde.)

Problem 40P (a) Show the product that results when fructose is treated with an excess of methyl iodide and silver oxide. (b) Show what happens when the product of part (a) is hydrolyzed using dilute acid. (c) Show what the results of parts (a) and (b) imply about the hemiacetal structure of fructose.

Problem 44P Does lactose mutarotate? Is it a reducing sugar? Explain. Draw the two anomeric forms of lactose.

Problem 22P Draw and name the products of nitric acid oxidation of (a) D-mannose (b) D-galactose

Problem 45P Is gentiobiose a reducing sugar? Does it mutarotate? Explain your reasoning.

Problem 23P Two sugars, A and B, are known to be glucose and galactose, but it is not certain which one is which. On treatment with nitric acid, A gives an optically inactive aldaric acid, while B gives an optically active aldaric acid. Which sugar is glucose, and which is galactose?

Problem 16P Propose a mechanism for the base-catalyzed epimerization of erythrose to a mixture of erythrose and threose.

Problem 28P Treatment of either anomer of fructose with excess ethanol in the presence of a trace of HCl gives a mixture of the ? and ? anomers of ethyl-D-fructofuranoside. Draw the starting materials, reagents, and products for this reaction. Circle the aglycone in each product.

Problem 29P Propose a mechanism for methylation of any one of the hydroxyl groups of methyl ?-D-glucopyranoside, using NaOH and dimethyl sulfate.

Problem 30P Draw the expected product of the reaction of the following sugars with excess methyl iodide and silver oxide. (a) ?-D-fructofuranose (b) ?-D-galactopyranose

(a) An aliphatic aminoglycoside is relatively stable to base, but it is quickly hydrolyzed by dilute acid. Propose a mechanism for the acid-catalyzed hydrolysis. Equation Transcription: Text Transcription: HO-CH_2 OH OH H_{3}O^{+} R_{2}NH_{2}

All of the rings of the four heterocyclic bases are aromatic. This is more apparent when the polar resonance forms of the amide groups are drawn, as is done for thymine at the right. Redraw the hydrogen-bonded guanine-cytosine and adenine-thymine pairs shown in Figure 23-25, using the polar resonance forms of the amides. Show how these forms help to explain why the hydrogen bonds involved in these pairings are particularly strong. Remember that a hydrogen bond arises between an electron-deficient hydrogen atom and an electron-rich pair of nonbonding electrons. Equation Transcription: Text Transcription: A:::T G:::C CH_3

Problem 52SP Glucose is the most abundant monosaccharide. From memory, draw glucose in (a) the Fischer projection of the open chain (b) the most stable chair conformation of the most stable pyranose anomer (c) the Haworth projection of the most stable pyranose anomer

Problem 72SP Retroviruses like HIV, the pathogen responsible for AIDS, incorporate an RNA template that is copied into DNA during infection. The reverse transcriptase enzyme that copies RNA into DNA is relatively nonselective and error-prone, leading to a high mutation rate. Its lack of selectivity is exploited by the anti-HIV drug AZT (3’-azido-2’,3’ dideoxythymidine), which becomes phosphorylated and is incorporated by reverse transcriptase into DNA, where it acts as a chain terminator. Mammalian DNA polymerases are more selective, having a low affinity for AZT, so its toxicity is relatively low. (a) Draw the structures of AZT and natural deoxythymidine. (b) Draw the structure of AZT 5’-triphosphatethe, derivative that inhibits reverse transcriptase.

Problem 73SP Exposure to nitrous acid (see Section 19-16), sometimes found in cells, can convert cytosine to uracil. (a) Propose a mechanism for this conversion. (b) Explain how this conversion would be mutagenic upon replication. (c) DNA generally includes thymine, rather than uracil (found in RNA). Based on this fact, explain why the nitrous acid-induced mutation of cytosine to uracil is more easily repaired in DNA than it is in RNA.

H. G. Khorana won the Nobel Prize in Medicine in 1968 for developing the synthesis of DNA and RNA and for helping to unravel the genetic code. Part of the chemistry he developed was the use of selective protecting groups for the \(5^{\prime}\ \mathrm{OH}\) group of nucleosides. The trityl ether derivative of just the \(5^{\prime}\ \mathrm{OH}\) group is obtained by reaction of the nucleoside with trityl chloride, MMT chloride, or DMT chloride and a base like \(\mathrm{Et}_{3} \mathrm{~N}\).The trityl ether derivative can be removed in dilute aqueous acid. DMT derivatives hydrolyze fastest, followed by MMT derivatives, and trityl derivatives slowest. (a) Draw the product with the trityl derivative on the \(5^{\prime}\) oxygen. (b) Explain why the trityl derivative is selective for the \(5^{\prime}\ \mathrm{OH}\) group. Why doesn’t it react at or \(2^{\prime}\) or \(3^{\prime}\)? (c) Why is the DMT group easiest to remove under dilute acid conditions? Why does the solution instantly turn orange when acid is added to a DMT derivative? Equation Transcription: Text Transcription: 5' OH HO OH OH Ph Ph-C-OR Ph H_{3}O Ph C-OR Ph OCH_{3} H_{3}CO C-OR Ph 5' OH Et_{3}N 5' 5' OH 2' 3'

Problem 42P Draw the structures of the individual mutarotating ? and ? anomers of maltose.

Problem 41P (a) Draw the reaction of methyl ?-D-fructofuranoside with periodic acid, and predict the products. (b) Draw the structure of a hypothetical methyl ?-D-fructopyranoside, and predict the products from periodic acid oxidation. (c) The reaction of methyl ?-D-glucopyranoside with periodic acid (shown above) gives only the D-1+2 enantiomer of glyceraldehyde (among other products). If you oxidized an aldohexose glycoside with periodic acid and one of the products was the L-(-) enantiomer of glyceraldehyde, what would that tell you about the sugar?

Problem 43P Give an equation to show the reduction of Tollens reagent by maltose.

Which of the sugars mentioned in Problems 23-59, 23-60, and 23-61 are reducing sugars? Which ones would undergo mutarotation? Reference: Problem 59:Draw the following sugar derivatives. (a) methyl \(\beta\)-D-glucopyranoside (b) 2,3,4,6-tetra-O-methyl-D-mannopyranose (c) 1,3,6-tri-O-methyl-D-fructofuranose (d) methyl 2,3,4,6- tetra-O- methyl-\(\beta\)-D-glucopyranoside Reference: Problem 60: Draw the structures (using chair conformations of pyranoses) of the following disaccharides. (a) 4-O-(\(\alpha\)-D-glucopyranosyl)-D-galactopyranose (b) \(\alpha\)-D-fructofuranosyl-\(\beta\)-D-mannopyranoside (c) 6-O-(\(\beta\)-D-galactopyranosyl)-D-glucopyranose Reference: Problem 61: Give the complete systematic name for each structure Equation Transcription: Text Transcription: beta beta alpha alpha beta beta HOCH_{2} OCH_{3} CH_{2}OH OH OCH_{3} CH_{2} HO CH_{3}O OH OH HOCH_{2} CH_{2}OH HO OH HO CH_{2}OH OH OH HO CH_{2}OH HO HO NH C=O CH_{3}

After a series of Kiliani-Fischer syntheses on (+)-glyceraldehyde, an unknown sugar is isolated from the reaction mixture. The following experimental information is obtained: (1) Molecular formula \(\mathrm{C}_{6} \mathrm{H}_{12} \mathrm{O}_{6}\). (2) Undergoes mutarotation. (3) Reacts with bromine water to give an aldonic acid. (4) Reacts with phenylhydrazine to give an osazone, mp \(178\ ^{\circ} \mathrm{C}\). (5) Reacts with \(\mathrm{HNO}_{3}\) to give an optically active aldaric acid. (6) Ruff degradation followed by \(\mathrm{HNO}_{3}\) oxidation gives an optically inactive aldaric acid. (7) Two Ruff degradations followed by \(\mathrm{HNO}_{3}\) oxidation give meso-tartaric acid. (8) Formation of the methyl glycoside (using \(\mathrm{CH}_{3} \mathrm{OH}\) and \(\mathrm{HCl}\)), followed by periodic acid oxidation, gives a mixture of products that includes (+)-glyceraldehyde. (a) Draw a Fischer projection for the open-chain form of this unknown sugar. Use Figure to name the sugar. (b) Draw the most stable conformation of the most stable cyclic hemiacetal form of this sugar, and give the structure a complete systematic name. Equation Transcription: Text Transcription: C_{6}H_{12}O_{6} 178 ^{o}C HNO_{3} HNO_{3} HNO_{3} CH_{3}OH HCl

Problem 64SP An unknown reducing disaccharide is found to be unaffected by invertase enzymes. Treatment with an ?- galactosidase cleaves the disaccharide to give one molecule of D-fructose and one molecule of D-galactose. When the disaccharide is treated with excess iodomethane and silver oxide and then hydrolyzed in dilute acid, the products are 2,3,4,6-tetra-O-methylgalactose and 1,3,4-tri-O-methylfructose. Propose a structure for this disaccharide, and give its complete systematic name.

Problem 26P The mechanism of glycoside formation is the same as the second part of the mechanism for acetal formation. Propose a mechanism for the formation of methyl ?-D-glucopyranoside.

Draw the structures of the compounds named in Problem 23-24 parts (a), (c), and (d). Allose is the C3 epimer of glucose, and ribose is the C2 epimer of arabinose.

Problem 27P Show the products that result from hydrolysis of amygdalin in dilute acid. Can you suggest why amygdalin might be toxic to tumor (and possibly other) cells?

Problem 47P Raffinose is a trisaccharide (C18H32O16) isolated from cottonseed meal. Raffinose does not reduce Tollens reagent, and it does not mutarotate. Complete hydrolysis of raffinose gives D-glucose, D-fructose, and D-galactose. When raffinose is treated with invertase, the products are D-fructose and a reducing disaccharide called melibiose. Raffinose is unaffected by treatment with a ?-galactosidase but an ?-galactosidase hydrolyzes it to D-galactose and sucrose. When raffinose is treated with dimethyl sulfate and base followed by hydrolysis, the products are 2,3,4-tri-O-methylglucose, 1,3,4,6-tetra-O-methylfructose, and 2,3,4,6-tetra-O-methylgalactose. Determine the complete structures of raffinose and melibiose, and give a systematic name for melibiose.

Problem 48P Cellulose is converted to cellulose acetate by treatment with acetic anhydride and pyridine. Cellulose acetate is soluble in common organic solvents, and it is easily dissolved and spun into fibers. Show the structure of cellulose acetate.

Problem 49P Cytosine, uracil, and guanine have tautomeric forms with aromatic hydroxyl groups. Draw these tautomeric forms.

Problem 69SP Draw the structures of the following nucleotides. (a) guanosine triphosphate (GTP) (b) deoxycytidine monophosphate (dCMP) (c) cyclic guanosine monophosphate (cGMP)

Problem 70SP Draw the structure of a four-residue segment of DNA with the following sequence. (3’end) G-T-A-C (5’ end)

Problem 71SP Erwin Chargaff’s discovery that DNA contains equimolar amounts of guanine and cytosine and also equimolar amounts of adenine and thymine has come to be known as Chargaff’s rule: G = C and A = T (a) Does Chargaff’s rule imply that equal amounts of guanine and adenine are present in DNA? That is, does G = A? (b) Does Chargaff’s rule imply that the sum of the purine residues equals the sum of the pyrimidine residues? That is, does A + G = C + T? (c) Does Chargaff’s rule apply only to double-stranded DNA, or would it also apply to each individual strand if the double helical strand were separated into its two complementary strands?

Problem 37P The Wohl degradation, an alternative to the Ruff degradation, is nearly the reverse of the Kiliani–Fischer synthesis. The aldose carbonyl group is converted to the oxime, which is dehydrated by acetic anhydride to the nitrile (a cyanohydrin). Cyanohydrin formation is reversible, and a basic hydrolysis allows the cyanohydrin to lose HCN. Using the following sequence of reagents, give equations for the individual reactions in the Wohl degradation of D-arabinose to D-erythrose. Mechanisms are not required. (1) hydroxylamine hydrochloride (2) acetic anhydride (3) -OH, H2O

On treatment with phenylhydrazine, aldohexoses A and B give the same osazone. On treatment with warm nitric acid, A gives an optically inactive aldaric acid, but sugar B gives an optically active aldaric acid. Sugars A and B are both degraded to aldopentose C, which gives an optically active aldaric acid on treatment with nitric acid. Aldopentose C is degraded to aldotetrose D, which gives optically active tartaric acid when it is treated with nitric acid. Aldotetrose D is degraded (+)-glyceraldehyde to Deduce the structures of sugars A, B, C, and D, and use Figure 23-3 to determine the correct names of these sugars.

Problem 59SP Draw the following sugar derivatives. (a) methyl ?-D-glucopyranoside (b) 2,3,4,6-tetra-O-methyl-D-mannopyranose (c) 1,3,6-tri-O-methyl-D-fructofuranose (d) methyl 2,3,4,6- tetra-O- methyl-?-D-glucopyranoside

Problem 60SP Draw the structures (using chair conformations of pyranoses) of the following disaccharides. (a) 4-O-( ?-D-glucopyranosyl)-D-galactopyranose (b) ?-D-fructofuranosyl- ? -D-mannopyranoside (c) 6-O-( ? -D-galactopyranosyl)-D-glucopyranose

Give the complete systematic name for each structure. Equation Transcription: Text Transcription: HOCH_{2} OCH_{3} HO OH CH_{2}OH OCH_{3} CH_{2} HO CH_{3}O OH OH HOCH_{2} CH_{2}OH OH HO CH_{2}OH HO OH OH HO CH_{2}OH HO NH OH C=O CH_{3}

Which of the following are reducing sugars? Comment on the common name sucrose for table sugar. (a) methyl \(\alpha\)-D-galactopyranoside (b) \(\beta\)-L-idopyranose (an aldohexose) (c) \(\alpha\)-D-allopyranose (d) ethyl \(\beta\)-D-ribofuranoside Equation Transcription: Text Transcription: alpha beta alpha beta HO CH_{2}OH HO OH CH_{2} HO HO OH OH HO CH_{2}OH HO OH HOCH_{2} HO OH CH_{2}OH

Problem 46P Trehalose is a nonreducing disaccharide (C12H 22O11) isolated from the poisonous mushroom Amanita muscaria. Treatment with an ?-glucosidase converts trehalose to two molecules of glucose, but no reaction occurs when trehalose is treated with a ?-glucosidase. When trehalose is methylated by dimethyl sulfate in mild base and then hydrolyzed, the only product is 2,3,4,6-tetra- O-methylglucose. Propose a complete structure and systematic name for trehalose.

Problem 65SP (a) Which of the D-aldopentoses will give optically active aldaric acids on oxidation with HNO3 ? (b) Which of the D-aldotetroses will give optically active aldaric acids on oxidation with HNO3? (c) Sugar X is known to be a D-aldohexose. On oxidation with HNO3,X gives an optically inactive aldaric acid. When X is degraded to an aldopentose, oxidation of the aldopentose gives an optically active aldaric acid. Determine the structure of X. (d) Even though sugar X gives an optically inactive aldaric acid, the pentose formed by degradation gives an optically active aldaric acid. Does this finding contradict the principle that optically inactive reagents cannot form optically active products? (e) Show what product results if the aldopentose formed from degradation of X is further degraded to an aldotetrose. Does HNO3? oxidize this aldotetrose to an optically active aldaric acid?

Problem 66SP When the gum of the shrub Sterculia setigera is subjected to acidic hydrolysis, one of the water-soluble components of the hydrolysate is found to be tagatose. The following information is known about tagatose: (1) Molecular formula C6H12O6. (2) Undergoes mutarotation. (3) Does not react with bromine water. (4) Reduces Tollens reagent to give D-galactonic acid and D-talonic acid. (5) Methylation of tagatose (using excess CH3I and Ag2O) followed by acidic hydrolysis gives 1,3,4,5-tetra-O-methyltagatose. (a) Draw a Fischer projection structure for the open-chain form of tagatose. (b) Draw the most stable conformation of the most stable cyclic hemiacetal form of tagatose.

Some protecting groups can block two OH groups of a carbohydrate at the same time. One such group is shown here, protecting the 4-OH and 6-OH groups of \(\beta\)-D-glucose. (a) What type of functional group is involved in this blocking group? (b) What did glucose react with to form this protected compound? Equation Transcription: Text Transcription: OH 4-OH 6-OH beta Ph HO OH OH

Problem 31P Predict the products formed when the following sugars react with excess acetic anhydride and pyridine. (a) ?-D-glucopyranose (b) ?-D-ribofuranose

Problem 32P a) Show that D-glucose, D-mannose, and D-fructose all give the same osazone. Show the structure and stereochemistry of this osazone. (b) D-Talose is an aldohexose that gives the same osazone as D-galactose. Give the structure of D-talose, and give the structure of its osazone.

Problem 33P Show that Ruff degradation of D-mannose gives the same aldopentose (D-arabinose) as does D-glucose.

Problem 53SP Without referring to the chapter, draw the chair conformations of (a) ? -D-mannopyranose (the C2 epimer of glucose) (b) ?-D-allopyranose (the C3 epimer of glucose) (c) ?-D-galactopyranose (the C4 epimer of glucose) (d) N-acetylglucosamine, glucose with the C2 oxygen atom replaced by an acetylated amino group

Classify the following monosaccharides. (Examples: D-aldohexose, L-ketotetrose.) Equation Transcription: Text Transcription: CHO HO HO OH HO CH_{2}OH CH_{2}OH C=O OH OH CH_{2}OH CHO OH HO CH_{2}OH CHO NHCOCH_3 HO OH OH CH_{2}OH

Use Figure 23-3 (the D family of aldoses) to name the following aldoses. (a) the C2 epimer of D-arabinose (b) the C3 epimer of D-mannose (c) the C3 epimer of D-threose (d) the enantiomer of D-galactose (e) the C5 epimer of D-glucose

Problem 34P D-Lyxose is formed by Ruff degradation of galactose. Give the structure of D-lyxose. Ruff degradation of D-lyxose gives D-threose. Give the structure of D-threose.

Problem 35P D-Altrose is an aldohexose. Ruff degradation of D-altrose gives the same aldopentose as does degradation of D-allose, the C3 epimer of glucose. Give the structure of D-altrose.

Problem 36P Ruff degradation of D-arabinose gives D-erythrose. The Kiliani–Fischer synthesis converts D-erythrose to a mixture of D-arabinose and D-ribose. Draw out these reactions, and give the structure of D-ribose.

Problem 56SP (a) Give the products expected when ( + )- glyceraldehyde reacts with HCN. (b) What is the relationship between the products? How might they be separated? (c) Are the products optically active? Explain.

Problem 58SP Predict the products obtained when D-galactose reacts with each reagent. (a) Br2 and H2O (b) NaOH, H2O (c) CH3OH,H+ (d) Ag(NH3)2+-OH (e) H2, NI (f) excess Ac2O and pyridine (g) excess CH3I, Ag2O (h) NaBH4 (i) Br2, H2O, then H2O2 and Fe2(SO4)3 (j) HCN, then H3O+, then Na(Hg) (k) Excess HIO4

The relative configurations of the stereoisomers of tartaric acid were established by the following syntheses: (1) D-(+)-glyceraldehyde \(\stackrel{\mathrm{HCN}}{\longrightarrow}\) diastereomers A and B (separated) (2) Hydrolysis of A and B using aqueous \(\mathrm{Ba}(\mathrm{OH})_{2}\) gave C and D, respectively. (3) \(\mathrm{HNO}_{3}\) oxidation of C and D gave -tartaric acid and meso-tartaric acid, respectively. (a) You know the absolute configuration of -glyceraldehyde. Use Fischer projections to show the absolute configurations of products A, B,C and D. (b) Show the absolute configurations of the three stereoisomers of tartaric acid: -tartaric acid, -tartaric acid, and meso-tartaric acid. Equation Transcription: Text Transcription: _{rightarrow}^{HCN} Ba(OH)_2 HNO_3