Abstract:
The present invention provides a method for manufacturing betulin aldehyde from betulin. The method includes: (a) electrochemically forming a oxoammonium ion from a nitroxyl radical; and (b) contacting betulin with the oxoammonium ion, for a period of time effective to provide the betulin aldehyde. The betulin aldehyde can subsequently be converted to betulinic acid, employing, e.g., NaClO2 or KClO2. The betulinic acid can be purified from from any unreacted betulin by converting the betulinic acid into a corresponding salt (Na, K, Li, Na, Ca, Mg, Ba, or Al), and separating the salt from the unreacted betulin.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    Betulinic acid is useful as a potential therapeutic agent. For example, Pisha, E. et al., (1995) J. M. Nature Medicine, 1, 1046-1051 disclose that betulinic acid has antitumor activity against melanoma, e.g., MEL-1, MEL-2 and MEL4. In addition, Fujioka, T. et al., J. Nat. Prod., (1994) 57, 243-247 discloses that betulinic acid has anti-HIV activity in H 9  lymphocytic cells. 
         [0002]    Betulinic acid can be manufactured from betulin, which is present in large quantities in the outer birch bark of numerous species of birch trees. For example, a single paper mill in northern Minnesota generates nearly 30-70 tons of birch bark per day. Approximately 230,000 tons of birch bark are generated per year. Outer bark of  Betula verrucosa  (European commercial birth tree) contains nearly 25% betulin (Rainer Ekman, 1983, Horzforschung 37, 205-211). The outer bark of  Betula paparifera  (commercial birch of northern U.S. and Canada) contains nearly 5-18% betulin (see, U.S. Pat. Ser. No. 09/371,298). As such, vast quantities of betulin are available. 
         [0003]    U.S. Pat. No. 5,804,575 issued to Pezzuto et al. discloses a five-step process for the synthesis of betulinic acid from betulin. Due to the length of time required to carry out this process and the yield it provides, it is not ideal for the commercial scale (e.g., kilogram) production of betulinic acid. Additionally, the process uses solvents and reagents that are hazardous and expensive, and the disclosed purification steps are not feasible on a commercial scale. 
         [0004]    The first step in the preparation of betulinic acid from betulin-3-acetate was described by Ruzichka et al. (Helv. Chim. Acta., 21, 1706-1715 (1938)). The main obstacle for employing this method is the preparation of starting material (i.e., betulin-3-acetate). The selectivity of the hydrolysis of betulin-3, 28-diacetate with potassium hydroxide provided about 60% betulin-3-acetate. The use of magnesium alcoholates (Yao-Chang Xu et al., J. Org. Chem., 61, 9086-9089 (1996)) in the selective deprotection of betulin-3,28-diacetate (Yao-Chang Xu et al., J. Org. Chem., 61, 9086-9089 (1996)) has several serious drawbacks. The selectivity of this process is about 81%. Additionally, the cost of magnesium alcoholates is fairly high. As such, this method is not attractive for the commercial scale production of betulinic acid. 
         [0005]    The development of an industrially viable selective electrooxidation method for alcohols to aldehydes is a very desirable target in synthetic organic chemistry, including the specific synthesis of betulin-28-aldehyde. 
         [0006]    Zhao et al.,  Organic Synthesis , Vol. 81, p.195 (2005), describe the oxidation of primary alcohols to carboxylic acids with sodium chlorite catalyzed by TEMPO and bleach. Additionally, Semmelhack et al., JACS ,105, 4492, (1977); Z. Ma, et. al., Chem. Comm. 2745 (1996); and S. D. Rychnovsky, et. al., JOC 61, 1194 (1996) generate N-oxoammonium radicals for oxidative purposes. 
         [0007]    U.S. Pat. Nos. 6,407,270; 6,271,405; and 6,232,481 describe methods for manufacturing betulinic acid from betulin. Additionally, U.S. Pat. Nos. 6,815,553; 6,634,575; and 6,392,070 describe methods for isolating betulinic acid from birch bark. However, there exists a need for additional methods for preparing betulinic acid and synthetic precursors thereof. Such methods should require relatively little time, should provide a relatively high overall yield, should be cost effective (i.e., should require relatively inexpensive reagents and solvents) relative to known procedures, and/or should satisfy the contemporary industrial demands from both safety and environmental points of view. 
       SUMMARY OF THE INVENTION 
       [0008]    The present invention provides a relatively cost effective, safe and efficient maimer to convert a primary alcohol (e.g., betulin) to the corresponding aldehyde (e.g., betulin aldehyde). Specifically, the present invention provides a relatively cost effective, safe and efficient manner to convert betulin to betulin-28-aldehyde. The synthesis is a one-step method that typically affords up to about 90 wt. % aldehyde, and about 10 wt. % unreacted starting material. The oxidation employs an oxoammonium ion, which can be electrochemically produced from, e.g., compound of formula (XXV), e.g., TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl). The crude aldehyde can be converted to the corresponding carboxylic acid (betulinic acid), where it can be separated from the unreacted starting material (e.g., betulin) employing, e.g., an acid-base washing. 
         [0009]    The present invention provides a method for manufacturing an aldehyde from a primary alcohol, the method includes: (a) electrochemically forming a oxoammonium ion from a nitroxyl radical; and (b) contacting a primary alcohol with the oxoammonium ion, for a period of time effective to provide the aldehyde. 
         [0010]    The present invention also provides a method for manufacturing betulin aldehyde from betulin, the method includes: (a) electrochemically forming a oxoammonium ion from a nitroxyl radical; and (b) contacting betulin with the oxoammonium ion, for a period of time effective to provide the betulin aldehyde. 
         [0011]    The present invention also provides a method for manufacturing betulinic acid from betulin, the method includes: (a) electrochemically forming a oxoammonium ion from a nitroxyl radical; (b) contacting betulin with the oxoammonium ion, for a period of time effective to provide the betulin aldehyde; and (c) contacting the betulin aldehyde with NaClO 2 , KClO 2 , or a combination thereof, for a period of time effective to provide the betulinic acid. 
         [0012]    The present invention also provides a process of oxidizing a triterpene having a primary alcohol, to the corresponding triterpene having an aldehyde. The present invention also provides a process of subsequently oxidizing the triterpene having an aldehyde, to the corresponding triterpene having a carboxylic acid. The present invention also provides a process of oxidizing a triterpene having a primary alcohol, to the corresponding triterpene having a carboxylic acid. The triterpene having the primary alcohol optionally also includes a secondary alcohol, wherein the secondary alcohol is optionally protected with, e.g., an acyl group. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0013]    As used herein, the following terms and expressions have the indicated meanings. It will be appreciated that the compounds of the present invention contain asymmetrically substituted carbon atoms, and may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis, from optically active starting materials. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. 
         [0014]    As used herein, “physiologically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of physiologically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The physiologically acceptable salts include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, isethionic, and the like. 
         [0015]    The physiologically acceptable salts can be synthesized from the parent compound, which contains a basic or acidic moiety, by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington&#39;s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference. 
         [0016]    The phrase “physiologically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio. 
         [0017]    “Stable compound” and “stable structure” are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent. Only stable compounds are contemplated by and employed in the present invention. 
         [0018]    “Substituted” is intended to indicate that one or more (e.g., 1, 2, 3, 4, or 5; preferably 1, 2, or 3; and more preferably 1 or 2) hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom&#39;s normal valency is not exceeded, and that the substitution results in a stable compound. Suitable indicated groups include, e.g., alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, dialkylamino, trifluoromethylthio, difluoromethyl, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, and cyano. Alternatively, the suitable indicated groups can include, e.g., —X, —R, —O − , —OR, —SR, —S − , —NR 2 , —NR 3 , ═NR, —CX 3 , —CN, —OCN, —SCN, —N═C═O, —NCS, —NO, —NO 2 , ═N 2 , —N 3 , NC(═O)R, —C(═O)R, —C(═O)NRR—S(═O) 2 O − , —S(═O) 2 OH, —S(═O) 2 R, —OS(═O) 2 OR, —S(═O) 2 NR, —S(═O)R, —OP(═O)O 2 RR, —P(═O)O 2 RR —P(═O)(O − ) 2 , —P(═O)(OH) 2 , —C(═O)R, —C(═O)X, —C(S)R, —C(O)OR, —C(O)O − , —C(S)OR,—C(O)SR, —C(S)SR, —C(O)NRR, —C(S)NRR, —C(NR)NRR, where each X is independently a halogen: F, Cl, Br, or I; and each R is independently H, alkyl, aryl, hetero cycle, protecting group or prodrug moiety. When a substituent is keto (i.e., ═O) or thioxo (i.e., ═S) group, then 2 hydrogens on the atom are replaced. 
         [0019]    One diastereomer may display superior activity compared with the other. When required, separation of the racemic material can be achieved by HPLC using a chiral column or by a resolution using a resolving agent such as camphonic chloride as in Thomas J. Tucker, et al., J. Med. Chem. 1994 37, 2437-2444. A chiral compound may also be directly synthesized using a chiral catalyst or a chiral ligand, e.g. Mark A. Huffman, et al., J. Org. Chem. 1995, 60, 1590-1594. 
         [0020]    The term “alkyl” refers to a monoradical branched or unbranched saturated hydrocarbon chain preferably having from 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms, and more preferably from 1 to 4 carbon atoms. Examples are methyl (Me, —CH 3 ), ethyl (Et, —CH 2 CH 3 ), 1-propyl i-Pr, n-propyl, —CH 2 CH 2 CH 3 ), 2-propyl (i-Pr, i-propyl, —CH(CH 3 )2), 1-butyl (n-Bu, n-butyl, —CH 2 CH 2 CH 2 CH 3 ), 2-methyl-i-propyl (i-Bu, i-butyl, —CH 2 CH(CH 3 ) 2 ), 2-butyl (s-Bu, s-butyl, —CH(CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (n-Bu, t-butyl, —C(CH 3 ) 3 ), 1-pentyl (n-pentyl, —CH 2 CH 2 CH 2 CH 2 CH 3 ), 2-pentyl (—CH(CH 3 )CH 2 CH 2 CH 3 ), 3-pentyl (—CH(CH 2 CH 3 ) 2 ), 2-methyl-2-butyl (—C(CH 3 ) 2 CH 2 CH 3 ), 3-methyl-2-butyl (—CH(CH 3 )CH(CH 3 ) 2 ), 3-methyl-1-butyl (—CH 2 CH 2 CH(CH 3 ) 2 ), 2-methyl-1-butyl (—CH 2 CH(CH 3 )CH 2 CH 3 ), 1-hexyl (—CH 2 CH 2 CH 2 CH 2 CH 2 CH 3 ), 2-hexyl (—CH(CH 3 )CH 2 CH 2 CH 2 CH 3 ), 3-hexyl (—CH(CH 2 CH 3 )(CH 2 CH 2 CH 3 )), 2-methyl-2-pentyl (—C(CH 3 ) 2 CH 2 CH 2 CH 3 ), 3-methyl-2-pentyl (—CH(CH 3 )CH(CH 3 )CH 2 CH 3 ), 4-methyl-2-pentyl (—CH(CH 3 )CH 2 CH(CH 3 ) 2 ), 3-methyl-3-pentyl (—C(CH 3 )(CH 2 CH 3 ) 2 ), 2-methyl-3-pentyl (—CH(CH 2 CH 3 )CH(CH 3 ) 2 ), 2,3-dimethyl-2-butyl (—C(CH 3 ) 2 CH(CH 3 ) 2 ), 3,3-dimethyl-2-butyl (—CH(CH 3 )C(CH 3 ) 3 . The alkyl can be unsubstituted or substituted. 
         [0021]    The term “alkenyl” refers to a monoradical branched or unbranched partially unsaturated hydrocarbon chain (i.e. a carbon-carbon, sp 2  double bond) preferably having from 2 to 10 carbon atoms, preferably 2 to 6 carbon atoms, and more preferably from 2 to 4 carbon atoms. Examples include, but are not limited to, ethylene or vinyl (—CH═CH 2 ), allyl (—CH 2 CH═CH 2 ), cyclopentenyl (—C 5 H 7 ), and 5-hexenyl (—CH 2 CH 2 CH 2 CH 2 CH═CH 2 ). The alkenyl can be unsubstituted or substituted. 
         [0022]    The term “alkoxy” refers to the groups alkyl-O—, where alkyl is defined herein. Preferred alkoxy groups include, e.g., methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. The alkoxy can be unsubstituted or substituted. 
         [0023]    The term “aryl” refers to an unsaturated aromatic carbocyclic group of from 6 to 12 carbon atoms having a single ring (e.g., phenyl) or multiple condensed (fused) rings, wherein at least one ring is aromatic (e.g., naphthyl, dihydrophenanthrenyl, fluorenyl, or anthryl). The aryl can be unsubstituted or substituted. 
         [0024]    The term “cycloalkyl” refers to cyclic alkyl groups of from 3 to 10 carbon atoms having a single cyclic ring or multiple condensed rings. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, and the like, or multiple ring structures such as adamantanyl, and the like. The cycloalkyl can be unsubstituted or substituted. 
         [0025]    The term “halo” refers to fluoro, chloro, bromo, and iodo. Similarly, the term “halogen” refers to fluorine, chlorine, bromine, and iodine. “Haloalkyl” refers to alkyl as defined herein substituted by 1-4 halo groups as defined herein, which may be the same or different. Representative haloalkyl groups include, by way of example, trifluoromethyl, 3-fluorododecyl, 12,12,12-trifluorododecyl, 2-bromooctyl, 3-bromo-6-chloroheptyl, and the like. 
         [0026]    The term “heteroaryl” is defined herein as a monocyclic, bicyclic, or tricyclic ring system containing one, two, or three aromatic rings and containing at least one nitrogen, oxygen, or sulfur atom in an aromatic ring, and which can be unsubstituted or substituted, for example, with one or more, and in particular one to three, substituents, selected from alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, dialkylamino, trifluoromethylthio, difluoromethyl, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl and cyano. Examples of heteroaryl groups include, but are not limited to, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, 4nH-carbazolyl, acridinyl, benzo[b]thienyl, benzothiazolyl, β-carbolinyl, carbazolyl, chromenyl, cinnolinyl, dibenzo[b,d]furanyl, furazanyl, furyl, imidazolyl, imidizolyl, indazolyl, indolisinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, naptho[2,3-b], oxazolyl, perimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, thiadiazolyl, thianthrenyl, thiazolyl, thienyl, triazolyl, and xanthenyl. In one embodiment the term “heteroaryl” denotes a monocyclic aromatic ring containing five or six ring atoms containing carbon and 1, 2, 3, or 4 heteroatoms independently selected from the group non-peroxide oxygen, sulfur, and N(Z) wherein Z is absent or is H, O, alkyl, phenyl or benzyl. In another embodiment heteroaryl denotes an ortho-fused bicyclic heterocycle of about eight to ten ring atoms derived therefrom, particularly a benz-derivative or one derived by fusing a propylene, or tetramethylene diradical thereto. 
         [0027]    “Heterocycle” as used herein includes by way of example and not limitation those heterocycles described in Paquette, Leo A.;  Principles of Modem Heterocyclic Chemistry  (W. A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9;  The Chemistry of Heterocyclic Compounds, A Series of Monographs ” (John Wiley &amp; Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; and  J. Am. Chem. Soc.  (1960) 82:5566. In one specific embodiment of the invention “heterocycle” includes a “carbocycle” as defined herein, wherein one or more (e.g. 1, 2, 3, or 4) carbon atoms have been replaced with a heteroatom (e.g. O, N, or S). 
         [0028]    Examples of heterocycles include by way of example and not limitation pyridyl, dihydroypyridyl, tetrahydropyridyl (piperidyl), thiazolyl, tetrahydrothiophenyl, sulfur oxidized tetrahydrothiophenyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphtlialenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, azocinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, thienyl, thianthrenyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazoly, purinyl, 4H-quinolizinyl, phthalazinyl, naplithyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, isatinoyl, and bis-tetrahydrofuranyl: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0029]    By way of example and not limitation, carbon bonded heterocycles are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. Still more typically, carbon bonded heterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl. 
         [0030]    By way of example and not limitation, nitrogen bonded heterocycles are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of a isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or β-carboline. Still more typically, nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl. 
         [0031]    “Carbocycle” refers to a saturated, unsaturated or aromatic ring having 3 to 7 carbon atoms as a monocycle, 7 to 12 carbon atoms as a bicycle, and up to about 30 carbon atoms as a polycycle. Monocyclic carbocycles have 3 to 6 ring atoms, still more typically 5 or 6 ring atoms. Bicyclic carbocycles have 7 to 12 ring atoms, e.g., arranged as a bicyclo [4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged as a bicyclo [5,6] or [6,6] system. Examples of carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, phenyl, spiryl and naphthyl. 
         [0032]    The term “alkanoyl” refers to C(═O)R, wherein R is an alkyl group as previously defined. 
         [0033]    The term “alkoxycarbonyl” refers to C(═O)OR, wherein R is an alkyl group as previously defined. 
         [0034]    The term “amino” refers to —NH 2 , and the term “alkylamino” refers to —NR 2 , wherein at least one R is alkyl and the second R is alkyl or hydrogen. The term “acylamino” refers to RC(═O)N, wherein R is alkyl or aryl. 
         [0035]    The term “nitro” refers to —NO 2 . 
         [0036]    The term “trifluoromethyl” refers to —CF 3 . 
         [0037]    The term “trifluoromethoxy” refers to —OCF 3 . 
         [0038]    The term “cyano” refers to —CN. 
         [0039]    The term “hydroxy” refers to —OH. 
         [0040]    As to any of the above groups, which contain one or more substituents, it is understood, of course, that such groups do not contain any substitution or substitution patterns which are sterically impractical and/or synthetically non-feasible. In addition, the compounds of this invention include all stereochemical isomers arising from the substitution of these compounds. 
         [0041]    As used herein, “aldehyde” refers to the functional group—C(═O)H, or any compound that includes such a group. 
         [0042]    As used herein, “primary alcohol” refers to a hydroxyl group that is directly bonded to a carbon atom, wherein that carbon atom is directly bonded to exactly one other carbon atom. The term also refers to those compounds that include such a group (i.e., a hydroxyl group that is directly bonded to a carbon atom, wherein that carbon atom is directly bonded to exactly one other carbon atom). 
         [0043]    As used herein, “secondary alcohol” refers to a hydroxyl group that is directly bonded to a carbon atom, wherein that carbon atom is directly bonded to exactly two other carbon atoms. The term also refers to those compounds that include such a group (i.e., a hydroxyl group that is directly bonded to a carbon atom, wherein that carbon atom is directly bonded to exactly two other carbon atoms). 
         [0044]    As used herein, “electrochemical” or “electrochemically” refers to the inclusion of or involving electrochemistry in the reaction conditions. 
         [0045]    As used herein, “oxoammonium ion” refers to the functional group (N + ═O), and to compounds that include such a group. See, e.g., M. F. Semmelhack et al.,  J. Am. Chem. Soc.,  1983, 105, 4492-4494. 
         [0046]    As used herein, “nitroxyl radical” refers to functional group (N—O) and to compounds that include such a group. 
         [0047]    As used herein, “contacting” refers to the act of touching, making contact, or of immediate proximity, including at the molecular level. 
         [0048]    As used herein, “oligosaccharide” refers to a carbohydrate that contains two to 10 monosaccharide units. 
         [0049]    As used herein, “polysaccharide” refers to a carbohydrate that contains at least 10 monosaccharide units. 
         [0050]    As used herein, “cellulose” refers to the chief structural material of plants; a high molecular weight polysaccharide made up of glucose units. Cellulose is a complex carbohydrate, (C 6 H 10 O 5 )n wherein n is about 5,000 to about 10,000; that is composed of glucose units. On hydrolysis, cellulose gives cellobiose and ultimately glucose. This establishes its structure as a linear chain of glucopyranose units attached to each other by β-glycosidic linkages from carbon 1 of one unit to the hydroxyl group on carbon 4 of another unit. The structure consists of long chains of six-membered rings in the most stable chair conformation with all the larger substituents in the equatorial positions. 
         [0051]    As used herein, “hemicellulose” refers to any of several polysaccharides that are more complex than a sugar and less complex than cellulose, are easily hydrolyzable to simple sugars and other products, are found in plant cell walls and are produced commercially from corn grain hulls. 
         [0052]    As used herein, “starch” refers to the polysaccharide form in which plants store glucose for their energy needs. Starch is a naturally abundant nutrient carbohydrate, (C 6 H 10 O 5 ) n ; found chiefly in the seeds, fruits, tubers, roots, and stem pith of plants, notably in corn, potatoes, wheat, and rice, and varying widely in appearance according to source but commonly prepared as a white amorphous tasteless powder. Also called amylum. 
         [0053]    As used herein, “dextrin” refers to any of various soluble polysaccharides (C 6 H 10 O 5 ) n  obtained from starch by the application of heat or acids and used mainly as adhesives and thickening agents. 
         [0054]    As used herein, “maltodextrin” refers to easily digestible carbohydrates made from natural corn starch. The starch is cooked, and then acid and/or enzymes are used to break the starch into smaller polymers (a process similar to that used by the body to digest carbohydrate). 
         [0055]    As used herein, “carbohydrate” refers to polyhydroxy aldehydes or ketones. 
         [0056]    As used herein, “triterpene” or “triterpenoid” refers to a plant secondary metabolite that includes a hydrocarbon, or its oxygenated analog, that is derived from squalene by a sequence of straightforward cyclizations, functionalizations, and sometimes rearrangement. Triterpenes or analogues thereof can be prepared by methods known in the art, i.e., using conventional synthetic techniques or by isolation from plants. Suitable exemplary triterpenes and the biological synthesis of the same are disclosed, e.g., in R. B. Herbert,  The Biosynthesis of Secondary Plant Metabolites,  2nd. ed. (London: Chapman 1989). The term “triterpene” refers to one of a class of compounds having approximately 30 carbon atoms and synthesized from six isoprene units in plants and other organisms. Triterpenes consist of carbon, hydrogen, and optionally oxygen. Most triterpenes are secondary metabolites in plants. Most, but not all, triterpenes are pentacyclic. Examples of triterpenes include betulin, allobetulin, lupeol, friedelin, and all sterols, including lanosterol, stigmasterol, cholesterol, β-sitosterol, and ergosterol. 
         [0057]    As used herein, “betulin” refers to 3β28-dihydroxy-lup-20(29)-ene. Betulin is a pentacyclic triterpenoid derived from the outer bark of paper birch trees ( Betula papyrifera, B. pendula, B. verucosa,  etc.). The CAS Registry No. is 473-98-3. It can be present at concentrations of up to about 24% of the bark of white birch. Merck Index, twelfth edition, page 1236 (1996). Structurally, betulin is shown below: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0058]    As used herein, “betulinic acid” refers to 3(β)-hydroxy-20(29)-lupaene-28-oic acid; 9-hydroxy- 1-isopropenyl-5a,5b,8,8,11a-pentamethyl-eicosahydro-cyclopenta[a]chrysene-3a-carboxylic acid. The CAS Registry No. is 472-15-1. Structurally, betulinic acid is shown below: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0059]    As used herein, “betulin aldehyde” refers to 3(β)-hydroxy-lup-20(29)-en-28-al; Lup-20(29)-en-28-al, 3β-hydroxy-(8CI); Lup-20(30)-en-28-al, 3β-hydroxy-(7CI); 3aH-Cyclopenta[a]chrysene, lup-20(29)-en-28-al deriv.; Betulinaldehyde; Betulinic aldehyde; or Betunal. The CAS Registry Number is 13159-28-9. Structurally, betulin aldehyde is shown below: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0060]    As used herein, “carboxy” refers to—C(═O)O. 
         [0061]    As used herein, “3,7-dimethyl-2,6-octadienal” refers to the compound of the formula 
         [0000]      (CH 3 ) 2 C═CHCH 2 CH 2 C(CH 3 )═CHCHO 
         [0062]    As used herein, “jasminaldehyde” refers to the compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0063]    As used herein, “13-cis-Vitamin-A aldehyde” or “13-cis-Retinal” refers to the compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0064]    As used herein, “9-cis-Vitamin-A aldehyde” or “9-cis-Retinal” refers to the compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0065]    As used herein, “3,3-dimethylbutyraldehyde” refers to the compound of the formula 
         [0000]      (CH 3 ) 3 CCH 2 CHO 
         [0066]    As used herein, “3,6-dihydroxy-1,4-dioxane-2,5-dimethanol” refers to a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0067]    As used herein, “formylmethyl trimethyl ammonium chloride” refers to a compound of the formula 
         [0000]      (CH 3 ) 3 N + CH 2 CHO Cl −   
         [0068]    As used herein, “undecylenic aldehyde” refers to a compound of the formula (CH 2 ═CH(CH 2 ) 8 CHO). 
         [0069]    As used herein, “laurinaldehyde” refers to a compound of the formula (CH 3 (CH 2 ) 10 CHO). 
         [0070]    As used herein, “phenylpropionaldehyde” refers to a compound of the formula (C 6 H 5 CH 2 CH 2 CHO). 
         [0071]    As used herein, “decanal” refers to a compound of the formula (CH 3 (CH 2 ) 8 CHO). 
         [0072]    As used herein, “nonanal” refers to a compound of the formula (CH 3 (CH 2 ) 7 CHO). 
         [0073]    As used herein, “heptaldehyde” refers to a compound of the formula (CH 3 (CH 2 ) 5 CHO). 
         [0074]    As used herein, “trans, trans-2,4-hexadienal” refers to 3-propyleneacrolein; sorbaldehyde; or sorbic aldehyde; and is a compound of the formula CH 3 CH═CHCH═CHCHO. The CAS Registry Number is 142-83-6. 
         [0075]    As used herein, “undecanal” refers to a compound of the formula (CH 3 (CH 2 )CHO). 
         [0076]    As used herein, “α-amyl-b-phenylacrolein,” “α-amylcinnamal,” “α-amylcinnamaldehyde” or “α-pentylcinnamaldehyde” refers to 3-phenyl-2-amylpropenal, which is a compound of the formula (C 6 H 5 CH═C(C 5 H 11 )CHO). 
         [0077]    As used herein, “cinnamaldehyde” refers to 3-phenylpropenal, which is a compound of the formula (C 6 H 5 CH═CHCHO). The CAS Registry Number is 104-55-2. 
         [0078]    As used herein, “hydroxycinnamic aldehyde” refers to a compound of the formula (HOC6H4CH═CHCHO), pure isomer or a mixture thereof. 
         [0079]    As used herein, “caffeic aldehyde” refers to a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 68149-78-0.  
       [0080]    As used herein, “arylacrolien” refers to a compound of the formula compound of the formula (ArylCH═CHCHO), or (CH 2 ═CH(Aryl)CHO), wherein “Aryl” is defined herein. 
         [0081]    As used herein, “1,1-Dimethyl-2-carboxal-3-(2′,2′-dimethylvinyl)cyclopropane” refers to a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0082]    As used herein, “dimethylformamide” or “DMF” refers to a compound of the formula N(CH 3 ) 2 C(═O)H. The CAS Registry Number is 68-12-2. 
         [0083]    As used herein, “dimethylacetamide” refers to a compound of the formula CH 3 CON(CH 3 ) 2 . The CAS Registry Number is 127-19-5. 
         [0084]    As used herein, “γ-butyrolactone” or GBL refers to 4-Hydroxbutyric acid lactone or γ-Hydroxybutyric acid lactone; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 96-48-0.  
       [0085]    As used herein, “acetone” refers to a compound of the formula CH 3 C(═O)CH 3 . 
         [0086]    As used herein, “glyme” refers to ethylene glycol dimethyl ether; or 1,2-ethanediol, dimethyl ether. The CAS Registry Number is 110-71-4. 
         [0087]    As used herein, “2-butyn-1-al diethyl acetal” or 1,1-Diethoxy-2-butyne refers to a compound of the formula CH 3 ≡CCH(OCH 2 CH 3 ) 2 . The CAS Registry Number is 2806-97-5. 
         [0088]    As used herein, “acetaldehyde diethyl acetal” refers to a compound of the formula CH 3 CH(OC 2 H 5 ) 2 . The CAS Registry Number is 105-57-7. 
         [0089]    As used herein, “acetaldehyde dimethyl acetal” refers to a compound of the formula CH 3 CH(OCH 3 ) 2 . The CAS Registry Number is 534-15-6. 
         [0090]    As used herein, “acrolein diethyl acetal” refers to a compound of the formula CH 2 ═CHCH(OCH 2 CH 3 ) 2 . The CAS Registry Number is 3054-95-3. 
         [0091]    As used herein, “cyclohexanone diethyl acetal” refers to a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0092]    The CAS Registry Number is 1670-47-9. 
         [0093]    As used herein, “formaldehyde diethyl acetal” refers to a compound of the formula CH 2 (OC 2 H 5 ) 2 . The CAS Registry Number is 462-95-3. 
         [0094]    As used herein, “formaldehyde dimethyl acetal” refers to a compound of the formula CH 2 (OCH 3 ) 2 . The CAS Registry Number is 109-87-5. 
         [0095]    As used herein, “glyoxal 1,1-dimethyl acetal” refers to glyoxal 1,1-dimethyl acetal; dimethoxyacetaldehyde; glyoxal dimethyl acetal; or glyoxal 1-(dimethyl acetal); which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 51673-84-8.  
       [0096]    As used herein, “ketene diethyl acetal” refers to a compound of the formula CH 2 ═CH(OEt) 2 . The CAS Registry Number is 2678-54-8. 
         [0097]    As used herein, “N,N-dimethylacetamide dimethyl acetal” refers to a compound of the formula CH 3 C(OCH 3 ) 2 N(CH 3 ) 2 . The CAS Registry Number is 18871-66-4. 
         [0098]    As used herein, “N,N-dimethylformamide dibutyl acetal” refers to a compound of the formula (CH 3 ) 2 NCH(OCH 2 CH 2 CH 2 CH 3 ) 2 . The CAS Registry Number is 18503-90-7. 
         [0099]    As used herein, “N,N-dimethylformamide dicyclohexyl acetal” refers to 1,1-dicyclohexyloxytrimethylamine; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 2016-05-9.  
       [0100]    As used herein, “N,N-dimethylformamide diethyl acetal” refers to a compound of the formula (CH 3 ) 2 NCH(OC 2 H 5 ) 2 . The CAS Registry Number is 1188-33-6. 
         [0101]    As used herein, “N,N-dimethylformamide dimethyl acetal” refers to a compound of the formula (CH 3 ) 2 NCH(OCH 3 ) 2 . The CAS Registry Number is 4637-24-5. 
         [0102]    As used herein, “N,N-dimethylacetamide diethyl acetal” refers to 1,1-diethoxy-N,N-dimethyl ethanamine, which is the compound of formula ((C 2 H 5 O) 2 C(CH 3 )N(CH 3 ) 2 ). The CAS Registry Number is 19429-85-7. 
         [0103]    As used herein, “N,N-dimethylpropionamide” refers to a compound of the formula C 2 H 5 CON(CH 3 ) 2 . The CAS Registry Number is 758-96-3. 
         [0104]    As used herein, “N,N-diethylacetamide” refers to a compound of the formula CH 3 CON(C 2 H 5 ) 2 . The CAS Registry Number is 685-91-6. 
         [0105]    As used herein, “N,N-diethylformamide” refers to a compound of the formula HCON(C 2 H 5 ) 2 . The CAS Registry Number is 617-84-5. 
         [0106]    As used herein, “2-butanone” refers to methyl ethyl ketone or ethyl methyl ketone; which is a compound of the formula CH 3 CH 2 C(═O)CH 3 . The CAS Registry Number is 78-93-3. 
         [0107]    As used herein, “2-pentanone” refers to methyl propyl ketone; which is a compound of the formula CH 3 CH 2 CH 2 C(═O)CH 3 . The CAS Registry Number is 107-87-9. 
         [0108]    As used herein, “β-propiolactone” refers to hydracrylic acid β-lactone or 3-hydroxypropionic acid lactone; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 57-57-8.  
       [0109]    As used herein, “β-butyrolactone” refers to 4-Methyl-2-oxetanone; β-Methyl-β-propiolactone; or 3-Hydroxybutyric acid β-lactone; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 3068-88-0.  
       [0110]    As used herein, “TEMPO” refers to 2,2,6,6-tetramethylpiperidine 1-oxyl, having the CAS Registry No. of 2564-83-2, which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0111]    As used herein, “4-(2-Chloroacetamido)-TEMPO” refers to 4-(2-chloroacetamido)-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical, which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0112]    As used herein, “TEMPO, polymer-bound” refers to a polymeric material having a particle size 100-200 mesh, a TEMPO loading of 1.0 mmol/g, polystyrene 1% cross-linked with divinylbenzene; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0113]    wherein the wavy lines indicate bonds of the polystyrene monomeric units to adjacent monomeric units. 
         [0114]    As used herein, “4-(2-Bromoacetamido)-TEMPO” refers to 4-(2-bromoacetamido)-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 24567-97-3.  
       [0115]    As used herein, “4-(2-iodoacetamido)-TEMPO” refers to 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidine 1-oxyl or 4-(2-iodoacetamido)-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 25713-24-0.  
       [0116]    As used herein, “4-cyano-TEMPO” refers to a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 38078-71-6. 
       [0117]    As used herein, “4-maleimido-TEMPO” refers to 4-maleimido-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 15178-63-9.  
       [0118]    As used herein, “4-methoxy-TEMPO” refers to 4-methoxy-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 95407-69-5.  
       [0119]    As used herein, “4-oxo-TEMPO” refers to 4-Oxo-2,2,6,6-tetramethyl-1-piperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 2896-70-0.  
       [0120]    As used herein, “TEMPO on silica gel” refers to 2,2,6,6-Tetramethyl-1-piperinyloxy, free radical on silica gel; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
         [0121]    As used herein, “4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl” refers to 4-Amino-2,2,6,6-tetramethylpiperidine-1-oxyl; 4-Amino-2,2,6,6-tetramethylpiperidinyloxy, free radical; or 4-Amino-TEMPO; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 14691-88-4.  
       [0122]    As used herein, “4-carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl” refers to 4-carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl; 4-carboxy-TEMPO; or 4-carboxy-2,2,6,6-tetramethylpiperidinyloxy, free radical; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 37149-18-1.  
       [0123]    As used herein, “4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl” refers to 4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl; which is a compound of the formula 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 14691-89-5.  
       [0124]    As used herein, “4-(2-chloroacetamido)-2,2,6,6-tetramethylpiperidine 1-oxyl” refers to 4-(2-Chloracetamido)-TEMPO; which is a compound of the formula. 
         [0000]    
       
                 
         
             
             
         
       
     
       The CAS Registry Number is 36775-23-2.  
       [0125]    As used herein, “TEMPOL” refers to 4-hydroxy-TEMPO or 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl; which is a compound of the formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0126]    It is appreciated that those of skill in synthetic organic chemistry understand that starting materials, reagents, solvents and catalysts are typically characterized by their chemical name or structure, as they are introduced into a chemical reaction. While these compounds may undergo a substantial conversion prior to or during a specified reaction step, reference to these compounds is acceptable and appropriate to those of skill in synthetic organic chemistry. For example, TEMPO may be converted, in situ, to the corresponding N-oxoammonium ion, which oxidizes the primary alcohol (betulin) to the aldehyde (betulin-28-aldehyde), such that TEMPO itself does not, but the corresponding N-oxoammonium ion, contacts or oxidizes the primary alcohol (betulin). Reference to TEMPO contacting the primary alcohol (betulin) and/or reference to TEMPO oxidizing the primary alcohol (betulin), however, is acceptable and appropriate to those of skill in synthetic organic chemistry. As such, as used herein, “TEMPO” also includes, e.g., the corresponding N-oxoammonium ion as well as the corresponding hydroxylamine. This also applies to the compound of formula (I), e.g., the following compounds: 4-(2-Chloroacetamido)-TEMPO; TEMPO, polymer-bound; 4-(2-Bromoacetamido)-TEMPO; 4-(2-iodoacetamido)-TEMPO; 4-cyano-TEMPO; 4-maleimido-TEMPO; 4-methoxy-TEMPO; 4-oxo-TEMPO; TEMPO on silica gel; 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl; 4-carboxy-2,2,6,6-tetramethylpiperidine 1-oxyl; 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl; 4-(2-chloroacetamido)-2,2,6,6-tetramethylpiperidine 1-oxyl; and TEMPOL. 
         [0127]    As used herein, “electrolyte” refers to a chemical compound that ionizes when dissolved or molten to produce an electrically conductive medium. 
         [0128]    As used herein, “tetra-n-butylammonium perchlorate” refers to (CH 3 CH 2 CH 2 CH 2 ) 4 NClO 4 . The CAS Registry Number is 1923-70-2. 
         [0129]    As used herein, “lithium perchlorate” refers to LiClO 4 . The CAS Registry Number is 7791-03-9. 
         [0130]    As used herein, “tetraethylammonium-p-toluene sulfonate” refers to tetraethylammonium tosylate; or ethanaminium, N,N,N-triethyl, salt with 4-methylbenzenesulfonic acid. The CAS Registry Number is 733-44-8. 
         [0131]    As used herein, “NaClO 2 ” refers to sodium chlorite. 
         [0132]    As used herein, “KClO 2 ” refers to potassium chlorite. 
         [0133]    As used herein, “anode plate” refers to the electrode of an electrochemical cell at which oxidation occurs: as the positive terminal of an electrolytic cell; the negative terminal of a storage battery that is delivering current. 
         [0134]    As used herein, “cathode plate” refers to the electrode of an electrochemical cell at which reduction occurs: as the negative terminal of an electrolytic cell; the positive terminal of a storage battery that is delivering current. 
         [0135]    As used herein, “selectively oxidized” refers to a functional group (e.g., primary alcohol) of a compound undergoing a chemical conversion (e.g., to an aldehyde) and another functional group (secondary alcohol) of the same compound undergoing a chemical conversion (e.g., to a ketone), such that the ratio of the two functional group transformations is least about 90:10, at least about 95:5, or at least about 99:1, respectively. Alternatively, the term refers to a functional group (e.g., primary alcohol) of a compound undergoing a chemical conversion (e.g., to an aldehyde) and that same functional group (primary alcohol) undergoing a separate chemical conversion (e.g., to a carboxylic acid), such that the ratio of the two functional group transformations is least about 90:10, at least about 95:5, or at least about 99:1, respectively. 
         [0136]    As used herein, “selectively converted” refers to a functional group (e.g., primary alcohol) of a compound being oxidized (e.g., to an aldehyde) and another functional group (secondary alcohol) of the same compound undergoing a chemical conversion (e.g., to a ketone), such that the ratio of the two functional group transformations is least about 90:10, at least about 95:5, or at least about 99:1, respectively. Alternatively, the term refers to a functional group (e.g., primary alcohol) of a compound being oxidized (e.g., to an aldehyde) and the same functional group (primary alcohol) undergoing a separate chemical conversion (e.g., to a carboxylic acid), such that the ratio of the two functional group transformations is least about 90:10, at least about 95:5, or at least about 99:1, respectively. 
         [0137]    As used herein, “separating” refers to the process of removing solids from a mixture. The process can employ any technique known to those of skill in the art, e.g., decanting the mixture, filtering the solids from the mixture, or a combination thereof. 
         [0138]    Without being limited to any particular theory, it is believed that the oxidation of betulin to betulin-28-aldehyde and/or betulinic acid with TEMPO follows the mechanism as shown in Scheme 1 below (see,  Organic Synthesis,  Vol. 81, p. 195 (2005) and references cited therein). In that mechanism, TEMPO radical is first oxidized by NaOCl to the N-oxoammonium ion, which rapidly oxidizes the primary alcohol (betulin) to the aldehyde (betulin-28-aldehyde) and gives a molecule of the hydroxylamine. The aldehyde is then oxidized by NaOCl 2  to the carboxylic acid (betulinic acid) and regenerates a molecule of NaOCl. The hydroxylamine can either be directly oxidized or can undergo a syn proportionation to give two molecules of TEMPO radical. Although the exact mechanism of TEMPO-catalyzed oxidation of alcohols is still unclear, previous work has shown that N-oxoammonium ion and hydroxylamine are involved. 
         [0000]    
       
                 
         
             
             
         
       
     
       EXAMPLES 
     Example 1 
     Preparation of Betulin Aldehyde from Betulin 
       [0139]    450 ml of N,N-dimethylformamide, 20 g of betulin and 4 g of tetra-n-butylammonium perchlorate were loaded into a 500 ml Duran reaction vessel equipped with a heating mantle, mechanical stirrer, reflux condenser, glass-jacketed thermocouple and electrode bank of 3 flat platinum gauze anodes (50×50 mm) and 2 copper plate cathodes of the same size, clamped through 3 mm Teflon spacers. The mixture was heated up to 65° C. with stirring, then 20 ml of water and finally 1 g of TEMPO were added to mixture. After this, sufficient voltage was applied to the electrodes to maintain a 350-400 mA current. The process started at 2.9 V, then the voltage increased to 3.4-3.8 V and remained in this range for about 10 hours. At the end of the process the mixture turned from orange to colorless, and the voltage increased rapidly to 4 V and higher. The mixture was removed from the reactor to a flask, evaporated to about 200 ml, then diluted with 400 ml of water with stirring. The white deposit was filtered after the mixture cooled down, and was washed with water and dried at 70° C. Yield: 20 g of a mixture of 74% betulin aldehyde and 26% betulin as determined by GC analysis. 
       Example 2 
     Preparation of Betulin Aldehyde from Betulin 
       [0140]    2500 ml of N,N-dimethylformamide, 120 g of betulin and 20 g of tetraethylammonium p-toluenesulfonate were loaded into a 2500 ml Duran reaction vessel equipped with a heating mantle, mechanical stirrer, reflux condenser, glass-jacketed thermocouple and an electrode bank of a cylindrical platinum gauze anode of total surface area 550 cm 2  and 2 coaxial copper gauze cathodes, clamped through 4 mm Teflon rings. The mixture was heated up to 70° C. with stirring, then 100 ml of water and finally 5 g of TEMPO were added to the mixture. After this, sufficient voltage was applied on the electrodes to get a current of 3 A. The process started at 2.9 V, then the voltage increased to 3.4-3.8 V and remained in this range for about 25 hours. At the end of the process the mixture turned from orange to colorless, and the voltage increased rapidly to 4 V and higher. The mixture was removed from the reactor to a flask and diluted with 4 L of water with vigorous stirring. The white deposit was filtered after the mixture cooled down, washed with water, and dried at 70° C. Yield: 120 g of a mixture of 72% betulin aldehyde and 28% betulin as determined by GC analysis. 
       Example 3 
     Preparation of Betulin Aldehyde from Betulin 
       [0141]    2500 ml of N,N-dimethylacetamide, 120 g of betulin and 20 g of tetraethylammonium p-toluenesulfonate were loaded into the reaction vessel of Example 2. The mixture was heated up to 60° C. with stirring, then 60 ml of water and finally 5 g of TEMPO were added to mixture. After this, sufficient voltage was applied to the electrodes to get a current of 1.7 A. The voltage started at 2.6 V, then increased to 3.1±0.1 V and maintained in this range for about 35 hours. After the voltage further increased to 3.5 Volts, the process was maintained 8 hours more at constant voltage. At the end of process the mixture turned from orange to colorless. The mixture was removed from the reactor to a flask and diluted with 4 L of water with stirring. The white deposit was filtered after the mixture cooled down, washed with water, and dried at 70° C. Yield: 120 g of a mixture of 92% betulin aldehyde and 8% betulin. 
       Example 4 
     Preparation of Betulinic Acid from Betulin Aldehyde 
       [0142]    4a. 120 g of the dried product from Example 3 was dissolved in a mixture of 1000 ml of dichloromethane, 600 ml of tert-butyl alcohol and 150 ml of 2-methylbutene, then a solution of 100 g of sodium dihydrogen phosphate in 250 ml of water was added. After that, a solution of 70 g of sodium chlorite in 200 ml of water was added to the mixture in portions over 30 min. The mixture was stirred 4 hours, then poured into a rotary flask containing 2 L of water, and evaporated at 50° C. until 1000 ml of distillate was collected. The white deposit was filtered after the mixture cooled down, washed with water, and dried at 70° C. 
         [0143]    4b. The dried deposit from Example 4a (122 g) was refluxed with stirring in 2500 ml of 2-butanol until dissolved, then a solution of 12 g NaOH in 40 ml of water was added to the flask. The mixture was stirred with refluxing 2 hours more, then was filtered. The deposit of betulinic acid sodium salt was washed on a filter twice with 100 ml of hot 2-butanol, then dried. The dry deposit was then stirred vigorously in 500 ml 3% aqueous hydrochloric acid for 2 hours, then filtered, washed to neutral pH with water and dried at 70° C. Yield: 105 g of betulinic acid. 
       Example 5 
     Preparation of Betulinic Acid from Mixture of Betulin Aldehyde and Betulin 
       [0144]    5a. 300 g of a dry mixture containing 50% betulin aldehyde and 50% betulin was stirred in a flask with 3 L of dichloromethane, 2 L of tert-butyl alcohol and 300 ml of 2-methylbutene over 30 min, then a solution of 300 g of sodium dihydrogen phosphate in 800 ml of water was added. After that, a solution of 150 g of sodium chlorite in 400 ml of water was added to mixture by portions in 30 min. The mixture was stirred 4 hours, then poured into a rotary flask containing 6 L of water and evaporated at 50° C. until 3 L of distillate was collected. The white deposit was filtered after the mixture cooled down, washed with water, and dried at 70° C. 
         [0145]    5b. The dried deposit from Example 5a was stirred with refluxing in 6 L 2-butanol until dissolved, then a solution of 20 g NaOH in 40 ml of water was added to flask. The mixture was stirred with refluxing 2 hours more, then filtered. The deposit of betulinic acid sodium salt was washed on the filter twice with 200 ml of hot 2-butanol, then dried. The dry deposit was stirred vigorously in 600 ml of 3% aqueous hydrochloric acid 2 hours, then filtered, washed to neutral water and dried at 70° C. Yield: 140 g of betulinic acid. 
         [0146]    5c. The mother liquor from Example 5a (2-butanol, 6400 ml) was left to cool down to ambient temperature, then filtered. The deposit was washed on the filter twice with 100 ml of 2-butanol, then dried. Yield: 130 g of betulin, acceptable for reprocessing. 
         [0147]    All publications, patents, and patent documents cited herein are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.