Synthesis of amino/hydroxy

Synthesis of Amino/Hydroxy Substituted Cyclopentanes and a Carbocyclic Nucleoside... 

Synthesis of amino/hydroxy substituted cyclopentanes carbasugars... 

Halopurines are valuable intermediates in the synthesis of amino-, hydroxy-, or sulfanyl-substi-tuted purines and the C NMR chemical shifts of selected compounds are summarized in Table 11. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Tnflrc anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive triflates can be generated m situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoqumolines (equation 45) and synthesis of Al-hydroxy-a-amino acid denvatives (equation 46) via the intermediate covalent triflates... 

It was reported that the Niemeiitowski synthesis of 4-hydroxy-3-iiitro-7-pheiiyl-l,8-iiaphthyridiii-2(lH)-oiie (25) from ethyl 2-amiiio-6-pheiiyhii-cotiiiate (23) and ethyl nitroacetate (24) in the presence of sodium was unsuccessful, producing only traces of (25), while condensation of ethyl 2-amino-6-phenylnicotinate (23) with the less reactive ethyl acetate resulted in the formation of 4-hydroxy-7-phenyl-l,8-naphthyridin-2(lH)-one in good yield [66JCS(C)315]. It seems that the more reactive nitroacetate tends to precipitate rapidly from the reaction mixture as its sodio derivative, which explains the low yield of (25). 

Chiral 4,5-disubstituted oxazolidin-2-ones in stereoselective synthesis of (3-hydroxy-a-amino acids 97G475. 

It should be noted that this sequence shown in Scheme 31 is complementary to that depicted in Scheme 30 in which a-hydroxy-j9-amino acids are prepared. This chemistry of aziridine- and oxiranecarboxylic esters and the corresponding ring expansion reactions has been elaborated to a general protocol for the synthesis of j9-hydroxy-a-amino and a-hydroxy-j9-amino acids, respectively [1,411. 

Jackson and coworkers have used a new approach to the synthesis of P-hydroxy-a-amino acids using (arylthio)nitrooxiranes. D-Isopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of P,y-dihydroxyamino acids (Scheme 4.6). The key step is stereoselective nucleophilic epoxida-tion of the 1-arylthio-l-nitroalkene. Syn and anti epoxides are selectively obtained by appropriate choice of epoxidation reagent.51... 

Hydroxynitrile lyases (HNLs or oxynitrilases) catalyze C—C bond-forming reactions between an aldehyde or ketone and cyanide to form enantiopure cyanohydrins (Figure 1.15), which are versatile building blocks for the chiral synthesis of amino acids, hydroxy ketones, hydroxy acids, amines and so on [68], Screening of natural sources has led to the discovery of both... 

Warmerdam, E.G.J.C., van Rijn, R.D., Brussee, J. et al. (1996) Synthesis of a-hydroxy-/3-amino acids from chiral cyanohydrins. Tetrahedron Asymmetry, 7, 1723-1732. 

Paulsen, H. and Kuhne, H., Synthesis of a-hydroxy- and a-amino-phospho-nates of acyclic monosaccharides, Chem. Ber., 108, 1239, 1975. 

The addition of lithium or magnesium ester enolates to nitrones in THF at 78°C or in Et20 at — 20°C, constitutes a direct synthesis of /V-hydroxy- 3-amino acid esters (Scheme 2.180) (645). 

M. Horikawa, J. Bush-Petersen, E. J. Corey, Enantioselective Synthesis of P-Hydroxy-a-amino Acid Esters by Adol Coupling Using a Chiral Quaternary Ammonium Salt as Catalyst , Tetrahedron Lett. 1999, 40, 3843-3846. 

Remarks on Sections 6 and 7.-—The method here described for the synthesis of cyanohydrins—treatment of the bisulphite compound of the aldehyde with potassium cyanide—cannot be used in all cases. Concentrated solutions of hydrocyanic acid or anhydrous hydrogen cyanide are often used. The general method for the synthesis of a-amino-acids, the nitriles of which are formed by the union of ammonium cyanide with aldehydes or ketones (Strecker), is to be contrasted with that for the synthesis of a-hydroxy acids. For additional amino-acid syntheses see Chap. VII. 2, p. 276. 

Chiral cyanohydrins are versatile intermediates in the synthesis of a-hydroxy acids, /3-amino alcohols, amino nitriles, a-hydroxy ketones and aziridines. For the synthesis of enantiopure cyanohydrins, the use of hydroxynitrile lyases is currently the most effective approach.Application of an organic-solvent-free system allows thermodynamically hindered substrates to be converted with moderate to excellent yields. With the use of the highly selective hydroxynitrile lyase from Manihot esculenta, the syntheses of several acetophenone cyanohydrins with excellent enantioselectivities were developed (Figure 8.2). (5)-Acetophenone cyanohydrin was synthesized on a preparative scale. ... 

A review entitled a-heteroatom-substituted 1-alkenyllithium regents carbanions and carbenoids for C-C bond formation has addressed the methods of generation of such species, illustrated the carbenoid reactivity of a-lithiated vinyl halides and vinyl ethers, and emphasized the synthetic potential of the carbanion species in asymmetric synthesis of a-hydroxy- and a-amino-carbonyl compounds. ... 

The tcrt-butoxycarbonyl (BOC) group is often used for the protection of amino, hydroxy, and sulfhydryl groups. This kind of protection is usual in the chemistry of amino acids and peptide synthesis. 

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

Lin and Zhang reported the synthesis of l-hydroxy-3-methylcarbazole (23) starting from the nitro derivative 625 (578). This synthesis uses a Buchwald-Hartwig amination for the synthesis of the diphenylamine 628. After protection of the hydroxy group in the nitrophenol 625 as a benzyl ether, the nitro group was reduced to the corresponding amino derivative 627. Amination of 627 with iodobenzene under Buchwald-Hartwig conditions afforded the diarylamine 628. Palladium(ll)-mediated cyclization of 628 led to the carbazole derivative 629, albeit in low... 

In a similar manner, intramolecular cyclization of the O-stannyl ketyl derivatives 201 and 206, generated from the oxazolyl aldehydes 200 and 205, provides a facile method for the chiral synthesis of 3-hydroxy-2-(hydroxymethyl)-5-substimted-pyrrolidines 202 and 203 and the piperidine analogues 207 and 208 that can be successfully transformed into naturally occurring amino alcohols, (+)-bulgecinine 204 and (—)-desoxoprosopinine 209, respectively (Fig. 

JAP624149) and a wide variety of l-lV-alkylperhydro-l,7-naphthyridines (207) have been obtained by reaction of the ether (208) with various alkylamines (66KGS427). A convenient synthesis of 5-hydroxy-2-oxo-l,2,3,4-tetrahydro-l,7-naphthyridine (211) starts from the 3-substituted amino isonicotinaldehyde (209) which undergoes a Wittig reaction followed by reduction to give (210), a compound that cyclizes readily in acid solution to (211) (82CPB1257). 

The photoelectrochemical synthesis of amino acids from simple molecules has also been reported. Low efficiencies were observed in the conversion of mixtures of methane, ammonia and water to several amino acids on platinized TiOz Amino acids and peptides were reported when glucose replaced methane as the carbon source in a parallel experiment Higher quantum efficiencies (20-40%) were observed in the conversion of alpha-keto acids or alpha-hydroxy acids to the corresponding alpha-amino acids Moderate levels of enantiomeric selectivity (optical yields of about 50%) were reported when chiral starting materials were employed. Photoinduced Michael-like reactions were observed when alpha, beta unsaturated acids were used as substrates for the amino acid synthesis... 

Applications of the Conrad-Limpach reaction to the synthesis of 1-hydroxy-4,7-phenanthrolines or, more correctly, l-oxo-l,4-dihydro-4,7-phenanthrolines, from p-phenylenediamine or 6-aminoquinolines continue to be reported. l,10-Dihydroxy-3,8-dimethyl-4,7-phenanthroline has again been prepared from p-phenylenediamine,234 hot diphenyl ether being used to effect the cyclization. Other examples include the new or improved preparations of l-hydroxy-3-methyl-, 10-amino-l-hydroxy-3-methyl-,232 2-(y-chlorocrotonyl)- l,10-dihydroxy-3,8-dimethyl-, and 2,9-bis (y- chlorocrotonyl)-1,10- dihydroxy - 3,8 - dimethyl - 4,7 - phenanthro-lines.235 Compounds prepared in this way have been patented as antiasthmatic agents.178 A closely related synthesis employing poly-phosphoric acid as cyclizing agent has yielded l-hydroxy-3-phenyl-4,7-phenanthroline.236... 

Further examples of the Knorr reaction for the synthesis of 3-hydroxy-4,7-phenanthrolines are reported. A modification of the original synthesis239 of 3-hydroxy-1-methyl-4,7-phenanthroline involves isolation of the intermediate acetoacetanilide followed by ring closure with sulfuric acid.232 10-Amino-3-hydroxy-l-methyl-4,7-phenanthroline was obtained similarly from 4-amino-6-acetoacetamidoquinoline. Several 2-substituted l,3-dihydroxy-4,7-phenanthrolines were obtained likewise from diethyl alkylmalonates.101... 

Literature data on the carbon skeleton elongation may be classified according to the number of carbon atoms added. Such a classification, although far from being ideal, is useful from the synthetic viewpoint. Scheme 2 illustrates the usefulness of a-amino acids (in particular a-amino-(3-hydroxy acids e.g., serine, threonine, and their homologues) in the synthesis of amino sugars. 

A. Golfbiowski and J. Jurczak, a-Amino-P-hydroxy acids in the total synthesis of amino sugars, Synlett p. 241 (1993). 

These also presumably lead to a transient quinonoid-carbanionic intermediate. Addition of a proton at the original site of decarboxylation followed by breakup of the Schiff base completes the sequence. Decarboxylation of amino acids is nearly irreversible and frequently appears as a final step in synthesis of amino compounds. For example, in the brain glutamic acid is decarboxy-lated to y-aminobutyric acid (Gaba),193 196b while 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxy-... 

A synthesis of a-hydroxy-/f-(perfluoroalkyl)-/)-amino acids has been reported via s-hydroxy-/ -imino esters 18. Tmidoyl esters 17 are readily obtained from imidoy] chlorides 16 and undergo a 1.2-shift from oxygen to carbon under basic conditions.1 The authors propose an a,/f-epoxy ester intermediate. 

This synthesis of amino acids, called the Strecker synthesis, requires the presence of NH4+ (and NH3) in the primitive ocean. On the basis of the experimental equilibrium and rate constants it can be shown16 that equal amounts of amino and hydroxy acids are obtained when the NH4+ concentration is about 0.01 M at pH 8 and 25°C with this NH4+ concentration being insensitive to temperature and pH. This translates into a pNH3 in the atmosphere of 2 x 1(U7 atm at 0° and 4 x 10-6 atm at 25°C. This is a low partial pressure, but it would seem to be necessary for amino acid synthesis. Ammonia is decomposed by ultraviolet light, but mechanisms for resynthesis are available. The details of the ammonia balance on the primitive earth remain to be worked out. 

---