Reductic acids hydroxy-methyl

Pyrrole has been condensed under alkaline conditions with formaldehyde to give products of either N- or C-hydroxymethylation (Scheme 22). Although acid-catalyzed hydroxy-methylation is not a practical possibility, by addition of a reducing agent to the reaction mixture overall reductive alkylation can be achieved (Scheme 23). 

Another attempted synthesis of Tc(III)-EDTA and Tc(III)-HEDTA complexes (EDTA ethylenediaminetetraacetic acid HEDTA A -(2-hydroxy-methyl)ethylenediamine-N,AT, iV -triacetic acid) was carried out using [Tc(tu)6]3+ as the starting complex [40]. Technetium-EDTA complexes have been synthesized by the direct reduction of pertechnetate with a suitable reduc-tant in the presence of excess EDTA [41-43]. On addition of EDTA to the Tc(tu) + solution, the intensity of the absorption spectrum decreased with time and the solution color changed from reddish orange to light brown. An electrophoretic analysis for the Tc(III)-EDTA complex showed that more than 70%... 

DL-Dihydrostreptose and its ribo isomer were similarly obtained. Birch reduction of 2-methyl-3-furoic acid, followed by addition of methanol, bromination, and dehydrobromination, gave 402 as a mixture of the isomers. Hydroxylation of 402 with osmium tetraoxide-so-dium chlorate, and subsequent treatment with acetone-sulfuric acid afforded three isomeric acetals (403-405). The structures of these compounds were assigned on the basis of their H-n.m.r. spectra. In addition, the relationship between 403 and 404 was established by hydrolysis and reglycosidation. The methyl esters 403-405 were quantitatively reduced to the corresponding alcohols. The mixture of alcohols obtained from 403 and 404 was converted into crystalline 5-deoxy-3-C-(hydroxymethyl)-l,2-0-isopropylidene-a-DL-ribofuran-ose (406), which was compared directly with a sample prepared from D-xylose. Methyl 5-deox y-3-C-(hydroxy methyl)-2,3-O-isopropy lidene-/3-DL-lyxofuranoside (407), obtained by reduction of 405 with lithium aluminum hydride, was hydrolyzed with dilute hydrochloric acid, to give a,/3-DL-dihydrostreptose.2,ifi... 

Reactions using catecholborane proceed smoothly in toluene (Scheme 16) (40). The utility of catalytic hydroboration of ketones has been demonstrated by the efficient enantioselective synthesis of a series of biologically active compounds (41). Scheme 17 shows some compounds prepared by using this method. Enantioselective reduction of trichloro-methyl ketones is a general route to a-amino acids and a-hydroxy esters it also allows ready synthesis of a precursor to the carbonic anhy-drase inhibitor MK-0417 (42). 

The structure of the uronic acid was established as follows (a) periodate oxidation, followed by bromine oxidation, gave 2-hydroxy-3-methoxy-L-erj/f/tro-succinic acid 1413 (b) reduction of the methyl glycoside methyl ester with lithium aluminum hydride, followed by hydrolysis, gave 4-0-methyl-D-glucose.13... 

Recently, we [67] have described the reduction of the methyl ester of 4-chloro-3-oxobutanoic acid (39) to the methyl ester of S-( )-4-chloro-3-hydroxy-butanoic acid (40) (Fig. 13) by cell suspensions of Geotrichum candidum SC 5469., S ( )-(40) is a key chiral intermediate in the total chemical synthesis of a cholesterol antagonist (SQ 33600), which acts by inhibiting hydroxymethylglu-taryl CoA (HMG CoA) reductase. In the biotransformation process, a reaction... 

Stereoselective reduction of a-alkyl-3-keto acid derivatives represents an attractive alternative to stereoselective aldol condensation. Complementary methods for pr uction of either diastereoisomer of a-alkyl-3-hydroxy amides from the corresponding a-alkyl-3-keto amides (53) have been developed. Zinc borohydride in ether at -78 C gave the syn isomer (54) with excellent selectivity ( 7 3) in high yield via a chelated transition state. A Felkin transition state with the amide in the perpendicular position accounted for reduction with potassium triethylborohydride in ether at 0 C to give the stereochemi-cally pure anti diastereoisomer (55). The combination of these methods with asymmetric acylation provided an effective solution to the asymmetric aldol problem (Scheme 6). In contrast, the reduction of a-methyl-3-keto esters with zinc borohydride was highly syn selective when the ketone was aromatic or a,3-unsaturated, but less reliable in aliphatic cases. Hydrosilylation also provided complete dia-stereocontrol (Scheme 7). The fluoride-mediated reaction was anti selective ( 8 2) while reduction in trifluoroacetic acid favored production of the syn isomer (>98 2). No loss of optical purity was observed under these mild conditions. 

Although known for almost forty years, and in spite of a total synthesis of its racemate, the stereochemistry of doisynolic acid has remained in doubt. This problem has now been settled by a stepwise chemical conversion (Scheme 23) of 14)5-oestrone methyl ether (339), prepared from natural oestrone (114a), into c/s-doisynolic acid methyl ether (342). Osmium tetroxide oxidation of the enol acetate corresponding to (339) provided 16a-hydroxy-14)S-oestrone methyl ether. Subsequent periodic acid oxidation afforded the lactol (340), which upon treatment with diazomethane gave the aldehydo-ester (341). Electrochemical reduction of the aldehyde (341) afforded a methyl ester which by alkaline hydrolysis provided (-f )-ds-doisynolic acid 3-methyl ether (342), thus defining its complete stereochemistry. ... 

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

Further elucidation of the structure of insularinic acid came when it (LXXII) was heated at 130-145° in a sealed bomb with hydrogen bromide for one and one-half hours. The resulting product (LXIXVIII) on catalytic reduction followed by methylation with diazomethane and saponification yielded 4,5 -dicarboxy-2 -methyl-2,3-dimethoxydiphenyl ether (LXXIX). This was synthesized from the potassium salt of methyl 4-hydroxy-3-methylbenzoate and methyl 3-bromo-4,5-dimethoxybenzoate by the Ullmann condensation. 

Conversion of alditols to aldoses without the need to protect all hydroxy groups has been achieved by monotosylation of one primary hydroxy group, displacement with azide ion and photolysis in methanol to yield the aldimine,which was then hydrolyzed to the aldose. The procedure was illustrated using 3 4-0 isopro ylideno-D-mannitol to produce D-mannose. The synthesis of D-[U- Cjgalactose from methyl <-D-[n- Cjglucopyranoside via aqueous bromine oxidation to the 4.-uloside, reduction by sodium borohydride and hydrolysis has been described, along with the isolation of D-glucuronic acid and methyl o( D-mannopyranoside as by-products. 

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