An efficient synthesis of (R)-3-hydroxytetradecanoic acid

A short, efficient synthesis of (R)-3-hydroxytetradecanoic acid, a key component of bacterial endotoxins, using (R)-oxirane acetic acid ethyl ester as the source of chirality is described. The method is general and can be used in the preparation of other chiral 3-hydroxy acids.     

An efficient enantioselective synthesis of (S)-(-)-acromelobic acid

[reaction: see text] A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF(4) catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.     

A short enantioselective total synthesis of (R)- and (S)-pipecolic acid

A convenient and practical total synthesis of (R)- and (S)-pipecolic acid has been achieved by utilizing chiral cis-aziridine-2-carboxylate as the common synthetic precursor. The synthesis involves regioselective reductive cleavage of the aziridine ring and Wittig olefination as key reactions.     

Practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid

A practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid was accomplished via an unconventional Evans anti-aldol reaction followed by a one-pot azide reduction/reductive cyclization.     

A practical synthesis of (-)-kainic acid

A highly practical stereoselective total synthesis of (-)-kainic acid is described. This synthesis features the stereoselective alkylation of an iodolactone intermediate that was efficiently prepared from (+)-carvone and introduction of carboxylic acid by hydrolysis of a nitrile accompanied by epimerizaion. This synthetic route enabled us to obtain 14.6 g of (-)-kainic acid.     

A practical stereoselective synthesis of (S)-( - )-ofloxacin

A very efficient and practical procedure for preparation of ( S)-( - )-ofloxacin has been developed (10 steps, overall yield ≥ 45 % ) . The key step of this approach is the regioselective nucleophilic substitution of 2-position fluorine atom of 2,3,4-tirfluoronitrobenzene by (S)-glycerol acetonide.     

An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.     

A practical enantioselective total synthesis of (−)-(S)-stepholidine

A convergent enantioselective total synthesis of (−)-(S)-stepholidine, a drug candidate for the treatment of schizophrenia and/or drug abuse, was described, which represented the first example of successful auxiliary-assisted Bischler–Napieralski cyclization of amide bearing bromine atom at 2-position of the C ring, followed by an introduction of the aryl methyl ester via Br–Li exchange. (−)-(S)-Stepholidine was synthesized in 6 steps, with 52% overall yield and >99% ee. The reported synthesis is practically free from chromatographic separation.     

An enantioselective synthesis of (S)- and (R)-curcuphenol

The enantioselective synthesis of the phenolic sesquiterenses (S)- and (R)-curcuphenol is reported. The key step in this synthesis is the asymmetric conjugate addition using a readily available enantiomerically pure sulfoxide as the chiral auxiliary.     

A convenient enantioselective synthesis of (S)-alpha-trifluoromethylisoserine

[reaction: see text] This report describes two straightforward synthetic methodologies to obtain alpha-CF3-isoserine, a new alpha,alpha-disubstituted beta-amino acid, from alpha-(trifluoromethyl)acrylic acid. The routes involve the synthesis of five-membered cyclic sulfates (using sulfuryl chloride) or sulfamidates (using the Burgess reagent) from the corresponding chiral diols, which are obtained by a catalytic asymmetric dihydroxylation (AD) reaction.     

Simultaneous enzymatic synthesis of (S)-3-fluoroalanine and (R)-3-fluorolactic acid

A coupled enzymatic system for the simultaneous synthesis of (S)-3-fluoroalanine (1a) and (R)-3-fluorolactic acid (3) with l-alanine dehydrogenase (l-AlaDH) from Bacillus subtilis and rabbit muscle l-lactate dehydrogenase (l-LDH) using rac-1 and NAD⁺ is described. Analysis of isolated products of the laboratory preparative scale process revealed 1a in 60% yield and 88% ee and 3 in 80% yield and over 99% ee. The compounds 1a and 3 represent chiral building blocks for the synthesis of several products with pharmacological activity.     

A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic acid from geraniol

The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.     

A simple and practical approach to enantiomerically pure (S)-3-hydroxy-γ-butyrolactone: synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester

The oxidation of α- or β-(1,4) linked disaccharides or oligosaccharides with cumene hydroperoxide in the presence of a base gave (S)-3,4-dihydroxybutyric acid, which was cyclized under acidic conditions to furnish (S)-3-hydroxy-γ-butyrolactone. This was subsequently converted into (R)-cyano-3-hydroxybutyric acid ethyl ester, an intermediate for statin based drugs and other related compounds.     

A practical stereoselective synthesis of (2R,3S)-alloisoleucine

An efficient asymmetric Strecker synthesis of the unnatural α-amino acid, d-alloisoleucine (3), from commercially available and inexpensive (S)-2-methyl-1-butanol (4) was accomplished in four steps.     

Highly diastereoselective arylation of (S)-mandelic acid enolate: enantioselective synthesis of substituted (R)-3-hydroxy-3-phenyloxindoles and (R)-benzylic acids and synthesis of nitrobenzophenones

An easy access to substituted (R)-3-hydroxy-3-phenyloxindoles, (R)-benzylic acids, and benzophenones is described. The reaction of the lithium enolate of the (2S,5S)-cis-1,3-dioxolan-4-one derived from optically active (S)-mandelic acid and pivalaldehyde with several o- and p-halonitrobenzenes proceeds readily to give the corresponding arylation products in good yields and diastereoselectivities. The reduction of the nitro group with Zn/HCl/EtOH in the o-nitro arylation products with concomitant intramolecular aminolysis of the dioxolanone moiety leads directly to enantiomerically pure (R)-3-hydroxy-3-phenyloxindoles. On the other hand the basic hydrolysis of the dioxolanone moiety in all the arylation products (ortho and para) leads to enantiomerically pure substituted (R)-benzylic acids. The oxidative decarboxylation of these latter with oxygen as terminal oxidant in the presence of pivalaldehyde and the Co(III)-Me2opba complex as catalyst gives substituted nitrobenzophenones.     

A catalytic enantioselective total synthesis of (-)-wodeshiol

[formula: see text] (-)-Wodeshiol of > 99% ee has been synthesized from the alpha,beta-enone shown using a number of noteworthy steps including a novel C-C coupling reaction.     

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone

A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.     

A practical process for large-scale synthesis of (S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE)

($\text{S}$)-5-Hydroxy-6-$\text{trans}$-8,11,14-$\text{cis}$-eicosatetraenoic acid (5-HETE) (1) and its enantiomer are readily available by a chemical synthesis from arachidonic acid which includes a chromatographic separation of diastereomeric urethanes (3) made from (±)-5-HETE methyl ester and the isocyanate 4 derived from dehydroabietylamine.     

The enantioselective total synthesis of a beta-carboline alkaloid, (S)-(-)-dichotomine C

The first enantioselective synthesis of a beta-carboline alkaloid, dichotomine C, possessing antiallergic effects, was achieved by constructing a beta-carboline framework based on the microwave-assisted thermal electrocyclic reaction of a 1-azahexatriene system, followed by the Sharpless asymmetric dihydroxylation.