Practical, efficient, stereoselective, formal synthesis of (2R,3R,4R)-3-hydroxy-4-methylproline

A highly efficient and stereoselective synthesis of (2R,3R,4R)-HMP is disclosed employing the sulfinyl group as an internal nucleophile to functionalize an olefin in the key step of the reaction sequence. The proline ring is elaborated by a (4C+N) cyclization.     

The stereoselective total synthesis of (+)-18-(6S,9R,10R)-bovidic acid

An expedient stereoselective total synthesis of 18-carbon (+)-(6S,9R,10R)-bovidic acid, isolated from the pelage and skin of a gaur B. frontalis is described using l-proline catalysed sequential α-aminoxylation and Horner-Wadsworth-Emmons olefination of aldehyde, cross metathesis and tandem Sharpless asymmetric dihydroxylation-S_N2 cyclization reaction as the key steps.     

An efficient stereoselective synthesis of (2S,4S,5R)-(−)- and (2R,4R,5S)-(+)-bulgecinine

A short synthetic route to (−)-and (+)-bulgecinine, the amino acid moiety of the bulgecins was achieved from the readily available nonchiral pool starting material cis-2-butene-1,4-diol in which a Claisen orthoester rearrangement and a Sharpless asymmetric dihydroxylation were used as the key steps.     

First stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one

A stereoselective total synthesis of (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one is reported. The strategy utilizes an iterative Jacobsen hydrolytic kinetic resolution, ring opening with a chiral propargylic synthon and a preferential (Z)-Wittig olefination reaction and lactonization as the key steps.     

Stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucines

A stereoselective synthesis of (2R,3R) and (2R,3S)-3-hydroxyleucine is disclosed. The key step of the reaction sequence involves, stereo- and regioselective bromohydration of 7, using a brominating agent derived in situ from N-bromosuccinimide and 2,6-lutidine, via intramolecular sulfinyl group participation.     

The first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one

Iterative asymmetric allylations and ring-closing metathesis have been effectively performed for the first stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one, a novel α,β-unsaturated-δ-lactone having antifungal activity, isolated from Ravensara crassifolia.     

Chemoenzymatic synthesis of (3S,4S)- and (3R,4R)-3-methoxy-4-methylaminopyrrolidine

Facile chemoenzymatic enantioselective synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, a key intermediate for a new quinolone antitumor compound AG-7352 has been described. This methodology illustrates the preparation of 3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine starting from diallylamine via 1-benzyloxycarbonyl-3-pyrroline obtained by ring-closing metathesis (RCM) employing Grubbs’ catalyst. Enzymatic transesterification employing PS-C lipase gave (3S,4S)-3-azido-1-benzyloxycarbonyl-4-hydroxypyrrolidine in >99% ee, which upon methylation of the hydroxyl group followed by sequential reactions gave the desired intermediates, (3S,4S)-1-tert-butoxycarbonyl-3-tert-butoxycarbonylamino-4-methoxypyrrolidine.     

A concise synthesis of (2S,4R)- and (2S,4S)-4-methylglutamic acid

A concise, multi-gram scale method for producing the bioactive and enantiomerically pure epimers, (2S,4R)- and (2S,4S)-glutamic acids, in a single synthetic scheme is described.     

An efficient stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine

A concise enantioselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine 1 is described starting from l-phenyl-glycine and using a Grignard reaction as a key step.     

An efficient stereoselective synthesis of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol from (S)-diethylmalate

A concise stereoselective synthesis of an imino sugar, (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol from (S)-diethylmalate has been developed in five steps and in overall yield of 28%.     

Concise and practical synthesis of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6-iminosugars

The syntheses of (2S,3R,4R,5R) and (2S,3R,4R,5S)-1,6-dideoxy-1,6 iminosugars 1a and 1b, respectively, from d-glucose are described. The key transformations in this reaction sequence include regio-selective epoxide ring opening with N-benzylamine followed by intramolecular reductive amination of amino-aldehyde.     

4-Formylazetidin-2-ones, synthon for the synthesis of (2R,3S) and (2S,3R)-3-amino-2-hydroxydecanoic acid (AHDA)

An efficient synthesis of 3-amino-2-hydroxydecanoic acid (AHDA), a nonproteinogenic amino acid, using enantiopure 3-benzyloxy-4-formylazetidin-2-one as a building block is described. Both the enantiomers of AHDA have been synthesized from the corresponding enantiomer of 3-benzyloxy-4-formylazetidin-2-one in good yield and optical purity.     

A stereoselective synthesis of (2R,3S)-2-amino-3,4-dihydroxybutyric acid using an ether directed aza-Claisen rearrangement

A new approach for the stereoselective synthesis of (2R,3S)-2-amino-3,4-dihydroxybutyric acid, an α-amino acid from Lyophyllum ulmarium, has been accomplished using an ether directed aza-Claisen rearrangement. On investigation of optimal conditions for this key step it was shown for the first time that Au(I) can be used to catalyse this transformation.     

Synthetic approaches to imino sugar (2R,3R,4S)-2-(hydroxymethyl)-4-methylpyrrolidine-3,4-diol from naturally occurring sugar and amino acid

Imino sugar compound 3 was prepared by two alternative routes starting from ribose and d-serine. From d-serine (3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methylpyrrolidin-2-one was prepared in five steps in 50% overall yield, which was further converted into (2R,3R,4S)-2-(hydroxymethyl)-4-methylpyrrolidine-3,4-diol in three steps in 23% overall yield.     

A short and efficient synthesis of the NMDA glycine site antagonist: (3R,4R)-3-amino-1-hydroxy-4-methyl pyrrolidin-2-one (L-687,414)

A short and efficient synthesis of the NMDA glycine site antagonist: (3R,4R)-3-amino-1-hydroxy-4-methyl pyrrolidin-2-one (L-687,414) is described.     

Chiral synthesis of (R)-( -)-mellein and (3R,4aS)-( + )-ramulosin

By employing an intramolecular Diels-Alder reaction as the key-step, (R)-(—)-mellein 1a (a metabolite of Aspergittus melleus) and (3R,4aS)-( +)-ramulosin 2 (a metabolite of Pestalotia ramulosa) were synthesised from ethyl (R)-3-hydroxybutanoate 3a.     

A scalable synthesis of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

A stereoselective and scalable synthesis of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid (3a) is described. Key to the success of the devised route was the realization that the stereoselectivity of a cyclopropanation step could be controlled by the composition of the functional group at C-α.     

A concise synthesis of protected (2S,4R)-4-hydroxyornithine

A short synthesis of the nonproteinogenic amino acid, (2S,4R)-4-hydroxyornithine is described. Starting from racemic benzyl glycidol, the scaffold of the target compound was constructed in high enantio- and diastereoselectivity using Jacobsen’s hydrolytic kinetic resolution (HKR) and regioselective opening of an epoxide as key steps.     

Hetero-Diels-Alder and pyroglutamate approaches to (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid

The stereoselective syntheses of fully protected (2S,4R)-2-methylamino-5-hydroxy-4-methylpentanoic acid, a non-coded amino acid of cyclomarin A, and its diastereomer are reported. A pyroglutamate template was employed in the key diastereoselective alkylation used for introducing the 4-methyl stereochemistry. In addition, the first diastereoselective intramolecular hetero-Diels-Alder of a 2-cyano-1-azadiene with an electron deficient dienophile is described.     

Stereoselective synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine

An efficient stereoselective approach for the synthesis of (3R,4S)-3-methoxy-4-methylaminopyrrolidine, a part of the structure of quinoline antibacterial compound (1a) and the naphthyridine antitumour agent (1b) has been described.