Enantioselective synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine

An efficient and short synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine 1a-b is described using Sharpless asymmetric dihydroxylation and regioselective nucleophilic opening of a cyclic sulfite as the key steps.     

An asymmetric dihydroxylation route to (2S,3S)-3-hydroxypipecolic acid

A concise enantioselective synthesis of (2S,3S)-3-hydroxypipecolic acid 1 starting from 1,4-butanediol using Sharpless asymmetric dihydroxylation and the regioselective nucleophilic opening of a cyclic sulfate as the key steps is described.     

Enantioselective synthesis of functionalized γ-butyrolactones

Sharpless asymmetric dihydroxylation and aminohydroxylation of (E)-dimethyl-2-alkylidene glutarates 2 were shown to afford enantio-enriched or enantiopure highly functionalized γ-butyrolactones 3 and 7.     

Formation of chiral tertiary homoallylic alcohols via Evans aldol reaction or enzymatic resolution and their influence on the Sharpless asymmetric dihydroxylation

Enantioenriched tertiary homoallylic alcohol derivatives (S)-2c and (S)-2a were obtained via Evans aldol methodology and enzymatic resolution of racemic tertiary acetate 2e, respectively. In order to study asymmetric 1,3-induction of the stereogenic center present in 2, congener (R)-2a as well as its O-protected derivatives (R)-2b-d were submitted to Sharpless asymmetric dihydroxylation to yield the diastereomeric 1,2,4-triol derivatives (2R,4R)- and (2S,4R)-3a-d, revealing that neither the substrate nor the Sharpless catalyst exert any stereocontrol. Similar observations were made for the less bulky alkynyl-substituted derivative 12b. However, by using a directed dihydroxylation, the anti product (2R,4R)-3a was favored.     

Application of the asymmetric aminohydroxylation reaction for the syntheses of HIV-protease inhibitor, hydroxyethylene dipeptide isostere and γ-amino acid derivative

An enantioselective synthesis of lactone 1, a precursor to the (2R,4S,5S) hydroxyethylene dipeptide isostere and amino acid AHPPA 2 has been accomplished from the common intermediate 5 employing Sharpless asymmetric aminohydroxylation as the key step.     

Total synthesis of (−)-physovenine from (−)-3a-hydroxyfuroindoline

Total synthesis of calabar bean alkaloid (−)-physovenine (−)-3 has been achieved in a concise manner starting from optically active (−)-3a-hydroxyfuroindoline (−)-2, synthesized via modified Sharpless epoxidation of tryptophol 1. Our strategy involved a stereospecific radical substitution reaction and regioselective oxidation at the C5 position.     

Regioselective Baeyer-Villiger lactonization of 2-substituted pyrrolidin-4-one. Synthesis of statine

Nine 2-substituted pyrrolidin-4-ones 4a-i were obtained via a series of functional group transformation of known prolinol 5 by facile six kinds of methodologies. The target structure of 1,3-amino alcohols 2a-i was constructed in the regioselective Baeyer-Villiger lactonization of ketones 4a-i and reduction of the resulting 4-substituted tetrahydro-1,3-oxazin-6-ones 3a-i. A new and straightforward synthesis of (3S,4S)-statine (6) has been established starting from trans-(2S,4R)-4-hydroxyproline (1).     

Synthesis of arylated highly congested indans using a domino sequence

A novel and efficient regioselective synthesis of various arylated highly congested 7-aryl-5-methylsulfanylindan-4-carbonitriles (3a-f), methyl 7-aryl-5-methylsulfanylindan-4-carboxylates (10a-e) and 7-aryl-5-methylsulfanylindan-4-carboxylic acids (11a-e) through base-catalyzed reaction of 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (1a-f) and methyl 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (9a-e) by cyclopentanone (2) has been delineated. The synthetic potential of 2-pyranone was explored further to generate molecular diversity using 6-aryl-4-sec-amino-2-oxo-2H-pyran-3-carbonitriles (7a-h), 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (5a,b) and methyl 5,6-diaryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (12a,b) as precursors for the ring transformation by cyclopentanone to assess the effects of substituents on the course of the reaction to obtain highly congested indans, 6,7-diaryl-5-methylsulfanylindan-4-carbonitriles (6a,b), 7-aryl-5-(piperidin-1-yl)indan-4-carbonitriles (8a-h) and methyl 6,7-diaryl-5-methylsulfanylindan-4-carboxylates (13a,b).     

An efficient and regioselective one-pot multi-component synthesis of pyrimido[4,5-d]pyrimidine derivatives in water

Pyrimido[4,5-d]pyrimidine derivatives 4 have been prepared in an efficient and regioselective manner in water via multi-component reaction of isothiocyanate 1, aromatic aldehyde 2, N,N-dimethyl-6-amino uracil 3 in the presence of p-toluenesulfonic acid (p-TSA) as a Lewis acid catalyst.     

Enantioselective syntheses of (−)-pinellic acid, α- and β-dimorphecolic acid

An efficient enantioselective convergent approach for the synthesis of (−)-pinellic acid 1, α- and β-dimorphecolic acid (2 and 3) from 1,9-nonane diol is described. The synthetic strategy features Sharpless asymmetric hydroxylation, Sonogashira coupling and Birch reduction.     

Chemistry of xanthorrhizol: synthesis of several bisabolane sesquiterpenoids from xanthorrhizol

(−)-Xanthorrhizol (1) isolated from the rhizomes of Curcuma xanthorrhiza has been transformed to several bisabolane-type sesquiterpenoids, in a stereoselective manner. 10R- and 10S-10,11-dihydro-10,11-dihydroxyxanthorrhizols (2, 3), (−)-curcuquinone (4), (−)-curcuhydroquinone (5), helibisabonol A (7) and allylic alcohol 8 have been prepared from xanthorrhizol in optically active forms. All the routes involved a Sharpless AD to introduce the stereogenic centre at C-10.     

Enantioselective synthesis of (−)-galantinic acid

An efficient enantioselective synthesis of (−)-galantinic acid 1, a non-proteogenic amino acid is described using Sharpless asymmetric epoxidation, dihydroxylation and the regioselective nucleophilic opening of a cyclic sulfite as the key steps.     

Four new ginkgolic acids from Ginkgo biloba

Four new compounds, 2-hydroxy-6-(12′-hydroxyheptadec-13′(E)-en-1-yl)benzoic acid (1), 2-hydroxy-6-(13′-hydroxyheptadec-11′(E)-en-1-yl)benzoic acid (2), 2-hydroxy-6-(10′-hydroxypentadec-11′(E)-en-1-yl)benzoic acid (3), and 2-hydroxy-6-(11′-hydroxypentadec-9′(E)-en-1-yl)benzoic acid (4) were isolated from the leaves of Ginkgo biloba and the structures of new ginkgolic acids were deduced on the basis of spectroscopic methods and chemical means. Compounds 1 and 2, and 3 and 4 examined as an inseparable mixture of hydroxyl and double bond positional isomers, were ultimately defined by total synthesis. Compounds 1–4 showed moderate lipid droplets accumulation inhibitory activity on mouse pre-adipocyte cell line, MC3T3-G2/PA6.     

Synthesis of terminal disaccharide unit of Klebsiella pneumoniae ssp. R20

Synthesis of the terminal disaccharide unit of a novel α-(1→2) linked heptoglycan of K. pneumoniae ssp. strain R20 from methyl α-d-mannopyranoside has been presented. Central to the strategy is the application of Sharpless asymmetric dihydroxylation to introduce a new center at C-6 position of mannopyranoside. The coupling of two heptoglycans (12 and 13) was accomplished by a Lewis acid catalyst.     

Efficient and regioselective chromium(0)-catalyzed reaction of 2-substituted furans with diazo compounds: stereoselective synthesis of (2E,4Z)-2-aryl-hexadienedioic acid diesters

Pentacarbonyl(η²-cis-cyclooctene)chromium(0) (1) catalyzes efficiently reactions of diazo compounds with electron-rich furans. The reaction of 2-methoxyfuran (2) with alkyl α-diazoarylacetate (3a-g) furnishes the (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g) in excellent yields. These reactions are highly regioselective. The cyclopropanation intermediates formed from 1 and diazo compounds 3a-g always arise from a carbene addition to the less substituted CC bond of 2. The resulting cyclopropanation product undergoes a ring opening reaction to form the corresponding (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g). The pentacarbonylchromium(0)-catalyzed reactions of 2-alkylfuran (5a-b) with ethyl α-diazophenylacetate (3a) and 9-diazo-9H-fluorene (3h) produce the 1(E),3(E)-butadienes (6a-d) in very good yields.     

Synthesis of optically active seven-membered 1,5-anhydrocarbasugars and 1,4,5-tribenzoyloxy-2-ethoxy cycloheptanes via [5+2] cycloaddition

[5+2] Cycloaddition followed by asymmetric dihydroxylation procedure have been utilized to prepare novel cyclitols. Accordingly, rac-2α-hydroxy-6α-ethoxy-1,5-anhydro cyclohept-3-ene, 10 derived from [5+2] cycloaddition of 3-oxidopyrylium ylide and vinyl ether has been recognized as a seven-membered carbasugar equivalent and elaborated to 1,4,5-tribenzoyloxy-2-ethoxy cycloheptanes through a flexible, regio- and stereoselective strategy involving Sharpless asymmetric dihydroxylation conditions to resolve the compounds obtained. The structures and relative configurations of newly synthesized (+)-2α-acetoxy-6α-ethoxy-3β,4β-dihydroxy-1,5-anhydro cycloheptane ((+)-12)); (−)-1β,4β,5β-tribenzoyloxy-6α-ethoxy cycloheptane ((−)-17) and (+)-1α,4α,5α-tribenzoyloxy-6β-ethoxy cycloheptane ((+)-17) are unambiguously established by single crystal X-ray analysis and duly supported by ¹H and ¹³C NMR spectroscopy data.     

Bisleuconins A-D: a pair of epimeric ent-kauranoid dimers and two new asymmetric analogues isolated from Isodonleucophyllus

A phytochemical investigation of Isodon leucophyllus led to the isolation of four novel ent-kauranoid dimers: bisleuconins A-D (1-4), and one known compound, rabdoloxin A (5). It was interesting that the structures of bisleuconins A (1) and B (2) were elucidated as a pair of epimeric ent-kauranoid dimers with unique linkage pattern C-16→C-17′ to connect two monomers. Bisleuconins C (3) and D (4) were two new asymmetric ent-kauranoid dimers. A possible biogenetic pathway of 1 and 2 was also proposed.     

Synthesis of substituted (S)-2-aminotetralins via ring-opening of aziridines prepared from l-aspartic acid β-tert-butyl ester

This paper describes the total synthesis of the hydrochloride salts of (2S)-2-amino-7-methoxytetralin (21-HCl) and (2S)-2-amino-6-fluoro-7-methoxytetralin (ST1214), from a common enantiomerically pure aziridine 4b, which was available from l-aspartic acid β-tert-butyl ester. The synthesis of 21-HCl and ST1214 proceeded in nine steps and 5 and 6% overall yields, respectively. Key steps are the regioselective ring-opening of 4b with ArMgBr/CuBr·SMe₂ and the intramolecular Friedel-Crafts cyclisation providing α-tetralone. Substituted naphthalenes were formed as side products in the latter reaction.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

Synthesis of the ABC and IJ ring fragments of yessotoxin

Synthesis of a 6/6/6 tricyclic ether system (3) corresponding to the ABC ring fragment of yessotoxin (1) has been achieved via coupling of a triflate and a 2-lithiofuran followed by intramolecular hetero-Michael addition. The IJ ring fragment (4) of 1 was readily synthesized via successive Sharpless epoxidation and 6-endo cyclization of the resulting vinyl epoxide.