Synthesis of (E)- and (Z)-α,β-difluorourocanic acid

Horner-Emmons fluoroolefination of an aryl aldehyde followed by introduction of a second fluorine via “FBr” addition provides an original approach to the preparation of 1-alkyl-2-aryl-1,2-difluoroethenes. The utility of this procedure is demonstrated by the preparation of (E and Z)-α,β-difluorourocanic acid.     

Synthesis and transformations of [1,2-O-isopropylidene-α-d-erythro (and α-d-ribo)furanose]-3-spiro-3′-(4′-amino-5′H-2′,3′-dihydroisothiazole-1′,1′-dioxide) derivatives

The carbanion-mediated sulfonamide cyclisations (CSIC protocols) of glyco-α-sulfonamidonitriles derived from readily available uloses 1A and 1B have been investigated using different bases (potassium carbonate, cesium carbonate, LDA and n-BuLi). As a result, a series of enantiomerically pure [1,2-O-isopropylidene-α-d-erythro (and α-d-ribo)furanose]-3-spiro-3′-(4′-amino-5′H-2′,3′-dihydroisothiazole-1′,1′-dioxide) derivatives have been prepared and isolated in good yields.     

The first stereoselective total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide

The first total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone 1 and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide 2 have been achieved in five steps in a highly stereoselective manner using Maruoka allylation, olefin cross-metathesis, and Sharpless asymmetric dihydroxylation as key steps.     

Stereoselective synthesis of (22Z)-25-hydroxyvitamin D2 and (22Z)-1α,25-dihydroxyvitamin D2

Two new vitamin D₂ analogues, (22Z)-25-(OH)-D₂ and (22Z)-1α,25-(OH)₂-D₂, were serendipitously synthesized from vitamin D₂ and using the Julia-Kocienski olefination.     

π-Extended conjugate phenylacetylenes. Synthesis of 4-[(E) and (Z)-2-(4-ethenylphenyl)ethenyl]pyridine. Dimerization, quaternation and formation of charge-transfer complexes

The conjugate (E)- and (Z)-(4′-pyridylethenyl)-4-phenylethyne (E-4 and Z-4) has been satisfactorily prepared by two different routes: (a) by dehydrohalogenation of 4′-pyridylethenyl-4-phenyl-β-chloroethene; (b) by the Wittig reaction between p-(iodobenzyl)(triphenyl)phosphine ylide and 4-pyridinecarboxaldehyde, E/Z isomer separation, and cross-coupling with 2-methyl-but-3-yn-2-ol followed the propanone elimination. The Glaser oxidative dimerization of (Z)-4 yields (Z,Z)-1,4-di[(4′-pyridylethenyl)-4-phenyl]-buta-1,3-diyne in good yield, (Z,Z)-5. (E,E)-5 was obtained by phase transfer oxidative dimerisation of (E)-4 in presence of their N-methyl salt (E)-10. Mono- and di-N-methylated salts of conjugate (E,E)-5 and (Z,Z)-5, were obtained by quaternation with iodomethane. The (Z,Z)-5 di-N-methylated salt forms charge-transfer complexes with TCNE, TCNQ and TMPD.     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

Total synthesis of (6Z,9S)-3,4-trans-9-hydroxy-3-methyldodec-cis-6-en-4-olide and (6Z)-3,4-trans-9-oxo-3-methyldodec-cis-6-en-4-olide γ-butyrolactones

The first total synthesis of (6Z,9S)-3,4-trans-9-hydroxy-3-methyldodec-cis-6-en-4-olide and (6Z)-3,4-trans-9-oxo-3-methyldodec-cis-6-en-4-olide was achieved in a convergent pathway. The salient features of our synthesis include Ohira–Bestmann reaction, regioselective alkyne addition to terminal epoxide, TEMPO/BAIB mediated oxidative lactonization, and partial hydrogenation.     

Synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone

Radical-mediated opening of a chiral trisubstituted epoxy alcohol using cp₂TiCl furnished the ‘2-methyl-1,3-diol’ moiety with the desired stereochemistry, which led to a total synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone 1.     

Total synthesis of two γ-butyrolactone containing compounds (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide

The first total synthesis of (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide was accomplished using Jacobsen hydrolytic kinetic resolution, Ohira–Bestmann reaction, regioselective alkyne addition to terminal carbon atom of epoxide, intramolecular TEMPO/BAIB mediated oxidative lactonization and partial hydrogenation as the key steps.     

An efficient synthesis of 3(S)-aminopiperidine-5(R)-carboxylic acid as a cyclic β,γ′-diamino acid

An orthogonally protected β,γ′-diamino acid 6 possessing conformationally-constrained ring system was synthesized as a novel cyclic amino acid analogue. This synthesis involves as key steps chemoselective enzymatic hydrolysis of cis-piperidine-3,5-dicarboxylic ester derivative followed by efficient kinetic resolution of the partially resolved half-acid to afford the C₁-symmetric piperidine-3,5-dicarboxylic acid monoester in high enantiomeric excess (>98% ee). The optically active half-acid was transformed to the cyclic amino acid via Curtius-type rearrangement.     

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.     

新型1-取代-2-(1′,3′-二氧五环-4′-基)苯并咪唑的合成

以地沟油水解副产物甘油和多聚甲醛为原料,经醇醛缩合和次氯酸钠催化氧化反应制得1,3-二氧杂环戊-4-酸(DIC); DIC与邻苯二胺或其衍生物进行酰胺化-环化反应高效地合成了3种新型的1-取代-2-(1′,3′-二氧五环-4′-基)苯并咪唑类化合物,其结构经UV-Vis, ¹H NMR, ¹³C NMR, IR和GC-MS表征。     

Regioselective [3+4] cycloaddition of an azomethine ylide to meso-meso, β-β, β′-β′ triply linked diporphyrins

Thermal reaction of meso-meso, β-β, β′-β′ triply linked diporphyrins with an azomethine ylide produced seven-membered cycloadducts via formal [3+4] cycloaddition at the bay-area. Bischlorin structures of the cycloadducts are characterized on the basis of spectroscopic data and confirmed by single crystal X-ray diffraction analysis. Interestingly, the stability of the cycloadducts depends on the central metal ions in the porphyrin core.     

Synthesis and properties of siRNAs containing 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides

Short interfering RNAs (siRNAs) containing P3′→N5′ phosphoramidate linkages were successfully synthesized by introducing 2′-deoxy-2′-fluororibonucleoside and 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleoside in succession. It was found that the introduction of 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides into siRNAs improved the nuclease-resistant properties of the siRNAs without loss of their silencing efficacy.     

A facile stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones

Palladium-catalyzed hydrostannylation of acetylenic sulfones 1 in benzene at room temperature gives highly regio- and stereoselectively (E)-α-stannylvinyl sulfones 2 in high yields. (E)-α-Stannylvinyl sulfones 2 are new difunctional group reagents which undergo Stille coupling reactions with acyl chlorides 3 to afford stereoselectively (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 in good yields. A one-pot stereoselective synthesis of (Z)-α-arylsulfonyl-α,β-unsaturated ketones 4 has also been achieved by tandem hydrostannylation-Stille coupling reaction of acetylenic sulfones 1 under mild conditions.     

One-pot synthesis of (Z)-β-sulfonyl enoates from ethyl propiolate

β-Sulfonyl enoates may be synthesized through a one-pot two-step sequence from ethyl propiolate with good to excellent selectivity for the Z isomer. Trialkylamines catalyze thioconjugate additions of aryl thiols, and alkoxides catalyze the addition of aliphatic thiols. Addition of meta-chloroperbenzoic acid (mCPBA) and LiClO₄ to the reaction mixture provides rapid access to the sulfonyl enoates. Yields of the pure Z isomer range from 51-90%.     

Facile synthesis of (−)-tabtoxinine-β-lactam and its (3′R)-isomer

A concise and high yielding synthesis of (−)-tabtoxinine-β-lactam 1, the cause of tobacco wildfire disease, was achieved from l-serine using a zinc-mediated coupling reaction, Sharpless asymmetric dihydroxylation and lactamization of N-OBn amide as the key steps.     

新型螺[氧化吲哚-3,3′-吡唑]-5′-二氟甲基-4′-甲酸酯类化合物的合成

以原位生成的二氟甲基重氮甲烷（CF₂HCHN₂）与靛红衍生的3-烯基氧化吲哚为原料,通过[3+2]环加成反应和1,3-H迁移过程,合成了3种结构新型的螺[氧化吲哚 3,3′-吡唑]-5′-二氟甲基-4′-甲酸酯类化合物,收率41~68%, dr 91: 9~99 : 1,其结构经¹H NMR, ¹³C NMR, ¹⁹F NMR和HR-MS(ESI-TOF)表征。并通过单晶X-射线单晶衍射确定其相对构型。     

Silver-promoted trans-hydrofluorination of ynamides: a regio- and stereoselective approach to (Z)-α-fluoroenamides

A highly regio- and stereoselective trans-hydrofluorination of N-sulfonyl ynamides has been realized with AgF as the fluorination reagent, affording (Z)-α-fluoroenamides in good to excellent yields. The reaction proceeds under mild reaction conditions and shows good functional group compatibility.