Automatic analysis of multiplex ligation-dependent probe amplification products (exemplified by a commercial kit for prenatal aneuploidy detection)

For use in routine prenatal diagnostics, we developed software and methods for automatic aneuploidy detection based on a commercial multiplex ligation-dependent probe amplification (MLPA) kit. Software and methods ensure a reliable, objective, and fast workflow, and may be applied to other types of MLPA kits. Following CE of MLPA amplification products, the software automatically identified the peak area for each probe, normalized it in relation to the neighboring peak areas of the test sample, computed the ratio relative to a reference created from normal samples, and compensated the ratio for a side effect of the normalization procedure that scaled all chromosomally normal DNA peak areas slightly up or down depending on the kind of aneuploidy present. For the chromosomes 13, 18, 21, X, and Y, probe reliability weighted mean ratio values and corresponding SDs were calculated, and the significance for being outside a reference interval around ratio 1.0 was tested. p < or = 1% suggested aneuploidy and 1 < p < or = 5% suggested potential aneuploidy. Individual peaks, where the normalized area was situated more than 4 SD from the corresponding reference, suggested possible partial deletion or gain. Sample quality was automatically assessed. Control probes were not required. Having used the software and methods for two years, we conclude that a reliable, objective, and fast workflow is obtained.     

光学活性含硅氨基酸的合成

光学纯的硅取代氨基酸是一类非天然的手性氨基酸合成子，在药物，植物保护 剂和精细化学品的合成具有极为广阔的应用前景，其合成方法包括化学不对称合成 及化学合成外消旋体－生物学拆分两种，综述了该方面的研究进展。     

含松香骨架的新型手性季铵盐相转移催化剂的合成及其在不对称环氧化反应中的应用

以天然松香为原料合成了4个新型手性季铵盐类相转移催化剂, 并用于催化不对称查尔酮环氧化反应, 发现这类手性相转移催化剂可以有效地催化查尔酮的不对称环氧化, 环氧化产物ee最高达20%.     

手性5-(R)-(1′R,2′S,5′R)-孟氧基丁内酯并[3,4-b]-2(S)-6(R)-1-N-环己基氮杂环丙烷的合成及晶体结构

环己胺与手性元5-(R)-(1′R,2′S,5′R)-孟氧基-3-溴-2(5H)-呋喃酮的不对称M ichael加成/分子内亲核取代反应,得到含有两个新手性中心的氮杂环丙烷/稠合丁内酯标题化合物。对其进行了谱学表征和X-射线单晶衍射测定。标题化合物分子式为C20H33NO3,M r=335.47,三斜晶系,P1空间群,晶胞参数:a=5.438(11)。A,b=8.117(2)。A,c=11.572(2)。A,α=96.84(3)°,β=94.48(3)°,γ=101.86(3),°V=493.5(2)。A3,Z=1,D c=1.129g/cm3,R=0.0867,wR=0.2344。     

Catalytic, asymmetric synthesis of α,α-disubstituted amino acids

Copper(salen) complex 1 has been found to catalyse the asymmetric alkylation of enolates derived from a variety of amino acids. There is a clear relationship between the size of the side chain in the substrate and the enantioselectivity of the process, so that the enantioselectivity decreases in the order alanine>aminobutyric acid>allylglycine>leucine>phenylalanine>valine. A transition state model which accounts for the influence of the size of the side chain on the enantioselectivity of the reactions is presented.     

N-(6-甲基-2-亚甲基吡啶)-( )-樟脑亚胺体系的不对称烷基化反应

目前,不对称合成光学活性化合物取得了较大进展,不对称合成α-氨基酸、β-氨基醇、α-取代苄胺的报道很多。但是,不对称合成生物碱类物质——α-取代氨甲基吡啶类化合物还未见文献报道,而此类化合物有潜在的应用前景。为此,我们以( )-樟脑为手性试剂     

Useful dual Diels-Alder behavior of 2-azetidinone-tethered aryl imines as azadienophiles or azadienes: a beta-lactam-based stereocontrolled access to optically pure highly functionalized indolizidine systems

Imines derived from 4-oxoazetidine-2-carbaldehydes have been found to be versatile Diels-Alder reagents in that they exhibit two reactivity patterns. 2-Azetidinone-tethered imines undergo diastereoselective reaction with Danishefsky's diene in the presence of different Lewis acids. The effect of the amount of catalyst on the conversion rate as well as on the product ratio has been studied. Under standard reaction conditions, indium(III) chloride and zinc(II) iodide provided the best yields, and indium(III) triflate the highest diastereoselectivity in the Lewis acid promoted aza-Diels-Alder cycloaddition. Treatment of the aforementioned imines with cyclopentadiene, 2,3-dimethyl-1,3-butadiene or 3,4-dihydro-2 H-pyran led to cycloadducts arising from inverse electron-demand condensation involving the beta-lactam-tethered aryl imine as the heterodiene component. In addition, the first methodology for preparing indolizidines from beta-lactams has been developed. This process involves amide bond cleavage of the beta-lactam ring in the aza-Diels-Alder cycloadducts with concomitant cyclization. Full chirality transfer occurs when the reaction is performed with an enantiomerically pure substrate.     

Asymmetric Diels–Alder reactions in supercritical carbon dioxide catalyzed by rare earth complexes

The rare earth(III) salt catalysed asymmetric Diels–Alder reaction of cyclopentadiene with a chiral dienophile in supercritical carbon dioxide (scCO₂) proceeded rapidly to give the adduct with a higher diastereoselectivity than that in dichloromethane; Yb(ClO₄)₃ gave the endo adduct with value up to 77% de at 40°C, 8 MPa. The chiral rare earth diketonate catalyzed hetero Diels–Alder reaction of the Danishefsky's diene with benzaldehyde gave a higher yield and an enantioselectivity in scCO₂ than that in dichloromethane. Scandium/pybox 8a complex catalysed asymmetric Diels–Alder reaction of 3-crotonoyl-2-oxazolidinone with cyclopentadiene in the presence of MS4A proceeded smoothly in scCO₂ to give the endo adduct 10 in a good yield with up to 88% ee.     

An aldol approach to the total synthesis of (+)-brefeldin A

A convergent selective route to (+)-brefeldin A (BFA) and 7-epi-BFA was developed, with the crucial C-4/C-5 stereogenic centers were established using Crimmins asymmetric aldolization.