生物化學(xué)ChapterSteroChemistry市公開(kāi)課獲獎(jiǎng)?wù)n件

1、Exercises:7.1-7.37.6-7.177.22-7.247.26-7.327.37,7.41第1頁(yè)第1頁(yè)Chapter 7 Stereochemistry第2頁(yè)第2頁(yè)Stereoisomers: isomers that have the same atoms bonded to one another (same constitution), but different 3-D orientation of the atoms in space.Conformational stereoisomers: interconvert by rotation about a bonds

2、taggered and eclipsed conformersgauche and anti conformerschair-chair conformersConfigurational stereoisomers: cant be interconvertedcis and trans isomersE and Z isomersTwo new ones:enantiomers: stereoisomers that are nonsuperimposable mirror images diastereomers: stereoisomers that are not mirror i

3、mages第3頁(yè)第3頁(yè)IsomerConstitutional IsomersStereoisomersCis -TransIsomersIsomers that contain chirality centers Isomers: Nonidentical compounds having the same molecular formula第4頁(yè)第4頁(yè)Cis-Trans Isomers第5頁(yè)第5頁(yè) 7.1 Molecular Chirality. EnantiomersEnantiomerism(光學(xué)異構(gòu)現(xiàn)象) Chirality: 物體與其鏡像不重疊性質(zhì)第6頁(yè)第6頁(yè)Why is chir

4、ality important?Chiral species fits in chiral binding site (matched key and lock)第7頁(yè)第7頁(yè)Chiral species does not fit in binding site (mismatched key and lock)第8頁(yè)第8頁(yè)第9頁(yè)第9頁(yè)(a) Structures A and B are mirror-image representations of bromochlorofluoromethane A B陳立第10頁(yè)第10頁(yè)第11頁(yè)第11頁(yè)Enantiomersnonsuperimposabl

5、e mirror-image molecules第12頁(yè)第12頁(yè)(b) Reorient B by turning it 180 B = B陳立180第13頁(yè)第13頁(yè)(c) Compare A and B. The two do not match. A B 第14頁(yè)第14頁(yè) Stereoisomers that are related as an object and its nonsuperposable mirror image are classified as enantiomers. (對(duì)映異構(gòu)體)手性分子 ( Chiral molecules) 實(shí)體與鏡象不能重合分子手性中心(

6、Chiral center )： 與四個(gè)不同原子或基團(tuán)相接原子 主要有： C, N, S, P手性分子特點(diǎn)： 分子中一個(gè)碳原子與四個(gè)不同原子或基團(tuán)相連接 對(duì)應(yīng)碳原子稱之為手性碳( 慣用 C * 表示 )Achiral compounds have superimposable mirror imagesChiral compounds have nonsuperimposable mirror images第15頁(yè)第15頁(yè)Mirro-image forms of chloroflouromethane are superposable (可置于上面,可重疊, 可疊合)upon one anot

7、her. Chlorodifluoromethane is achiral. (非手性)第16頁(yè)第16頁(yè)Chloroflouromethane第17頁(yè)第17頁(yè)第18頁(yè)第18頁(yè)Drawing EnantiomersPerspective formulaFischer projection第19頁(yè)第19頁(yè)A stereocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer第20頁(yè)第20頁(yè)7.2 The Stereogenic CenterA ster

8、eocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer第21頁(yè)第21頁(yè)第22頁(yè)第22頁(yè)7.3 Symmetry in Achiral StructuresSymmetry Axis 對(duì)稱軸Plane of symmetry 對(duì)稱面Center of symmetry 對(duì)稱中心第23頁(yè)第23頁(yè)Symmetry Axis 對(duì)稱軸 一條直線通過(guò)度子，使分子繞此直線旋轉(zhuǎn)一定角度后而能與本來(lái)分子重疊直線第24頁(yè)第24頁(yè)繞軸轉(zhuǎn)動(dòng)，轉(zhuǎn)動(dòng) 角度后能與原分子重疊

9、，則 360/ = n為該分子 n 重對(duì)稱軸，用Cn表示第25頁(yè)第25頁(yè)P(yáng)lane of symmetry 對(duì)稱面對(duì)稱面 ( )：但成份子所有原子都在同一平面上，或平面能夠通過(guò)度子并將其分成互為鏡象兩個(gè)部分。陳立苯：七個(gè)對(duì)稱面第26頁(yè)第26頁(yè)CH2Cl2第27頁(yè)第27頁(yè)Center of symmetry 對(duì)稱中心對(duì)稱中心 ( i ): 通過(guò)度子中心與分子中任何一個(gè)原子連始終線，然后將此直線問(wèn)相反方面延長(zhǎng)，并在離中心等距處碰到完全相同原子，則此中心是該分子對(duì)稱中心。It is characterised by an atom which has different groups bound t

10、o it in such a manner that its mirror image is nonsuperimposable. 反1,3二氟反2,4二氯環(huán)丁烷第28頁(yè)第28頁(yè)Chirality and Symmetry判斷分子有無(wú)手性辦法：對(duì)稱面: 非手性對(duì)稱中心: 非手性Carbon-based Stereogenic Centers: The most prevalent stereogenic centers in organic chemistry are carbon atoms, which have four different groups bound to them. 第

11、29頁(yè)第29頁(yè)第30頁(yè)第30頁(yè)Diastereomers are stereoisomers that are not enantiomersIsomers with more than one chiral carbon: a maximum of2n stereoisomers can be obtained第31頁(yè)第31頁(yè)Identification of Asymmetric Carbons in Cyclic Compoundsthese two groupsare differentcis-1-bromo-3-methylcyclohexanetrans-1-bromo-3-met

12、hylcyclohexane第32頁(yè)第32頁(yè)Meso CompoundsHave two or more asymmetric carbons and a plane of symmetryThey are achiral molecules第33頁(yè)第33頁(yè)第34頁(yè)第34頁(yè)As long as any one conformer of a compound has a plane of symmetry, the compound will be achiralplane ofsymmetryplane ofsymmetry第35頁(yè)第35頁(yè) 7.4 Properties of Chiral M

13、olecules: Optical Activity7.4.1 Plane - polarized light 偏振光光波：電磁波，電場(chǎng)或磁場(chǎng)沿光波邁進(jìn)垂直方向振。電場(chǎng)振動(dòng)平面與磁場(chǎng)振動(dòng)平面垂直。第36頁(yè)第36頁(yè)Nicol prisms:Plane - polarized light 偏振光: 通過(guò)棱鏡后光線電場(chǎng)或磁場(chǎng)只在一個(gè)平面上振動(dòng)第37頁(yè)第37頁(yè)7.4.2 Optical Activity 旋光性 A substance which does not cause rotation of the plane of polarized light is said to be opticall

14、y inactive.第38頁(yè)第38頁(yè) A substance which causes the plane of polarized light to undergo a rotation is said to be optical active . The angle of rotation is simple referred to as observed rotation ( 旋光度 ).Chenli陳立第39頁(yè)第39頁(yè)The physical properties of enantiomers are identical (m.p., b.p., n, d, m, etc.)exce

15、pt the direction in which they rotate plane polarized light.Enantiomers are optical isomers.samplepolarizerplane-polarizeddextrorotatory(d) or (+)levorotatory(l) or ()opticallyinactiveoptically active第40頁(yè)第40頁(yè)第41頁(yè)第41頁(yè)Chiral compounds are optically active; they rotate the plane of polarized light.Cloc

16、kwise (+)Counterclockwise (-)Different from R,S configurationAchiral compounds do not rotate the plane of polarized light. They are optically inactive.第42頁(yè)第42頁(yè)Measuring Optical Activity: Optical activity is the ability of a chiral molecule to rotate the plane of plane-polarized light. It is measured

17、 using a polarimeter, which consists of a light source, polarising lens, sample tube and analyzing lens. Rotation of the plane of polarized light in the clockwise sense is taken as positive ( + ), while rotation in anticlockwise sense is taken as a negative ( - ).The classic terms for positive and n

18、egative rotations are dextrorotatory (右旋) ( d ) ( + ) and levorotatory ( 左旋 ) ( l ) ( - ) .第43頁(yè)第43頁(yè)When rotation is quantified using a polarimeter it is known as an observed rotation, because rotation is affected by path length (l, the time the light travels through a sample) and concentration (c, h

19、ow much of the sample is present that will rotate the light). When these effects are eliminated a standard for comparison of all molecules is obtained, the specific rotation(比旋光度), a. a = 100a / cl when concentration is expressed as g sample /100ml solution第44頁(yè)第44頁(yè)A polarizer measures the degree of

20、optical rotation of a compoundThe observed rotation (a)T is the temp in C is the wavelength is the measured rotation in degreesl is the path length in decimetersc is the concentration in grams per mLEach optically active compound has a characteristic specificrotation比旋光度第45頁(yè)第45頁(yè)Optically PureIf only

21、 one enantiomer is present a sample is considered to be optically pure. When a sample consists of a mixture of enantiomers, the effect of each enantiomer cancels out, molecule for molecule. Determining Optical Purity: The optical purity or the enantiomeric excess (ee%) of a sample can be determined

22、as follows: Optical purity = % enantiomeric excess = % enantiomer1 - % enantiomer2 = 100 amixture / apure sample ee% = 100 (R-S) / (R+S) where R = concentration of the R-isomer S = concentration of the S-isomer第46頁(yè)第46頁(yè)A racemic (外消旋)mixture, which contains an equal amount of the two enantiomers, is

23、optically inactiveoptical purity = observed specific rotationspecific rotation of the pure enantiomerenantiomeric excess = excess of a single enantiomerentire mixture第47頁(yè)第47頁(yè)P(yáng)olarimeter旋光儀 測(cè)定液體或溶液旋光程度儀器工作原理:第48頁(yè)第48頁(yè)The classic terms for positive and negative rotations are dextrorotatory (右旋) ( d ) (

24、 + ) and levorotatory ( 左旋 ) ( l ) ( - ) .比旋光度表示：葡萄糖（水溶液） (Glucose) ( 20 C, 鈉光燈 )陳立 = + 52.5 ( H2O) 20D第49頁(yè)第49頁(yè)Enantiomers(對(duì)映(結(jié)構(gòu))體 )will rotate the plane of polarisation in exactly equal amounts (same magnitude) but in opposite directions. Dextrorotary designated as (+), clockwise rotation (to the r

25、ight) Levorotary designated as (-), anti-clockwise rotation (to the left)第50頁(yè)第50頁(yè)7.4.3 Chirality and Optical Activity手性只能在手性環(huán)境中辨認(rèn) 在非手性環(huán)境中（除了旋光性），對(duì)映體物理，化學(xué)性質(zhì)相同辨認(rèn)手性慣用手段是測(cè)定旋光性手性化合物在液態(tài)或溶液中是旋光有些非手性化合物在液晶狀態(tài)下有旋光性旋光方向與構(gòu)型沒(méi)有相應(yīng)關(guān)系外消旋體 (Racemic modification): 由等量對(duì)映體構(gòu)成無(wú)旋光性物質(zhì)Chenli第51頁(yè)第51頁(yè) 7.5 Absolute and Relative

26、 ConfigurationAbsolute Configuration 絕對(duì)構(gòu)型 When the precise arrangement of substituents at a stereogenic centre is known the absolute configuration of the molecule is known. This is usually accomplished by solving the x-ray crystal structure of a molecule, a method that is not always readily availabl

27、e. 按要求構(gòu)型式表示立體異構(gòu)體與其真正構(gòu)型相同構(gòu)型式第52頁(yè)第52頁(yè)Relative Configuration相對(duì)構(gòu)型The arrangement of atoms in an optically active molecule, based on chemical interconversion from or to a known compound, is a relative configuration. Relative, because there is no way of knowing just by looking at a structure whether the a

28、ssignment of (+) or (-) is correlated相關(guān)to a particular isomer, R or S. If the name of a compound includes both the sign of rotation and the designation R or S then the absolute configuration of that compound is known. 第53頁(yè)第53頁(yè)Reactions of compounds that contain an asymmetric carbon.No reaction at th

29、e asymmetric carbon; both the reagent and the product have the same relative configuration. If a reaction breaks a bond at the asymmetric carbon, you need to know the reaction mechanism in order to predict the relative configuration of the product.第54頁(yè)第54頁(yè) Relative Configuration1906, Rosanoff A M 選定

30、D- (+)- glyceraldehyde L- (- )- glyceraldehyden.化甘油醛Isotopes: H vs D ? Still use atomic number so D H Same atom attached ? By moving out one unit at a time, locate the first point of difference and apply rules there. 第55頁(yè)第55頁(yè)關(guān)聯(lián)構(gòu)型： 在不涉及與手性碳連接四個(gè)鍵斷裂前提下 D型: 由D- ( + ) -甘油醛反應(yīng)取得或可轉(zhuǎn)變?yōu)镈- (+) -甘油醛化合物構(gòu)型 。 L 型

31、: 由L- ( - ) -甘油醛反應(yīng)取得或可轉(zhuǎn)變?yōu)長(zhǎng)- (-) -甘油醛化合物構(gòu)型 相對(duì)構(gòu)型： 由于直接或間接與甘油醛關(guān)聯(lián)手性化合物構(gòu)型。第56頁(yè)第56頁(yè)實(shí)例： 1951, Bijvoet J M 擬定( + ) 酒石酸絕對(duì)構(gòu)型，從而推斷出( + ) 甘油醛構(gòu)型與Rosanoff假設(shè)型相同。結(jié)論：（）甘油醛相對(duì)構(gòu)型即為絕對(duì)構(gòu)型； 所有與（） 甘油醛關(guān)聯(lián)得出構(gòu)型也都是絕對(duì)構(gòu)型第57頁(yè)第57頁(yè)第58頁(yè)第58頁(yè)7.6 The Cahn一Ingold-Prelog R-S Notational System The Cahn-Ingold-Prelog R/S rules are used for n

32、aming enantiomers.Assign priorities to the four groups according to the Sequence Rules.Orient the molecule so that the lowest priority group points away from you.Determine the direction of procession of the other three groups, from highest to lowest:If this is clockwise, then the center is R (Latin:

33、 rectus = right) clockwise = R (rectus)If this is counterclockwise, then it is S (Latin: sinister = left) counterclockwise = S (sinister)第59頁(yè)第59頁(yè)Naming EnantiomersRank the groups (atoms) bonded to the chirality center The R,S system of nomenclature第60頁(yè)第60頁(yè)R/S命名法:Clockwise: Anticlockwise: Rectus Sini

34、ster左側(cè) ( R )- lactic acid ( S )- lactic acidIf the name of a compound includes both the sign of rotation and the designation R or S then the absolute configuration of that compound is known.第61頁(yè)第61頁(yè)Absolute configurations: R and S(R)-2-butanol(S)-2-butanol第62頁(yè)第62頁(yè)Designate the configuration of atoms

35、 at a stereocenter.We can designate which is which by assigning an absolute configurationto each of these (R or S) by a set of rules, but which is (+) and which is ()?There is no relationship between a molecules absolute configurationand its optical rotation (its relative configuration).()(+)Answer:

36、but,第63頁(yè)第63頁(yè)Name the following compounds, including R or S designation.第64頁(yè)第64頁(yè)Name the following compounds, including R or S designation.(S)-1-bromo-2-methylbutane12341234(R)-3-methylcyclohexene第65頁(yè)第65頁(yè)7.7 Fischer Projection Formulas7.7.1 Projection Formulas 投影式 要求：橫向棱邊：指向觀測(cè)者，用虛線表示垂直棱邊：背向觀測(cè)者，用實(shí)線表示第

37、66頁(yè)第66頁(yè)等同于：第67頁(yè)第67頁(yè)The vertical(垂直)bonds at the stereogenic center are directed away from you .The horizontal bonds points toward you.注： 習(xí)慣上，含碳基團(tuán)置于豎鍵方向； 命名時(shí)編號(hào)最小碳原子置于上端7.7.2 Fischer Projection Formulas第68頁(yè)第68頁(yè)Determining R and S in Fischer projections:(R)-2-butanolwhen lowest priority group is on a v

38、erticalbond (back): read normally(S)-2-butanol-when lowest priority group is on a horizontalbond (forward): read backward第69頁(yè)第69頁(yè)Fischer Projection 能夠在紙面上旋轉(zhuǎn) 902n 構(gòu)型保持 在紙面上旋轉(zhuǎn) 90(2n + 1 ) 構(gòu)型翻轉(zhuǎn)第70頁(yè)第70頁(yè) Fischer投影式不可離開(kāi)紙面翻轉(zhuǎn) Fischer投影式中任意三個(gè)基團(tuán)可同時(shí)在不改變彼此相對(duì)位置下沿閉合環(huán)移動(dòng)第71頁(yè)第71頁(yè)Manipulating Fischer projections:第72頁(yè)

39、第72頁(yè)實(shí)例:第73頁(yè)第73頁(yè)Assign R and S configurations. Then determine whether the structures in each of the following pairs are enantiomers or identical.Check Answer第74頁(yè)第74頁(yè)Answer: Assign R and S configurations. Then determine whether the structures in each of the following pairs are enantiomers or identical

40、.12434231S S identical RS enantiomers31214234 S R enantiomersS R enantiomers第75頁(yè)第75頁(yè)Louis Pasteuronly products originating under the influence of life are asymmetric, because the cosmic i.e. generative, life forces that preside over their formation are themselves asymmetric. Asymmetry differentiates

41、 the organic world and the mineral world.Spontaneous generation is a chimera“Germ theory (annihilating the spontaneous generation theory) foundation of all microbiological techniques 第76頁(yè)第76頁(yè)7.8 Physical Properties of Enantiomers第77頁(yè)第77頁(yè)第78頁(yè)第78頁(yè)7.9 Stereochemistry in Chemical Reactions That Produce

42、Chiral Molecules7.9.1 Reactions that create a chiral centerRule: Optically inactive starting material can give only optically inactive products第79頁(yè)第79頁(yè)Stereochemistry of Electrophilic Addition Reactions of AlkenesWhat is the absolute configuration of the product?第80頁(yè)第80頁(yè)Addition reactions that form

43、one asymmetric carbon 第81頁(yè)第81頁(yè)sp2, planar50/50 Mixture第82頁(yè)第82頁(yè)第83頁(yè)第83頁(yè)Reactions that create a chiral center第84頁(yè)第84頁(yè) Draw the products of the following reactions, showing stereochemistry where relevant.第85頁(yè)第85頁(yè)Draw the products of the following reactions, showing stereochemistry where relevant.第86頁(yè)第8

44、6頁(yè)7.10 Chiral Molecules with Two or More Stereogenic Centers7.10.1 Diastereomers and EnantiomersDiastereomers: stereoisomers that are not mirror imagese.g.eclipsed and staggeredanti and gauchecis and transconformational diastereomersconfigurational diastereomersDiastereomers have different physical

45、properties (i.e., can be separated).n chiral carbons 2n possible stereoisomers第87頁(yè)第87頁(yè)e.g.22 = 4 possible stereoisomersenantiomersenantiomersdiastereomers第88頁(yè)第88頁(yè)Draw all stereoisomers of 2-bromo-3-chloropentane. Indicate R and S configurations of each stereogenic center. Give the relationships betw

46、een each pair of stereoisomers.Check Answer第89頁(yè)第89頁(yè)Be systematic. Draw one stereoisomer. Then draw its mirror image. Then change one chiral center and draw its mirror image.SRSRSRRSEnantiomers: I and II; III and IVDiastereomers: I and III; I and IV, II and III; II and IV第90頁(yè)第90頁(yè)7.10.2 Diastereomers:

47、 pairs of enantiomerserythro diastereomer threo diastereomerErythro (赤式) Threo (蘇式)第91頁(yè)第91頁(yè)P(yáng)erspective formulaFischer projection第92頁(yè)第92頁(yè)3 chiral carbons 23 = 8 possible stereoisomersR, R, R : S, S, SR, R, S : S, S, RR, S, R : S, R, SS, R, R : R, S, Senantiomersdiastereomers第93頁(yè)第93頁(yè)Draw all stereoiso

48、mers of 2,3-dibromohexane. Indicate R and S configurations of each stereogenic center. Give the relationships between each pair of stereoisomers. Check Answer第94頁(yè)第94頁(yè)Since III has a plane of symmetry, so is meso, there are only three stereoisomers. (The mirror image of III would not an enantiomer, b

49、ut would be identical to III.)RSSSRREnantiomers: I and IIDiastereomers: I and III; II and IIIplane of symmetry;meso第95頁(yè)第95頁(yè)7.10.4 Stereoisomers in substituted cycloalkanessachiral(plane of symmetry)but:chiral, enantiomers第96頁(yè)第96頁(yè)cis-Cyclopropane-1,3-dicarboxylic acidCyclopropane第97頁(yè)第97頁(yè)第98頁(yè)第98頁(yè)Stere

50、oisomers in substituted cyclohexanes第99頁(yè)第99頁(yè)1第100頁(yè)第100頁(yè)Indicate whether each of the following cyclic structures would be chiral or achiral. If a compound is chiral, give the R or S configuration. If a compound is achiral, explain why.Check Answer第101頁(yè)第101頁(yè)Look for stereogenic carbons and planes of s

51、ymmetry. Remember that a plane of symmetry can dissect an atom or a bond. achiral:mesochiralachiral: nostereogenic carbonachiral:mesoachiral:mesoRRRRRSSS第102頁(yè)第102頁(yè)第103頁(yè)第103頁(yè)Determine whether each of the following pairs of structures represent identical compounds, enantiomers, or diastereomers.第104頁(yè)第

52、104頁(yè) Determine whether each of the following pairs of structures represent identical compounds, enantiomers, or diastereomers.enantiomersdiastereomersenantiomersenantiomersdiastereomersenantiomers第105頁(yè)第105頁(yè)7.13 Chemical Reactions That Produce Diastereomersbutstereospecific reaction: different stereoisomeric starting materials givedifferent stereoiosmeric productsracemic mixtureracemic mixturediastereomers第106頁(yè)第106頁(yè)racemicmeso第107頁(yè)第107頁(yè)68%32%optically activeGeneration of a new chiral center in a chiral molecule does not necessarily produce equal a