Exam 3 Key - Fall 2005

Name ______ Pg 1F.05.215e3p1 I. (2 points) N O O H H N O O N O O H H N O In the mid/late 1950s, mainly in Europe, arcemic ixture of thalidomide (se below) as prescribed to alviat "ornig ickes" i fist imst prgnat wmn. Tis was tragic incident i th istry of odern edice bau while the (R)-teoiser is a efctive dtive, the (S)-streoisme turn ut o b apotnt mtagn i fotus, and until thi s trak on tr wer thuands of baies brn with sevre birth defcts. A naive rspose to ti dicovery was "We should seprte the entiomes, purify th (R)-isor and oly us it a th drug." Th pblem it ti sltion could b idtifd ith asimple xperimet: i acidc olutions, pe samles of thalidoide underg mutarotaion. A indicatd blow, solutions f pre aml of ithr te (R) r (S)-stroismer, when plced i mild, aqueos ci slutin, becme oticly inactive solution f thalidomide. (R)-(+)-thalidomide optical rotin = +63° (S)-()-thalidomide optical rotin = -63° 2% H 2 SO 4 /H 2 O rom tep opticaly intive solution of thalidmide 2% H 2 SO 4 /H 2 O rom tep opticaly intive solution of thalidmide Explain, i afew ords, the observation f mutarotaion t an opticaly inactive solution f thlidomid in trms f t mchnism that st be tkig plce. (a) (b)Using H 3 O + /H 2 O as your Bronsted acid/base pair, provide the curved arow mechanism for the acid-catlyzed proces that explains the osrvtin f mutarotaion, strting it te (R)-ismr. N O O H H N O O (c)Why are the rsults of thes mutarotaion experiments enough to be skeptical that just prescribng te (R)-talidomide t prgnat wme is agod ia? 4 14 4 An opticaly inactive solution f thalidode means arcemic ixture (1: R:S), s the molecule is undrgig acnge that quilbrts th onfigation f the streocnter. HOH 2 N O O H H N O O 2 N O O H N O O H H 2 N O O H H N O O N O O H H N O O + mech = 2 intred 2 bsic idea out raceization racemization i acid would ean that he molecule cound also undergo racemization, nd so the bad (S) frm l b ford basic idea ut he S isoer forming Name ______ Pg 2F.05.215e3p2 I. (3 points) O O H 3 CO 3 H When the !-form of the folwing carbohydrate drivatie (Compound A) is treatd with methanol in acid, t " t glycside (Cmpun B) is obsrvd t be the majo pouct ue to t nomeric efct, but when th a startig material i teat wit iodethane and sodi hydrie, the !-glyoside (Compoud ) i foed. H O H H 3 CO 3 OCH 3 O OCH 3 H 3 CO 3 H CH 3 O cat. 2 SO 4 CH 3 I NaH Compound A Compound B Compound C Draw the structre of the ky intermediate in te convsatin Compoud A to Compud B tht explains it abilty t undergo inversion f cofigurtion? (a) (b)Explain, briefly, using words and rawings, why te fomatio f Cmpu C tke plac with n chnge in the configuration at the noeri etr. A. B.(a) Using the Fischer projection, drw the structr fo L-histide that il b in geatst prortion in solutio f pH = 3.9 Se frt cver fr Ka vlues (b) Galctose is the C-4 epimer of glus. Draw t struct r "-Lgalctopyranoe. (c) Draw the open chain Fishe) frm f aldotrose that becomes pticaly inctiv whn tretd with sodiu bohyride an acid. (d) Using the Fischer projection, raw the structr fo th mthyl estr of L-poline that wil be in gratest rrtio in solutio of pH = 5. (e) Draw the amphiathic (amphiilc) molecule: moniu exdenote 4 4 5 5 5 5 5 O H 3 CO 3 H open shel res form OK deprotatin of th OH both does not impact he stchemistry te C n O O H 3 CO 3 H main idea = 2 relvt pic H 3 NH N N H OO O OH OH HO HO HOH CH 2 O O OH CH 2 O OR H 2 NH O OC 3 NH 4 O O wrong imidazole = -2 epi-glu = 2 alha 1 L = 2 no partial amonium = 2; hexadecanoate = 3 must be ionic! conectivty = 3 r pronation = 2 conect = 3 prt sae 2 H Name ______ Pg 3F.05.215e3p I. (31 points) A. You wil recal, perhaps, that when alkens uch as tyren (Compound D) are trated with Os 4 or related oxidzing nt, 1,2-diol is formed. Wen phylacetyle (Compoun E) is treatd with oxizing aets uch as Os 4 , the crsponig aditon rtion prduct is t obervd; instea it is prosd that e intil aditon rati rduct, whic is a e-iol, ndergs an isomriztion reactin to give mixture of tw difernt C 8 HO 2 isomer.Wht ar thes two ismer? OH OH Compound DCompound E en-diol itrmeiate + B. The two mst acidc protns i ascorbic aid (also known as Vitamin C) have pKa vlues of 4.17 and 1.59. Whic of the t i i i crepd to the ost acidc on, nd why? O OO H H O O O H H cirle te most acidc prtn use words and rawings to explain C. D.-Fructose is the ketose drivd from D- gluc; show the Fisher prjections for te pai of pimeric alcohls that rsult frm te odi bohydrie ruction f D-fuctos. 3 3 2 6 5 4 4 C H 3 NH CH 2 Ph O O C O lO C(H 3 ) (CH 32 ) 3 N whic amino acid is this? use its brevition a your anr 4 with (1) (2) H 3 O O OH OH O H can be in either box no partil no partil O OO H O O O H H best resace tailty in conjugate base O OO H O O O H H no partial words 3 pix C HNH CH 2 Ph O OH C O (H 3 C) 3 conectivty = 3 sta of pronation 2 Phe CH 2 O H OH HO H C 2 O CH 2 O HO H HO H C 2 O can be in either box OK as long as true pimer Name ______ Pg 4F.05.215e3p4 IV. (18 points) A.n acid-catlyzed alol reaction is observd when dihydroxyacetone is combined with glyerlehd. acid catlyst H 2 SO 4 (a) Using HB as Bronsted acid and B as its conjugate base, show the step-wise mechanism for the formtion f th ulophilc form of dihydrxycton requird for thi ratio. nucleophilc form (b) Given the prior frmation f the nucleophilc form of dihydroxyacetone, provide the complet stp-wis mechanis fr t rati btwen dihyrxacetn d glyceralyd. 6 2 10 C CH 2 O CH 2 O O dihydroxyacetone C H CH 2 O O H H CH 2 O C H 2 O OHH COH mixture of sterismers h C CH 2 O CH 2 O O C H CH 2 O O H H CH 2 O C H 2 O OHH COH H B C CH 2 O C O H H H B- C H 2 O C H OH H mech 2 intred 2 ech 2 H B C H CH 2 O O H C H 2 O H OH H H CH 2 O C CH 2 O OHH COH B- prot mech = 2 ald adn ech = 2 prot prod de mech = 2 PLEAS NOTE: HIS I XCTLY H SAME S-UP D PROBL A GE V N T SECON XAM Name ______ Pg 5F.05.215e3p5 V. (16 points) A.n itersting, yet complex, molecule was recntly preared (JOC 205, 70, 58). For the sak of clarit, th lcul is rprsntd ordig to sm of its proertis rather tan its ctul stutre. NH O HN O N O THIS I A COMPLEX MOLECULAR FRAGMENT: N SID F IT IS YDOPHBI WHLE HE OTHER SIDE S YROPILC hydrophbic side hydrophilc side FOUR OF THES MOLECULAR UNITS HAVE BN ATHD TO CILR OLECULAR FRMEWK (shown o the right). NH O HN O N O Molecular Shape in water Molecular Shape in organic slvnt W In a organic solvent, he molecule takes on the shape rpresnted by Structre O, wher the hydrphil grups gatr tgthr nd hydrgn bond to ach otr. In wat, th molcul spontaeously take on the sape sugest by Strucre W. Descibe riefly y the spontaeous rergizatin i mlcular tructr tak place is thmodynamialy ational wn ti mlcl i placd in wter. B. Draw the Fischer projection for the open chain form of D-idose, an ldohexose hos IUPAC nam is (2S, 3R, 4S, 5R)-2,34,56-pentahyrxyhxal. C.The tiration curve for L-lysine is hown below. Provide the main structes i eqilbium at h pint idicatd belw. 1 2 3 4 5 6 7 8 9 10 12 equivalents of based ade 0 1 2 32.51.50.5 6 4 3 3 the ydrophbic efct: he ydrophbic portins of the molecule turn i toward each oter in ore t miniz t surface ntat etwe ts parts f th molecule ith wter. the rason fr this i that water at hydrophbic surface has lower ntropy, so heding thes wat mlecule into te bulk of te slvent ires t ntrpy f the stem desriptio f hydrophbic fct/phono = 3; imact on tropy = 3 HOH O HOH O CH 2 O H 3 N CH 22 CH 22 NH 3 O H 3 N CH 22 CH 22 NH 2 O can be eithr box no partil pH OK IF THE DPROTNATION IS OWN F HE HER N GRUP ISTAD bcoppola1 Microsoft Word - f05215e3k.doc