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E4_W08_key[1] - |(44 points J00 2007 72 9181 a Ha IS easuly...

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Unformatted text preview: | (44 points) J00, 2007, 72, 9181 a) Ha IS easuly deprotonated Wlth K2003. Usmg drawings and a few words. explain why Ha has such a low pKa. A“ Ha o NHBn The NHBn NHBn kr/ H‘l7l conjugate OCH3 base IS OCH3 OCH3 0:3:0 resonance stabilized by the tosyl group J. Am. Chem. 800., 1999, 121. 6507 Alkaloids are of synthetic interest due to their antifungal and antibiotic activity. The following synthesis was used towards the synthesis of the tetracyclic core of two alkaloids. Complete the synthesis. OCHZCHg 0) H0 0 Hi 20H3___CH20H CH30H20 OKJs N(CH20H3)3 / OH cat H2804 ALWO 1) /LO'K (reversible base) THF, -78 °C OCH20H3 CH30H20 0 (Ex/O + O 2) H3O (protonation) Nature Struct. Biol., 2001, 8, 858 e) The polysaccharide shown on the right is found in bacterial and parasitic cell walls, including pathogens such as Mycobacterium tuberculosis. Characterizeldescribe each of the glycosidic linkages. f) How many of the monomers are D- sugars? (circle one) - OH OH + CH3CH20H Q) How many of the furanoses are a anomers? (circle one) @ 1 2 3 4 5 h) Is this pentasaccharide a reducing sugar? (circle one) -or no II ( 39 points) A} J00, 2008, 73. 661 H3O [EH3 HOHZQ CHZOH 0%“ o HOHZC NHZ CHZOH compound B B) Ninhydrin is used to detect the presence of uncoupled amino acids during peptide synthesis. Ninhydrin reacts with a free a-amino group of the amino acid to form molecule E . 0 t 'd 0 CH3 cat. acid 0 ca.acr —h- 0H __ H20 + me + H2N2KITOH whim 0H 0 O O 0 ninhydrin molecule E The acid-catalyzed reaction between ninhydrin and the amino acid begins with the formation of an imine C. Show the stepwise mechanism. You may use HB as your acid and B' as its conjugate base. No stereochemistry needs to be shown. f“ B' 0 0 H2 0 H <‘ (1 CH3 H—B %_5 CH3 HN/ CH3 0 + ROH —» __ @j; H2N 80 OH O OH O O O K fl 0 H-B 0 CH3 0 | *— --\€LOH \JLOH 0 H 0H ‘J CH3 CH 3 (sz OH 3 B' o 9 0 L r‘ H-B mechanism where the carbonyl is protonated in first step was also accepted 0 CH3 OH III (43 points) A) Imine c (from the ninhydrin reaction on the previous page) undergoes a decarboxylation to form another imine intermediate D. In the presence of water, Imine D further reacts with water to yield molecule E and an aldehyde. Show the stepwise, acid catalyzed mechanism for the transformation of Imine D to molecule E. You should use HB for your catalytic acid and B' for its conjugate base. “20) f +H20___ ®NH 3 —- 0 Ho 0 Imine D H O + B' ("K H-B O 0 H2 H.) E; 9H . matrm / H CH3 H CH3 0 0 ' o B | HAR o mum HJkCH3 molecule E B) Molecule E then condenses with another equivalent of ninhydrin to form a symmetrical imine that has a deep purple color indicating the presence of the uncoupled amino acid. Draw the purple imine below. 1) NaBH4 or LiAIH4 2) H30+ IV (36 points) Peptide nucleic acids (PNA) are DNA mimetics in which the ribose phosphodiester backbone has been replaced by N-(2—aminoethyl)glycine units. DNA mimetics are of interest due to their potential as gene therapy agents. Base Base Base Base Q 0 Base: adenine, O OH.) O Oi) O O c osIne,guanIne or N N Z715] go O—P—O O—l3% thymIne #K/ Wnk/ \/\n O O 9 DNA a PNA Complete the synthesis of two monomers incorported into a PNA dimer. A) Monomer A synthesis Monomer A O BI'CH280CH3 HN 1) NaOH (aq.) I ' K2CO3 O 2) H30+ H1, 0 CH (protonation) Name the heterocyclic base: Cytosine Complete the reagents and products in the dimerization of Monomers A and B to form the PNA Dimer. Number separate steps if needed. H Base/\l‘rO N OCH20H3 2) 30020 or N3Boc H DCC 9) 1) CH30H20H, cat. TSOH A 0 0 >= i1 8:0 H HZNNNJLOH 1‘) NH2 Base NJ] A )OL Kfo 0 0% N o N/VNJLOCHQCHg Kfoofi H H2NAV NJNNN 311‘? if structure of either base was drawn, it was accepted PNA Dimer Adenine binds to thymine via two hydrogen bonds, while cytosine binds to guanine via two hydrogen bonds. What two DNA b -. = = a . expect the PNA Dim d to? (Circle two) cytosine, @ thymine V (40 points) (J. Am. Chem. 800., 2008, 130, 2351) Ustiloxin D posesses OH \ 0 antimitotic activity and prevents cell division. Thus it shows promise ,9 OH as an anti-cancer agent. Synthetically. it is derived from two modified HO N/\n’ amino acids (B-hydroxyisoleucine and N-methyl-B-hydroxytyrosine) HN H and two standard amino acids. Cleavage of an ether bond between 0 the B—hydroxyisoleucine and N—methyl—B—hydroxytyrosine in Ustiloxin 2: N H l— O D results in the structure shown on the right. HO“- HN\ O A) Draw the structures of the two modified amino acids. B) Draw the structures of the two standard amino acids and write their names in the bottom box. For B) structu e of tyrosine and isoleucine we e [50 accepted H0“- HNX N-methyl-B-hydroxytyrosine fi—hydroxyisoleucine C) (J. Am. Chem. Soc. 1996, 118, 495) H” in the product of the following reaction. o OBn 1) CIAWCI OBn BnOh, scan 0 DMSO —h 3'10 2) (CH3CH2)3N 6H li’(OBn)2 o I_=j(osn)2 0 (Swern) 0 D) (J. Am. Chem. Soc. 1996, 118, 495) Inositol and its phosphate esters play critical roles in both cellular structure and the regulation of cellular processes. Biosynthesis of inositol begins with the enzyme myo- r'nositoi 1-phosphate synthase which carries out an oxidation, enolization. intramolecular aldol reaction and reduction on the substrate glucose 6-phosphate. Complete the following scheme showing these four steps. No stereochemistry needs to be shown at newly: formed stereocenters. 0P0 H 3 2 H0 0P03H2 HO ‘ HO ___ / Hgfifo —b O I45-16%.f0 0” H “9&0 OH H —1 open chain form of glucose 6-phosphate enolization of 05 (with rotation around 05) OHH NAD+ oxidation of cs ii) 0 0P03H2 H 0P03H2 910 OH HO OH H HQMOH aldol reaction reforms 6—membered ring OH H reduction of 05 with NADH VI (38 points) A) Science, 2001, 294, 369 Part of the proposed mechanism for D-2-deoxyribose-5-phosphate aldolase is shown below. Provide the products of the first step and the arrows needed to complete the second step . mechanism showino L 3201 product + arrows deprotonating Lys167 al 0 accepted $9201 w Lys 201 B) (J. Am. Chem. Soc. 1997, 119, 4285-4291) Cysteine proteases have been implicated in diseases such as rheumatoid arthritis, muscular dystrophy and cancer metastasis; therefore, they are important targets in medicinal chemistry which has sought to develop inhibitors for this class of proteases. Complete the synthesis of the frame for a cysteine protease inhibitor. No stereochemistry needs to be shown. 1)LDA. 0 O THE-78 °c 0 0 CH3CH2CH20JJ\L fiOCHzCHQCH‘g —* H3CH2CH2CO 2) H30+ O (protonation) O +CH2CHZCH30H O s s Hs/fi CH3CH2CH20J-Kri SH 0 cat TsOH | anhydrous BF30(CH2CH3)2 Ph 0 (Lewis Acid) H 0 —" H2N A H20 0 HO CF3 0 + SHCH20H28H I] ...
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