S. Zhang 591 Pt. 1 Material (Heterocyclic Chemistry, Mapk)

Front 1

Types of ring opening reactions, epoxides

Back 1

Acid/enzyme catalyzed

Nucleophilic

Front 2

Reagent to reduce epoxides to alcohols

Back 2

LiAlH4

Front 3

oxirane synthesis from olefins

Back 3

Uses peroxy acids, proceeds through butterfly intermediate

Front 4

Common names for the three types of aliphatic 3-membered heterocycles

Back 4

N-containing: ethylenimine

O-containing: ethylene oxide/epoxide

S-containing: ethylene sulfide/episulfide

Front 5

Examples of epoxides in our system

Back 5

Vitamin K epoxide (cofactor in reaction of descarbosy-prothrombin to prothrombin)

Squalene epoxide (precursor to cholesterol)

Front 6

Strain in three-membered rings makes protons more _____

Back 6

acidic b/c increased s-character in bonds

Front 7

Methods of aziridine synthesis

Back 7

From animoalcohol with thionyl chloride or sulfuric accid

From azide and alkene

From epoxide (stereochemical inversion)

Front 8

Description of MAPK's

Back 8

Evolutionarily conserved enzymes connecting cell surface receptors to critical regulatory targets within cells

Front 9

MAPK stands for

Back 9

Mitogen activated protein kinase

Front 10

Types of MAPKs in mammalian cells

Back 10

1. Extracellular signal-regulated kinases (ERK1/2)

2. c-Jun N-terminal kinases (JNK1/2/3)

3. p38 kinases (p38alpha/beta/gamma/delta)

4. ERK5 (big MAPK/BMK)

5. ERK3s (ERK3/4)

6. ERK7s (ERK 7/8)

Front 11

Common features of MAPKs

Back 11

1. Proline-targeted serine/threonine kinases

2. Activation occurs on phosphorylation of two residues in kinase activation loop

3. regulated through tree-tiered cascade of protein phosphorylation

Front 12

MAPK regulation cascade

Back 12

mitogen --> MAP3K (MAPK kinase kinase) --> MAP2K (MAPK kinase kinase) --> MAPK

Front 13

Processes MAPKs are involved with, for example

Back 13

Transcription

Cell cycle regulation

apoptosis

Front 14

RSK stands for

Back 14

Ribosomal s6 kinase

Front 15

MSK stands for

Back 15

Mitogen- and stress- activated protein kinase

Front 16

Signaling cascade in response to mitogens

Back 16

Mitogens -->

MEK1/2 -->

ERK1/2 -->

RSK 1-4 (cell survival, proliferation), MNK 1/2 (mRNA translation), MSK1/2 (nuclear response to stress)

Front 17

Signaling cascade in response to stress cytokines

Back 17

Stress cytokines -->

MEK3/6 -->

p38 -->

MNK1 (mRNA translation), MSK1/2 (nuclear response to stress), MK2,3,6 (mRNA stability)

Front 18

MAPKs are regulated by

Back 18

interactions with substrates via docking motifs, scaffold proteins, subcellular localization, phosphatases

Front 19

Reason why MEK is a dual-specificity kinase

Back 19

two amino acid residues are on the target protein

Front 20

Examples of docking motifs that regulate MAPKs

Back 20

D motif, DEF motif

Front 21

CD domain stands for

Back 21

Common Docking domain

Front 22

Back 22

Common name: ethylene sulfide, episulfide

Systematic name: thiirane

Front 23

Relative reactivity of oxirane and thiirane

Back 23

Both highly reactive, but oxirane is more reactive (because more strained)

Front 24

Reactions of thiirane

Back 24

1.nucleophilic ring opening

2. Oxidation by NaIO4 or peroxy acid, yields alkene and SO

Front 25

Thiirane synthesis methods

Back 25

1. from 2-chloroethyl mercaptan, with base

2. from 2-hydroxyethane thiol, with COCl2 (phosgene)

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Back 26

Common name: trimethylene oxide

Systematic name: oxetane

Front 27

Relative reactivity: oxetane to oxirane

Back 27

Similar reactivity, but oxirane is faster

Front 28

Reactions of oxetanes

Back 28

1. acid-catalyzed opening to 1,3-diol

2. Lewis acid-catalyzed polymerization

Front 29

Methods of oxetane synthesis

Back 29

1. cyclization of 1,3-diol with base and SO2R

2. Paterno Buchi Reaction (cycloaddition of alkene and carbonyl)

Front 30

Scientist who discovered penicillin

Back 30

Alexander Fleming

Front 31

Taxol contains this type of aliphatic heterocycle

Back 31

Oxetane

Front 32

Back 32

Azetidine

Front 33

Beta lacatam mechanism

Back 33

Bind to penicillin binding protein

Front 34

How do bacteria get resistance to beta lactams?

Back 34

Beta lactamase hydrolyzes amide bond

Front 35

Solution to beta lactam resistance

Back 35

use suicide inhibitor that binds to beta lactamase

Front 36

Differences between THF and diethyl ether

Back 36

Oxygen in THF is less sterically hindered, increasing its solvation and making it more H2O soluble

Front 37

What does alpha-substitution with a carbonyl do to THF?

Back 37

1. Changes it to gamma lactone

2. Makes it very unstable - very prone to acid or base hydrolysis