Synthesizing a Key Synthesizing a Key Piece for an Antibiotic Piece for an Antibiotic

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Synthesizing a Key Synthesizing a Key Piece for an Antibiotic Piece for an Antibiotic

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Latasha Anderson and Jacqueline Latasha Anderson and Jacqueline PetroskiPetroski

Organic Chemistry Research

• Natural Product Synthesis• Ripostatin Antibiotics• Myxobacterium• Handedness• The Process• The Big Picture

Natural Product Synthesis

-A natural product is a “product (molecule) that is derived from plants, animals or microbial sources.

-They can have medicinal value.

-Synthesis means doing chemical reactions on a small molecule to add on or build up to bigger molecules.

Why It’s Important• For decades, natural products have been a

wellspring of drugs and drug leads.

• Penicillin (a miracle drug) was discovered around WWII . It came from a mold!

• There were 877 new chemical molecules introduced as drugs worldwide during 1981–2002.

• 61% of those can be traced to or were inspired by natural products [J. Nat. Prod., 66, 1022 (2003)].

Ripostatins: Potential New Antibiotics

O

HO

CO2R3

O

R2

R1

Ripostatin A: R1, R2 = O R3 = HRipostatin B: R1 = H, R2 = OH R3 = H

Augustiniak, H.; Irschik, H.; Reichenbach, H.; Hofle, G. Liebigs Ann. 1996, 1657-1663.

Myxobacterium• Any of numerous gram-negative,

rod-shaped saprophytic bacteria of the phylum Myxobacteria, typically found embedded in slime in which they form complex colonies and noted for their ability to move by gliding along surfaces without any known organ of locomotion.

Myxobacterium

-Bacteria that predominantly live in the soil and other places……..

Organic Molecules are Handed

• They have a particular arrangement in 3-dimensional space.

• The left and the right hand are not superimposable

Example of Handedness with

Molecules

X

C

Y

OHH

X

C

Y

HOH

OUR GOAL

• Our goal was to make a molecule called a sulfoxide and get as much purity in the handedness as possible.

The Process• We made a ligand that blocked one

face of the molecule so that the reaction had to occur from the other face.

Sun, J.; Zhu, C.; Dai, Z.; Yang, M.; Pan, Y.; Hu, H.

Journal of Organic Chemistry 2004, 69, 8500-8503.

NH HN

OH HO

Our reaction

SCH3

It is an oxidation reaction. Sulfur is oxidized from one particular face and the peroxide is reduced to water.

Note: The pair of electrons on sulfur are coming out of the plane of the molecule and the phenyl ring (Ph) is going behind the plane of the molecule.

S

O

CH3

Ph

Ph

H2O2

VO(acac)2

CHCl3ligand (L) (R)-sulfoxide

• We left it in the freezer overnight.

• Since there were some impurites in our reaction we went through three different steps for purification.

~Seperatory Funnel~Flash Column Chromotagraphy/’Columning”~Distilation

The Bottom Line: Our Molecule’s Handedness• We made a significant amount of

sulfoxide (at least 12g(!) purified)

• To check our molecules handedness we took an optical rotation and found that out of 100 molecules, 85 were ‘right’ handed and 15 were ‘left’ handed. (Not too shabby!!)

Big Picture

S

O

CH3

Ph

O

HO

CO2H

O

OH

H

Sources• http://www.naturalingredient.org/naturalingredi

ents.htm• http://pubs.acs.org/cen/coverstory/8141/8141p

harmaceuticals.html• http://encyclopedia.laborlawtalk.com/myxobact

eria

Acknowledments• Howard Hughes

Medical Institiute• Kim Minor• Haverford College• Fran (not Blasé)

Blase• Doug, Aaron, and

Hernan

Dirty Glassware

Aaron and Doug

Clean Glassware