Introduction to Chemistry 32B Spring 2009

Instructor: Dr. Tyler Johnsonemail: tjohnson@sjcc.edu

Office Hours: Wednesday 12:15-1:15pm S-205

Text: General, Organic and Biochemistry, Bettelheim, Brown and March, 7th ed. 2004,Thomson-Brookes/Cole: (a) workshop Workbook,

(b) Chime molecular modeling exercises (c) Laboratory manual - purchased in the campus bookstore

(in separate shrink wrap)Lecture: M/W: 10:45-12:10pm in S-205

Laboratory: M: 12:40-3:45pm in S-201 (computer) or S-211 (wet lab)

Preliminary Syllabus (PLEASE COPY DOWN)

Week of Page No. in Text Chapter, WS, & Lab Topics(Mon) 1/26 704-719 29 Nutrition and digestion

lab check in, Safety contractSafety video worksheet

(Wed) 1/28 70-83 3 Chemical bonds (Review)269-282 10 Organic Chemistry

Updated Syllabus

Introduction to Chemistry 32B - Spring 2009

Text: General, Organic and Biochemistry, Bettelheim, Brown and March, 7th ed. 2004,Thomson-Brookes/Cole:

Introduction to Chemistry 32B - Spring 2009

Required Questionnaire: Please fill out: . . . Pass to the front

1. Name?

2. MAJOR?

3. Why are you taking Chem 32B?

4. What are your career goals?

5. What do you hope to learn from this course?

6. Your email, (please print)

First Assignment

My Expectations of YouIntroduction to Chemistry 32B - Spring 2009

1. Read the chapter before lecture

2. DO ALL THE ASSIGNED HOMEWORK PROBLEMS - Understand

3. Do not wait until last minute to Study(Unlike BIO, O-Chem cannot be crammed the night before)

4. Plan to set aside, min 3-4 hrs/ day reading the chapter, answering Homework Qs

5. O-Chem not terribly difficult . . .really . . . It just takes a lot of time to master, unlike most science classes

6. GET SERIOUS, Just study (3-4hrs/day) and you should be fine

Most test Qs -- from H-work directly or very similar and Lecture Problems

A COMPREHENSIVE REINVESTIGATION INTO THE BIOACTIVE SECONDARY METABOLITES

OF AN INDO-PACIFIC MARINE SPONGE:Cacospongia mycofijiensis

A dissertation submitted in partial satisfaction ofthe requirements for the degree of

DOCTOR OF PHILOSOPHYin

CHEMICAL OCEANOGRAPHYby

Tyler A. Johnson

November 2008

BACKGROUND Marine Natural Products

Where & Why . . .

What We Study . . .

SOURCES FOR CHEMICALLY PROLIFIC SIMPLE MARINE ORGANISMS

BACKGROUND

Why, Marine Natural Products

-Structural Diversity

Recreated from Feher and Schmidt J. Chem. Inf. Comput. Sci. 2003, 43: 218-227

6,540

434

18,293

1871

8,246

Percent of bioactive ‘Hits” against the NCI-60 cell line(s)

Recreated from Munro, M. H. G. et al., J. Biotechnol. 1999, 70, 15-25.

-Bioactive Hit Rate (NCI 60 cell line)

Why Sponges?

Percent of marine natural products reported by phylum1

(1) Harvey, A. L. Advances in drug discovery techniques; John Wiley & Sons: Chichester , NY, 1998.

Over-Arching Goals

1. Discover Structurally distinct Novel Chemistry (e.g. psymberin)

3. Locate the Mechanism of Action

Bengamide B LAF 289(Phase II)

2. Identify & Develop biologically active Marine Natural Products

Approach to Achieve Objectives

Preclinical (In Vivo) evaluation Clinical Evaluation (6 years)

Development

1/5000

Structure Elucidation NMR, MS In vitro Map Coll Site/ Obs.Chem.

1, 21,4

3

GPS

Collection Extraction (Bioassay/Analytical) Purification

Discovery (3-5 years)

HPLC

Discovery (3-5 years)

Disk Diffusion Soft Agar Colony Formation Assay

Valeriote, F.; Grieshaber, C. K.; Media, J.; et al. J. Exp. Ther. Oncol. 2002, 2, 228-236.

= extract/compound

fijianolide B

Paclitaxel (Taxol)

Pharmakokinetic Analysis of Fijianolide B

Pharmacokinetic analysis of 2 in HCT-116 tumor-bearing SCID mice. The observed concentration of 2 in the plasma (●) and HCT-116 tumor (■) over a 24h period (1440 minutes). At 24h concentration of 2: plasma = 0.2 ug/mL, tumor = 2.8 ug/mg.

Johnson, T. A.; Tenney, K.; Cichewicz, R. H.; Morinaka, B. I.; White, K. N.; Amagata, T.; Subramanian, B.; Media, J.; Mooberry, S. L.; Valeriote, F. A.; Crews, P. J. Med. Chem. 2007, 50, 3795-3803.

Johnson, T. A.; Tenney, K.; Cichewicz, R. H.; Morinaka, B. I.; White, K. N.; Amagata, T.; Subramanian, B.; Media, J.; Mooberry, S. L.; Valeriote, F. A.; Crews, P. J. Med. Chem. 2007, 50, 3795-3803.

In vivo Evaluation of Fijianolide B

In vivo assessment of 2 using HCT-116 tumor-bearing SCID mice. The average tumor weight measured per day after daily inoculation of 2 for 5 days: 25 mg/kg/day (■), 12.5 mg/kg/day (▲), and control (♦).

NOTES:+ preclinical in vivo of 2-Launch Phase I clinical trial . .

General, Organic, and General, Organic, and Biochemistry, 8eBiochemistry, 8e

Bettelheim, BrownBettelheim, Brown

Campbell, & FarrellCampbell, & Farrell