Progress in the Chemistry of Organic Natural Products / Fortschritte der Chemie organischer Naturstoffe, Volume 84

About this book

Of the porphyrinoid structures occurring in nature the most important and most widespread are the red blood pigment heme (1), the green pigment of plant photosynthesis chlorophyll a (2), the bacterial photo- synthetic pigment bacteriochlorophyll a (3), and the "antipernicious" red pigment vitamin BJ2 (4). The basic function of these cofactors are determined by the incorporation of the different metal ions into the macrotetracycles. The different oxidation levels of the macrocyclic ligand system regulate the fine tuning of these functions. The final adaptation of the cofactors to their special molecular environments in the cell compartments is effected by variation of the substitution patterns of the chromophores. HCO,C 3 CO,Phytyl 2 Heme Chlorophyll a CONH, CONH, ~ H,NOC 1 , CONH, /I(Y N~ 3 4 Bacteriochlorophyll a Vitamin B" HO References, pp. 42-51 Naturally Occurring Cyclic Tetrapyrroles 3 Until the mid-1970s the four classic cyclic tetrapyrrolic structures with their porphyrin, chi orin, bacteriochlorin, and corrin skeletons were almost the only representatives in the class of porphyrinoid natural products (1-10). Although other partially reduced porphyrins were conceivable, none of these partially saturated porphyrinoid structures had hitherto been found in nature.

Reprint of the original 2002 edition.

Contents

Naturally Occurring Cyclic Tetrapyrroles

1. Introduction

2. Classification

3. General Aspects of Cyclic Tetrapyrrole Biosynthesis

4. Porphyrins
4.1. Occurrence, Structure, and Biological Function
4.2. Biosynthesis
4.3. Aspects of Synthesis

5. Chlorins
5.1. Occurrence, Structure, and Biological Activity
5.2. Biosynthesis
5.3. Aspects of Synthesis

6. Bacteriochlorins
6.1. Occurrence, Structure, and Biological Activity
6.2. Aspects of Synthesis

7. Isobacteriochlorins
7.1. Occurrence, Structure, and Biological Activity
7.2. Biosynthesis
7.3. Aspects of Synthesis

8. Higher Saturated Hydroporphyrins
8.1. Occurrence, Structure, and Biological Activity
8.2. Biosynthesis

9. Corrins

Acknowledgments
References

The Chemistry of Taxol and Related Taxoids
1. Introduction

2. A-Ring Chemistry
2.1. Modifications of the 11,12-Double Bond
2.2. Modifications at C-13
2.3. Modifications at C-14
2.4. Modifications at C-18

3. B-Ring Chemistry
3.1. Modifications at C-10
3.2. Modifications at C-9
3.3. Modifications at C-19
3.4. Modifications at C-2
3.5. Modifications at C-l
3.6. Other B-Ring Analogs
3.7. SAR of B-Ring Analogs

4. C-Ring Chemistry
4.1. The C-7 Hydroxyl Group
4.2. Products Derived from 6,7-Dehydrotaxol
4.3. Modifications at C-4

5. D-Ring Chemistry
5.1. Ring Opening by Electrophiles
5.2. Ring-Opening by Nucleophiles
5.3. D-Ring Analogs
5.4. Spectroscopic and Theoretical Studies

6. Rearrangements and Related Reactions
6.1. Rearrangements Leading to 11(15?1)-abeo taxols (A-nortaxols)
6.2. Rearrangements Involving the B-Ring
6.3. Rearrangements Involving Both A- and B-Rings
6.4. Rearrangements of Ring C

7. The Side Chain
7.1. Synthesis of the Side Chain by the -lactam Approach
7.2. Synthesis of the Side Chain via an Epoxide Intermediate
7.3. Synthesis of the Side Chain by Sharpless Asymmetric Aminohydroxylation
7.4. Synthesis of the Side Chain by Coupling Reactions
7.5. Synthesis of Cyclically Protected Side Chains
7.6. Miscellaneous Syntheses
7.7. Syntheses of Phosphonate Side Chain Analogs

8. Synthesis of Taxol and Taxol Side Chain Analogs from Baccatin III
8.1. Synthesis of Taxol and Docetaxel
8.2. Synthesis of N-Acyl Analogs of Taxol
8.3. Synthesis of 3?-Aryl Analogs of Taxol
8.4. Taxol Analogs with Modified N-Acyl and 3?-Aryl Groups
8.5. Taxol Analogs Modified Both on the Side Chain and the Ring System
8.6. Synthesis of Taxol Analogs with Highly Modified Side Chains
8.7. Side Chain Chemistry

9. Taxol Metabolites

10. Taxol Analogs and Prodrugs
10.1. Simple Ester Derivatives and Prodrugs
10.2. Phosphate Ester and other Prodrugs
10.3. Taxol Analogs with Polymeric Acyl Substitutions
10.4. Targeted Analogs of Taxol

11. Labeled Taxol Analogs
11.1. Isotopically Labeled Taxols
11.2. Photoaffinity Labeled Taxols
11.3. Fluorescent and Other Labeled Taxols

12. The Synthesis of Taxol and Taxol Analogs from Precursors other than Baccatin III

13. The Synthesis of Simplified and Unusual Taxol Analogs
13.1. Simplified Analogs
13.2. Dimeric Analogs

14. The Synthesis of Taxol
14.1. The Holton Synthesis
14.2. The Nicolaou Synthesis
14.3. The Danishefsky Synthesis
14.4. The Wender Synthesis
14.5. The Kuwajima Synthesis
14.6. The Mukaiyama Synthesis

15. The Interaction of Taxol with Tubulin
15.1. Photoaffinity Labeling Studies
15.2. Fluorescence Spectroscopic Studies
15.3. Nuclear Magnetic Resonance Studies
15.4. The Taxol Pharmacophore

Addendum
Acknowledgements
References
Author Index

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