Synthetic Studies in Phytochrome Chemistry

Abstract

An account is given of the author’s several approaches to the synthesis of the parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole derivative that controls photomorphogenesis in higher plants. These studies culminated in enantioselective syntheses of both (2R)- and (2S)-phytochromobilin (4), as well as several ¹³C-labeled derivatives designed to probe the site of Z,E-isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and recombinant-derived phytochrome apoprotein N-C produced a protein-bound chromophore with identical difference spectra to naturally occurring 1.

1 Introduction and Background

2 Early Interests

3 The Azomethine Imine Strategy to Rings A and B:
A Saxitoxin Connection

4 The Sigmatropic Rearrangement Strategy: First Success

5 Regrouping with Pd Chemistry

6 Constructing the C,D-Ring Pyrromethenone of ­Phytochrome

7 Instability Issues: The ‘BC + D + A’ Strategy

8 Enantioselective Syntheses of (R)- and (S)-Phyto­chromobilin

9 Probing the Site of Pr Photoisomerization

Key words

phytochrome - pyrroles - lactams - alkynes - palladium

References

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21

The structure of dihydropyrromethenone 63b (E-isomer, R = CO₂Me) and alkyne acid 88c were unequivocally established by single crystal X-ray analysis performed by Ms Gayle Schulte, Yale University.

25

As expected, enamides 82 exhibited atropisomerism due to hindered N-N bond rotation, although each isomer had identical photochemical behavior.

43

We are grateful to Professor Albert Gossauer, of the Université de Fribourg Suisse, for providing us with NMR and IR spectra for 132.

46

Manuscript in preparation: O’Neal, W. G.; Roberts, W. P.; Jacobi, P. A. ‘A Practical Synthesis of C,D-Unsymmetrical Chlorins’.

48

We are grateful to Dr. Victor G. Young, X-ray Crystallographic Laboratory, Department of Chemistry, University of Minnesota, for carrying out the X-ray analysis of 167b.

51

We are grateful to Dr. Hui Liu of this department for carrying out these experiments.

52

Sheila graciously made the move to Dartmouth during her last year, and provided invaluable continuity for the project.

57

In addition to Professor Lagarias, I am indebted to his associates who carried out these experiments, Dr. Nicole Frankenberg and in particular Ms. Lixia Shang. Professor Lagarias’ research in this area is supported by NIH Grant GM068552, which is gratefully acknowledged.

60

Personal communication, Professor Richard A. Mathies, University of California, Berkeley, USA.