The total synthesis of chlorophyll a

Abstract

Chlorophyll a, the major green pigment of the plant world, is certainly the most widespread and conspicuous of organic natural products. Few can be unaware of its decorative function, and all are beneficiaries of its central role in transforming sunlight into substance and sustenance. Yet the fruitful chemical study of this green badge of life did not commence until fairly recent times. For chlorophyll a is a very reactive, sensitive, and complicated substance. Only when, early in this century, the genius of Willstatter applied itself to the problem, were the first sure steps taken. That great investigator isolated the pigment-and its closely related frequent minor concomitant chlorophyll b as well-in the pure state, established correctly the empirical formula of the substance, and laid down a sound and extensive preliminary basis of transformation and degradation. These achievements can be measured against the fact that the isolation of chlorophyll in a state of purity is even now, after more than fifty years, no mean feat, and, further, that the empirical formula defined by Willstatter, repeatedly called into question by subsequent investigators, has stood the test of time. For some period after this solid foundation had been laid by Willstatter there was little activity until three new groups took the field late in the 1920s. Stoll, who had played a prominent role in the early studies as a collaborator of Willstatter, took up the work anew, and made important contributions, as did Conant in the United States. But by far the greatest contribution was made by Hans Fischer and his collaborators at Munich. Fresh from his dramatic conquest of the blood pigment, Fischer hurled his legions into the attack on chlorophyll, and during a period of approximately fifteen years, built a monumental corpus of fact. As this chemical record, almost unique in its scope and depth, was constructed, the molecule was transformed and rent asunder in innumerable directions, and the fascination and intricacy of the chemistry of chlorophyll and its congeners was fully revealed. These massive contributions were crowned by the proposal, in 1940, of a structure which was complete except for stereochemical detail. Finally, in a series of elegant investigations completed only during the last few years, Linstead and his associates at Imperial College were able to solve the stereochemical problem and to provide definitive confirmatory detail in respect of the number and disposition of saturated carbon atoms within the nuclear framework. Half a century of structural study had culminated in the complete formula (I) for chlorophyll aI, 8. Our active interest in chlorophyll was initiated four years ago, in 1956. The first questions we asked were very general ones. The structural investigations had been carried out almost entirely during the twilight of the classical period of organic chemistry. Only the very simplest basic * A brief communication recording the results on which this lecture is based has appeared in

Breakdown of chlorophyll: A nonenzymatic reaction accounts for the formation of the colorless “nonfluorescent” chlorophyll catabolites

“…The FCCs are shown to be programmed by nature to further isomerize to the NCCs in an acidic medium. This feature of Chl breakdown has a remarkable manmade parallel in Woodward's total synthesis of Chl: There a surprisingly effective, stereoselective build-up of the ring D periphery of the chlorin macrocycle was achieved by strategic exploitation of the principle ''that two things cannot be at the same place at the same time'' (36,37).…”

The Quest for Quinine: Those Who Won the Battles and Those Who Won the War

“…The catalogue of Woodwards achievements in the total synthesis of natural products include quinine [(AE )-homomeroquinene (17) or (+)-quinotoxine, 1944], patulin (1950), [94] cholesterol and cortisone (1952), [95] lanosterol (1954), [96] lysergic acid and strychnine (1954), [97] reserpine (1958), [98] ellipticine (1959), [99] chlorophyll a (1960), [100] tetracycline (1962), [101] colchicine (1965), [102] cephalosporin C (1966), [103] prostaglandin F 2a (1973), [104] and his paramount achievement: the synthesis of vitamin B 12 (1973, with A. Eschenmoser). [105] The total synthesis of erythromycin A was published in 1981, [106] after his death.…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…One molecule belonging to this class, chlorophyll-a (5), is a crucial prerequisite for sustaining life on our planet by its ability to participate in the conversion of carbon dioxide into carbohydrates with concomitant liberation of molecular oxygen by photosynthesis. The total synthesis of chlorophyll-a (5) conducted by Woodward constitutes one of the most prominent achievements in organic chemistry [27]. This, and several related pigments, is biosynthesized from the common building block porphobilinogen (6) [28][29][30].…”